LRRC75A
Chr 17leucine rich repeat containing 75A
Also known as: C17orf76, FAM211A
The protein functions as a substrate adaptor for the Cul2-RING ubiquitin ligase complex, facilitating proteasome-mediated protein degradation in the cytoplasm. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and motor dysfunction. The gene shows significant constraint against loss-of-function variants (LOEUF 0.58), suggesting intolerance to complete protein loss.
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 gain-of-function.
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
111 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 | 27 | 0 | 27 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 52 | 17 | 0 | 69 |
Likely Benign | 1 | 9 | 1 | 1 | 12 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 1 | 62 | 45 | 1 | 109 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LRRC75A · 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