SLC35A2
Chr XSomaticXLDsolute carrier family 35 member A2
Also known as: CDG2M, CDGX, UDP-Gal-Tr, UGALT, UGAT, UGT, UGT1, UGT2
The protein transports UDP-galactose from the cytosol into Golgi vesicles where it serves as a glycosyl donor for glycan generation. Mutations cause congenital disorder of glycosylation type IIm (CDG2M) with X-linked dominant inheritance, though somatic mosaicism can also occur. The moderate constraint scores suggest mutations can cause disease predominantly through loss-of-function, disrupting normal glycosylation pathways.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
300 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 10 | 3 | 34 | 0 | 47 |
Likely Pathogenic | 3 | 8 | 1 | 0 | 12 |
VUS | 2 | 83 | 13 | 1 | 99 |
Likely Benign | 2 | 22 | 15 | 52 | 91 |
Benign | 0 | 10 | 1 | 3 | 14 |
Conflicting | — | 13 | |||
| Total | 17 | 126 | 64 | 56 | 276 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC35A2 · 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
Clinical and Basic Investigations Into Congenital Disorders of Glycosylation
RECRUITINGAVTX-801 D-galactose Supplementation in SLC35A2-CDG
NOT YET RECRUITINGGenetic and Electrophysiologic Study in Focal Drug-resistant Epilepsies
RECRUITINGExternal Resources
Links to major genomics databases and tools