Affinage

CST3

Cystatin-C · UniProt P01034

Round 2 corrected
Length
146 aa
Mass
15.8 kDa
Annotated
2026-04-28
61 papers in source corpus 19 papers cited in narrative 19 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Cystatin C is a ubiquitously expressed, secreted cysteine proteinase inhibitor that potently inhibits cathepsins B, H, L, and other papain-family proteases, with its N-terminal segment essential for high-affinity inhibition of cathepsins B and L but dispensable for cathepsin H inhibition (PMID:6203523, PMID:1996959). The protein dimerizes through three-dimensional domain swapping, and the amyloidogenic L68Q mutation destabilizes the monomer to promote aggregation underlying hereditary cystatin C amyloid angiopathy (HCCAA), while distinct C-terminal truncating variants cause adult-onset leukodystrophy without amyloid angiopathy (PMID:11276250, PMID:2900981, PMID:38489591). Beyond protease inhibition, cystatin C exerts anti-fibrotic activity in lung and kidney by blocking TGF-β/Smad signaling in fibroblasts and maintains retinal vascular integrity by upregulating tight junction proteins via Rap1 signaling (PMID:29724997, PMID:29653105, PMID:39147193). In vascular smooth muscle, TGF-β1 induces cystatin C secretion to counterbalance cathepsin-mediated elastolysis, and its depletion in atherosclerotic lesions contributes to arterial wall remodeling (PMID:10545518).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1984 High

    Establishing cystatin C as a broad-spectrum cysteine proteinase inhibitor resolved the identity of 'gamma-trace' protein and defined its biochemical function as the dominant extracellular regulator of cathepsins B, H, and L.

    Evidence Enzyme kinetic inhibition assays (Ki measurements) with purified protein from biological fluids

    PMID:6203523

    Open questions at the time
    • No structural basis for inhibitory mechanism yet determined
    • Physiological targets in vivo not identified
  2. 1986 High

    Demonstrating that cystatin C accounts for nearly all cysteine proteinase inhibitory activity in CSF, seminal plasma, and milk established it as the principal extracellular cystatin, while identification of mutant L68Q cystatin C in cerebral amyloid fibrils linked the gene to hereditary cerebral hemorrhage with amyloidosis (Icelandic type).

    Evidence Affinity chromatography with immunochemical quantification across body fluids; protein sequence analysis of amyloid fibrils from patient brain tissue

    PMID:3488317 PMID:3517880

    Open questions at the time
    • Mechanism by which the L68Q mutation promotes amyloid formation unknown
    • No gene-level confirmation of the mutation
  3. 1988 High

    Identifying the L68Q point mutation in the CST3 gene across eight HCCAA families established the molecular genetic basis of this autosomal dominant cerebral amyloid angiopathy.

    Evidence Southern blot with cystatin C cDNA probe and RFLP analysis across affected families

    PMID:2900981

    Open questions at the time
    • Structural mechanism of mutation-induced aggregation not resolved
    • No animal model of disease
  4. 1990 High

    Characterization of the CST3 gene structure — three exons, housekeeping-type promoter with Sp1 sites but no TATA/CAAT boxes — explained the ubiquitous tissue expression pattern and provided the basis for studying transcriptional regulation.

    Evidence Genomic cloning and sequencing of 7.3 kb segment; Northern blot across multiple human tissues

    PMID:2363674

    Open questions at the time
    • Transcription factor regulation of the promoter not identified
    • No regulatory variant analysis
  5. 1991 High

    Showing that leucocyte elastase cleaves the N-terminal decapeptide of cystatin C, reducing cathepsin B/L inhibition >1000-fold while sparing cathepsin H inhibition, revealed that extracellular proteolytic processing modulates cystatin C's inhibitory specificity in vivo.

    Evidence Proteolytic cleavage with leucocyte elastase followed by enzyme kinetic assays against papain, cathepsins B, H, and L

    PMID:1996959

    Open questions at the time
    • In vivo relevance of N-terminal processing at inflammatory sites not demonstrated
    • No structural explanation for differential effect on cathepsin H
  6. 1999 High

    Demonstrating that cystatin C is depleted in atherosclerotic and aneurysmal aortic lesions, and that TGF-β1 restores cystatin C secretion to block cathepsin-mediated elastolysis, established a protease–inhibitor imbalance mechanism in vascular remodeling.

    Evidence Immunohistochemistry of human vascular lesions; in vitro elastolytic activity assays with TGF-β1-treated vascular smooth muscle cells

    PMID:10545518

    Open questions at the time
    • Causal role not tested by genetic deletion in vascular disease models
    • Which cathepsin(s) are the principal targets in vivo unclear
  7. 2001 High

    The crystal structure of cystatin C revealed three-dimensional domain swapping as the dimerization mechanism and showed that the L68Q mutation destabilizes the monomer, providing a structural explanation for aggregation and amyloid formation in HCCAA.

    Evidence X-ray crystallography of human cystatin C

    PMID:11276250

    Open questions at the time
    • Kinetic pathway from domain-swapped dimer to amyloid fibril not resolved
    • No structure of the L68Q mutant itself
  8. 2018 Medium

    Two independent studies demonstrated that cystatin C suppresses fibroblast activation and collagen production in kidney and lung by blocking TGF-β/Smad signaling, expanding its function beyond direct protease inhibition to an anti-fibrotic signaling role.

    Evidence Primary fibroblast assays with pathway analysis and in vivo mouse models (unilateral ureter obstruction, pulmonary fibrosis)

    PMID:29653105 PMID:29724997

    Open questions at the time
    • Molecular target on the TGF-β receptor complex not identified
    • Whether the anti-fibrotic activity requires protease-inhibitory function is untested
  9. 2024 Medium

    Discovery that cystatin C maintains retinal vascular barrier integrity through Rap1-dependent upregulation of tight junction proteins, and that dominant C-terminal truncating CST3 variants cause adult-onset leukodystrophy distinct from L68Q amyloid angiopathy, revealed new tissue-specific roles and a second disease mechanism.

    Evidence siRNA/recombinant protein experiments in retinal endothelial cells with OIR mouse model; whole-exome/genome sequencing in 16 leukodystrophy patients from 8 families with autopsy confirmation

    PMID:38489591 PMID:39147193

    Open questions at the time
    • Rap1 activation mechanism by cystatin C unresolved
    • No biochemical characterization of truncated cystatin C aggregation properties
    • Leukodystrophy mechanism (astrocyte loss, oligodendrocyte apoptosis) not linked to protease inhibition or gain-of-function
  10. 2024 Medium

    Identification of NR3C1 as a direct transcriptional repressor of CST3, stabilized by USP10-mediated deubiquitination, established the first characterized transcription factor–promoter axis controlling cystatin C expression and linked it to bone homeostasis.

    Evidence ChIP of NR3C1 at the CST3 promoter; overexpression/knockdown with in vivo ovariectomy mouse model

    PMID:39236936

    Open questions at the time
    • Whether NR3C1 regulation of CST3 operates in tissues beyond bone is unknown
    • Downstream bone-remodeling targets of cystatin C not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the molecular mechanism by which cystatin C inhibits TGF-β/Smad signaling independently of protease inhibition, the structural basis of C-terminal truncation-driven aggregation in leukodystrophy, and whether protease-inhibitory and signaling functions are separable in vivo.
  • No separation-of-function mutant distinguishing protease inhibition from signaling roles
  • No structure of L68Q or C-terminal truncation variants
  • In vivo contribution of individual cathepsins to cystatin C-regulated processes not genetically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 2
Partners
CTSBCTSHCTSLNR3C1TIMP1

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 Cystatin C (gamma-trace) was identified as a potent inhibitor of cysteine proteinases including papain, ficin, and human cathepsins B, H, and L, with the tightest binding to cathepsin B among known protein inhibitors. Its widespread distribution in tissues and extracellular fluids suggested a physiological role in regulating cysteine proteinase activity. Enzyme kinetic inhibition assays (Ki measurements) with purified protein from biological fluids Biochemical and biophysical research communications High 6203523
1986 Six cysteine proteinase inhibitors were isolated from human urine by affinity chromatography; cystatin C had the highest molar concentration in seminal plasma, cerebrospinal fluid, and milk, and accounted for nearly all cysteine proteinase inhibitory activity in those biological fluids. Affinity chromatography on insolubilized carboxymethylpapain, ion-exchange chromatography, immunosorption, enzyme kinetic assays, immunochemical quantification The Journal of biological chemistry High 3488317
1986 Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis (Icelandic type) were identified as a variant of cystatin C (gamma-trace) carrying an amino acid substitution (Gln for Leu at position 68), establishing that mutant cystatin C forms pathological amyloid deposits in brain arteries. Protein sequence analysis of amyloid fibril components isolated from patient brain tissue Proceedings of the National Academy of Sciences of the United States of America High 3517880
1988 A point mutation in the CST3 gene (abolishing an AluI restriction site) at the codon for leucine at position 68 was identified as the cause of hereditary cystatin C amyloid angiopathy (HCCAA), an autosomal dominant disorder causing brain hemorrhage and death. Southern blot analysis with cystatin C cDNA probe, restriction fragment length polymorphism (RFLP) analysis across eight affected families Lancet High 2900981
1990 The human CST3 gene has three exons, no TATA or CAAT boxes in the promoter, and shares features with housekeeping gene promoters (Sp1 sites, GC-rich region); it is ubiquitously expressed in all human tissues examined, with highest expression in seminal vesicles. Genomic cloning and sequencing of a 7.3 kb segment, Northern blot analysis across multiple tissues The Biochemical journal High 2363674
1991 Leucocyte elastase cleaves the Val-10–Gly-11 bond of cystatin C, removing the N-terminal decapeptide and reducing inhibitory affinity for papain by >240-fold, for cathepsins B and L by ~1000-fold, but for cathepsin H by only 5-fold. This established that the N-terminal segment is essential for inhibition of cathepsins B and L but not cathepsin H, and that leucocyte elastase can regulate extracellular cysteine-proteinase inhibitory activity. Proteolytic cleavage with leucocyte elastase, enzyme kinetic inhibition assays with papain and cathepsins B, H, L; peptidyl diazomethane inhibitor studies The Biochemical journal High 1996959
1993 The CST3 gene and other family II cystatin genes are clustered on chromosome 20p11.2 within a 300-kb BssHII fragment, as established by FISH, Southern blot, and pulsed-field gel electrophoresis. FISH, Southern blot, pulsed-field gel electrophoresis (PFGE) Genomics High 8486384
1993 A G/A transition polymorphism in the CST3 coding region results in an Ala/Thr variation at the penultimate amino acid of the signal peptide, detectable by SstII restriction site loss (B allele), establishing this as the basis of the CST3 A/B polymorphism. Direct DNA sequencing, PCR-RFLP Human genetics High 8103758
1995 The mouse Cst3 gene has the same overall organization as human CST3 with two introns at identical positions, a promoter lacking TATA/CAAT boxes but containing Sp1-binding motifs, an androgen-responsive element core sequence, and AP-1 binding sites; it is expressed in all thirteen tissues examined. Mouse Cst3 maps to distal chromosome 2. Genomic DNA sequencing (6.1 kb), Northern blot across 13 tissues, chromosomal mapping Gene High 7835704
1999 Cystatin C is severely reduced in atherosclerotic and aneurysmal aortic lesions compared to normal vascular smooth muscle cells. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins whose elastolytic activity is blocked when cystatin C secretion is induced by TGF-β1 treatment, establishing an imbalance between cysteine proteases and cystatin C as a mechanism in arterial wall remodeling. Immunohistochemistry of human lesions, in vitro elastolytic activity assays with TGF-β1-treated vascular SMCs, ultrasonographic measurement of aortic diameter correlated with serum cystatin C The Journal of clinical investigation High 10545518
2001 Crystal structure of human cystatin C revealed that the protein dimerizes through three-dimensional domain swapping, forming tight two-fold symmetric dimers while retaining secondary structure. The L68Q mutation (causing HCCAA) destabilizes the monomer and makes the partially unfolded intermediate less unstable, explaining increased aggregation propensity. Higher-order aggregates can arise through open-ended domain swapping. X-ray crystallography Nature structural biology High 11276250
2010 The CST3 BB genotype leads to reduced secretion of cystatin C protein (in vitro) and was associated with lower CSF cystatin C levels and dementia in Lewy body disease patients. Demented patients had decreased CSF cystatin C, and the correlation between CSF cystatin C and Aβ42 levels was high in non-demented but poor in demented subjects, suggesting cystatin C acts as a carrier of soluble Aβ42 in CSF. CST3 genotyping, CSF immunoassay for cystatin C and Aβ42, correlation analysis in 132 subjects Journal of Alzheimer's disease : JAD Medium 20157249
2018 CST3 (cystatin C) exerts anti-fibrotic activity in kidney fibroblasts by blocking the TGF-β receptor signaling pathway, inducing apoptotic cell death and reducing collagen production in primary fibroblasts isolated from kidneys subjected to ureteral obstruction. Cytokine array screening, primary fibroblast cell assays (apoptosis, collagen production), TGF-β receptor signaling pathway analysis, in vivo mouse unilateral ureter obstruction model Biochemical and biophysical research communications Medium 29653105
2018 CST3 (cystatin C) secreted by epithelial cells inhibits the growth and activation of lung fibroblasts by inactivating the TGF-Smad pathway. CST3 expression is markedly reduced in fibrotic mouse and human lungs, and restoration of CST3 alleviated fibrotic changes in mouse lungs. Conditioned media experiments, fibroblast proliferation/activation assays, TGF-Smad pathway analysis, in vivo mouse pulmonary fibrosis model Cell death & disease Medium 29724997
2023 TGF-β1 secreted by M2 macrophages downregulates CST3 expression in colorectal cancer cells to promote migration. Conversely, CST3 overexpression in CRC cells suppressed TGF-β1 expression in M2 macrophages. These findings establish a bidirectional regulatory relationship between CST3 and TGF-β1 in the tumor microenvironment. Co-culture system (Transwell), TGF-β1 neutralization, CST3 overexpression, in vivo mouse CRC model with MC-LR/AOM/DSS treatment International journal of molecular sciences Medium 37445705
2024 NR3C1 (a transcription factor) binds to the CST3 promoter and represses its transcription in osteoclast and osteoblast precursor cells. USP10-mediated deubiquitination stabilizes NR3C1, increasing its suppression of CST3. Downregulation of CST3 reversed the bone-protective effects of NR3C1 knockdown, placing CST3 downstream of USP10/NR3C1 in bone homeostasis regulation. Chromatin immunoprecipitation (ChIP) of NR3C1 at CST3 promoter, overexpression/knockdown experiments, in vivo ovariectomy mouse model Biochemical pharmacology Medium 39236936
2024 CST3 promotes retinal vascular integrity by upregulating tight junction and adherens junction proteins (claudin-5, VE-cadherin, ZO-1) in retinal endothelial cells via the Rap1 signaling pathway. Silencing CST3 induced retinal vascular leakage in vivo, while intravitreal CST3 injection reduced leakage in oxygen-induced retinopathy mice. siRNA knockdown, exogenous protein addition, in vivo intravitreal injection, OIR mouse model, Western blot for Rap1 pathway components and junction proteins Experimental eye research Medium 39147193
2024 Dominant stop-gain or frameshift variants in CST3 cause adult-onset leukodystrophy without amyloid angiopathy. Structural comparison of the variants suggests that C-terminal truncations of cystatin C render the protein more prone to aggregation, causing white matter degeneration with astrocyte activation/loss and oligodendrocyte apoptosis, distinct from the L68Q-associated amyloid angiopathy. Whole-exome/genome sequencing in 16 patients from 8 families, histopathological analysis of 2 autopsy cases, protein structural comparison Brain : a journal of neurology Medium 38489591
2025 TIMP1 interacts with CST3 in human dermal fibroblasts to promote fibroblast differentiation toward a myofibroblast phenotype, upregulating α-SMA and CTGF and enhancing proliferation and migration, contributing to skin scar formation. scRNA-seq and bulk RNA-seq analysis, in vitro co-culture, protein interaction analysis, overexpression/knockdown of TIMP1 and CST3 International immunopharmacology Low 40925202

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2007 Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nature genetics 1399 17192785
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2004 Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney international 807 15086483
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2010 New loci associated with kidney function and chronic kidney disease. Nature genetics 681 20383146
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Factors other than glomerular filtration rate affect serum cystatin C levels. Kidney international 628 19119287
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1990 Structure and expression of the human cystatin C gene. The Biochemical journal 523 2363674
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1986 Isolation of six cysteine proteinase inhibitors from human urine. Their physicochemical and enzyme kinetic properties and concentrations in biological fluids. The Journal of biological chemistry 434 3488317
2012 Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney international 423 22622496
1999 Cystatin C deficiency in human atherosclerosis and aortic aneurysms. The Journal of clinical investigation 364 10545518
2001 Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping. Nature structural biology 345 11276250
1982 Human gamma-trace, a basic microprotein: amino acid sequence and presence in the adenohypophysis. Proceedings of the National Academy of Sciences of the United States of America 327 6283552
1986 Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C). Proceedings of the National Academy of Sciences of the United States of America 318 3517880
2017 RIPK1 mediates a disease-associated microglial response in Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 313 28904096
1984 The place of human gamma-trace (cystatin C) amongst the cysteine proteinase inhibitors. Biochemical and biophysical research communications 282 6203523
2004 An investigation into the human serum "interactome". Electrophoresis 247 15174051
2009 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). Journal of proteome research 237 19199708
2004 Biochemistry and clinical role of human cystatin C. Critical reviews in clinical laboratory sciences 222 15603510
2010 Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals. Human molecular genetics 204 20534741
2013 Update on cystatin C: incorporation into clinical practice. American journal of kidney diseases : the official journal of the National Kidney Foundation 203 23701892
1988 Mutation in cystatin C gene causes hereditary brain haemorrhage. Lancet (London, England) 175 2900981
1984 Human cystatin, a new protein inhibitor of cysteine proteinases. Biochemical and biophysical research communications 174 6365094
2006 Identification of potential CSF biomarkers in ALS. Neurology 173 16481598
2001 The DNA sequence and comparative analysis of human chromosome 20. Nature 168 11780052
1991 Human cystatin C. role of the N-terminal segment in the inhibition of human cysteine proteinases and in its inactivation by leucocyte elastase. The Biochemical journal 167 1996959
2017 LncRNA Snhg1, a non-degradable sponge for miR-338, promotes expression of proto-oncogene CST3 in primary esophageal cancer cells. Oncotarget 77 28423738
1993 Cystatin C (CST3), the candidate gene for hereditary cystatin C amyloid angiopathy (HCCAA), and other members of the cystatin gene family are clustered on chromosome 20p11.2. Genomics 69 8486384
1989 The human cystatin C gene (CST3), mutated in hereditary cystatin C amyloid angiopathy, is located on chromosome 20. Human genetics 66 2567273
2002 CST3 genotype associated with exudative age related macular degeneration. The British journal of ophthalmology 62 11815350
1989 The human cystatin C gene (CST3) is a member of the cystatin gene family which is localized on chromosome 20. Biochemical and biophysical research communications 58 2764935
2018 CST3 and GDF15 ameliorate renal fibrosis by inhibiting fibroblast growth and activation. Biochemical and biophysical research communications 41 29653105
1995 Structural organization, expression and chromosomal mapping of the mouse cystatin-C-encoding gene (Cst3). Gene 39 7835704
2018 Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis. Cell death & disease 35 29724997
2012 Meta-analysis of the cystatin C(CST3) gene G73A polymorphism and susceptibility to Alzheimer's disease. The International journal of neuroscience 34 22435454
2010 The CST3 BB genotype and low cystatin C cerebrospinal fluid levels are associated with dementia in Lewy body disease. Journal of Alzheimer's disease : JAD 30 20157249
2015 A missense variant in CST3 exerts a recessive effect on susceptibility to age-related macular degeneration resembling its association with Alzheimer's disease. Human genetics 25 25893795
1993 An Ala/Thr variation in the coding region of the human cystatin C gene (CST3) detected as a SstII polymorphism. Human genetics 23 8103758
2010 Quantification of cystatin C in cerebrospinal fluid from various neurological disorders and correlation with G73A polymorphism in CST3. Brain research 19 20849835
2023 Microcystin-LR-Induced Interaction between M2 Tumor-Associated Macrophage and Colorectal Cancer Cell Promotes Colorectal Cancer Cell Migration through Regulating the Expression of TGF-β1 and CST3. International journal of molecular sciences 14 37445705
2008 Lack of an association between Alzheimer's disease and the cystatin C (CST3) gene G73A polymorphism in Mainland Chinese. Dementia and geriatric cognitive disorders 14 18408364
2009 The CST3 B haplotype is associated with frontotemporal lobar degeneration. European journal of neurology 13 19674067
2021 Association Between CST3 Gene Polymorphisms and Large-Artery Atherosclerotic Stroke. Frontiers in neurology 11 34721268
2022 Long Non-Coding RNA ZEB2-AS1 Augments Activity of Trophoblast Cells and Prevents the Development of Recurrent Spontaneous Abortion in Mice Through EZH2-Mediated CST3 Inhibition. Reproductive sciences (Thousand Oaks, Calif.) 10 35075612
2020 Analyses Mutations in GSN, CST3, TTR, and ITM2B Genes in Chinese Patients With Alzheimer's Disease. Frontiers in aging neuroscience 8 33192475
2024 Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy. Brain : a journal of neurology 7 38489591
2009 Flanking markers of cystatin c (CST3) gene do not show association with Alzheimer's disease. Dementia and geriatric cognitive disorders 7 19293566
2020 Effects of CST3 Gene G73A Polymorphism on Cystatin C in a Prospective Multiethnic Cohort Study. Nephron 5 32050196
2011 Association between CST3 rs2424577 polymorphism and corpulence related phenotypes during lifetime in populations of European ancestry. Obesity facts 5 21577020
2024 CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway. Experimental eye research 3 39147193
2024 USP10-mediated deubiquitination of NR3C1 regulates bone homeostasis by controlling CST3 expression. Biochemical pharmacology 3 39236936
2021 Association of CST3 Gene with Its Protein: Cystatin C in Health and Severe Periodontal Disease. Genetic testing and molecular biomarkers 3 34037438
2025 Cystatin C 3 (CST3) drives pathological progression in recurrent spontaneous abortion. Journal of reproductive immunology 1 39914057
2025 The ferroptosis-associated gene TIMP1 facilitates skin scar formation through the interaction with CST3 in fibroblasts. International immunopharmacology 1 40925202
2025 Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3. Journal of the neurological sciences 1 41033143
2026 Non-neuronal cell microenvironment control retinal vascular remodeling by CST3 in the oxygen-induced retinopathy in mice. Experimental eye research 0 41534651
2025 Multi-Omics discovery and clinical validation of IGFBP2, B2M, and CST3 as a serum biomarker panel for diabetic kidney disease progression. Gene 0 41167578