AFF4

Chr 5AD

ALF transcription elongation factor 4

Also known as: AF5Q31, CHOPS, MCEF

NCBI Gene: 27125 ENSG00000072364 UniProt: Q9UHB7 OMIM: 604417

AFF4 encodes a key component of the super elongation complex that increases RNA polymerase II transcription efficiency by suppressing polymerase pausing along DNA. Mutations cause CHOPS syndrome, a multisystem disorder with cognitive disability, colobomas, heart defects, obesity, pulmonary involvement, short stature, and skeletal abnormalities. The condition follows autosomal dominant inheritance and AFF4 is highly constrained against loss-of-function variants, indicating intolerance to protein disruption.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

CHOPS syndromeMIM #616368

Clinical highlights

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.14

LOEUF· LoF intol.

GOF*

Mechanism· G2P

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GeneReview available — AFF4