BAX

protein-coding

BCL2 associated X, apoptosis regulator, the group of BCL2 family

Gene summary

The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. The association and the ratio of BAX to BCL2 also determines survival or death of a cell following an apoptotic stimulus. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis. Multiple alternatively spliced transcript variants, which encode different isoforms, have been reported for this gene. [provided by RefSeq, Dec 2019]

MANE transcript

NM_138761.4

Inheritance

—

ClinVar variants

P:3U:30B:4

Top phenotype

Carcinoma of colon

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr19:48,954,815-48,961,798

External References & Databases

Ensembl (ENSG00000087088)

Transcript & Mutation Effects

hg38 • Region Span ~7.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

leukemia, acute lymphocytic, susceptibility to, 1LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013108

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BAX variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 4

Carcinoma of colonTotal: 2

T-cell acute lymphoblastic leukemiaTotal: 2

Developmental and epileptic encephalopathy, 5Total: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138761.4. 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	1 clinvar	3
missense	1 clinvar		26 clinvar	1 clinvar		28
nonsense						0
start loss						0
frameshift	2 clinvar		1 clinvar			3
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	3	0	30	3	1	37

Highest pathogenic variant AF is 0.00002050293

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138761.4	RefSeq	NP_620116.1	6	MANE Select
ENST00000345358.12	Ensembl	ENSP00000263262.9	6	MANE Select
NM_001291428.2	RefSeq	NP_001278357.1	6	Standard
NM_001291429.2	RefSeq	NP_001278358.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Prion diseases - Homo sapiens (human)
Non-small cell lung cancer - Homo sapiens (human)
Chronic myeloid leukemia - Homo sapiens (human)
Gastric cancer - Homo sapiens (human)
Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)

Biological Process

ovarian follicle development
neuron migration
T cell homeostatic proliferation
B cell homeostasis
B cell apoptotic process

Molecular Function

protein binding
lipid binding
channel activity
Hsp70 protein binding
identical protein binding

Cellular Component

nucleus
nuclear envelope
cytoplasm
mitochondrion
mitochondrial outer membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000293288
Coding exons: 5
Length: 6984
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125698
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.299	120	130	0.926	0.00000802	1390
Missense (PolyPhen)		23	36.846	0.62423		437
Synonymous	-0.268	57	54.5	1.05	0.00000357	450
Loss of Function	2.04	2	8.38	0.239	6.37e-7	73

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000028	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the mitochondrial apoptotic process. Under normal conditions, BAX is largely cytosolic via constant retrotranslocation from mitochondria to the cytosol mediated by BCL2L1/Bcl-xL, which avoids accumulation of toxic BAX levels at the mitochondrial outer membrane (MOM) (PubMed:21458670). Under stress conditions, undergoes a conformation change that causes translocation to the mitochondrion membrane, leading to the release of cytochrome c that then triggers apoptosis. Promotes activation of CASP3, and thereby apoptosis. {ECO:0000269|PubMed:10772918, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:18948948, ECO:0000269|PubMed:21199865, ECO:0000269|PubMed:21458670, ECO:0000269|PubMed:8358790, ECO:0000269|PubMed:8521816}.;

Recessive Scores

pRec: 0.852

Intolerance Scores

LoFtool: 0.854
RVIS EVS: -0.6
RVIS percentile EVS: 17.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.990

Gene Damage Prediction

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