Affinage

SNTG1

Gamma-1-syntrophin · UniProt Q9NSN8

Length
517 aa
Mass
58.0 kDa
Annotated
2026-04-28
56 papers in source corpus 2 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNTG1 encodes gamma-1 syntrophin, a neuronal cell-specific cytoplasmic peripheral membrane protein that associates directly with the C-terminus of dystrophin as part of the dystrophin-associated protein complex (PMID:15088139). Chromosomal disruption of SNTG1 co-segregates with idiopathic scoliosis in a family study and in an independent case with a de novo interstitial deletion, implicating gamma-1 syntrophin in postural control pathways (PMID:15088139, PMID:34048959). The precise molecular mechanism by which gamma-1 syntrophin functions within the dystrophin-associated complex in neurons remains poorly characterized.

Mechanistic history

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

    Positional cloning of a chromosomal inversion breakpoint within SNTG1 established that this neuronal dystrophin-associated protein complex member is a candidate gene for idiopathic scoliosis, answering the question of which gene at 8q11-q12 underlies the phenotype in the affected family.

    Evidence FISH mapping and BAC sequencing of inversion breakpoints in a scoliosis family; mutational screening of SNTG1 exons in 152 sporadic patients

    PMID:15088139

    Open questions at the time
    • No functional assay demonstrated how loss of gamma-1 syntrophin leads to scoliosis
    • No causative point mutations were identified in sporadic scoliosis patients screened
    • Interaction partners beyond dystrophin in neurons are uncharacterized
  2. 2021 Low

    A second independent genomic disruption of SNTG1 (de novo deletion) in a patient with scoliosis and cognitive impairment provided supporting genetic evidence, reinforcing that gamma-1 syntrophin dysfunction contributes to scoliosis pathogenesis through its neuronal expression.

    Evidence Array-CGH identification of de novo 8q11.21q11.23 deletion disrupting SNTG1; clinical phenotyping

    PMID:34048959

    Open questions at the time
    • Single case report without functional rescue or model organism validation
    • Deletion encompasses additional genomic material, so causality is not isolated to SNTG1
    • No mechanistic link between dystrophin complex disruption in neurons and spinal phenotype has been established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular function of gamma-1 syntrophin within the dystrophin-associated complex in neurons — including its specific binding partners beyond dystrophin, signaling roles, and the mechanism linking its loss to scoliosis — remains unresolved.
  • No biochemical or structural characterization of gamma-1 syntrophin's domains or interactors beyond dystrophin
  • No animal model with targeted SNTG1 disruption has been reported for phenotypic analysis
  • Neuronal signaling pathways downstream of gamma-1 syntrophin are unknown

Mechanism profile

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

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 SNTG1 (gamma1-syntrophin) gene encodes a neuronal cell-specific cytoplasmic peripheral membrane protein that associates directly with dystrophin; a chromosomal inversion breakpoint between exons 10 and 11 of SNTG1 co-segregates with idiopathic scoliosis in a family, implicating SNTG1 disruption in the disorder. FISH mapping of chromosomal breakpoints, genomic sequencing of BAC clones spanning breakpoints, mutational analysis of SNTG1 exons in 152 sporadic IS patients Human genetics Medium 15088139
2021 SNTG1 disruption (interstitial deletion 8q11.21q11.23) in a patient with scoliosis and cognitive impairment further supports that gamma1-syntrophin, as part of the dystrophin-associated protein complex interacting with the C-terminal of dystrophin and expressed specifically in neurons (including brain regions implicated in postural control), contributes to scoliosis pathogenesis. Array-CGH identification of de novo deletion disrupting SNTG1; clinical phenotyping Bone Low 34048959

Source papers

Stage 0 corpus · 56 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 98 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 59 15331531
2010 Genomic aberrations in lung adenocarcinoma in never smokers. PloS one 58 21151896
2009 Cohesin gene defects may impair sister chromatid alignment and genome stability in Arabidopsis thaliana. Chromosoma 45 19533160
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 41 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
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
2016 QTL Mapping of Low-Temperature Germination Ability in the Maize IBM Syn4 RIL Population. PloS one 34 27031623
2017 Coupling of vinculin to F-actin demands Syndecan-4 proteoglycan. Matrix biology : journal of the International Society for Matrix Biology 33 28062282
2007 The Arabidopsis cohesin protein SYN3 localizes to the nucleolus and is essential for gametogenesis. The Plant journal : for cell and molecular biology 33 17488242
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
2012 The Arabidopsis SYN3 cohesin protein is important for early meiotic events. The Plant journal : for cell and molecular biology 26 22381039
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
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
2011 Bioinformatic analyses identifies novel protein-coding pharmacogenomic markers associated with paclitaxel sensitivity in NCI60 cancer cell lines. BMC medical genomics 22 21314952
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
2015 Syntaxin 4 Overexpression Ameliorates Effects of Aging and High-Fat Diet on Glucose Control and Extends Lifespan. Cell metabolism 21 26331606
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 13 35610344
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
2024 SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations. Nature communications 11 39738056
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
2018 Targeting Neuroplasticity, Cardiovascular, and Cognitive-Associated Genomic Variants in Familial Alzheimer's Disease. Molecular neurobiology 8 30112632
2023 Effect of intravenous fluid volume on biomarkers of endothelial glycocalyx shedding and inflammation during initial resuscitation of sepsis. Intensive care medicine experimental 7 37062769
2022 Abnormal TNS3 gene methylation in patients with congenital scoliosis. BMC musculoskeletal disorders 7 35987623
2013 Expression of epitope-tagged SYN3 cohesin proteins can disrupt meiosis in Arabidopsis. Journal of genetics and genomics = Yi chuan xue bao 7 24656235
2015 Crystal structure of syndesmos and its interaction with Syndecan-4 proteoglycan. Biochemical and biophysical research communications 6 26100207
2017 Pharmacogenetics of response to neoadjuvant paclitaxel treatment for locally advanced breast cancer. Oncotarget 5 29290962
2023 Extracellular vesicle treatment partially reverts epigenetic alterations in chronically ischemic porcine myocardium. Vessel plus 4 37982029
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
2024 Effects of syndecan-4 silencing on the extracellular matrix remodeling in anoikis-resistant endothelial cells. Cell biology international 3 38591778
2023 Towards universal synthetic heterotrophy using a metabolic coordinator. Metabolic engineering 3 37406763
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
2021 Scoliosis with cognitive impairment in a girl with 8q11.21q11.23 microdeletion and SNTG1 disruption. Bone 2 34048959
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