SLC35A5

Chr 3

solute carrier family 35 member A5

NCBI Gene: 55032 ENSG00000138459 UniProt: Q9BS91 OMIM: 620298

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a transmembrane protein which belongs to subfamily 35A of the solute carrier superfamily. The encoded protein is a nucleoside-sugar transporter. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.15

Clinical Summary— SLC35A5

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

51 VUS of 63 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 1.12

OE 0.70 (0.44–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.07Z-score

OE missense 1.01 (0.91–1.13)

226 obs / 223.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.70 (0.44–1.15)

0≤0.351.4

Missense OE?1.01 (0.91–1.13)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 11 / 15.8Missense obs/exp: 226 / 223.0Syn Z: -0.96

This gene — mechanism propensity

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

63 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	1	50	51
Likely Benign	0	3	3
Benign	0	0	0
Total	1	53	54

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap SLC35A5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →