PMAIP1
protein-codingphorbol-12-myristate-13-acetate-induced protein 1, the group of BCL2 homology region 3 (BH3) only
Gene summary
This gene belongs to a pro-apoptotic subfamily within the BCL-2 protein family, referred to as the BCL-2 homology domain 3 (BH3)-only subfamily, which determine whether a cell commits to apoptosis. In response to death-inducing stimuli, BH3-only members inhibit the anti-apoptotic BCL-2 family members, which under steady-state conditions keep the multi-BH domain proteins BAX and BAK, in an inactive state. [provided by RefSeq, Aug 2020]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.3 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 PMAIP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021127.3. 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 | 0 | |||||
| missense | 6 | 6 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 6 | 0 | 0 | 6 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066950.1 | 2 | MANE Select | |
| Ensembl | ENSP00000326119.7 | 2 | MANE Select | |
| RefSeq | NP_001369544.1 | 3 | Standard | |
| RefSeq | NP_001369545.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- p53 signaling pathway - Homo sapiens (human)
- Apoptosis - multiple species - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- Viral carcinogenesis - Homo sapiens (human)
- Apoptosis - Homo sapiens (human)
Biological Process
- release of cytochrome c from mitochondria
- protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
- apoptotic process
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- cellular response to DNA damage stimulus
Molecular Function
- protein binding
Cellular Component
- nucleus
- mitochondrion
- mitochondrial outer membrane
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000316660
- Coding exons
- 2
- Length
- 4359
- Individuals with no LoFs
- 125596
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125597
- p
- 0.00000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.282 | 25 | 29.3 | 0.854 | 0.00000151 | 337 |
| Missense (PolyPhen) | 3 | 4.507 | 0.66563 | 63 | ||
| Synonymous | -0.493 | 14 | 11.8 | 1.18 | 5.84e-7 | 110 |
| Loss of Function | 0.317 | 1 | 1.41 | 0.712 | 5.94e-8 | 17 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1 (By similarity). Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1. {ECO:0000250, ECO:0000269|PubMed:10807576, ECO:0000269|PubMed:15694340, ECO:0000269|PubMed:15705586, ECO:0000269|PubMed:17374615, ECO:0000269|PubMed:17389404}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.719
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |