PHB2
protein-codingprohibitin 2
Gene summary
Enables obsolete amide binding activity; protein dimerization activity; and sphingolipid binding activity. Involved in several processes, including RIG-I signaling pathway; antiviral innate immune response; and regulation of DNA-templated transcription. Located in several cellular components, including cell surface; mitochondrial membrane; and nuclear matrix. Part of mitochondrial prohibitin complex. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.5 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 PHB2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001144831.2. 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 | 2 | 2 | ||||
| missense | 28 | 28 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 0 | 0 | 30 | 0 | 3 | 33 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001138303.1 | 10 | MANE Select | |
| Ensembl | ENSP00000441875.1 | 10 | MANE Select | |
| RefSeq | NP_001254629.1 | 9 | Standard | |
| Ensembl | ENSP00000382362.4 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Transport of small molecules
- Mitochondrial calcium ion transport
- Validated nuclear estrogen receptor alpha network
- Processing of SMDT1
Biological Process
- obsolete protein import into nucleus, translocation
- mitochondrial calcium ion transmembrane transport
- mitochondrion organization
- sister chromatid cohesion
- regulation of complement activation
Molecular Function
- protein binding
- protein C-terminus binding
- estrogen receptor binding
- amide binding
- protein N-terminus binding
Cellular Component
- nucleus
- cytoplasm
- mitochondrion
- mitochondrial outer membrane
- mitochondrial inner membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000535923
- Coding exons
- 10
- Length
- 5499
- Individuals with no LoFs
- 124481
- Homozygous LoFs
- 3
- Heterozygous LoFs
- 201
- Defined
- 124685
- p
- 0.000818
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.99 | 102 | 176 | 0.579 | 0.0000100 | 1910 |
| Missense (PolyPhen) | 25 | 67.874 | 0.36833 | 735 | ||
| Synonymous | 0.960 | 60 | 70.2 | 0.854 | 0.00000357 | 608 |
| Loss of Function | 2.77 | 8 | 22.0 | 0.363 | 0.00000142 | 199 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0063 | 0.0062 | notable |
| Latino/Admixed American | 0.00064 | 0.00064 | rare |
| Ashkenazi Jewish | 0.0012 | 0.0012 | notable |
| East Asian | 0.0024 | 0.0022 | notable |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00018 | 0.00018 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0.0010 | 0.00099 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a mediator of transcriptional repression by nuclear hormone receptors via recruitment of histone deacetylases (By similarity). Functions as an estrogen receptor (ER)-selective coregulator that potentiates the inhibitory activities of antiestrogens and represses the activity of estrogens. Competes with NCOA1 for modulation of ER transcriptional activity. Probably involved in regulating mitochondrial respiration activity and in aging. {ECO:0000250|UniProtKB:O35129, ECO:0000269|PubMed:10359819, ECO:0000303|PubMed:11302691}.;
Intolerance Scores
- LoFtool
- 0.523
- RVIS EVS
- -0.41
- RVIS percentile EVS
- 26.23
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |