dHMN-5B

Genetic Context

HGNC-Approved Gene Symbol

REEP1

Gene Full Name

Receptor Accessory Protein 1

HGNC Gene Alias(es)

C2ORF23

Chromosome

2p11.2

Zygosity of Responsible Variant

Heterozygous

Mitochondrial Involvement

Yes

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Haploinsufficiency

Confidence:
Medium

Prediction:
The literature predicts a loss-of-function, haploinsufficiency mechanism for dHMN-5B: REEP1 is a dosage-sensitive ER-shaping and microtubule-interacting protein, and its dominant alleles are predominantly truncating variants expected to trigger nonsense-mediated decay, with Reep1-null models recapitulating axonal degeneration, so a single reduced copy suffices and restored wild-type is predicted to rescue. Because some C-terminal alleles escape decay and may add a toxic component, confidence holds at medium.

Rationale:
dHMN-5B is driven by REEP1 haploinsufficiency, since its dominant alleles are predominantly decay-prone truncating variants and Reep1-null models degenerate, so restored wild-type is predicted to rescue. Because C-terminal decay-escaping alleles may add a toxic component, confidence holds at medium.

ClinVar Pathogenic Variants

View dHMN-5B ClinVar Variants

dHMN-5B OMIM Entry

dHMN-5B OMIM

REEP1 OMIM Entry

REEP1 OMIM