HUWE1 variants were first reported in relation to non-syndromic X-linked intellectual disability in 2007 (PMID:18047645). HUWE1 encodes a protein that plays a role in anti-apoptotic protein Mcl1 ubiquitination and degradation. The phenotypes associated with variants in HUWE1 include varying degrees of intellectual disability, dysmorphic facial features, macro- and microcephaly, and short stature.
At least 8 unique variants (missense) reported in 18 probands from 9 publications (PMIDs:27130160, 27615324, 23721686, 26587761, 23092983, 18252232, 25652354, 24307393, 18047645) have been included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached.
This gene-disease relationship is also supported by experimental evidence including biochemical functional studies, animal models, rescue, and functional alteration of patient cells (PMIDs:28193319, 20007713, 20231446, 28445732, 18047645, 27130160).
In summary, there is definitive evidence to support the gene-disease relationship between HUWE1 and non-syndromic X-linked intellectual disability. This classification was approved by the Intellectual Disability and Autism Gene Curation Expert Panel on October 20, 2017. As of June 2022, this record underwent administrative updates to include an evidence summary text and update scoring to be consistent with SOP Version 9. No new evidence has been added.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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