CLPB

Chr 11ADAR

ClpB family mitochondrial disaggregase

Also known as: ANKCLB, ANKCLP, HSP78, MEGCANN, MGCA7, MGCA7A, SCN9, SKD3

This protein functions as an ATP-dependent disaggregase that maintains mitochondrial protein solubility and plays a role in granulocyte differentiation. Mutations cause 3-methylglutaconic aciduria with cataracts and neutropenia, as well as severe congenital neutropenia, with both autosomal dominant and autosomal recessive inheritance patterns described. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.536), reflecting its tolerance to certain types of mutations while still causing disease.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.543 OMIM phenotypes
Clinical SummaryCLPB
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.000
Z-score 3.81
OE 0.34 (0.220.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.05Z-score
OE missense 0.86 (0.790.94)
378 obs / 440.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.220.54)
00.351.4
Missense OE0.86 (0.790.94)
00.61.4
Synonymous OE0.88
01.21.6
LoF obs/exp: 13 / 38.5Missense obs/exp: 378 / 440.1Syn Z: 1.21
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCLPB-related 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropeniaLOFAR

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

DN
0.6839th %ile
GOF
0.5563th %ile
LOF
0.3939th %ile

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.

Literature Evidence

DNIn each individual, we identified one of four different de novo monoallelic missense variants in CLPB. We show that these variants disturb refoldase and to a lesser extent ATPase activity of CLPB in a dominant-negative manner.PMID:34140661

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CLPB · 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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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC