HSN w/SPG

Genetic Context

HGNC-Approved Gene Symbol

CCT5

Gene Full Name

Chaperonin Containing TCP1 Subunit 5

HGNC Gene Alias(es)

CCTE, KIAA0098

Chromosome

5p15.2

Zygosity of Responsible Variant

Homozygous

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Biallelic

Confidence:
Medium

Prediction:
The literature predicts a biallelic loss-of-function mechanism for HSN with spastic paraplegia: the recessive homozygous CCT5 His147Arg substitution impairs the CCT/TRiC chaperonin, so two defective copies reduce chaperonin protein-folding activity, and restored wild-type CCT5 is predicted to rescue, consistent with recessive loss rather than a dominant effect.

Rationale:
The recessive homozygous CCT5 His147Arg substitution impairs CCT/TRiC chaperonin activity, and unaffected heterozygous carriers argue against a dominant effect, so restored wild-type is predicted to rescue: a biallelic loss of function. The mutant subunit's exact functional consequence is only partly characterized, holding confidence at medium.

ClinVar Pathogenic Variants

View HSN w/SPG ClinVar Variants

HSN w/SPG OMIM Entry

HSN w/SPG OMIM

CCT5 OMIM Entry

CCT5 OMIM