HSN-1F

Genetic Context

HGNC-Approved Gene Symbol

ATL3

Gene Full Name

atlastin GTPase 3

Chromosome

11q13.1

Zygosity of Responsible Variant

Heterozygous

Variant Mechanism

Dominant-Negative

Details

Confidence:
Medium

Prediction:
The literature predicts a dominant-negative mechanism for HSN-1F: the ATL3 variants Y192C and P338R produce atlastin-3 that still tethers apposed endoplasmic reticulum membranes but arrests before the bilayers merge, and because normal subunits are recruited into the same stalled tether, the mutant withdraws working protein from the fusion cycle instead of simply being absent. A trapped intermediate is evidence of interference rather than a neomorphic activity, though how much fusion capacity survives in patient cells is unresolved.

Rationale:
Peripheral sensory axons maintain an endoplasmic reticulum network running their full length, so a tether that holds two membranes together without fusing them leaves that network studded with unresolved junctions. Normal atlastin-3 drawn into a stalled tether is immobilized rather than compensating, so the deficit scales with mutant protein present rather than with protein missing.

ClinVar Pathogenic Variants

View ATL3 ClinVar Variants

ClinGen Curation

View ATL3 ClinGen Curation

HSN-1F OMIM Entry

HSN-1F OMIM

ATL3 OMIM Entry

ATL3 OMIM