BCLAF1

protein-coding

BCL2 associated transcription factor 1, the group of WTAP complex

Gene summary

This gene encodes a transcriptional repressor that interacts with several members of the BCL2 family of proteins. Overexpression of this protein induces apoptosis, which can be suppressed by co-expression of BCL2 proteins. The protein localizes to dot-like structures throughout the nucleus, and redistributes to a zone near the nuclear envelope in cells undergoing apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014739.3

Inheritance

—

ClinVar variants

P:2U:145B:21

Top phenotype

BCLAF1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr6:136,256,627-136,289,851

External References & Databases

Ensembl (ENSG00000029363)

Transcript & Mutation Effects

hg38 • Region Span ~33.2 kb

Loading mutation effect viewer...

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 BCLAF1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 125

BCLAF1-related disorderTotal: 7

not providedTotal: 6

Pulmonary artery atresiaTotal: 2

Epidermolysis bullosa simplex with nail dystrophyTotal: 1

Fraser syndrome 3Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014739.3. 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			2 clinvar	12 clinvar		14
missense	2 clinvar		122 clinvar	4 clinvar	5 clinvar	133
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			21 clinvar			21
Total	2	0	145	16	5	168

Highest pathogenic variant AF is 0.0000034431182

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 71 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014739.3	RefSeq	NP_055554.1	11	MANE Select
ENST00000531224.6	Ensembl	ENSP00000435210.1	11	MANE Select
NM_001077440.3	RefSeq	NP_001070908.1	10	Standard
NM_001077441.3	RefSeq	NP_001070909.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Interactome of polycomb repressive complex 2 (PRC2)

Biological Process

apoptotic process
positive regulation of apoptotic process
regulation of DNA-templated transcription in response to stress
negative regulation of transcription, DNA-templated
cellular response to leukemia inhibitory factor

Molecular Function

DNA binding
RNA binding
protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000531224
Coding exons: 11
Length: 32989
Individuals with no LoFs: 123059
Homozygous LoFs: 0
Heterozygous LoFs: 2687
Defined: 125746
p: 0.0107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-4.36	667	417	1.60	0.0000219	5477
Missense (PolyPhen)		36	22.244	1.6184		256
Synonymous	-7.26	252	142	1.77	0.00000725	1582
Loss of Function	1.92	28	41.3	0.678	0.00000279	531

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0025	0.0025	notable
Latino/Admixed American	0.0038	0.0038	notable
Ashkenazi Jewish	0.013	0.012	notable
East Asian	0.0061	0.0061	notable
Finnish	0.016	0.016	notable
European (Non-Finnish)	0.0078	0.0078	notable
South Asian	0.033	0.033	notable
Other	0.012	0.012	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Death-promoting transcriptional repressor. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. {ECO:0000269|PubMed:18794151}.;

Recessive Scores

pRec: 0.182

Intolerance Scores

LoFtool: 0.873
RVIS EVS: 1.99
RVIS percentile EVS: 97.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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