PHIP

Chr 6

PHIP subunit of CUL4-Ring ligase complex

Also known as: BRWD2, CHUJANS, DCAF14, DIDOD, RepID, WDR11, ndrp

NCBI Gene: 55023 ENSG00000146247 UniProt: Q8WWQ0

This gene encodes a protein that regulates insulin and insulin-like growth factor signaling pathways, stimulates cell proliferation through cyclin transcription regulation, and has anti-apoptotic activity through AKT1 phosphorylation. Mutations cause Chung-Jansen syndrome, an autosomal dominant neurodevelopmental disorder. The gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.113), indicating intolerance to protein-disrupting mutations.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that binds to the insulin receptor substrate 1 protein and regulates glucose transporter translocation in skeletal muscle cells. The encoded protein may also regulate growth and survival of pancreatic beta cells. Elevated copy number of this gene may be associated with melanoma severity and the encoded protein may promote melanoma metastasis in human patients. [provided by RefSeq, Oct 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtChung-Jansen syndrome

Clinical highlights

Gene-disease validity (ClinGen)

PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome · 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

124

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.11

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)