Affinage

SNTG1

Gamma-1-syntrophin · UniProt Q9NSN8

Length
517 aa
Mass
58.0 kDa
Annotated
2026-06-10
52 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNTG1 encodes gamma-1 syntrophin, a cytoplasmic peripheral membrane protein that associates with the C-terminal domain of dystrophin as part of the dystrophin-associated protein complex, with expression restricted to neuronal cells (PMID:15088139). Genomic disruption of SNTG1 by a pericentric chromosome 8 inversion, together with a 6-bp exon 10 deletion and intronic splice-site mutations absent from controls, links the gene to idiopathic scoliosis in patients (PMID:15088139). Beyond this genetic association and the prior-knowledge assignment of dystrophin binding and neuronal expression, no direct biochemical reconstitution or functional dissection of the gamma-1 syntrophin protein has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2004 Medium

    Established that SNTG1 disruption is genetically associated with idiopathic scoliosis, anchoring an otherwise neuronally-expressed dystrophin-complex protein to a postural phenotype.

    Evidence FISH breakpoint mapping, BAC genomic sequencing, and mutational screening of SNTG1 exons in 152 scoliosis patients versus 480 control chromosomes

    PMID:15088139

    Open questions at the time
    • Direct biochemical demonstration of dystrophin binding by the SNTG1 product was not performed, only cited as prior knowledge
    • No functional mechanism linking SNTG1 loss to scoliosis was established
    • Causality of the identified variants was inferred from absence in controls, not from functional assay
  2. 2021 Low

    A second independent genomic case reinforced SNTG1 disruption in a patient with cognitive impairment and scoliosis, supporting a neuronal/postural role.

    Evidence Array-CGH identification of a de novo 8q11.21q11.23 deletion disrupting SNTG1 in a single case report

    PMID:34048959

    Open questions at the time
    • Single case report with no functional experiment on the SNTG1 protein
    • DAPC membership and neuronal expression were restated from prior literature, not measured here
    • Deletion spans a region beyond SNTG1, limiting attribution to this gene alone

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular function of gamma-1 syntrophin within the dystrophin-associated protein complex and the mechanism connecting its loss to scoliosis and neuronal postural control remain undefined.
  • No reconstituted dystrophin–gamma-1 syntrophin interaction reported
  • No identified downstream signaling or scaffolding partners beyond dystrophin
  • No animal model linking SNTG1 loss to a postural/scoliosis phenotype

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005886 plasma membrane 1
Partners
DMD
Complex memberships
dystrophin-associated protein complex (DAPC)

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 SNTG1 encodes gamma-1 syntrophin, a cytoplasmic peripheral membrane protein that associates directly with dystrophin (the Duchenne muscular dystrophy gene product); expression of gamma1-syntrophin is restricted to neuronal cells. A pericentric inversion of chromosome 8 was found to disrupt SNTG1 between exons 10 and 11, and mutational analysis of SNTG1 exons in 152 sporadic idiopathic scoliosis patients identified a 6-bp deletion in exon 10 and intronic splice-site mutations not found in 480 control chromosomes. FISH mapping of chromosomal breakpoints; BAC genomic sequencing; mutational analysis of SNTG1 exons in patient cohort vs. controls Human genetics Medium 15088139
2021 SNTG1 encodes γ-1 Syntrophin protein that is part of the dystrophin-associated protein complex (DAPC) and interacts directly with the C-terminal of dystrophin; its expression is restricted to neurons, particularly in brain regions suggested to control postural balance. A de novo interstitial deletion 8q11.21q11.23 disrupting SNTG1 was identified by array-CGH in a patient with cognitive impairment and scoliosis, supporting a role for SNTG1 in neuronal function and postural control. Array-CGH identification of SNTG1-disrupting deletion; literature-based assignment of protein complex membership and subcellular/tissue expression Bone Low 34048959

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Directional migration of neural crest cells in vivo is regulated by Syndecan-4/Rac1 and non-canonical Wnt signaling/RhoA. Development (Cambridge, England) 226 18403410
1999 Depletion of syntaxins in the early Caenorhabditis elegans embryo reveals a role for membrane fusion events in cytokinesis. Current biology : CB 136 10421575
2001 Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance. The Journal of clinical investigation 99 11375421
2014 Dynamic catch of a Thy-1-α5β1+syndecan-4 trimolecular complex. Nature communications 87 25216363
2011 Syndecan-4 prevents cardiac rupture and dysfunction after myocardial infarction. Circulation research 84 21493899
2012 Syntaxin-3 regulates newcomer insulin granule exocytosis and compound fusion in pancreatic beta cells. Diabetologia 67 23132338
2004 Syntaxin 4 transgenic mice exhibit enhanced insulin-mediated glucose uptake in skeletal muscle. Diabetes 60 15331531
2010 Genomic aberrations in lung adenocarcinoma in never smokers. PloS one 58 21151896
2009 A role for Syndecan-4 in neural induction involving ERK- and PKC-dependent pathways. Development (Cambridge, England) 42 19144724
2004 SNTG1, the gene encoding gamma1-syntrophin: a candidate gene for idiopathic scoliosis. Human genetics 42 15088139
2007 Alcohol redirects CCK-mediated apical exocytosis to the acinar basolateral membrane in alcoholic pancreatitis. Traffic (Copenhagen, Denmark) 39 17451559
2003 Insulin resistance in tetracycline-repressible Munc18c transgenic mice. Diabetes 39 12882905
2011 Gelsolin associates with the N terminus of syntaxin 4 to regulate insulin granule exocytosis. Molecular endocrinology (Baltimore, Md.) 36 22108804
2016 QTL Mapping of Low-Temperature Germination Ability in the Maize IBM Syn4 RIL Population. PloS one 35 27031623
2015 Syntaxin-4 mediates exocytosis of pre-docked and newcomer insulin granules underlying biphasic glucose-stimulated insulin secretion in human pancreatic beta cells. Diabetologia 35 25762204
1999 Expression pattern alterations of syndecans and glypican-1 in normal and pathological trophoblast. The Journal of pathology 35 10629564
2017 Coupling of vinculin to F-actin demands Syndecan-4 proteoglycan. Matrix biology : journal of the International Society for Matrix Biology 34 28062282
2002 Localization of the transmembrane proteoglycan syndecan-4 and its regulatory kinases in costameres of rat cardiomyocytes: a deconvolution microscopic study. The Anatomical record 30 12209563
2011 Syndecan-4 deficiency limits neointimal formation after vascular injury by regulating vascular smooth muscle cell proliferation and vascular progenitor cell mobilization. Arteriosclerosis, thrombosis, and vascular biology 28 21330609
2016 Syndecan-4 modulates the proliferation of neural cells and the formation of CaP axons during zebrafish embryonic neurogenesis. Scientific reports 25 27143125
2013 Polyphenols differentially inhibit degranulation of distinct subsets of vesicles in mast cells by specific interaction with granule-type-dependent SNARE complexes. The Biochemical journal 24 23252429
2004 Role of Syndecan-4 in the cellular invasion of Orientia tsutsugamushi. Microbial pathogenesis 24 15001228
2011 Bioinformatic analyses identifies novel protein-coding pharmacogenomic markers associated with paclitaxel sensitivity in NCI60 cancer cell lines. BMC medical genomics 23 21314952
2021 QTL mapping of seedling tolerance to exposure to low temperature in the maize IBM RIL population. PloS one 22 34242344
2016 Measurement of lipocalin-2 and syndecan-4 levels to differentiate bacterial from viral infection in children with community-acquired pneumonia. BMC pulmonary medicine 22 27439403
2015 Syntaxin 4 Overexpression Ameliorates Effects of Aging and High-Fat Diet on Glucose Control and Extends Lifespan. Cell metabolism 22 26331606
2010 Population and computational analysis of the MGEA6 P521A variation as a risk factor for familial idiopathic basal ganglia calcification (Fahr's disease). Journal of molecular neuroscience : MN 22 20838928
2021 Genetic Contributors of Incident Stroke in 10,700 African Americans With Hypertension: A Meta-Analysis From the Genetics of Hypertension Associated Treatments and Reasons for Geographic and Racial Differences in Stroke Studies. Frontiers in genetics 16 34992631
2021 Mutational landscape of primary pulmonary salivary gland-type tumors through targeted next-generation sequencing. Lung cancer (Amsterdam, Netherlands) 15 34364112
2022 No association between intravenous fluid volume and endothelial glycocalyx shedding in patients undergoing resuscitation for sepsis in the emergency department. Scientific reports 14 35610344
2024 SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations. Nature communications 13 39738056
2020 Expression of circular RNAs in the vascular dementia rats. Neuroscience letters 13 32534097
2021 Identification of key miRNA-gene pairs in gastric cancer through integrated analysis of mRNA and miRNA microarray. American journal of translational research 12 33527022
2021 Identification of Copy Number Variants in a Southern Chinese Cohort of Patients with Congenital Scoliosis. Genes 11 34440387
2024 Serum Fusion Transcripts to Assess the Risk of Hepatocellular Carcinoma and the Impact of Cancer Treatment through Machine Learning. The American journal of pathology 10 38537933
2023 Effect of intravenous fluid volume on biomarkers of endothelial glycocalyx shedding and inflammation during initial resuscitation of sepsis. Intensive care medicine experimental 9 37062769
2018 Targeting Neuroplasticity, Cardiovascular, and Cognitive-Associated Genomic Variants in Familial Alzheimer's Disease. Molecular neurobiology 8 30112632
2022 Abnormal TNS3 gene methylation in patients with congenital scoliosis. BMC musculoskeletal disorders 7 35987623
2015 Crystal structure of syndesmos and its interaction with Syndecan-4 proteoglycan. Biochemical and biophysical research communications 6 26100207
2023 Extracellular vesicle treatment partially reverts epigenetic alterations in chronically ischemic porcine myocardium. Vessel plus 5 37982029
2017 Pharmacogenetics of response to neoadjuvant paclitaxel treatment for locally advanced breast cancer. Oncotarget 5 29290962
2024 Effects of syndecan-4 silencing on the extracellular matrix remodeling in anoikis-resistant endothelial cells. Cell biology international 4 38591778
2020 Investigation of gene-gene interactions in cardiac traits and serum fatty acid levels in the LURIC Health Study. PloS one 4 32915819
2025 Mapping the landscape of childhood obesity: genomic insights and socioeconomic status in Indian school-going children. Obesity (Silver Spring, Md.) 3 40000390
2023 Towards universal synthetic heterotrophy using a metabolic coordinator. Metabolic engineering 3 37406763
2021 Scoliosis with cognitive impairment in a girl with 8q11.21q11.23 microdeletion and SNTG1 disruption. Bone 3 34048959
2011 Synthesis of syn-4,6-dimethyldodecanal, the male sex pheromone and trail-following pheromone of two species of the termite Zootermopsis. Natural product research 3 21391118
2022 Location and Identification on Chromosome 3B of Bread Wheat of Genes Affecting Chiasma Number. Plants (Basel, Switzerland) 2 36079661
2012 Cellular localization of mitotic RAD21 with repetitive amino acid motifs in Allium cepa. Gene 2 23201414
2025 Maize SERRATE 1B positively regulates seed germinability under low-temperature. Plant science : an international journal of experimental plant biology 1 40057047
2025 Synergistic glyphosate degradation in a rice-duckweed-microbe system: Mechanistic insights and sustainable remediation potential. Journal of hazardous materials 0 41389483
2024 Enhancement of the flavor and functional characteristics of cod protein isolate using an enzyme-microbe system. Food & function 0 39380384

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