DMXL2

Chr 15ADAR

Dmx like 2

Also known as: DEE81, DFNA71, EIEE81, PEPNS, RC3

NCBI Gene: 23312 ENSG00000104093 UniProt: Q8TDJ6 OMIM: 612186

This protein contains 12 WD domains and serves as a scaffold protein for synaptic vesicle components, functioning as a key controller of neuronal and endocrine homeostatic processes. Mutations cause developmental and epileptic encephalopathy 81, polyendocrine-polyneuropathy syndrome, and autosomal dominant deafness, with both autosomal dominant and recessive inheritance patterns reported. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.158), indicating that even single functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein with 12 WD domains. Proteins with WD domains are involved in many functions including participation in signal transduction pathways. Participation of the encoded protein in regulation of the Notch signaling pathway has been demonstrated in vitro using several human cell lines (PMID:20810660). A gene encoding a similar protein is located on chromosome 5. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Deafness, autosomal dominant 71MIM #617605

?Polyendocrine-polyneuropathy syndromeMIM #616113

Developmental and epileptic encephalopathy 81MIM #618663

Clinical highlights

Gene-disease validity (ClinGen)

nonsyndromic genetic hearing loss · ADLimitednot for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.16

LOEUF· LoF intol.

LOF

Mechanism· predicted