AFG2A

Chr 4AR

AAA ATPase AFG2A

Also known as: AFG2, EHLMRS, NEDHSB, SPAF, SPATA5

NCBI Gene: 166378 ENSG00000145375 UniProt: Q8NB90 OMIM: 613940

AFG2A encodes an ATP-dependent chaperone that is part of a chromatin-associated complex essential for DNA replication fork progression, genome stability, and ribosomal particle maturation. Biallelic mutations cause a neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities with autosomal recessive inheritance. The gene shows very low constraint against loss-of-function variants, consistent with the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the ATPase associated with diverse activities family, whose members are defined by a highly conserved ATPase domain. Members of this family participate in diverse cellular processes that include membrane fusion, DNA replication, microtubule severing, and protein degradation. The protein encoded by this gene has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Allelic variants in this gene have been associated with epilepsy, hearing loss, and cognitive disability syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalitiesMIM #616577

Clinical highlights

Gene-disease validity (ClinGen)

syndromic complex neurodevelopmental disorder · ARDefinitivesufficient evidence for diagnostic panels

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

1.08

LOEUF

LOF

Mechanism· G2P