dHMN-7A

Genetic Context

HGNC-Approved Gene Symbol

SLC5A7

Gene Full Name

Solute Carrier Family 5 Member 7

Chromosome

2q12.3

Zygosity of Responsible Variant

Heterozygous

Variant Mechanism

Dominant-Negative

Details

Mechanistic basis:
Dominant-negative

Confidence:
Medium

Prediction:
The literature predicts a dominant-negative mechanism for dHMN-7A: the heterozygous C-terminal truncating variants in SLC5A7, encoding the high-affinity choline transporter CHT1, produce mistrafficked, altered transporters that reduce choline uptake below the level of simple haploinsufficiency, consistent with the mutant interfering with the wild-type transporter. This contrasts with biallelic loss-of-function SLC5A7 alleles that cause a recessive congenital myasthenic syndrome, so added wild-type CHT1 is not predicted to fully rescue.

Rationale:
The heterozygous C-terminal truncating SLC5A7 alleles produce mistrafficked mutant CHT1 that disrupts the wild-type transporter rather than causing simple haploinsufficiency, as the recessive biallelic-null alleles do in a separate congenital myasthenic syndrome, so co-expressed wild-type is not predicted to fully rescue. The interference remains inferred, holding confidence at medium.

ClinVar Pathogenic Variants

View dHMN-7A ClinVar Variants

ClinGen Curation

View SLC5A7 ClinGen Curation

dHMN-7A OMIM Entry

dHMN-7A OMIM

SLC5A7 OMIM Entry

SLC5A7 OMIM