AFF1

protein-coding

ALF transcription elongation factor 1, the group of Super elongation complex|AF4/FMR2 family

Gene summary

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]

Previous symbols:

PBM1
MLLT2

MANE transcript

NM_001166693.3

Inheritance

—

ClinVar variants

U:193B:23

Top phenotype

Teratoma

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr4:86,935,002-87,141,039

External References & Databases

Ensembl (ENSG00000172493)

Transcript & Mutation Effects

hg38 • Region Span ~206.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AFF1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 193

not providedTotal: 13

TeratomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001166693.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	5 clinvar	2 clinvar	11
missense			186 clinvar	15 clinvar	1 clinvar	202
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	193	20	3	216

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001166693.3	RefSeq	NP_001160165.1	20	MANE Select
ENST00000395146.9	Ensembl	ENSP00000378578.4	20	MANE Select
NM_001313959.2	RefSeq	NP_001300888.1	20	Standard
NM_001313960.2	RefSeq	NP_001300889.1	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transcriptional misregulation in cancer - Homo sapiens (human)

Biological Process

regulation of transcription, DNA-templated

Molecular Function

double-stranded DNA binding
DNA-binding transcription factor activity
protein binding

Cellular Component

nucleus
transcription elongation factor complex
ELL-EAF complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395146
Coding exons: 20
Length: 206053
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.406	700	670	1.04	0.0000381	7979
Missense (PolyPhen)		131	116.93	1.1203		1508
Synonymous	-2.40	311	262	1.19	0.0000159	2399
Loss of Function	5.30	11	52.5	0.210	0.00000271	658

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.000031	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00023	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Note=A chromosomal aberration involving AFF1 is associated with acute leukemias. Translocation t(4;11)(q21;q23) with KMT2A/MLL1. The result is a rogue activator protein.;

Recessive Scores

pRec: 0.185

Intolerance Scores

LoFtool: 0.657
RVIS EVS: -1.18
RVIS percentile EVS: 5.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.928

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium