Motor Neurone Disease

Gene: DNAJC7

Green List (high evidence)

To date, DNAJC7 variants have not been associated with a phenotype in OMIM, Gen2Phen or Mondo. Numerous DNAJC7 variants have been reported in amyotrophic lateral sclerosis (ALS) patients (PMID: 31768050; 35039179;34233860; 32897108; 37870677; 35456894). ClinGen classifies the gene disease association between DNAJC7 variants and ALS as Limited (27th Oct 2022), because the ALS Gene Curation Expert Panel only scores protein truncating variants in DNAJC7 as part of the gene disease association classification process. In a survey of variants from various international sources, Farhan et al (PMID: 31768050) collated five DNAJC7 truncating variants in ALS patients.

Created: 9 Jan 2024, 6:13 p.m. | Last Modified: 9 Jan 2024, 6:13 p.m.

Panel Version: 1.8

Phenotypes
amyotrophic lateral sclerosis

Publications

• 31768050
• 35039179
• 34233860
• 32897108
• 37870677
• 35456894

I don't know

No segregation or functional data. A small number of individuals with LOF variants are present in gnomad albeit less than expected. Given these are cohort studies, and an adult-onset condition, potentially of variable penetrance, I agree with a cautious approach and Amber rating.

Created: 8 Sep 2020, 10:36 p.m. | Last Modified: 8 Sep 2020, 10:36 p.m.

Panel Version: 0.54

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
amyotrophic lateral sclerosis

I don't know

Two cohort studies in ALS patients identified 11 and 1 patient, respectively, with variants in DNAJC7. Seven of these are putative PTVs. However gene described as risk factor, unclear why.

DOI: https://doi.org/10.1212/NXG.0000000000000503
Sources: Literature

Created: 7 Sep 2020, 6:05 a.m.

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

Phenotypes
amyotrophic lateral sclerosis

Publications

• 31768050