MOSMO
Chr 16modulator of smoothened
Also known as: ATTHOG, BC030336, C16orf52
The protein acts as a negative regulator of hedgehog signaling by promoting internalization and degradation of smoothened protein in the ciliary membrane, and participates in sonic hedgehog-induced spinal neural progenitor cell differentiation. Mutations cause mosaic variegated aneuploidy syndrome, a rare disorder characterized by growth retardation, intellectual disability, microcephaly, and predisposition to cancer. The condition follows autosomal recessive inheritance.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
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
134 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 55 |
Likely Pathogenic | — | — | — | — | 16 |
VUS | — | — | — | — | 49 |
Likely Benign | — | — | — | — | 4 |
Benign | — | — | — | — | 1 |
Conflicting | — | 4 | |||
| Total | — | 129 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MOSMO · 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