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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SRGAP3
SLIT-ROBO Rho GTPase activating protein 3
Chromosome 3 · 3p25.3
NCBI Gene: 9901Ensembl: ENSG00000196220.17HGNC: HGNC:19744UniProt: O43295
47PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpostsynapseregulation of synapse assemblynervous system developmentneurodegenerative diseasesevere acute respiratory syndromeCOVID-19sign or symptom
✦AI Summary

SRGAP3 encodes a Rho GTPase-activating protein that primarily inactivates RAC1 to regulate actin cytoskeletal dynamics 1. The protein functions in both cytoplasmic and nuclear compartments, with cytoplasmic SRGAP3 localizing to leading edges via its F-BAR domain to inhibit lamellipodia formation through interaction with lamellipodin 2. Nuclear SRGAP3 interacts with the SWI/SNF chr3 remodeler Brg1 to influence gene expression and dendrite morphology 3. These mechanisms are essential for dendritic spine development and synaptic assembly during neurodevelopment 1. SRGAP3 mutations are associated with intellectual disability in humans 3, and knockout mice exhibit enlarged brain ventricles with ependymal ciliopathy, increased hippocampal volume, and altered behaviors including reduced marble-burying consistent with autism-spectrum phenotypes 4, 5. SRGAP3 is also implicated in neuropathic pain pathogenesis through dendritic spine remodeling 6, and genome-wide association studies identify SRGAP3 as a schizophrenia risk gene 3. Additionally, SRGAP3 shows pleiotropic associations with body fat and Parkinson disease risk 7. Thus, SRGAP3 represents a multifunctional regulator critical for neuronal morphogenesis and neurodevelopmental health.

Sources cited
1
SRGAP3 regulates actin cytoskeleton via RAC1 inhibition; essential for dendritic spine development and cognitive function
PMID: 23127797
2
SRGAP3 mutations cause intellectual disability; nuclear SRGAP3 interacts with Brg1 chromatin remodeler to regulate gene expression and dendrite complexity
PMID: 24561795
3
SRGAP3 F-BAR domain localizes to cell membrane leading edge; inhibits lamellipodia formation through lamellipodin interaction
PMID: 22159416
4
SRGAP3 knockout mice display increased brain weight, hippocampal volume, and altered autism-related behaviors
PMID: 27184948
5
SRGAP3 deficiency causes enlarged lateral ventricles and ependymal ciliary defects
PMID: 26104135
6
SRGAP3 and RAC1 regulate dendritic spine dynamics in neuropathic pain pathogenesis
PMID: 32998955
7
SRGAP3 shows pleiotropic association with body fat measures and Parkinson disease risk
PMID: 39578713
8
SRGAP3 identified in novel lipid loci with suggested roles in brain biology and lipid metabolism
PMID: 38028628
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
severe acute respiratory syndromeOpen Targets
0.33Weak
COVID-19Open Targets
0.33Weak
sign or symptomOpen Targets
0.32Weak
gestational diabetesOpen Targets
0.31Weak
placenta praeviaOpen Targets
0.31Weak
Moyamoya diseaseOpen Targets
0.26Weak
generalized dystoniaOpen Targets
0.24Weak
facial morphologyOpen Targets
0.24Weak
renal osteodystrophyOpen Targets
0.23Weak
intestinal infectious diseaseOpen Targets
0.22Weak
protozoa infectious diseaseOpen Targets
0.19Weak
lung adenocarcinomaOpen Targets
0.19Weak
squamous cell lung carcinomaOpen Targets
0.19Weak
astrocytomaOpen Targets
0.19Weak
hepatocellular carcinomaOpen Targets
0.19Weak
breast ductal adenocarcinomaOpen Targets
0.18Weak
esophageal adenocarcinomaOpen Targets
0.18Weak
gastric adenocarcinomaOpen Targets
0.18Weak
superficial spreading melanomaOpen Targets
0.18Weak
Pathogenic Variants1
NM_014850.4(SRGAP3):c.2281C>T (p.Arg761Cys)Likely pathogenic
Moyamoya angiopathy
☆☆☆☆→ Residue 761
View on ClinVar ↗
Related Genes
CDC42Protein interaction100%ABI2Protein interaction95%FMNL1Protein interaction87%WASF1Protein interaction87%TRIP10Protein interaction87%HYDINProtein interaction83%
Tissue Expression6 tissues
Brain
100%
Ovary
38%
Heart
34%
Bone Marrow
28%
Liver
8%
Lung
6%
Gene Interaction Network
Click a node to explore
SRGAP3CDC42ABI2FMNL1WASF1TRIP10HYDIN
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O43295
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.31 [0.24–0.41]
RankingsWhere SRGAP3 stands among ~20K protein-coding genes
  • #9,279of 20,598
    Most Researched47
  • #5,124of 5,498
    Most Pathogenic Variants1
  • #2,094of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedSRGAP3
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
The cellular function of srGAP3 and its role in neuronal morphogenesis.
PMID: 23127797
Mech Dev · 2013
1.00
2
A link between the nuclear-localized srGAP3 and the SWI/SNF chromatin remodeler Brg1.
PMID: 24561795
Mol Cell Neurosci · 2014
0.90
3
Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci.
PMID: 38028628
Front Genet · 2023
0.80
4
Morphological and behavioral characterization of adult mice deficient for SrGAP3.
PMID: 27184948
Cell Tissue Res · 2016
0.70
5
Sculpting Dendritic Spines during Initiation and Maintenance of Neuropathic Pain.
PMID: 32998955
J Neurosci · 2020
0.60