PRX

Chr 19ARAD

periaxin

Also known as: CMT4F

NCBI Gene: 57716ENSG00000105227UniProt: Q9BXM0OMIM: 605725

This gene encodes a protein involved in peripheral nerve myelin upkeep. The encoded protein contains 2 PDZ domains which were named after PSD95 (post synaptic density protein), DlgA (Drosophila disc large tumor suppressor), and ZO1 (a mammalian tight junction protein). Two alternatively spliced transcript variants have been described for this gene which encode different protein isoforms and which are targeted differently in the Schwann cell. Mutations in this gene cause Charcot-Marie-Tooth neuoropathy, type 4F and Dejerine-Sottas neuropathy. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…
MultiplemechanismAR/ADLOEUF 0.982 OMIM phenotypes
Clinical Summary— PRX
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Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease type 4 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
72 unique Pathogenic / Likely Pathogenic· 687 VUS of 1191 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — PRX
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.98LOEUF
pLI 0.000
Z-score 1.63
OE 0.71 (0.53–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.13Z-score
OE missense 1.01 (0.96–1.07)
862 obs / 851.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.71 (0.53–0.98)
0≤0.351.4
Missense OE?1.01 (0.96–1.07)
0≤0.61.4
Synonymous OE?1.00
0≤1.21.6
LoF obs/exp: 27 / 37.9Missense obs/exp: 862 / 851.2Syn Z: -0.01

This gene — mechanism propensity

DN
0.6647th %ile
GOF
0.6541th %ile
LOF
0.3844th %ile

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.

DNprediction above median
GOFprediction above median

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

1191 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic32
VUS687
Likely Benign383
Benign13
Conflicting31
40
Pathogenic
32
Likely Pathogenic
687
VUS
383
Likely Benign
13
Benign
31
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
37
1
2
0
40
Likely Pathogenic
30
2
0
0
32
VUS
21
649
10
7
687
Likely Benign
0
9
35
339
383
Benign
0
0
11
2
13
Conflicting
—31
Total88661583481,186

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

4 pathogenic / likely-pathogenic (of 8) ClinVar copy-number / structural variants overlap PRX — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

PRX · 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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients