SORBS3

Chr 8

sorbin and SH3 domain containing 3

Also known as: SCAM-1, SCAM1, SH3D4

NCBI Gene: 10174ENSG00000120896UniProt: O60504

The protein encoded by this gene is an SH3 domain-containing adaptor protein called vinexin that regulates actin stress fiber formation, cell spreading, and JNK/SAPK signaling activation. This gene is extremely intolerant to loss-of-function mutations (pLI ~1.0), but specific disease associations have not been established based on the provided information. The inheritance pattern and clinical phenotypes associated with SORBS3 mutations are not defined in the available data.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
82
P/LP submissions
0%
P/LP missense
0.80
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SORBS3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
82 unique Pathogenic / Likely Pathogenic· 145 VUS of 284 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.80LOEUF
pLI 0.000
Z-score 2.61
OE 0.57 (0.42–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.92Z-score
OE missense 1.13 (1.04–1.22)
476 obs / 422.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.57 (0.42–0.80)
0≤0.351.4
Missense OE1.13 (1.04–1.22)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 25 / 43.6Missense obs/exp: 476 / 422.6Syn Z: -0.22
DN
0.78top 25%
GOF
0.6931th %ile
LOF
0.3844th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

284 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic78
Likely Pathogenic4
VUS145
Likely Benign14
Benign9
Conflicting1
78
Pathogenic
4
Likely Pathogenic
145
VUS
14
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
78
0
78
Likely Pathogenic
0
0
4
0
4
VUS
0
139
6
0
145
Likely Benign
0
9
1
4
14
Benign
0
6
0
3
9
Conflicting
—1
Total0154897251

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SORBS3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients