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| Motor Neurone Disease v2.4 | CLCC1 | Bryony Thompson Classified gene: CLCC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v2.4 | CLCC1 | Bryony Thompson Gene: clcc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Motor Neurone Disease v2.3 | CLCC1 |
Bryony Thompson gene: CLCC1 was added gene: CLCC1 was added to Motor Neurone Disease. Sources: Literature Mode of inheritance for gene: CLCC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CLCC1 were set to 37916886; 37142673 Phenotypes for gene: CLCC1 were set to amyotrophic lateral sclerosis MONDO:0004976 Review for gene: CLCC1 was set to AMBER Added comment: PMID 37916886 reports four unrelated ALS patients and PMID 37142673 reports nine ALS patients, all with heterozygous CLCC1 variants. Across both studies, 13 probands are described carry qualifying loss‑of‑function variants (two truncating alleles and three missense alleles with functional validation, including a recurrent p.Ser263Arg). Functional work in PMID 37142673 demonstrates channel loss‑of‑function in planar‑bilayer assays and ALS‑like motor‑neuron pathology in knock‑in mice, supporting a loss‑of‑function disease mechanism. The PMID 37916886 cohort did not achieve statistical significance for a CLCC1‑ALS association, reducing confidence in the gene‑disease link. All reported families are from Chinese cohorts; no replication in additional ethnic populations has yet been demonstrated. LoF variants present as VUS in ClinVar with no reports of an association with ALS. Sources: Literature |
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