UFD1

Chr 22AD

ubiquitin recognition factor in ER associated degradation 1

Also known as: UFD1L

NCBI Gene: 7353 ENSG00000070010 UniProt: Q92890 OMIM: 601754

UFD1 encodes an essential component of the ubiquitin-dependent proteolytic pathway that forms a complex with VCP and NPLOC4 to degrade misfolded proteins and regulate nuclear envelope formation during mitosis. Mutations cause autosomal dominant Charcot-Marie-Tooth disease type 2Y, frontotemporal dementia and/or amyotrophic lateral sclerosis 6, and inclusion body myopathy with early-onset Paget disease and frontotemporal dementia. The gene is highly constrained against loss-of-function variants, reflecting its essential cellular functions.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene forms a complex with two other proteins, nuclear protein localization-4 and valosin-containing protein, and this complex is necessary for the degradation of ubiquitinated proteins. In addition, this complex controls the disassembly of the mitotic spindle and the formation of a closed nuclear envelope after mitosis. Mutations in this gene have been associated with Catch 22 syndrome as well as cardiac and craniofacial defects. Alternative splicing results in multiple transcript variants encoding different isoforms. A related pseudogene has been identified on chromosome 18. [provided by RefSeq, Jun 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 2YMIM #616687

Frontotemporal dementia and/or amyotrophic lateral sclerosis 6MIM #613954

Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1MIM #167320

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.

LOF

Mechanism· predicted