CMT-CFAP276

Genetic Context

HGNC-Approved Gene Symbol

CFAP276

Gene Full Name

cilia and flagella associated protein 276

HGNC Gene Alias(es)

C1ORF194

Chromosome

1p13.3

Zygosity of Responsible Variant

Heterozygous

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Haploinsufficiency

Confidence:
Medium

Prediction:
The literature predicts a loss-of-function mechanism for CMT-CFAP276: Sun et al. (2019) reported heterozygous CFAP276 (C1orf194) variants p.Lys28Ile and p.Ile122Asn, and p.Lys28Ile lowers steady-state protein. Heterozygous null mice develop a dominant-intermediate CMT with reduced conduction velocity, demyelination and shortened internodes, and AAV9 delivery of the human coding sequence corrects motor and nerve measures in nulls, placing the lesion in how much functional protein the nerve retains.

Rationale:
One inactivated copy suffices in the mouse and adding the gene back repairs the nerve, the pairing a dosage-sensitive loss predicts. The p.Ile122Asn product is unusually stable and forms cytoplasmic aggregates, but it has not been shown to be toxic or to acquire an activity of its own, and a knock-in of that allele reproduces the phenotype the null already produces. Confidence holds at medium while the aggregating allele stays unexplained.

ClinVar Pathogenic Variants

View CFAP276 ClinVar Variants

CFAP276 OMIM Entry

CFAP276 OMIM