ATF7IP
Chr 12activating transcription factor 7 interacting protein
Also known as: AM, ATF-IP, ATF7IP1, MCAF, MCAF1, p621
ATF7IP encodes a nuclear protein that regulates gene expression by recruiting transcriptional complexes to chromatin and facilitating histone modifications, particularly H3K9 trimethylation for gene silencing. Mutations cause autosomal dominant neurodevelopmental disorder with intellectual disability, seizures, and behavioral abnormalities. This gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.21), indicating that heterozygous mutations are likely pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
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
220 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 | 38 | 0 | 38 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 130 | 3 | 0 | 133 |
Likely Benign | 0 | 11 | 1 | 2 | 14 |
Benign | 0 | 5 | 0 | 3 | 8 |
| Total | 0 | 146 | 45 | 5 | 196 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATF7IP · 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