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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SRGAP2C
SLIT-ROBO Rho GTPase activating protein 2C
Chromosome 1 · 1p11.2
NCBI Gene: 653464Ensembl: ENSG00000171943.13HGNC: HGNC:30584UniProt: P0DJJ0
13PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
inhibitory synapse assemblypositive regulation of neuron migrationprotein homodimerization activityglutamatergic synapsebreast carcinomaAlzheimer diseasegoutluminal A breast carcinoma
✦AI Summary

SRGAP2C is a human-specific protein that emerged during early Homo lineage evolution through gene duplication and acts as a critical modifier of cortical circuit architecture 1. As a truncated paralog of the ancestral SRGAP2A, SRGAP2C functions by heterodimerizing with SRGAP2A and promoting its proteasome-dependent degradation, thereby inhibiting SRGAP2A's role in suppressing synaptic density 23. This inhibition leads to increased density of both excitatory and inhibitory synapses and protracted synaptic maturation in cortical pyramidal neurons 31. Structurally, SRGAP2C's defective F-BAR extension domain renders it intrinsically unstable but enables effective heterodimerization with SRGAP2A 4. At the circuit level, SRGAP2C increases local and long-range cortico-cortical connectivity to layer 2/3 pyramidal neurons and enhances sensory-evoked neural responses 1. In transgenic models, SRGAP2C expression improves sensory discrimination learning and motor planning 15. Recent evidence indicates SRGAP2C regulates synaptic neoteny through CTNND2, linking human-specific genes to developmental disability pathways 6. Mutations in SRGAP2 orthologs associate with early infantile epileptic encephalopathy 7, highlighting clinical relevance to neurodevelopmental disorders.

Sources cited
1
SRGAP2C increases excitatory and inhibitory synapse density in layer 2/3 pyramidal neurons and enhances sensory-discrimination task learning
PMID: 34707291
2
SRGAP2C inhibits SRGAP2A through heterodimerization, increasing synaptic density and protracted maturation
PMID: 27373832
3
SRGAP2C heterodimerizes with SRGAP2A and reduces SRGAP2A levels through proteasome-dependent degradation
PMID: 31822692
4
SRGAP2C has a defective Fx-domain that compromises solubility; hetero-dimers with SRGAP2A are insoluble and inhibit SRGAP2A activity
PMID: 28333212
5
Transgenic macaques with SRGAP2C show delayed brain development, delayed synaptic maturation, and improved motor planning
PMID: 38090550
6
SRGAP2C enhances CTNND2 synaptic accumulation and contributes to synaptic neoteny in humans
PMID: 39352808
7
SRGAP2 mutations cause early infantile epileptic encephalopathy and altered excitatory-inhibitory neuron balance
PMID: 39314374
Disease Associationsⓘ20
breast carcinomaOpen Targets
0.21Weak
Alzheimer diseaseOpen Targets
0.13Weak
goutOpen Targets
0.13Weak
luminal A breast carcinomaOpen Targets
0.12Weak
endocrine system diseaseOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
estrogen-receptor positive breast cancerOpen Targets
0.09Suggestive
breast neoplasmOpen Targets
0.06Suggestive
acute lymphoblastic leukemiaOpen Targets
0.02Suggestive
acute myeloid leukemiaOpen Targets
0.01Suggestive
osteosarcomaOpen Targets
0.01Suggestive
gastric cancerOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
posterior cortical atrophyOpen Targets
0.00Suggestive
Abnormal sperm morphologyOpen Targets
0.00Suggestive
epilepsyOpen Targets
0.00Suggestive
Intellectual disabilityOpen Targets
0.00Suggestive
intraepithelial neoplasiaOpen Targets
0.00Suggestive
oligospermiaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ARHGAP11BProtein interaction72%SRGAP2BShared pathway43%SRGAP1Shared pathway43%SRGAP3Shared pathway38%SRGAP2Shared pathway28%LSAMPShared pathway25%
Tissue Expression6 tissues
Brain
100%
Ovary
59%
Lung
54%
Bone Marrow
42%
Liver
29%
Heart
15%
Gene Interaction Network
Click a node to explore
SRGAP2CARHGAP11BSRGAP2BSRGAP1SRGAP3SRGAP2LSAMP
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt P0DJJ0
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.91LoF Tolerant
pLIⓘ
0.03Tolerant
Observed/Expected LoF1.32 [0.52–1.91]
RankingsWhere SRGAP2C stands among ~20K protein-coding genes
  • #16,317of 20,598
    Most Researched13
  • #17,356of 17,882
    Most Constrained (LOEUF)1.91
Genes detectedSRGAP2C
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A human-specific modifier of cortical connectivity and circuit function.
PMID: 34707291
Nature · 2021
1.00
2
The human-specific paralogs SRGAP2B and SRGAP2C differentially modulate SRGAP2A-dependent synaptic development.
PMID: 31822692
Sci Rep · 2019
0.90
3
Brain developmental and cortical connectivity changes in transgenic monkeys carrying the human-specific duplicated gene
PMID: 38090550
Natl Sci Rev · 2023
0.80
4
Structural History of Human SRGAP2 Proteins.
PMID: 28333212
Mol Biol Evol · 2017
0.70
5
CTNND2 moderates the pace of synaptic maturation and links human evolution to synaptic neoteny.
PMID: 39352808
Cell Rep · 2024
0.60