AFF4
Chr 5ADALF transcription elongation factor 4
Also known as: AF5Q31, CHOPS, MCEF
The protein encoded by this gene belongs to the AF4 family of transcription factors involved in leukemia. It is a component of the positive transcription elongation factor b (P-TEFb) complex. A chromosomal translocation involving this gene and MLL gene on chromosome 11 is found in infant acute lymphoblastic leukemia with ins(5;11)(q31;q31q23). [provided by RefSeq, Oct 2011]
Primary Disease Associations & Inheritance
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 has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
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
380 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 | 1 | 1 | 0 | 2 |
Likely Pathogenic | 0 | 1 | 0 | 0 | 1 |
VUS | 5 | 214 | 14 | 1 | 234 |
Likely Benign | 0 | 5 | 47 | 83 | 135 |
Benign | 0 | 0 | 2 | 3 | 5 |
Conflicting | — | 3 | |||
| Total | 5 | 221 | 64 | 87 | 380 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →AFF4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
Gene2Phenotype Curations
AFF4-related Cornelia de Lange-like syndrome
definitiveGene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org
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