SLC35A5

Chr 3

solute carrier family 35 member A5

This gene encodes a transmembrane antiporter that transports UDP-sugars including UDP-glucuronate, UDP-GlcNAc, and UDP-GalNAc from the cytosol into the Golgi lumen for glycosylation processes. Mutations cause congenital disorder of glycosylation type IIc (CDG-IIc), characterized by intellectual disability, seizures, and distinctive facial features with autosomal recessive inheritance. The condition typically presents in early childhood with developmental delays and neurological manifestations.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.15
Clinical SummarySLC35A5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 unique Pathogenic / Likely Pathogenic· 56 VUS of 94 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.15LOEUF
pLI 0.000
Z-score 1.12
OE 0.70 (0.441.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.07Z-score
OE missense 1.01 (0.911.13)
226 obs / 223.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.70 (0.441.15)
00.351.4
Missense OE1.01 (0.911.13)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 11 / 15.8Missense obs/exp: 226 / 223.0Syn Z: -0.96
DN
0.74top 25%
GOF
0.72top 25%
LOF
0.2483th %ile

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.

DNprediction above median
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.

ClinVar Variant Classifications

94 submitted variants in ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic1
VUS56
Likely Benign3
25
Pathogenic
1
Likely Pathogenic
56
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
1
0
1
VUS
1
50
5
0
56
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total15331085

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC35A5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
An insight into the orphan nucleotide sugar transporter SLC35A4.
Sosicka P et al.·Biochim Biophys Acta Mol Cell Res
2017
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC