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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SNTA1
syntrophin alpha 1
Chromosome 20 · 20q11.21
NCBI Gene: 6640Ensembl: ENSG00000101400.7HGNC: HGNC:11167UniProt: B3KTR0
91PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein-containing complexventricular cardiac muscle cell action potentialprotein bindingregulation of sodium ion transmembrane transportlong QT syndrome 12Romano-Ward syndromeProlonged QT intervalhair color
✦AI Summary

SNTA1 encodes α-1-syntrophin, an adapter protein that organizes subcellular localization of membrane proteins and links receptors to the actin cytoskeleton via the dystrophin glycoprotein complex. In cardiomyocytes, SNTA1 plays a critical role in proper localization of Nav1.5 sodium channels and Kir2.1 potassium channels, which are essential for cardiac excitability and conduction 1. SNTA1 deficiency disrupts cardiac calcium homeostasis, resulting in hypertrophic phenotype, reduced contractility, and impaired calcium transient intensity in human cardiomyocytes 2. Additionally, SNTA1 maintains perivascular aquaporin-4 localization in the brain; its loss impairs glymphatic clearance and promotes amyloid-β accumulation, potentially contributing to Alzheimer's disease pathology 3. SNTA1 mutations are associated with cardiac arrhythmias including Long QT syndrome, Brugada syndrome, and sudden infant death syndrome 1. However, evidence for SNTA1 as a definitive Long QT syndrome causative gene is limited; an international evidence-based reappraisal classified SNTA1 among genes with only limited or disputed evidence for LQTS causation 4. Outside the cardiovascular system, SNTA1 regulates Rac1 activation and reactive oxygen species generation in breast cancer cells, influencing cell migration and malignant potential 5.

Sources cited
1
SNTA1 is essential for proper Nav1.5 localization and affects cardiac field potential duration and conduction velocity in human cardiomyocytes
PMID: 40835660
2
SNTA1-deficient human cardiomyocytes show hypertrophic phenotype, reduced contractility, and impaired calcium homeostasis
PMID: 35773684
3
SNTA1 maintains perivascular aquaporin-4 localization; SNTA1 deletion impairs glymphatic clearance and promotes amyloid-β accumulation
PMID: 35473943
4
SNTA1 has limited or disputed evidence as a Long QT syndrome-causative gene in an international evidence-based reappraisal
PMID: 31983240
5
SNTA1 activates Rac1, increases ROS generation, and enhances cell migration in breast cancer cells
PMID: 24434436
6
SNTA1 transfection in DMD cardiomyocytes restores NaV1.5-Kir2.1 channelosome function and prevents reentrant arrhythmias
PMID: 35762211
Disease Associationsⓘ21
long QT syndrome 12Open Targets
0.61Moderate
Romano-Ward syndromeOpen Targets
0.42Moderate
Prolonged QT intervalOpen Targets
0.35Weak
hair colorOpen Targets
0.31Weak
amyotrophic lateral sclerosisOpen Targets
0.27Weak
skin neoplasmOpen Targets
0.27Weak
actinic keratosisOpen Targets
0.27Weak
atrial fibrillationOpen Targets
0.27Weak
familial long QT syndromeOpen Targets
0.19Weak
Abnormality of the cardiovascular systemOpen Targets
0.19Weak
long QT syndrome 1Open Targets
0.15Weak
Duchenne muscular dystrophyOpen Targets
0.12Weak
Becker muscular dystrophyOpen Targets
0.12Weak
dilated cardiomyopathy 3BOpen Targets
0.12Weak
sick sinus syndromeOpen Targets
0.12Weak
Brugada syndromeOpen Targets
0.11Weak
ventricular fibrillationOpen Targets
0.11Weak
ventricular fibrillation, paroxysmal familial, type 1Open Targets
0.11Weak
Wolff-Parkinson-White SyndromeOpen Targets
0.11Weak
Abnormality of the skeletal systemOpen Targets
0.08Suggestive
Long QT syndrome 12UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DAG1Protein interaction99%DTNAProtein interaction98%NOS1Protein interaction98%SGCDProtein interaction97%SNTG2Protein interaction97%SCN5AProtein interaction96%
Tissue Expression6 tissues
Heart
100%
Brain
24%
Ovary
11%
Liver
9%
Lung
4%
Bone Marrow
2%
Gene Interaction Network
Click a node to explore
SNTA1DAG1DTNANOS1SGCDSNTG2SCN5A
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q13424
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.98LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.73 [0.55–0.98]
RankingsWhere SNTA1 stands among ~20K protein-coding genes
  • #5,272of 20,598
    Most Researched91
  • #9,359of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedSNTA1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome.
PMID: 31983240
Circulation · 2020
1.00
2
SNTA1-deficient human cardiomyocytes demonstrate hypertrophic phenotype and calcium handling disorder.
PMID: 35773684
Stem Cell Res Ther · 2022
0.90
3
The genetic basis of long QT and short QT syndromes: a mutation update.
PMID: 19862833
Hum Mutat · 2009
0.80
4
Loss of perivascular aquaporin-4 localization impairs glymphatic exchange and promotes amyloid β plaque formation in mice.
PMID: 35473943
Alzheimers Res Ther · 2022
0.70
5
Results of genetic testing in 855 consecutive unrelated patients referred for long QT syndrome in a clinical laboratory.
PMID: 23631430
Genet Test Mol Biomarkers · 2013
0.60