SRGAP3

Chr 3

SLIT-ROBO Rho GTPase activating protein 3

Also known as: ARHGAP14, MEGAP, SRGAP2, WRP

The protein functions as a GTPase-activating protein that regulates RAC1 and CDC42 signaling in neurons and is involved in postsynapse assembly and regulation of cell migration. Mutations cause autosomal recessive intellectual disability with additional features that may include behavioral abnormalities and developmental delays. This gene is highly constrained against loss-of-function variants in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.24
Clinical SummarySRGAP3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
3 unique Pathogenic / Likely Pathogenic· 70 VUS of 100 total submissions
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GeneReview available — SRGAP3
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 1.000
Z-score 5.94
OE 0.13 (0.070.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.11Z-score
OE missense 0.77 (0.720.83)
516 obs / 670.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.13 (0.070.24)
00.351.4
Missense OE0.77 (0.720.83)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 7 / 54.1Missense obs/exp: 516 / 670.0Syn Z: -1.26
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedSRGAP3-related intellectual disabilityLOFAD
DN
0.4587th %ile
GOF
0.5268th %ile
LOF
0.68top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.24

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic3
VUS70
Likely Benign6
3
Pathogenic
70
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
0
0
0
VUS
1
68
1
0
70
Likely Benign
0
4
0
2
6
Benign
0
0
0
0
0
Total1724279

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

View in ClinVar →

Protein Context — Lollipop Plot

SRGAP3 · 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

No active trials found for this gene.

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Clinical Literature
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