CLPP

Chr 19AR

caseinolytic mitochondrial matrix peptidase proteolytic subunit

Also known as: DFNB81, PRLTS3

The encoded protease functions as part of the mitochondrial ClpXP complex to degrade proteins and peptides in an ATP-dependent manner, serving essential housekeeping functions within mitochondria. Biallelic mutations cause Perrault syndrome 3, an autosomal recessive disorder characterized by sensorineural hearing loss in both sexes and ovarian dysgenesis in females. The gene shows significant constraint against loss-of-function variants (LOEUF 0.565), indicating intolerance to haploinsufficiency in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.561 OMIM phenotype
Clinical SummaryCLPP
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Gene-Disease Validity (ClinGen)
Perrault syndrome 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.57) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.56LOEUF
pLI 0.571
Z-score 2.54
OE 0.18 (0.070.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.95Z-score
OE missense 0.57 (0.480.68)
93 obs / 163.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.18 (0.070.56)
00.351.4
Missense OE0.57 (0.480.68)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 2 / 11.1Missense obs/exp: 93 / 163.0Syn Z: -0.52
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCLPP-related Perrault syndromeOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6552th %ile
GOF
0.4579th %ile
LOF
0.50top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CLPP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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