TRIP12

Chr 2

thyroid hormone receptor interactor 12

Also known as: MRD49, TRIP-12, TRIPC, ULF

NCBI Gene: 9320 ENSG00000153827 UniProt: Q14669

The encoded E3 ubiquitin-protein ligase degrades the p19ARF tumor suppressor isoform and regulates USP7 stability in DNA damage response pathways. Loss-of-function mutations cause autosomal dominant intellectual developmental disorder. The gene is extremely intolerant to loss-of-function variants, indicating haploinsufficiency as the disease mechanism.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is an E3 ubiquitin-protein ligase involved in the degradation of the p19ARF/ARF isoform of CDKN2A, a tumor suppressor. The encoded protein also plays a role in the DNA damage response by regulating the stability of USP7, which regulates tumor suppressor p53. [provided by RefSeq, Jan 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtClark-Baraitser syndrome

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

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

—

P/LP missense

0.06

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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