BCL2L12

protein-coding

BCL2 like 12, the group of BCL2 family

Gene summary

This gene encodes a member of a family of proteins containing a Bcl-2 homology domain 2 (BH2). The encoded protein is an anti-apoptotic factor that acts as an inhibitor of caspases 3 and 7 in the cytoplasm. In the nucleus, it binds to the p53 tumor suppressor protein, preventing its association with target genes. Overexpression of this gene has been detected in a number of different cancers. There is a pseudogene for this gene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MANE transcript

NM_138639.2

Inheritance

—

ClinVar variants

U:49B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr19:49,665,142-49,673,916

External References & Databases

Ensembl (ENSG00000126453)

Transcript & Mutation Effects

hg38 • Region Span ~8.8 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 BCL2L12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 44

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138639.2. 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			1 clinvar			1
missense			45 clinvar	2 clinvar		47
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	49	2	0	51

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 72 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138639.2	RefSeq	NP_619580.2	6	MANE Select
ENST00000246784.8	Ensembl	ENSP00000246784.4	6	MANE Select
NM_001040668.2	RefSeq	NP_001035758.2	6	Standard
NM_001282516.2	RefSeq	NP_001269445.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of Apoptosis by Parathyroid Hormone-related Protein

Biological Process

apoptotic process
positive regulation of transcription by RNA polymerase II
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
inhibition of cysteine-type endopeptidase activity involved in apoptotic process
negative regulation of cellular senescence

Molecular Function

p53 binding

Cellular Component

nucleus
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000246785
Coding exons: 7
Length: 8351
Individuals with no LoFs: 125588
Homozygous LoFs: 0
Heterozygous LoFs: 159
Defined: 125747
p: 0.000632

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.139	196	202	0.973	0.0000122	2052
Missense (PolyPhen)		78	91.091	0.85628		911
Synonymous	-0.388	85	80.6	1.05	0.00000434	749
Loss of Function	0.435	14	15.9	0.882	9.14e-7	157

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.0015	0.0015	notable
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00070	0.00069	rare
South Asian	0.00027	0.00026	rare
Other	0.00083	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0973

Intolerance Scores

LoFtool: 0.929
RVIS EVS: 0.86
RVIS percentile EVS: 88.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.709

Gene Damage Prediction

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