PRX
Chr 19ARADperiaxin
Also known as: CMT4F
The protein maintains peripheral nerve myelin through its two PDZ domains and is differentially targeted within Schwann cells via alternatively spliced isoforms. Mutations cause Charcot-Marie-Tooth disease type 4F and Dejerine-Sottas neuropathy through both autosomal recessive and autosomal dominant inheritance patterns. The predicted gain-of-function mechanism suggests that mutations disrupt normal myelin maintenance leading to peripheral neuropathy.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
699 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 | 21 | 0 | 2 | 0 | 23 |
Likely Pathogenic | 15 | 1 | 0 | 0 | 16 |
VUS | 7 | 393 | 7 | 3 | 410 |
Likely Benign | 0 | 8 | 26 | 204 | 238 |
Benign | 0 | 0 | 0 | 1 | 1 |
Conflicting | — | 6 | |||
| Total | 43 | 402 | 35 | 208 | 694 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PRX · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools