ATAD3A

Chr 1ADAR

ATPase family AAA domain containing 3A

Also known as: HAYOS, PHRINL

NCBI Gene: 55210 ENSG00000197785 UniProt: Q9NVI7 OMIM: 612316

ATAD3A encodes a mitochondrial membrane protein essential for mitochondrial network organization, metabolism, protein synthesis, and cholesterol metabolism. Mutations cause Harel-Yoon syndrome and a neonatal lethal form of pontocerebellar hypoplasia with hypotonia and respiratory insufficiency, following both autosomal dominant and autosomal recessive inheritance patterns. The gene is extremely intolerant to loss-of-function variants, consistent with the severe neonatal phenotypes observed.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a ubiquitously expressed mitochondrial membrane protein that contributes to mitochondrial dynamics, nucleoid organization, protein translation, cell growth, and cholesterol metabolism. This gene is a member of the ATPase family AAA-domain containing 3 gene family which, in humans, includes two other paralogs. Naturally occurring mutations in this gene are associated with distinct neurological syndromes including Harel-Yoon syndrome. High-level expression of this gene is associated with poor survival in breast cancer patients. A homozygous knockout of the orthologous gene in mice results in embryonic lethality at day 7.5 due to growth retardation and defective development of the trophoblast lineage. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Harel-Yoon syndromeMIM #617183

ADAR

Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethalMIM #618810

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.83

LOEUF

Multiple*

Mechanism· G2P