NCOA1
Chr 2nuclear receptor coactivator 1
Also known as: F-SRC-1, KAT13A, RIP160, SRC1, bHLHe42, bHLHe74
NCOA1 encodes a nuclear receptor coactivator that directly binds steroid and nuclear hormone receptors to stimulate hormone-dependent gene transcription and has histone acetyltransferase activity. Mutations cause autosomal dominant intellectual disability and developmental delay, often with additional features including growth abnormalities and endocrine dysfunction. This gene is extremely intolerant to loss-of-function variants (pLI = 1.0, LOEUF = 0.25), indicating that functional copies are critical for normal development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
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
462 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 | 19 | 0 | 19 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 2 | 264 | 17 | 2 | 285 |
Likely Benign | 0 | 5 | 13 | 103 | 121 |
Benign | 0 | 0 | 1 | 4 | 5 |
| Total | 2 | 269 | 51 | 109 | 431 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
NCOA1 · 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
External Resources
Links to major genomics databases and tools