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Fetal anomalies

Gene: CACHD1

Amber List (moderate evidence)
CACHD1 (cache domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000158966
EnsemblGeneIds (GRCh37): ENSG00000158966
CACHD1 is in 2 panels

2 reviews

Anna de Burca (Oxford University Hospitals NHS Foundation Trust)

I don't know

Sufficient cases to justify gene-disease association but most consistent clinical features (genital, anorectal & ear anomalies) might be difficult to visualise on USS and other common features (structural renal & cardiac anomalies) not currently criteria for R21. However, could justify inclusion on the basis that it might explain a multisytem phenotype.
Created: 20 Feb 2025, 9:35 p.m. | Last Modified: 20 Feb 2025, 9:35 p.m.
Panel Version: 5.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Syndromic complex neurodevelopmental disorder, MONDO:0800439

Publications

Created: 20 Feb 2025, 9:35 p.m.
Last Modified: 20 Feb 2025, 9:35 p.m.
Panel version: 5.15

Achchuthan Shanmugasundram (Genomics England Curator)

I don't know

This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Created: 20 Feb 2025, 9:40 p.m. | Last Modified: 20 Feb 2025, 9:40 p.m.
Panel Version: 5.16
Comment on list classification: There are two fetal cases reported from the same family, although there are six cases from four families reported in total. In addition, there is functional evidence. Hence, this gene can be rated amber with the current evidence.
Created: 7 Jan 2025, 10:37 p.m. | Last Modified: 7 Jan 2025, 10:37 p.m.
Panel Version: 5.7
PMID:38158856 reported six affected individuals from four unrelated families with biallelic (either homozygous or compound heterozygous) CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant).

Of these, two cases from the fourth family are fetal cases. Excluding these two fatal cases, all others were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Cognitive impairment was reported to be mild in three cases from three different families, while the fourth case had no cognitive impairment. Psychomotor delay was reported in two unrelated cases and seizure was reported in one.

Facial dysmorphism and ear and genitourinary abnormalities were reported in the two fetal cases, while congenital malformations of the digestive tract was reported in one of them.

Functional evidence from human stem cell-derived neural models and zebrafish mutants are also available in support of the disease association.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Created: 7 Jan 2025, 10:34 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
syndromic complex neurodevelopmental disorder, MONDO:0800439

Publications

Created: 7 Jan 2025, 10:34 p.m.

Panel version: 5.16

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Amber
  • Literature
Phenotypes
  • syndromic complex neurodevelopmental disorder, MONDO:0800439
Clinvar variants
Variants in CACHD1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

20 Feb 2025, Gel status: 2

Added New Source

Achchuthan Shanmugasundram (Genomics England Curator)

Source NHS GMS was added to CACHD1.

7 Jan 2025, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: cachd1 has been classified as Amber List (Moderate Evidence).

7 Jan 2025, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

gene: CACHD1 was added gene: CACHD1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CACHD1 were set to 38158856 Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder, MONDO:0800439 Review for gene: CACHD1 was set to AMBER