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Intellectual disability

Gene: ERCC4

Red List (low evidence)
ERCC4 (ERCC excision repair 4, endonuclease catalytic subunit)
EnsemblGeneIds (GRCh38): ENSG00000175595
EnsemblGeneIds (GRCh37): ENSG00000175595
OMIM: 133520, Gene2Phenotype
ERCC4 is in 24 panels

5 reviews

Sarah Leigh (Genomics England Curator)

Red List (low evidence)

Comment on publications: PMID: 39769235 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Created: 25 Mar 2025, 10:10 a.m. | Last Modified: 25 Mar 2025, 10:10 a.m.
Panel Version: 8.189
Biallelic ERCC4 variants have been associated with Fanconi anemia, complementation group Q (OMIM: 615272), Xeroderma pigmentosum, group F (OMIM:278760) and XFE progeroid syndrome (OMIM: 610965). Intellectual disability has been reported in a few cases of OMIM:278760 and OMIM: 610965. PMID: 39769235 reports two consanguineous siblings, where one had moderate intellectual disability and the other had mild intellectual disability. Both of the siblilings were homozygous for ERCC4: NM_005236.3:c.2176C>T;p.Arg726Cys. They were also homozygous for a 317 kb (chr16: 21,561,888–21,878,568) deletion which encompasses several genes (METTL9, IGSF6 and OTOA). An analysis of the run of homozygosity showed that it included ERCC4 and OTOA. Due to complex nature of the variants in these samples, it not possible to ascertain the contribution of the ERCC4 variants to the phenotype of the siblings in PMID: 39769235.
Created: 24 Mar 2025, 4:19 p.m. | Last Modified: 24 Mar 2025, 4:19 p.m.
Panel Version: 8.178

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 24 Mar 2025, 4:19 p.m.
Last Modified: 24 Mar 2025, 4:19 p.m.
Panel version: 8.178

Arina Puzriakova (Genomics England Curator)

Following discussion with the clinical team, this gene has been demoted from Amber to Red, in accordance with the external review by Zornitza Stark
Created: 17 Aug 2020, 9:32 a.m. | Last Modified: 17 Aug 2020, 9:32 a.m.
Panel Version: 3.251
Created: 17 Aug 2020, 9:32 a.m.
Last Modified: 17 Aug 2020, 9:32 a.m.
Panel version: 3.251

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Intellect normal in xeroderma pigmentosum; mild learning difficulties described in XFE progeroid syndrome.
Created: 2 Feb 2020, 4:51 a.m. | Last Modified: 2 Feb 2020, 4:51 a.m.
Panel Version: 3.0

Phenotypes
Xeroderma pigmentosum, group F, MIM#278760; XFE progeroid syndrome, MIM# 610965

Created: 2 Feb 2020, 4:51 a.m.
Last Modified: 2 Feb 2020, 4:51 a.m.
Panel version: 3.0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 5:39 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 2 Aug 2017, 5:18 p.m.

Panel version: 1.354

Louise Daugherty (Genomics England Curator)

Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to assess inclusion and pertinence to this panel.
Created: 20 Jul 2017, 11:45 a.m.
Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to assess inclusion and pertinence to this panel.
Created: 20 Jul 2017, 11:43 a.m.
Created: 20 Jul 2017, 11:43 a.m.

Panel version: 1.197

History Filter Activity

25 Mar 2025, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: ERCC4 were set to 39769235

24 Mar 2025, Gel status: 1

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: ERCC4 were set to

24 Mar 2025, Gel status: 1

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: ERCC4 were changed from Xeroderma pigmentosum, group F, 278760; XFE progeroid syndrome, 610965; Fanconi anemia, complementation group Q, 615272; Xeroderma pigmentosum, type F/Cockayne syndrome, 278760 to Xeroderma pigmentosum, group F 278760; XFE progeroid syndrome, OMIM: 610965

12 Oct 2020, Gel status: 1

Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Red was added to ERCC4. Rating Changed from Amber List (moderate evidence) to Red List (low evidence)

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

20 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

20 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

19 Jul 2017, Gel status: 0

Added New Source

BRIDGE consortium (NIHRBR-RD)

ERCC4 was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene

19 Jul 2017, Gel status: 0

Created

BRIDGE consortium (NIHRBR-RD)

ERCC4 was created by BRIDGE