BNIP3
protein-codingBCL2 interacting protein 3, the group of BCL2 homology region 3 (BH3) only
Gene summary
This gene is encodes a mitochondrial protein that contains a BH3 domain and acts as a pro-apoptotic factor. The encoded protein interacts with anti-apoptotic proteins, including the E1B 19 kDa protein and Bcl2. This gene is silenced in tumors by DNA methylation. [provided by RefSeq, Dec 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.3 kbGenCC 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 BNIP3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004052.4. 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 | 1 | 1 | ||||
| missense | 23 | 23 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 25 | 0 | 0 | 25 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004043.4 | 6 | MANE Select | |
| Ensembl | ENSP00000357625.6 | 6 | MANE Select | |
| Ensembl | ENSP00000446145.3 | 5 | Standard | |
| Ensembl | ENSP00000446145.3 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Legionellosis - Homo sapiens (human)
- Autophagy - animal - Homo sapiens (human)
- FoxO signaling pathway - Homo sapiens (human)
- Mitophagy - animal - Homo sapiens (human)
- Busulfan Pathway, Pharmacodynamics
Biological Process
- autophagy of mitochondrion
- response to hypoxia
- apoptotic process
- cell death
- granzyme-mediated apoptotic signaling pathway
Molecular Function
- protein binding
- identical protein binding
- protein homodimerization activity
- protein heterodimerization activity
- GTPase binding
Cellular Component
- nucleus
- nuclear envelope
- nucleoplasm
- cytoplasm
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000368636
- Coding exons
- 6
- Length
- 13858
- Individuals with no LoFs
- 125730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125748
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.827 | 90 | 115 | 0.783 | 0.00000670 | 1283 |
| Missense (PolyPhen) | 29 | 45.196 | 0.64166 | 503 | ||
| Synonymous | 0.304 | 41 | 43.6 | 0.941 | 0.00000279 | 357 |
| Loss of Function | 0.534 | 8 | 9.80 | 0.816 | 4.16e-7 | 120 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates in mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. Plays an important role in the calprotectin (S100A8/A9)-induced cell death pathway. {ECO:0000269|PubMed:19935772, ECO:0000269|PubMed:22292033}.;
Recessive Scores
- pRec
- 0.310
Intolerance Scores
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 53.19
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.970
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |