SLC35D2
Chr 9solute carrier family 35 member D2
Also known as: HFRC1, SQV7L, UGTrel8, hfrc
The protein transports UDP-N-acetylglucosamine and UDP-glucose from the cytosol into the Golgi lumen, supplying donor substrates essential for heparan sulfate synthesis and other glycosylation processes. Mutations in this gene cause congenital disorder of glycosylation type IIx, which presents with intellectual disability, seizures, and dysmorphic features, following an autosomal recessive inheritance pattern. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with the recessive disease mechanism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SLC35D2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools