HERPUD1

Chr 16

homocysteine inducible ER protein with ubiquitin like domain 1

Also known as: HERP, HERPUD1-IT1, Mif1, SUP

NCBI Gene: 9709 ENSG00000051108 UniProt: Q15011 OMIM: 608070

The protein functions as a component of the endoplasmic reticulum quality control system, facilitating ubiquitin-dependent degradation of misfolded ER proteins and enhancing presenilin-mediated amyloid-beta generation. HERPUD1 is highly constrained against loss-of-function variants, but no established human disease associations have been reported in the provided data. Additional clinical and genetic studies would be needed to determine if mutations in this gene cause human disease.

OMIM ResearchSummary from RefSeq, UniProt

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the ER stress response. This response includes the inhibition of translation to prevent further accumulation of unfolded proteins, the increased expression of proteins involved in polypeptide folding, known as the unfolded protein response (UPR), and the destruction of misfolded proteins by the ER-associated protein degradation (ERAD) system. This gene may play a role in both UPR and ERAD. Its expression is induced by UPR and it has an ER stress response element in its promoter region while the encoded protein has an N-terminal ubiquitin-like domain which may interact with the ERAD system. This protein has been shown to interact with presenilin proteins and to increase the level of amyloid-beta protein following its overexpression. Alternative splicing of this gene produces multiple transcript variants encoding different isoforms. The full-length nature of all transcript variants has not been determined. [provided by RefSeq, Jan 2013]

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)

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P/LP submissions

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P/LP missense

0.23

LOEUF· LoF intol.

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Mechanism