HMSN-6B

Genetic Context

HGNC-Approved Gene Symbol

SLC25A46

Gene Full Name

Solute Carrier Family 25 Member 46

Chromosome

5q22.1

Zygosity of Responsible Variant

Homozygous or Compound Heterozygous

Mitochondrial Involvement

Yes

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Biallelic

Confidence:
High

Prediction:
The literature predicts a biallelic loss-of-function mechanism for HMSN-6B: recessive SLC25A46 variants destabilize or truncate this outer mitochondrial membrane protein, sharply reducing its steady-state levels and disrupting mitochondrial fission and fusion. Because pathogenic alleles act by loss of protein and phenotypes track reduced abundance, restored wild-type SLC25A46 is predicted to rescue, consistent with recessive loss rather than a dominant-negative or gain-of-function effect.

Rationale:
Recessive SLC25A46 alleles destabilize or truncate the outer-membrane protein and lower its steady-state abundance, so restored wild-type is predicted to rescue: a biallelic loss of function rather than an allele disrupting the wild-type or acting neomorphically.

ClinVar Pathogenic Variants

View HMSN-6B ClinVar Variants

ClinGen Curation

View SLC25A46 ClinGen Curation

HMSN-6B OMIM Entry

HMSN-6B OMIM

SLC25A46 OMIM Entry

SLC25A46 OMIM