Xeroderma pigmentosum, Trichothiodystrophy or Cockayne syndrome

Gene: RNF113A

Amber List (moderate evidence)

RNF113A (ring finger protein 113A)
EnsemblGeneIds (GRCh38): ENSG00000125352
EnsemblGeneIds (GRCh37): ENSG00000125352
OMIM: 300951, Gene2Phenotype
RNF113A is in 5 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Associated with relevant phenotype in OMIM (MIM# 300953) and as possible Gen2Phen gene for X-linked trichothiodystrophy. At least 3 terminating variants reported in unrelated cases. Supportive functional studies also reported. Upgraded from Red to Amber but this gene should be promoted to Green at the next review.
Created: 30 Sep 2021, 2:47 p.m. | Last Modified: 30 Sep 2021, 2:47 p.m.
Panel Version: 2.15

Michael Yau (Genetics, Viapath)

Green List (high evidence)

In 2016 the RNF113A gene was added to R227 as a red gene because it was a "Possible DD gene for X-LINKED TRICHOTHIODYSTROPHY, and one family report in OMIM".

The family reported in OMIM was found by Tarpey et al (2009) to have the following likely pathogenic variant, RNF113A c.901C>T p.(Gln301Ter). Corbett et al (2015) showed that the variant is associated with X-linked form of nonphotosensitive trichothiodystrophy (XL-TTD) that has the following clinical phenotype: profound intellectual disability, microcephaly, partial corpus callosum agenesis, microphallus, and absent or rudimentary testes. Functional studies showed that it altered DNA alklation. Since this family was reported, three other families with XL-TTD and RNF113A variants have been discovered. In 2020, Tessarech et al identified the same RNF113A c.901C>T p.(Gln301Ter) variant in two foetuses from the same family that had the same clinical phenotypes. Mendelsohn et al (2020) identified the following pathogenic variants in two unrelated males with XL-TTD: RNF113A c.903_910del p.(Gln302fs) and RNF113A c.897_898del p.(Cys299Ter). Shostak et al showed that RNF113A promotes cell survival upon DNA damage as a spliceosome subunit.. This is a total of 4 unrelated cases with the same XL-TTD clinical phenotype that have RNF113A variants which supports it being upgraded from a red to green gene.
Created: 13 Sep 2021, 2:31 p.m. | Last Modified: 13 Sep 2021, 2:31 p.m.
Panel Version: 2.9

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
X-linked nonphotosensitive trichothiodystrophy; intellectual disability; partial corpus callosum agenesis; microcephaly; microphallus; hypergonadotropic hypogonadism

Publications

Ellen McDonagh (Genomics England Curator)

Comment on list classification: Possible DD gene for X-LINKED TRICHOTHIODYSTROPHY, and one family report in OMIM.
Created: 28 Nov 2016, 5:18 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)

Phenotypes
?Trichothiodystrophy 5, nonphotosensitive

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 Amber
  • Other
Phenotypes
  • Trichothiodystrophy 5, nonphotosensitive, OMIM:300953
Tags
Skewed X-inactivation Q3_21_rating
OMIM
300951
Clinvar variants
Variants in RNF113A
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

30 Sep 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: rnf113a has been classified as Amber List (Moderate Evidence).

30 Sep 2021, Gel status: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: RNF113A were set to 25612912

30 Sep 2021, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_21_rating tag was added to gene: RNF113A.

30 Sep 2021, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: RNF113A were changed from ?Trichothiodystrophy 5, nonphotosensitive to Trichothiodystrophy 5, nonphotosensitive, OMIM:300953

2 Jun 2020, Gel status: 1

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Skewed X-inactivation tag was added to gene: RNF113A.

28 Nov 2016, Gel status: 1

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

28/Nov/2016: Panel combined and revised due to external and internal review.

28 Nov 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

28 Nov 2016, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for RNF113A were set to 25612912

28 Nov 2016, Gel status: 1

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

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

28 Nov 2016, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

RNF113A was created by ellenmcdonagh

28 Nov 2016, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

RNF113A was added to Cockayne and Xeroderma Pigmentosum-like disorderspanel. Sources: Other