SMCO1
Chr 3single-pass membrane protein with coiled-coil domains 1
Also known as: C3orf43
SMCO1 encodes a protein predicted to be located in cellular membranes, though its specific function remains unclear. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and brain abnormalities. The gene shows high tolerance to loss-of-function variants, consistent with the recessive inheritance pattern observed in affected patients.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
125 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 | 85 | 0 | 85 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 21 | 13 | 0 | 34 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 0 | 0 | 0 |
Conflicting | — | 1 | |||
| Total | 0 | 23 | 100 | 0 | 124 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SMCO1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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 →No open access results found
External Resources
Links to major genomics databases and tools