SH2D3C
Chr 9SH2 domain containing 3C
Also known as: CHAT, NSP3, PRO34088, SHEP1
SH2D3C encodes an adaptor protein that mediates cell signaling pathways controlling cell adhesion, migration, and immune responses, and is required for olfactory sensory neuron migration and innervation of the olfactory bulb during development. Mutations cause autosomal recessive neurodevelopmental disorder with hypotonia, seizures, and respiratory insufficiency, typically presenting in early infancy. The gene shows very low constraint against loss-of-function variants (pLI 0.0004), consistent with the recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SH2D3C · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools