WRNIP1

Chr 6

WRN helicase interacting protein 1

Also known as: CFAP93, FAP93, WHIP, bA420G6.2

NCBI Gene: 56897 ENSG00000124535 UniProt: Q96S55 OMIM: 608196

The encoded protein functions as a modulator of DNA polymerase delta-mediated DNA synthesis and plays a role in innate immune defense against viruses by stabilizing RIG-I dsRNA interactions and promoting RIG-I polyubiquitination. Mutations cause autosomal recessive intellectual developmental disorder with cardiac arrhythmia, typically presenting in infancy with developmental delays and cardiac conduction abnormalities. This gene is highly constrained against loss-of-function variants (LOEUF 0.582), indicating that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

Werner's syndrome is a rare autosomal recessive disorder characterized by accelerated aging that is caused by defects in the Werner syndrome ATP-dependent helicase gene (WRN). The protein encoded by this gene interacts with the exonuclease-containing N-terminal portion of the Werner protein. This protein has a ubiquitin-binding zinc-finger domain in the N-terminus, an ATPase domain, and two leucine zipper motifs in the C-terminus. It has sequence similarity to replication factor C family proteins and is conserved from E. coli to human. This protein likely accumulates at sites of DNA damage by interacting with polyubiquinated proteins and also binds to DNA polymerase delta and increases the initiation frequency of DNA polymerase delta-mediated DNA synthesis. This protein also interacts with nucleoporins at nuclear pore complexes. Two transcript variants encoding different isoforms have been isolated for this gene. [provided by RefSeq, Jul 2012]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.58

LOEUF

Mechanism· predicted