PJVK

Chr 2AR

pejvakin

Also known as: DFNB59

NCBI Gene: 494513 ENSG00000204311 UniProt: Q0ZLH3 OMIM: 610219

The protein encoded by PJVK is a peroxisome-associated protein that protects auditory hair cells against noise-induced damage by regulating peroxisome proliferation and promoting autophagy of oxidatively damaged peroxisomes. Mutations cause autosomal recessive non-syndromic sensorineural hearing loss (DFNB59). The gene shows low constraint to loss-of-function variants, consistent with its autosomal recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the gasdermin family, a family which is found only in vertebrates. The encoded protein is required for the proper function of auditory pathway neurons. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal recessive type 59 (DFNB59). [provided by RefSeq, Dec 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.151 OMIM phenotype

Clinical Summary— PJVK

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · 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

46 unique Pathogenic / Likely Pathogenic· 94 VUS of 297 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PJVK

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 1.07

OE 0.73 (0.48–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.13Z-score

OE missense 0.97 (0.86–1.10)

181 obs / 186.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.73 (0.48–1.15)

0≤0.351.4

Missense OE?0.97 (0.86–1.10)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 14 / 19.1Missense obs/exp: 181 / 186.1Syn Z: 0.77

ClinVar Variant Classifications

297 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29

Likely Pathogenic17

VUS94

Likely Benign125

Benign14

Conflicting17

Pathogenic

Likely Pathogenic

VUS

125

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	26	3	0	0	29
Likely Pathogenic	13	2	1	1	17
VUS	1	75	15	3	94
Likely Benign	0	4	52	69	125
Benign	0	0	14	0	14
Conflicting	—				17
Total	40	84	82	73	296

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap PJVK — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →