AFF1

Chr 4

ALF transcription elongation factor 1

Also known as: AF4, FEL, MLLT2, PBM1

This gene encodes a member of the AF4/ lymphoid nuclear protein related to the Fragile X E syndrome (FRAXE) family of proteins, which have been implicated in human childhood lymphoblastic leukemia, fragile chromosome X intellectual disability, and ataxia. It is the prevalent mixed-lineage leukemia fusion gene associated with spontaneous acute lymphoblastic leukemia. Members of this family have three conserved domains: an N-terminal homology domain, an AF4/ lymphoid nuclear protein domain, and a C-terminal homology domain. The protein functions as a regulator of RNA polymerase II-mediated transcription through elongation and chromatin remodeling functions. Through RNA interference screens, this gene has been shown to promote the expression of CD133, a plasma membrane glycoprotein required for leukemia cell survival. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

OMIMResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
48
Pubs (1 yr)
P/LP submissions
P/LP missense
0.35
LOEUF· LoF intol.
LOF
Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.35LOEUF
pLI 0.710
Z-score 5.30
OE 0.21 (0.130.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
-0.41Z-score
OE missense 1.04 (0.981.11)
700 obs / 670.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.21 (0.130.35)
00.351.4
Missense OE?1.04 (0.981.11)
00.61.4
Synonymous OE?1.19
01.21.6
LoF obs/exp: 11 / 52.5Missense obs/exp: 700 / 670.4Syn Z: -2.40

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

AFF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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