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Intellectual disability

Gene: JMJD1C

Amber List (moderate evidence)

JMJD1C (jumonji domain containing 1C)
EnsemblGeneIds (GRCh38): ENSG00000171988
EnsemblGeneIds (GRCh37): ENSG00000171988
OMIM: 604503, Gene2Phenotype
JMJD1C is in 3 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team) it was agreed that there is currently not enough evidence to support this gene-disease association. Rating Amber until further evidence emerges (added watchlist tag).
Created: 28 Jun 2021, 2:28 p.m. | Last Modified: 28 Jun 2021, 2:31 p.m.
Panel Version: 3.1149
Literature search suggested a potential link with ID or other relevant phenotypes; however, overall the evidence is inconclusive.

- PMID: 26181491 - 7 different variants identified by targeted sequencing in patients with ID (3), ASD (3), Rett syndrome (1) - but segregation only confirmed in 2 (as de novo), and only 1 variant was functionally analysed.

- PMID: 31954878 - 7 unrelated patients with variable neurodevelopmental phenotypes including an ID diagnosis in 2 individuals. However, all 7 patients had either mosaic variants or accompanying variants in other ID‐associated genes, or a variant that was present in a public database.

- PMID: 32996679 - Patient with learning disability (but normal IQ) and myoclonic epilepsy who had apparently synonymous but de novo splice‐disrupting variant that led to 21 bp deletion of the JMJD1C transcript

- PMID: 28378413 - Microdeletion disrupting the JMJD1C gene (and 83 others) found in patient with severe DD and multiple congenital anomalies.

- Autism cohorts - PMIDs: 22495311, 25363768; 17290275, 33591602 - SNVs and structural variants affecting this gene have been reported in multiple autism cohorts (mostly limited clinical data but several said to have normal IQ)
Created: 28 Jun 2021, 2:20 p.m. | Last Modified: 28 Jun 2021, 2:20 p.m.
Panel Version: 3.1146

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Intellectual disability; Autism

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Reported in ID cohort (with Rett-like phenotypic overlap) with supporting functional studies (PMID: 26181491). 7 individuals with rare variants identified, and variants demonstrated to be de novo in 2, one with a Rett-like phenotype and the other with ID. Functional study of the JMJD1C mutant Rett syndrome patient demonstrated that the altered protein had abnormal subcellular localization, diminished activity to demethylate the DNA damage-response protein MDC1, and reduced binding to MECP2. JMJD1C protein shown to be widely expressed in brain regions and that its depletion compromised dendritic activity.

Splice-disrupting JMJD1C variant reported in association with learning disability and myoclonic epilepsy (PMID 32996679).

Disruption of gene due to balanced translocation (PMID 33591602) implicated in autism spectrum disease phenotype.
Sources: Expert Review
Created: 27 Apr 2021, 2:42 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Intellectual disability

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Intellectual disability
  • Autism
Tags
watchlist
OMIM
604503
Clinvar variants
Variants in JMJD1C
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Jun 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: JMJD1C.

28 Jun 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: jmjd1c has been classified as Amber List (Moderate Evidence).

28 Jun 2021, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: JMJD1C were changed from Intellectual disability to Intellectual disability; Autism

28 Jun 2021, Gel status: 0

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: JMJD1C were set to 26181491; 32996679

27 Apr 2021, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: JMJD1C was added gene: JMJD1C was added to Intellectual disability. Sources: Expert Review Mode of inheritance for gene: JMJD1C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: JMJD1C were set to 26181491; 32996679 Phenotypes for gene: JMJD1C were set to Intellectual disability Review for gene: JMJD1C was set to GREEN gene: JMJD1C was marked as current diagnostic