SLC35A3

Chr 1AR

solute carrier family 35 member A3

Also known as: AMRS

NCBI Gene: 23443 ENSG00000117620 UniProt: Q9Y2D2 OMIM: 605632

The protein transports UDP-N-acetylglucosamine from the cytosol into the Golgi apparatus, supplying substrate for glycosyltransferases that generate complex N-glycans and keratan sulfate. Autosomal recessive mutations cause a syndrome characterized by arthrogryposis, impaired intellectual development, and seizures.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a UDP-N-acetylglucosamine transporter found in the golgi apparatus membrane. In cattle, a missense mutation in this gene causes complex vertebral malformation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.801 OMIM phenotype

Clinical Summary— SLC35A3

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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

58 unique Pathogenic / Likely Pathogenic· 94 VUS of 371 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.003

Z-score 2.17

OE 0.42 (0.24–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.42Z-score

OE missense 0.68 (0.58–0.80)

109 obs / 159.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.24–0.80)

0≤0.351.4

Missense OE?0.68 (0.58–0.80)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 7 / 16.5Missense obs/exp: 109 / 159.3Syn Z: 0.74

This gene — mechanism propensity

0.78top 25%

GOF

0.7030th %ile

LOF

0.2092th %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

371 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29

Likely Pathogenic29

VUS94

Likely Benign173

Benign34

Conflicting3

Pathogenic

Likely Pathogenic

VUS

173

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	21	0	8	0	29
Likely Pathogenic	28	1	0	0	29
VUS	1	78	10	5	94
Likely Benign	1	4	53	115	173
Benign	0	3	29	2	34
Conflicting	—				3
Total	51	86	100	122	362

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap SLC35A3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →