OTUD7A

Chr 15AR

OTU deubiquitinase 7A

Also known as: C15orf16, C16ORF15, CEZANNE2, NEDHS, OTUD7

NCBI Gene: 161725 ENSG00000169918 UniProt: Q8TE49 OMIM: 612024

OTUD7A encodes a deubiquitinase that cleaves lysine-11-linked polyubiquitin chains and regulates nuclear factor kappa B signaling through its action on TRAF6. Mutations cause autosomal recessive neurodevelopmental disorder with hypotonia and seizures. The gene is highly constrained against loss-of-function mutations (pLI 0.95, LOEUF 0.33), indicating that functional copies are essential for normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a deubiquitinizing enzyme and possible tumor suppressor. The encoded protein acts on TNF receptor associated factor 6 (TRAF6) to control nuclear factor kappa B expression. However, this gene is downregulated by SNAIL1 in hepatocellular carcinoma cells, contributing to their progression and malignancy. [provided by RefSeq, Aug 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia and seizuresMIM #620790

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · 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

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P/LP missense

0.33

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — OTUD7A