PHB1
protein-codingprohibitin 1
Gene summary
This gene is evolutionarily conserved, and its product is proposed to play a role in human cellular senescence and tumor suppression. Antiproliferative activity is reported to be localized to the 3' UTR, which is proposed to function as a trans-acting regulatory RNA. Several pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
- PHB
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.9 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 PHB1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002634.4. 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 | 2 | |||
| missense | 14 | 2 | 16 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 16 | 1 | 3 | 20 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002625.1 | 6 | MANE Select | |
| Ensembl | ENSP00000300408.3 | 6 | MANE Select | |
| RefSeq | NP_001268425.1 | 6 | Standard | |
| RefSeq | NP_001268426.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Integrated Breast Cancer Pathway
- RAF activation
- Disease
- Signal Transduction
- Transport of small molecules
Biological Process
- negative regulation of transcription by RNA polymerase II
- ovarian follicle development
- ovarian follicle atresia
- osteoblast differentiation
- regulation of transcription, DNA-templated
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- complement component C3a binding
- complement component C3b binding
- protein binding
- protein C-terminus binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrion
- mitochondrial inner membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000300408
- Coding exons
- 6
- Length
- 10833
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125717
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.45 | 79 | 169 | 0.469 | 0.0000105 | 1734 |
| Missense (PolyPhen) | 8 | 28.398 | 0.28171 | 408 | ||
| Synonymous | 0.895 | 61 | 70.6 | 0.864 | 0.00000458 | 583 |
| Loss of Function | 2.89 | 2 | 13.4 | 0.149 | 8.06e-7 | 136 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.0000089 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Prohibitin inhibits DNA synthesis. It has a role in regulating proliferation. As yet it is unclear if the protein or the mRNA exhibits this effect. May play a role in regulating mitochondrial respiration activity and in aging. {ECO:0000269|PubMed:11302691}.;
Recessive Scores
- pRec
- 0.685
Intolerance Scores
- LoFtool
- 0.0551
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.64
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.896
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |