Curated summary · agent-written · kb/genes/curated/hgnc_16410.md

All 11 claims checked against the KB draft

DNAJC30 across dismech

DNAJC30 (DnaJ heat shock protein family (Hsp40) member C30) is named by 2 disorder entries.

Normal function

ai-gene-review gives DNAJC30's core molecular function as enzyme binding, located in the mitochondrial inner membrane. The review records its role in complex I N-module repair without a molecular-function term, because the biochemical activity has not been established.

Causative records

Both entries type DNAJC30 as causative and germline: Leber Hereditary Optic Neuropathy; and Leber-like Hereditary Optic Neuropathy, Autosomal Recessive 1. In Leber-like Hereditary Optic Neuropathy, Autosomal Recessive 1 the gene sits on the node DNAJC30 Loss of Function, and ClinGen rates the relationship definitive. Nodes naming DNAJC30 conform to the module complex_i_deficiency.

Where the layers agree and disagree

The KB binds the gene-bound node to the process protein-containing complex remodeling, standing for exchange of complex I N-module subunits, and binds the molecular function enzyme binding for DNAJC30's interaction with complex I subunits, at the same generic level as the review's core molecular function; neither layer asserts a chaperone activity. The review binds no GO process to this core function, so the layers share 0 process terms.

Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.

Normal function · from ai-gene-review (Q96LL9, commit 79fe13b38970) · AI-generated, not KB evidence

DNAJC30 (WBSCR18) is a mitochondrial inner-membrane DnaJ/HSP40 (J-domain) protein encoded in the 7q11.23 Williams-Beuren syndrome critical region. Imported via an N-terminal transit peptide and anchored by a single transmembrane helix, it has two intertwined roles in oxidative phosphorylation. It is an auxiliary component of the ATP synthase machinery, interacting directly with MT-ATP6 and ATP5MC2 and facilitating ATP synthesis. It also acts as a chaperone in a mitochondrial complex I (NADH:ubiquinone oxidoreductase) repair mechanism, promoting the efficient exchange/turnover of N-module subunits damaged by reactive oxygen species and thereby maintaining complex I efficiency. DNAJC30 is highly expressed in brain (pyramidal neurons). Biallelic loss-of-function variants cause autosomal-recessive Leber hereditary optic neuropathy (LHONAR1), and hemizygous loss contributes to the mitochondrial dysfunction underlying neurodevelopmental features of Williams-Beuren syndrome.

Chaperone in the mitochondrial complex I repair pathway that promotes efficient exchange/turnover of complex I (NADH:ubiquinone oxidoreductase) N-module subunits damaged by reactive oxygen species, maintaining complex I functional efficiency. The biochemical activity by which it promotes N-module exchange (whether it binds damaged subunits directly or acts through HSP70) has not been established.

locations: mitochondrial inner membrane

Auxiliary component of the mitochondrial ATP synthase machinery that interacts directly with MT-ATP6 and ATP5MC2 and facilitates ATP synthesis and OXPHOS supercomplex/ATP-synthase-dimer integrity.

molecular function: enzyme binding · locations: mitochondrial inner membrane

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Leber Hereditary Optic Neuropathy	causative germline	mechanism: Complex I Subunit Missense Mutation subtype: arLHON variant: DNAJC30 p.Tyr51Cys scoped to subtype: arLHON
Leber-like Hereditary Optic Neuropathy, Autosomal Recessive 1	causative germline loss of function CLINGEN: definitive	mechanism: DNAJC30 Loss of Function

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
Leber-like hereditary optic neuropathy, autosomal recessive 1 MONDO:0958183	AR	Definitive 2025-09-18	Leber-like Hereditary Optic Neuropathy, Autosomal Recessive 1 causative

Mechanism modules · computed from kb/

complex_i_deficiency via Leber-like Hereditary Optic Neuropathy, Autosomal Recessive 1