SRGAP1

Chr 12ADSomatic

SLIT-ROBO Rho GTPase activating protein 1

Also known as: ARHGAP13, NMTC2

NCBI Gene: 57522ENSG00000196935UniProt: Q7Z6B7OMIM: 606523

SRGAP1 encodes a GTPase-activating protein that inactivates CDC42 and RhoA small GTPases and regulates neuronal migration through interaction with ROBO1 in response to SLIT signaling. Mutations cause nonmedullary thyroid cancer type 2 with autosomal dominant inheritance, though somatic mutations also occur. The gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.267), suggesting intolerance to protein loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/SomaticLOEUF 0.271 OMIM phenotype
Clinical Summary— SRGAP1
⚡
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.
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.998
Z-score 5.81
OE 0.15 (0.09–0.27)
Highly constrained

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

Missense Constraint
2.21Z-score
OE missense 0.75 (0.69–0.81)
454 obs / 607.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.15 (0.09–0.27)
0≤0.351.4
Missense OE0.75 (0.69–0.81)
0≤0.61.4
Synonymous OE0.88
0≤1.21.6
LoF obs/exp: 8 / 54.1Missense obs/exp: 454 / 607.0Syn Z: 1.39
DN
0.4487th %ile
GOF
0.5268th %ile
LOF
0.67top 25%

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

LOFprediction above median · LOEUF 0.27

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

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SRGAP1 · 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.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Genetic architecture for skeletal muscle glycolytic potential in Chinese Erhualian pigs revealed by a genome-wide association study using 1.4M SNP array
Xie X et al.·Front Genet
2023
Familial nonmedullary thyroid cancer: a case series in Iranian patients with a meta-review of case series.
Mohammadi Zaniani Z et al.·Lab Med
2023Review
Targeted sequencing and functional interrogation identified novel variant at 12q14.2 associated with risk of ovarian cancer in Han Chinese women.
Zhao Y et al.·Carcinogenesis
2025Functional
A neuronal Slit1-dependent program rescues oligodendrocyte differentiation and myelination under chronic hypoxic conditions.
Dai W et al.·Cell Rep
2025
Corrigendum to "Recombinant Slit2 attenuates neuroinflammation after surgical brain injury by inhibiting peripheral immune cell infiltration via Robo1-srGAP1 pathway in a rat model" [Neurobiology of Disease volume 85 (2016) 164-173/YNBDI_3628].
Sherchan P et al.·Neurobiol Dis
2024Functional
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Recombinant Slit2 suppresses neuroinflammation and Cdc42-mediated brain infiltration of peripheral immune cells via Robo1-srGAP1 pathway in a rat model of germinal matrix hemorrhage.
Li Q et al.·J Neuroinflammation
2023Open AccessFunctional
In silico whole-transcriptome analysis reveals a potential hsa_circ_0000375-miR-424-5p-TPM2/SRPX/SRGAP1 regulatory network related to liver metastasis of colorectal cancer.
Wei B et al.·Heliyon
2023Open Access
A proliferative to invasive switch is mediated by srGAP1 downregulation through the activation of TGF-β2 signaling.
Mondal C et al.·Cell Rep
2022Open Access
SRGAP1 Controls Small Rho GTPases To Regulate Podocyte Foot Process Maintenance.
Rogg M et al.·J Am Soc Nephrol
2021
Recombinant Slit2 attenuates neuronal apoptosis via the Robo1-srGAP1 pathway in a rat model of neonatal HIE.
Kaur H et al.·Neuropharmacology
2019Functional
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