Affinage

ALAS2

5-aminolevulinate synthase, erythroid-specific, mitochondrial · UniProt P22557

Length
587 aa
Mass
64.6 kDa
Annotated
2026-04-28
95 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ALAS2 is the erythroid-specific, mitochondrial 5-aminolevulinate synthase that catalyzes the rate-limiting condensation of glycine and succinyl-CoA to form 5-aminolevulinic acid, the first committed step in heme biosynthesis. The enzyme requires pyridoxal 5'-phosphate (PLP) as an essential cofactor that stabilizes protein folding and active-site integrity, and it physically associates with the beta subunit of succinyl-CoA synthetase (SUCLA2) in mitochondria to ensure efficient substrate channeling; its C-terminal extension normally constrains catalytic turnover, with gain-of-function truncations increasing Vmax and causing X-linked protoporphyria, while loss-of-function missense mutations reduce activity and cause X-linked sideroblastic anemia (PMID:18760763, PMID:10727444, PMID:22740690, PMID:7560104, PMID:30678654). Erythroid-specific transcription is governed by a GATA1/TAL1/LMO2/LDB1 enhancer complex at the intron 1 GATA site, which forms long-range chromatin loops with the intron 8 GATA site and proximal promoter; deletion of this element causes embryonic lethality from absent ALAS2 expression (PMID:28123038, PMID:23935018). ALAS2 deficiency leads to cytoplasmic iron overload and increased susceptibility to ferroptosis in erythroid precursors (PMID:12393610, PMID:35637209).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    Establishing how catalytic-domain mutations reduce ALAS2 function and why patients respond to pyridoxine: the F165L mutation reduces activity to ~26% of normal, and exogenous PLP rescues the mutant enzyme by stabilizing its structure, providing the first biochemical mechanism for pyridoxine-responsive X-linked sideroblastic anemia.

    Evidence Prokaryotic expression and purification of recombinant wild-type and F165L ALAS2; enzymatic activity assays ± PLP

    PMID:7949148

    Open questions at the time
    • Crystal structure of PLP-bound ALAS2 not determined
    • Mechanism of PLP stabilization at atomic level unknown
  2. 1995 High

    Generalization of the PLP-stabilization mechanism: two additional XLSA mutations (K299Q, A172T) showed marked thermolability rescued by PLP, confirming that cofactor-dependent stabilization—not catalytic rescue per se—is the primary basis for pyridoxine responsiveness across multiple ALAS2 variants.

    Evidence Recombinant mutant enzyme thermostability assays ± PLP

    PMID:7560104 PMID:7705839

    Open questions at the time
    • Number of PLP-binding sites and their structural basis unresolved
    • In vivo PLP pharmacokinetics in erythroblasts not addressed
  3. 2000 High

    Discovery that ALAS2 does not function in isolation: it physically interacts with the ATP-specific succinyl-CoA synthetase beta subunit (SCS-βA/SUCLA2) in mitochondria, and the XLSA mutant D190V disrupts this interaction, suggesting substrate channeling as a requirement for efficient heme synthesis.

    Evidence Yeast two-hybrid screen of human bone marrow cDNA library; reciprocal co-immunoprecipitation in mammalian cells

    PMID:10727444

    Open questions at the time
    • Stoichiometry and structural basis of the ALAS2–SUCLA2 complex unknown
    • Whether SUCLA2 interaction affects ALAS2 mitochondrial import unresolved
  4. 2002 High

    Demonstrating downstream cellular consequences of ALAS2 loss: ALAS2-null erythroblasts accumulate 15-fold excess cytoplasmic (not mitochondrial) non-heme iron and exhibit lipid peroxidation, establishing that ALAS2 deficiency per se—not just reduced heme—drives iron-mediated oxidative damage in sideroblastic anemia.

    Evidence ES cell-derived definitive erythroblasts from Alas2-null cells; non-heme iron quantification; electron microscopy; lipid peroxidation assays

    PMID:12393610

    Open questions at the time
    • Mechanism of cytoplasmic rather than mitochondrial iron accumulation not explained
    • Whether iron accumulation is cause or consequence of differentiation block unclear
  5. 2003 High

    Identification of the proximal promoter as a critical erythroid regulatory element: a point mutation at nucleotide −206 reduced reporter activity by 94% and patient erythroblast ALAS2 mRNA by 87%, showing that transcriptional regulation is an independent disease mechanism for congenital sideroblastic anemia.

    Evidence Luciferase reporter assay in K562 cells; mRNA quantification in patient erythroid precursors

    PMID:12663458

    Open questions at the time
    • Transcription factor(s) binding the −206 element not identified
    • Relationship between promoter and intron 1 enhancer elements not established
  6. 2008 High

    Reversal of the disease paradigm: C-terminal frameshift deletions (removing 19–20 residues) markedly increase ALAS2 activity rather than reducing it, causing X-linked protoporphyria—demonstrating that the C-terminal extension is an autoinhibitory domain and that gain-of-function and loss-of-function mutations in the same gene cause distinct porphyrias.

    Evidence Prokaryotic expression of frameshift mutant enzymes; enzymatic activity assays across eight families

    PMID:18760763

    Open questions at the time
    • Structural basis of C-terminal autoinhibition not resolved at atomic level
    • Whether C-terminal truncations alter subcellular localization in vivo unknown
  7. 2011 High

    Systematic kinetic profiling of ten XLSA mutations consolidated the PLP-stabilization model and revealed that the penultimate C-terminal residue (Y586) modulates ALA product release rate, extending the functional map of the C-terminal region beyond simple autoinhibition.

    Evidence Prokaryotic expression of ten XLSA and one gain-of-function (Y586F) mutant; kinetic and thermostability assays ± PLP

    PMID:21309041 PMID:21653323

    Open questions at the time
    • No crystal structure of C-terminal region
    • Product release kinetics not measured for all known gain-of-function variants
  8. 2012 High

    Defining the dual role of the C-terminus: C-terminal residues around Met567/Ser568 are required for SUCLA2 binding, and XLSA mutations that abolish this interaction lose in vivo function despite normal in vitro activity, establishing SUCLA2 coupling as essential for physiological heme synthesis; separately, R452 mutations disrupt succinyl-CoA cooperativity and PLP affinity.

    Evidence SUCLA2 affinity column binding assays; enzyme kinetics with multiple mutants

    PMID:22740690

    Open questions at the time
    • Whether SUCLA2 binding and autoinhibition are separable C-terminal functions not fully dissected
    • In vivo validation of SUCLA2-binding requirement lacking
  9. 2013 High

    Identification of the intron 1 GATA element as the master erythroid enhancer of ALAS2: GATA1 binds this 130-bp element in vivo and in vitro, and patient mutations disrupting the GATA site abolish enhancer activity and cause congenital sideroblastic anemia, linking cis-regulatory disruption to disease.

    Evidence ChIP, EMSA, luciferase reporter assays in K562 cells; patient mutation analysis

    PMID:23935018

    Open questions at the time
    • Full composition of the enhancer-bound complex not determined
    • Whether intron 1 GATA site functions autonomously or requires cooperation with other regulatory elements unclear
  10. 2016 High

    In vivo confirmation and mechanistic elaboration: CRISPR deletion of the 13-bp intron 1 GATA site in mice caused embryonic lethality from severe anemia, and chromatin conformation analysis revealed long-range loops connecting intron 1, intron 8, and the promoter, anchored by a GATA1/TAL1/LMO2/LDB1/Pol II complex.

    Evidence CRISPR/Cas9 mouse knockout; ChIP; chromatin loop analysis

    PMID:28123038

    Open questions at the time
    • Order of assembly of the enhancer complex unknown
    • Whether the intron 8 GATA site is independently required not tested
  11. 2019 High

    Mechanistic basis of C-terminal gain-of-function refined: XLP truncation mutations increase Vmax up to 5.6-fold with an inverse correlation between thermostability and activity, indicating that loss of C-terminal residues increases active-site flexibility and accelerates catalytic turnover.

    Evidence Site-directed mutagenesis; purified recombinant enzyme kinetics; thermostability assays

    PMID:30678654

    Open questions at the time
    • No direct structural evidence for active-site opening
    • Effect of gain-of-function on SUCLA2 interaction not systematically tested
  12. 2022 Medium

    Linking ALAS2 deficiency to ferroptosis: ALAS2 knockdown in human erythroblasts increases lipid peroxidation and ferroptosis susceptibility via BACH1-mediated repression of iron metabolism and glutathione synthesis genes, providing a pathway-level mechanism for the oxidative damage seen in sideroblastic anemia.

    Evidence CRISPR/base-editing of ALAS2 in cord blood-derived erythroblasts; erastin-induced ferroptosis; lipid peroxide quantification; gene expression profiling

    PMID:35637209

    Open questions at the time
    • BACH1 involvement not validated by genetic rescue
    • Whether ferroptosis contributes to ringed sideroblast formation in vivo unknown
    • Single-lab finding
  13. 2024 High

    Fine-mapping of C-terminal residue function: V562A decreases enzyme stability while M567I alters substrate cooperativity without gross structural change, demonstrating that individual C-terminal residues independently tune stability versus active-site geometry.

    Evidence Purified recombinant V562A and M567I mutant enzymes; kinetic and thermal stability assays; PLP binding

    PMID:38888931

    Open questions at the time
    • High-resolution crystal or cryo-EM structure of C-terminal extension still lacking
    • Whether these residues affect SUCLA2 binding differentially not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: the atomic-resolution structure of full-length ALAS2 (including the C-terminal extension), the structural basis and physiological relevance of heme feedback inhibition in erythroid cells, and how the ALAS2–SUCLA2 complex is organized to channel succinyl-CoA within the mitochondrial matrix.
  • No experimentally determined structure of full-length human ALAS2
  • Heme feedback mechanism demonstrated only in vitro (preprint) and not validated in vivo
  • In vivo stoichiometry and dynamics of ALAS2–SUCLA2 interaction unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 8 GO:0016874 ligase activity 3
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1643685 Disease 3
Partners
BACH1GATA1LDB1LMO2SUCLA2TAL1
Complex memberships
ALAS2-SUCLA2

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 C-terminal frameshift deletions in ALAS2 (p.E569GfsX24 and p.M567EfsX2) markedly increase enzymatic activity (gain-of-function), causing X-linked dominant protoporphyria rather than sideroblastic anemia, demonstrating that the 19-20 C-terminal residues normally constrain ALAS2 activity. Prokaryotic expression of mutant enzymes with enzymatic activity assays American journal of human genetics High 18760763
2000 ALAS2 (ALAS-E) physically interacts in mitochondria with the beta subunit of ATP-specific succinyl-CoA synthetase (SCS-betaA); the D190V XLSA mutant fails to associate with SCS-betaA, suggesting this interaction promotes efficient succinyl-CoA utilization or mitochondrial import of ALAS2. Yeast two-hybrid screen of human bone marrow cDNA library, followed by transient expression and co-immunoprecipitation in mammalian cells The Journal of clinical investigation High 10727444
2012 ALAS2 C-terminal residues (around Met567/Ser568) are required for binding to the beta subunit of succinyl-CoA synthetase (SUCLA2); mutations abolishing SUCLA2 binding cause XLSA even with normal in vitro enzymatic activity and stability, indicating that the ALAS2-SUCLA2 complex is required for full in vivo heme synthetic activity. Additionally, XLSA mutations R452C and R452H retain SUCLA2 binding but show loss of positive cooperativity for succinyl-CoA, increased Km for succinyl-CoA, and reduced vitamin B6 affinity. SUCLA2 affinity column binding assays, enzyme kinetics of expressed mutant proteins, in vitro substrate cooperativity analysis The Journal of biological chemistry High 22740690
1994 The F165L missense mutation in the first conserved catalytic domain of ALAS2 reduces specific enzymatic activity to ~26% of normal; pyridoxal 5'-phosphate (PLP) activates and stabilizes the mutant enzyme in vitro, mechanistically explaining pyridoxine responsiveness in affected patients. Prokaryotic expression and affinity purification of mutant and wild-type ALAS2 fusion proteins; enzymatic activity assays with and without PLP Blood High 7949148
1995 ALAS2 missense mutations K299Q and A172T cause marked thermolability of the recombinant enzyme; addition of pyridoxal 5'-phosphate in vitro stabilizes both mutant enzymes, demonstrating that PLP acts as a cofactor stabilizer and explaining pyridoxine responsiveness. In vitro expression of recombinant mutant ALAS2 enzymes; thermostability assays with and without PLP The Journal of clinical investigation High 7560104
2013 A 130-bp enhancer in intron 1 of ALAS2 contains a GATA1-binding cis-element essential for erythroid-specific ALAS2 expression; GATA1 binds this element in vivo and in vitro, and mutations disrupting the GATA site abolish enhancer activity and cause congenital sideroblastic anemia. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), luciferase reporter assays in K562 cells, patient mutation analysis Haematologica High 23935018
2016 The intron 1 GATA site (int-1-GATA) of ALAS2 is indispensable for ALAS2 expression in vivo; deletion of this 13-bp fragment in mice causes embryonic lethality from severe anemia due to absent ALAS2 expression. The int-1-GATA site forms a long-range chromatin loop with the intron 8 GATA site and the proximal promoter, anchoring an enhancer complex containing GATA1, TAL1, LMO2, LDB1, and Pol II. CRISPR/Cas9-mediated in vivo deletion in mice; chromatin conformation/loop analysis; ChIP for transcription factor occupancy Nucleic acids research High 28123038
2003 A C-to-G transversion at nucleotide -206 in the ALAS2 proximal promoter causes a 94% loss of luciferase reporter activity in K562 erythroid cells and reduces ALAS2 mRNA by 87% in patient erythroblasts, identifying this region as a critical erythroid regulatory element. Luciferase reporter assay in K562 cells; primer extension; mRNA quantification in patient erythroid precursors Blood High 12663458
2011 Ten ALAS2 missense mutations associated with XLSA were expressed in E. coli; five caused decreased enzymatic activity under standard conditions, and two showed decreased activity only without exogenous PLP and increased thermosensitivity, establishing that PLP-dependent stabilization is the primary mechanism for pyridoxine-responsive variants. Prokaryotic expression of mutant ALAS2 proteins; in vitro enzymatic activity assays with and without exogenous PLP; thermosensitivity assays Human mutation High 21309041
2019 XLP gain-of-function truncation mutations in the ALAS2 C-terminal region increase Vmax for both succinyl-CoA and glycine substrates (1.4- to 5.6-fold), with an inverse correlation between thermostability and activity increase, indicating that increased molecular flexibility/active-site openness in the C-terminal region is the mechanism of enhanced enzymatic function. Site-directed mutagenesis; prokaryotic expression and purification; enzyme kinetic assays for Vmax, Km; thermostability assays Molecular medicine High 30678654
2011 A gain-of-function ALAS2 mutation (Y586F, c.1757 A>T) significantly increases the rate of 5-aminolevulinate release compared to wild-type ALAS2, demonstrating that the penultimate C-terminal residue modulates catalytic turnover and that ALAS2 gain-of-function can act as a modifier gene in congenital erythropoietic porphyria. Prokaryotic expression of Y586F mutant ALAS2; enzymatic activity assay measuring ALA release rate Blood High 21653323
2002 ALAS2-null definitive erythroblasts (derived from Alas2-null ES cells differentiated in culture) accumulate 15-fold more non-heme iron in the cytoplasm (not mitochondria) and exhibit increased lipid peroxidation compared to wild-type, demonstrating that ALAS2 deficiency per se causes cytoplasmic iron accumulation and oxidative stress without blocking erythroid differentiation. ES cell differentiation to definitive erythroblast stage; quantitative non-heme iron measurement; electron microscopy for iron localization; lipid peroxidation assays Blood High 12393610
1998 The R411C ALAS2 mutation reduces enzymatic activity to 12-25% of wild-type (depending on PLP concentration), demonstrating a direct mechanistic link between this catalytic-core mutation and pyridoxine-responsive XLSA. E. coli expression and purification of mutant ALAS2; ALAS activity assays with and without PLP British journal of haematology High 9858242
1995 A G-to-A mutation at nucleotide 871 (exon 7) causing a Gly-to-Ser substitution in ALAS2 markedly decreases enzymatic activity of the expressed mutant protein, establishing the catalytic importance of this glycine residue. Prokaryotic expression of mutant ALAS2; enzymatic activity measurement Human genetics Medium 7705839
2015 The ALAS2 Y365C mutation impairs binding of the essential cofactor pyridoxal 5'-phosphate (PLP) to the enzyme, resulting in protein destabilization and loss of function; X inactivation in reticulocytes showed complete skewing toward the WT allele, indicating strong selective pressure against ALAS2-deficient erythroid precursors. Whole-exome sequencing; biochemical characterization of expressed mutant enzyme (PLP binding assay); X-inactivation analysis in blood fractions and primary erythroid cultures The Journal of clinical investigation High 25705881
2015 miR-218 directly targets the 3'-UTR of ALAS2 mRNA to repress its expression; overexpression of miR-218 in K562 cells inhibits erythroid differentiation and alters iron metabolism in a manner phenocopying ALAS2 knockdown. 3'-UTR luciferase reporter assay; miR-218 overexpression; ALAS2 shRNA knockdown as functional control; flow cytometry for erythroid differentiation markers International journal of molecular sciences Medium 26703568
2022 ALAS2 knockdown in human erythroblasts (XLSA model) increases susceptibility to ferroptosis, associated with elevated lipid peroxides, enhanced BACH1 expression, and BACH1-mediated repression of iron metabolism and glutathione synthesis genes. CRISPR/base-editing introduction of ALAS2 missense mutations in cord blood-derived erythroblasts; ferroptosis inducer (erastin) treatment; lipid peroxide measurement; gene expression profiling; BACH1 functional analysis Scientific reports Medium 35637209
2024 Two C-terminal ALAS2 loss-of-function variants (V562A and M567I) do not cause gross structural perturbations but show decreased enzyme stability (V562A) and altered cooperativity of substrate binding (M567I); PLP addition moderately increases stability of both variants, indicating that the C-terminal extension modulates active-site geometry and substrate cooperativity. Site-directed mutagenesis; prokaryotic expression and purification; enzyme kinetic assays; thermal stability assays; PLP binding assays Biochemistry High 38888931
2025 Mature human ALAS2 in the mitochondrial matrix is inhibited by heme through a reversible mixed-inhibition mechanism; structure-based modeling identifies two flexible regions of ALAS2 that interact with heme, locking the enzyme in an inactive conformation and occluding the active site, constituting a negative feedback loop for erythroid heme biosynthesis. Enzymatic inhibition assays with heme; structure-based computational modeling of heme-ALAS2 interaction; affinity measurements bioRxivpreprint Medium bio_10.1101_2025.06.09.658730
2016 Two ALAS2 missense mutations (p.Leu406Phe and p.Tyr500Cys) reduce ALAS2 specific enzymatic activity to 14% and 7% of control respectively when expressed in E. coli, confirming their pathogenic mechanism in XLSA. Prokaryotic expression; in vitro ALAS2 enzymatic activity assays Molecular genetics & genomic medicine Medium 27247955
2017 A novel 11-bp deletion in exon 10 of ALAS2 produces a monomeric rather than homodimeric protein structure (as predicted by SWISS model), resulting in marked loss of function and protein instability in a female infant with XLSA. Protein structural modeling (SWISS-MODEL); genetic mutation characterization Journal of pediatric hematology/oncology Low 28731922

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 C-terminal deletions in the ALAS2 gene lead to gain of function and cause X-linked dominant protoporphyria without anemia or iron overload. American journal of human genetics 215 18760763
2005 ASB proteins interact with Cullin5 and Rbx2 to form E3 ubiquitin ligase complexes. FEBS letters 98 16325183
1995 Late-onset X-linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. The Journal of clinical investigation 86 7560104
1994 X-linked sideroblastic anemia: identification of the mutation in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) in the original family described by Cooley. Blood 81 7949148
2001 ASB-2 inhibits growth and promotes commitment in myeloid leukemia cells. The Journal of biological chemistry 77 11682484
2000 Interaction between succinyl CoA synthetase and the heme-biosynthetic enzyme ALAS-E is disrupted in sideroblastic anemia. The Journal of clinical investigation 76 10727444
2013 Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia. Haematologica 75 23935018
2011 ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria. Blood 65 21653323
1999 Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis. Blood 63 10029606
2011 Sideroblastic anemia: molecular analysis of the ALAS2 gene in a series of 29 probands and functional studies of 10 missense mutations. Human mutation 59 21309041
1992 Assignment of human erythroid delta-aminolevulinate synthase (ALAS2) to a distal subregion of band Xp11.21 by PCR analysis of somatic cell hybrids containing X; autosome translocations. Genomics 56 1577484
2001 Functional analysis of Asb-1 using genetic modification in mice. Molecular and cellular biology 54 11509662
2001 ATRA-regulated Asb-2 gene induced in differentiation of HL-60 leukemia cells. FEBS letters 51 11566180
2002 Aberrant iron accumulation and oxidized status of erythroid-specific delta-aminolevulinate synthase (ALAS2)-deficient definitive erythroblasts. Blood 50 12393610
2000 Cloning and characterization of the genes encoding the ankyrin repeat and SOCS box-containing proteins Asb-1, Asb-2, Asb-3 and Asb-4. Gene 48 11111040
2005 Francisella tularensis proteome: low levels of ASB-14 facilitate the visualization of membrane proteins in total protein extracts. Journal of proteome research 46 16212441
2007 The use of ASB-14 in combination with CHAPS is the best for solubilization of human brain proteins for two-dimensional gel electrophoresis. Briefings in functional genomics & proteomics 45 17556486
2013 X-linked sideroblastic anemia due to ALAS2 intron 1 enhancer element GATA-binding site mutations. American journal of hematology 43 24166784
2006 Ankyrin repeat and suppressors of cytokine signaling box protein asb-9 targets creatine kinase B for degradation. The Journal of biological chemistry 43 17148442
2013 Protein interaction screening for the ankyrin repeats and suppressor of cytokine signaling (SOCS) box (ASB) family identify Asb11 as a novel endoplasmic reticulum resident ubiquitin ligase. The Journal of biological chemistry 42 24337577
2012 X-linked sideroblastic anemia due to carboxyl-terminal ALAS2 mutations that cause loss of binding to the β-subunit of succinyl-CoA synthetase (SUCLA2). The Journal of biological chemistry 42 22740690
2015 X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation. The Journal of clinical investigation 41 25705881
2006 X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns. Blood cells, molecules & diseases 39 16735131
2016 Intron 1 GATA site enhances ALAS2 expression indispensably during erythroid differentiation. Nucleic acids research 37 28123038
2003 A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia. Blood 37 12663458
2014 In ferrochelatase-deficient protoporphyria patients, ALAS2 expression is enhanced and erythrocytic protoporphyrin concentration correlates with iron availability. Blood cells, molecules & diseases 36 25179834
2022 METTL3-modified lncRNA-SNHG8 binds to PTBP1 to regulate ALAS2 expression to increase oxidative stress and promote myocardial infarction. Molecular and cellular biochemistry 35 36282350
1992 Identification of a highly polymorphic marker within intron 7 of the ALAS2 gene and suggestion of at least two loci for X-linked sideroblastic anemia. Human molecular genetics 32 1301172
2020 Epigenetics of Skeletal Muscle-Associated Genes in the ASB, LRRC, TMEM, and OSBPL Gene Families. Epigenomes 31 34968235
1995 A new mutation of the ALAS2 gene in a large family with X-linked sideroblastic anemia. Human genetics 31 7705839
2008 Ankyrin repeat and suppressor of cytokine signaling (SOCS) box-containing protein (ASB) 15 alters differentiation of mouse C2C12 myoblasts and phosphorylation of mitogen-activated protein kinase and Akt. Journal of animal science 28 18641171
2003 Molecular cloning and characterization of the human ASB-8 gene encoding a novel member of ankyrin repeat and SOCS box containing protein family. Biochemical and biophysical research communications 28 12559969
2011 Ankyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4 degradation. BMC neuroscience 24 21955513
2007 Ankyrin repeat and SOCS box containing protein 4 (Asb-4) interacts with GPS1 (CSN1) and inhibits c-Jun NH2-terminal kinase activity. Cellular signalling 24 17276034
2021 An unconventional role of an ASB family protein in NF-κB activation and inflammatory response during microbial infection and colitis. Proceedings of the National Academy of Sciences of the United States of America 23 33431678
2022 Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis. Scientific reports 21 35637209
2012 Radio-resistance in psychrotrophic Kocuria sp. ASB 107 isolated from Ab-e-Siah radioactive spring. Journal of environmental radioactivity 21 22809716
2019 Molecular expression, characterization and mechanism of ALAS2 gain-of-function mutants. Molecular medicine (Cambridge, Mass.) 20 30678654
1998 R411C mutation of the ALAS2 gene encodes a pyridoxine-responsive enzyme with low activity. British journal of haematology 19 9858242
2002 Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation. Blood 18 12393718
2021 Muscle atrophy induced by overexpression of ALAS2 is related to muscle mitochondrial dysfunction. Skeletal muscle 17 33785075
2006 ASB-1, a germline-specific isoform of mitochondrial ATP synthase b subunit, is required to maintain the rate of germline development in Caenorhabditis elegans. Mechanisms of development 17 17223323
2017 Non syndromic childhood onset congenital sideroblastic anemia: A report of 13 patients identified with an ALAS2 or SLC25A38 mutation. Blood cells, molecules & diseases 16 28772256
2009 Expression of ankyrin repeat and suppressor of cytokine signaling box protein 4 (Asb-4) in proopiomelanocortin neurons of the arcuate nucleus of mice produces a hyperphagic, lean phenotype. Endocrinology 16 19934378
2008 Solubilization of human erythrocyte membranes by ASB detergents. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 16 18820764
1994 Pyridoxine-refractory congenital sideroblastic anaemia with evidence for autosomal inheritance: exclusion of linkage to ALAS2 at Xp11.21 by polymorphism analysis. Journal of medical genetics 16 7912287
2015 MiR-218 Inhibits Erythroid Differentiation and Alters Iron Metabolism by Targeting ALAS2 in K562 Cells. International journal of molecular sciences 14 26703568
2011 Thermodynamic and structural characterization of zwitterionic micelles of the membrane protein solubilizing amidosulfobetaine surfactants ASB-14 and ASB-16. Langmuir : the ACS journal of surfaces and colloids 13 21657261
2006 Disparate phenotypic expression of ALAS2 R452H (nt 1407 G --> A) in two brothers, one with severe sideroblastic anemia and iron overload, hepatic cirrhosis, and hepatocellular carcinoma. Blood cells, molecules & diseases 13 16540354
2005 Iron overload in an African American woman with SS hemoglobinopathy and a promoter mutation in the X-linked erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. Blood cells, molecules & diseases 13 15885606
2004 Murine Asb-17 expression during mouse testis development and spermatogenesis. Zygote (Cambridge, England) 13 15460110
2008 Expression of murine Asb-9 during mouse spermatogenesis. Molecules and cells 12 18776735
2020 regSNPs-ASB: A Computational Framework for Identifying Allele-Specific Transcription Factor Binding From ATAC-seq Data. Frontiers in bioengineering and biotechnology 11 32850739
2006 Three kinships with ALAS2 P520L (c. 1559 C --> T) mutation, two in association with severe iron overload, and one with sideroblastic anemia and severe iron overload. Blood cells, molecules & diseases 11 16446107
2004 Nucleotide variation at Msn and Alas2, two genes flanking the centromere of the X chromosome in humans. Genetics 11 15166166
2016 Sideroblastic anemia: functional study of two novel missense mutations in ALAS2. Molecular genetics & genomic medicine 10 27247955
2014 X-linked sideroblastic anaemia due to ALAS₂ mutations in the Netherlands: a disease in disguise. The Netherlands journal of medicine 10 24829177
2008 Multi-organ iron overload in an African-American man with ALAS2 R452S and SLC40A1 R561G. Acta haematologica 10 19066423
2008 Stage-specific expression of ankyrin and SOCS box protein-4 (Asb-4) during spermatogenesis. Molecules and cells 8 18414003
2023 Protective effects of electroacupuncture on polycystic ovary syndrome in rats: Down-regulating Alas2 to inhibit apoptosis, oxidative stress, and mitochondrial dysfunction in ovarian granulosa cells. Tissue & cell 7 37075681
2023 Syntheses, Crystal Structure, and Second Harmonic Generation Response of Noncentrosymmetric Layered Selenites and Tellurites of Antimony(V), ASb3X2O12 (A = K, Rb, Cs, Tl; X = Se, Te). Inorganic chemistry 7 37171094
2014 Concomitant a novel ALAS2 mutation and GATA1 mutation in a newborn: a case report and review of the literature. American journal of blood research 7 25232504
2024 Rapid detection of blood using a novel application of RT-RPA integrated with CRISPR-Cas: ALAS2 detection as a model. Forensic science international. Genetics 6 39089060
2020 A Novel ALAS2 Missense Mutation in Two Brothers With Iron Overload and Associated Alterations in Serum Hepcidin/Erythroferrone Levels. Frontiers in physiology 6 33281618
2024 ALAS2 overexpression alleviates oxidative stress-induced ferroptosis in aortic aneurysms via GATA1 activation. Journal of thoracic disease 5 38738239
2020 X-linked dominant protoporphyria in a Chinese pedigree reveals a four-based deletion of ALAS2. Annals of translational medicine 5 32355788
2002 A novel mutation in exon 5 of the ALAS2 gene results in X-linked sideroblastic anemia. Clinica chimica acta; international journal of clinical chemistry 5 12031592
2023 Severe Microcytic Anemia Caused by Complex Hereditary Spherocytosis and X-Linked Sideroblastic Anemia with Mutations in SPTB and ALAS2 Genes. Journal of clinical medicine 4 36902777
2020 [Knockdown of ALAS2 Affects Erythroid Differentiation by Down-regulating Mitophagy Receptor BNIP3L]. Zhongguo shi yan xue ye xue za zhi 3 33067979
2014 [Congenital sideroblastic anemia-a new family with identification of K156E mutation of ALAS2 gene and literature review]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 3 24606657
2025 The role of genetic testing in accurate diagnosis of X-linked sideroblastic anemia: novel ALAS2 mutations and the impact of X-chromosome inactivation. Scientific reports 2 40195342
2024 Elucidating the Role of Human ALAS2 C-terminal Mutations Resulting in Loss of Function and Disease. Biochemistry 2 38888931
2024 The ASB@HNTs-PVA nanofiber membrane, possessing both anti-inflammatory and hemostatic activities, promotes the healing of T2D skin wounds. International immunopharmacology 2 39111148
2022 SNP within the bovine ASB-3 gene and their association analysis with stature traits in three Chinese cattle breeds. Gene 2 35772652
2021 A hemizygous p.R204Q mutation in the ALAS2 gene underlies X-linked sideroblastic anemia in an adult Chinese Han man. BMC medical genomics 2 33858445
2017 A Novel ALAS2 Mutation Resulting in Variable Phenotypes and Pyridoxine Response in a Family with X-linked Sideroblastic Anemia. Annals of clinical and laboratory science 2 28667034
2003 [Exogenous expression of SOCS box-deficient mutant ASB-8 suppresses the growth of lung adenocarcinoma SPC-A1 cells]. Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica 2 12796816
2000 [A novel mutation of the ALAS2 gene in a family with X-linked sideroblastic anemia]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 2 11877024
2025 20-Acetylsinularolide B (ASB) From Lobophytum crassum Exhibits Anticancer Activity In Vitro Through IGF1R/PI3K/AKT/mTOR Pathway. Chemistry & biodiversity 1 40246781
2025 X-Linked Sideroblastic Anemia Induced by a Novel ALAS2 Nonsense Mutation: A Case Report and Literature Review. Annals of clinical and laboratory science 1 41253474
2024 A novel and apparent de novo ALAS2 missense variant associated with congenital sideroblastic anemia. Frontiers in pediatrics 1 39281190
2018 [Successful treatment of X-linked sideroblastic anemia with ALAS2 R452H mutation using vitamin B6]. [Rinsho ketsueki] The Japanese journal of clinical hematology 1 29743399
2017 X-linked Sideroblastic Anemia in a Malay Boy With ALAS2 S568G Mutation. Journal of pediatric hematology/oncology 1 28644307
2017 A Novel g.55040074delT in ALAS2 Gene Resulting in a Monomeric Protein and Severe Sideroblastic Anemia Phenotype. Journal of pediatric hematology/oncology 1 28731922
2017 Natural overproduction of catalase by Kocuria sp. ASB 107: extraction and semi-purification. Iranian journal of microbiology 1 29487734
2026 ALAS2 Prevents Neonatal Necrotizing Enterocolitis by Improving Ferroptosis in Intestinal Epithelial Cells Through Inhibition of Oxidative Stress. Mediators of inflammation 0 41509986
2026 The neuronal ALAS2/5-ala axis mitigates chemotherapy-induced neurotoxicity via the BACH1/NRF2 pathway. British journal of pharmacology 0 41652971
2026 A case report of congenital sideroblastic anemia caused by a novel ALAS2 mutation in conjunction with thalassemia. Annals of hematology 0 41961321
2025 Case report: A novel 11-bp deletion in exon 11 causing a frameshift in the C-terminal of the ALAS2 gene leading to X-linked sideroblastic anemia-a family study. Frontiers in medicine 0 39995829
2025 X-Linked Sideroblastic Anaemia Caused by Intronic ALAS2 Variant Resulting in Highly Variable Expressive Phenotype in Male Siblings, a Case Report. EJHaem 0 40391332
2025 Multi-omics insight into the adaptation mechanism of desert cyanobacterium Chroococcidiopsis sp. ASB-02 under salinity stress. Plant physiology and biochemistry : PPB 0 41270500
2025 Verification testing in a multi-laboratory system using ANSI/ASB Standard 020. Journal of forensic sciences 0 41340182
2025 Hypoxia impairs monocyte/macrophage function and host defense via ALAS2-mediated heme biosynthesis in Japanese sea bass (Lateolabrax japonicus). Developmental and comparative immunology 0 41407058
2025 Comparison of antibiotic resistance and molecular characteristics of Escherichia coli isolated from patients with UTI, ASB, and uropathic bloodstream infection. Frontiers in medicine 0 41446853
2004 [Construction of recombinant vector expressing ALAS2 gene in X-linked sideroblastic anemia]. Zhongguo shi yan xue ye xue za zhi 0 15498136