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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SORBS1
sorbin and SH3 domain containing 1
Chromosome 10 · 10q24.1
NCBI Gene: 10580Ensembl: ENSG00000095637.23HGNC: HGNC:14565UniProt: A0A3B3IRW8
112PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
focal adhesionplasma membraneprotein bindinginsulin receptor bindingneurodegenerative diseaseatrial fibrillationurinary system diseasehypertension
✦AI Summary

SORBS1 encodes a cytoskeletal adaptor protein that plays critical roles in insulin signaling and vascular development. The protein contains a sorbin homology domain and three SH3 domains, functioning as an important adaptor in insulin-stimulated glucose transport by linking CBL to the insulin receptor 1. SORBS1 undergoes extensive alternative splicing, producing multiple isoforms ranging from 81.5 to 142.2 kDa, with tissue-specific expression patterns 1. Mechanistically, SORBS1 controls FAK/Src signaling and regulates cytoskeletal processes through Rac1 and RhoA GTPases, impacting cell-ECM contacts and cytoskeleton dynamics 2. The protein is essential for vascular development, particularly controlling secondary sprouting from axial veins and lymphatic vessel formation in zebrafish 2. Genetic variants of SORBS1 show significant clinical relevance, with the T228A polymorphism associated with protection against obesity and type 2 diabetes 3, while other variants influence glucose homeostasis, diabetes onset age 4, and blood pressure regulation 5. Additionally, SORBS1 alternative splicing defects contribute to neuromuscular junction degeneration in myotonic dystrophy type 1, highlighting its importance in neuromuscular system integrity 6. The protein also shows neuroprotective roles in insulin resistance-related neurodegeneration 7.

Sources cited
1
SORBS1 contains sorbin homology and SH3 domains, functions in insulin signaling, and shows multiple alternatively spliced isoforms
PMID: 11374898
2
SORBS1 controls FAK/Src signaling, cytoskeletal processes, and is required for vascular and lymphatic development
PMID: 38414014
3
T228A polymorphism in SORBS1 is protective against obesity and type 2 diabetes
PMID: 11532984
4
SORBS1 genetic variants are associated with glucose homeostasis and age at onset of diabetes
PMID: 30002559
5
SORBS1 variants are associated with blood pressure regulation and hypertension onset age
PMID: 26962801
6
SORBS1 alternative splicing defects contribute to neuromuscular junction degeneration in myotonic dystrophy type 1
PMID: 41250834
7
SORBS1 is involved in neuronal insulin resistance and neuroprotection
PMID: 38287296
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.46Moderate
atrial fibrillationOpen Targets
0.42Moderate
urinary system diseaseOpen Targets
0.39Weak
hypertensionOpen Targets
0.37Weak
uterine fibroidOpen Targets
0.36Weak
kidney transplantOpen Targets
0.31Weak
urethral diseaseOpen Targets
0.31Weak
ovarian neoplasmOpen Targets
0.30Weak
macular degenerationOpen Targets
0.26Weak
ovarian dysfunctionOpen Targets
0.25Weak
liver diseaseOpen Targets
0.24Weak
benign neoplasm of pituitary glandOpen Targets
0.21Weak
eye diseaseOpen Targets
0.19Weak
diverticular diseaseOpen Targets
0.12Weak
prostate cancerOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
Uterine leiomyomaOpen Targets
0.11Weak
chronic obstructive pulmonary diseaseOpen Targets
0.10Suggestive
infectionOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ITGA1Protein interaction100%ITGB5Protein interaction100%AFDNProtein interaction100%PXNProtein interaction100%TLN1Protein interaction100%VCLProtein interaction100%
Tissue Expression6 tissues
Heart
100%
Liver
9%
Brain
7%
Lung
5%
Ovary
2%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
SORBS1ITGA1ITGB5AFDNPXNTLN1VCL
PROTEIN STRUCTURE
Preparing viewer…
PDB2O9S · 0.83 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.69LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.56 [0.45–0.69]
RankingsWhere SORBS1 stands among ~20K protein-coding genes
  • #4,246of 20,598
    Most Researched112 · top quartile
  • #5,203of 17,882
    Most Constrained (LOEUF)0.69
Genes detectedSORBS1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Tirzepatide prevents neurodegeneration through multiple molecular pathways.
PMID: 38287296
J Transl Med · 2024
1.00
2
The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish.
PMID: 38414014
BMC Biol · 2024
0.90
3
Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of diabetes: A SAPPHIRe Cohort Study.
PMID: 30002559
Sci Rep · 2018
0.80
4
Genetic Variation in the Human SORBS1 Gene is Associated With Blood Pressure Regulation and Age at Onset of Hypertension: A SAPPHIRe Cohort Study.
PMID: 26962801
Medicine (Baltimore) · 2016
0.70
5
Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B.
PMID: 11374898
Genomics · 2001
0.60