SCML2
Chr XScm polycomb group protein like 2
This gene encodes a Polycomb group protein that maintains transcriptional repression of homeotic genes by forming multiprotein complexes and binding monomethylated histone lysine residues during development. Mutations cause X-linked intellectual disability, and the gene is highly constrained against loss-of-function variants (pLI 0.996, LOEUF 0.132), indicating intolerance to protein-disrupting changes. The condition follows X-linked inheritance with males typically more severely affected than carrier females.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
This gene — mechanism propensity
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
300 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 | 106 | 0 | 106 |
Likely Pathogenic | 0 | 0 | 6 | 0 | 6 |
VUS | 0 | 37 | 11 | 0 | 48 |
Likely Benign | 0 | 4 | 0 | 1 | 5 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 41 | 123 | 1 | 165 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SCML2 · 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 →External Resources
Links to major genomics databases and tools