CLPB

Chr 11

ClpB family mitochondrial disaggregase

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

NCBI Gene: 81570 ENSG00000162129 UniProt: Q9H078

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene belongs to the ATP-ases associated with diverse cellular activities (AAA+) superfamily. Members of this superfamily form ring-shaped homo-hexamers and have highly conserved ATPase domains that are involved in various processes including DNA replication, protein degradation and reactivation of misfolded proteins. All members of this family hydrolyze ATP through their AAA+ domains and use the energy generated through ATP hydrolysis to exert mechanical force on their substrates. In addition to an AAA+ domain, the protein encoded by this gene contains a C-terminal D2 domain, which is characteristic of the AAA+ subfamily of Caseinolytic peptidases to which this protein belongs. It cooperates with Hsp70 in the disaggregation of protein aggregates. Allelic variants of this gene are associated with 3-methylglutaconic aciduria, which causes cataracts and neutropenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProt3-methylglutaconic aciduria 7B

UniProt3-methylglutaconic aciduria 7A

UniProtNeutropenia, severe congenital 9, autosomal dominant

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARLimitednot for standalone diagnostic reporting

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.54

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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