Craniosynostosis

Gene: HUWE1

Green List (high evidence)

HUWE1 (HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase)
EnsemblGeneIds (GRCh38): ENSG00000086758
EnsemblGeneIds (GRCh37): ENSG00000086758
OMIM: 300697, Gene2Phenotype
HUWE1 is in 4 panels

3 reviews

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

3 female cases with R110Q mutation have CSS (Moortgat et al 2018). Same variant also reported previously with similar phenotype. Also 2 males with R110W and CSS. Other variants cause ID only.
Created: 5 Mar 2019, 11:33 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
X-linked intellectual disability with CSS

Eleanor Williams (Genomics England Curator)

I don't know

NOTE: Variants in a specific codon (R110) are associated with craniosynostosis. Variants in other codons are associated with intellectual disability.
Created: 21 May 2019, 12:35 p.m.
Comment on list classification: Upgrading from red to green. Green rating agreed at the GMS musculoskeletal specialist test group Webex on 2019-05-13.
Created: 21 May 2019, 12:33 p.m.
Comment on publications: Adding Moortgat et al 2018 PMID:29180823
Created: 2 May 2019, 4:09 p.m.
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: HUWE1; Suggested initial gene rating: green
Created: 5 Mar 2019, 11:21 a.m.

Andrew Wilkie (University of Oxford)

Green List (high evidence)

4 cases (2 male, 2 female) having craniosynostosis associated with mutation in identical codon p.Arg110; other mutations associated with X-linked intellectual disability. Mechanism of this genotype-phenotype specificity unknown but convincing regarding pathogenic link to mutations at this particular codon
Created: 11 Nov 2016, 12:23 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • NHS GMS
  • Expert list
Phenotypes
  • X-linked intellectual disability with CSS
OMIM
300697
Clinvar variants
Variants in HUWE1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

21 May 2019, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: HUWE1 were set to 25985138; 25590979:29180823

21 May 2019, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: HUWE1 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

21 May 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: huwe1 has been classified as Green List (High Evidence).

11 May 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Added phenotypes X-linked intellectual disability with CSS for gene: HUWE1

2 May 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: HUWE1 were set to 25985138; 25590979

2 May 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: HUWE1 were set to

5 Mar 2019, Gel status: 1

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to HUWE1.

1 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

27 Jul 2015, Gel status: 0

Added New Source

Eik Haraldsdottir (Genomics England)

HUWE1 was added to Craniosynostosis syndromespanel. Sources: Expert list