SMCR8
Chr 17SMCR8-C9orf72 complex subunit
Also known as: DENND8A
SMCR8 encodes a component of the C9orf72-SMCR8 complex that functions as a guanine nucleotide exchange factor and regulates autophagy by promoting RAB GTPase activation and inhibiting ULK1 kinase activity. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, developmental delay, and seizures. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.654), suggesting some tolerance for such mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
ClinVar Variant Classifications
272 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 113 | 0 | 113 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 141 | 3 | 0 | 144 |
Likely Benign | 0 | 2 | 1 | 2 | 5 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 144 | 117 | 2 | 263 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SMCR8 · 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