PHB2
Chr 12prohibitin 2
Also known as: BAP, BCAP37, Bap37, PNAS-141, REA, hBAP, p22
PHB2 encodes prohibitin-2, a multifunctional protein that serves as a mitochondrial chaperone, functions in cell signaling at the plasma membrane, and acts as a transcriptional co-regulator in the nucleus. Mutations cause spastic paraplegia 35, an autosomal recessive disorder characterized by progressive spasticity primarily affecting the lower limbs. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.655), consistent with its essential cellular functions across multiple compartments.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
97 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 43 | 0 | 43 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 25 | 12 | 0 | 37 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 1 | 0 | 0 | 2 | 3 |
| Total | 1 | 25 | 57 | 2 | 85 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PHB2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools