SLC35A2

Chr XSomaticXLD

solute carrier family 35 member A2

Also known as: CDG2M, CDGX, UDP-Gal-Tr, UGALT, UGAT, UGT, UGT1, UGT2

NCBI Gene: 7355 ENSG00000102100 UniProt: P78381 OMIM: 314375

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the nucleotide-sugar transporter family. The encoded protein is a multi-pass membrane protein. It transports UDP-galactose from the cytosol into Golgi vesicles, where it serves as a glycosyl donor for the generation of glycans. Mutations in this gene cause congenital disorder of glycosylation type IIm (CDG2M). Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Oct 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismSomatic/XLDLOEUF 0.561 OMIM phenotype

Clinical Summary— SLC35A2

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Gene-Disease Validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.72) — some intolerance to loss-of-function variants.

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ClinVar Variants

42 unique Pathogenic / Likely Pathogenic· 118 VUS of 349 total submissions

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Clinical Trials

3 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SLC35A2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.56LOEUF

pLI 0.718

Z-score 2.38

OE 0.12 (0.04–0.56)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.50Z-score

OE missense 0.46 (0.38–0.55)

76 obs / 166.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.12 (0.04–0.56)

0≤0.351.4

Missense OE?0.46 (0.38–0.55)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 1 / 8.5Missense obs/exp: 76 / 166.7Syn Z: -0.30

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSLC35A2-related epileptic encephalopathy due to congenital disorder of glycosylationLOFmonoallelic_X_heterozygous

This gene — mechanism propensity

0.4586th %ile

GOF

0.6444th %ile

LOF

0.55top 25%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOF55% of P/LP variants are LoF · ClinGen HI: Sufficient evidence for dosage pathogenicity

GOFprediction above median

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

349 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27

Likely Pathogenic15

VUS118

Likely Benign123

Benign26

Conflicting16

Pathogenic

Likely Pathogenic

118

VUS

123

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	20	5	2	0	27
Likely Pathogenic	3	12	0	0	15
VUS	4	108	4	2	118
Likely Benign	3	32	18	70	123
Benign	0	15	6	5	26
Conflicting	—				16
Total	30	172	30	77	325

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

42 pathogenic / likely-pathogenic (of 51) ClinVar copy-number / structural variants overlap SLC35A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →