SLC35A3

Chr 1AR

solute carrier family 35 member A3

Also known as: AMRS

NCBI Gene: 23443ENSG00000117620UniProt: Q9Y2D2

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]

Primary Disease Associations & Inheritance

Arthrogryposis, impaired intellectual development, and seizuresMIM #615553
AR
291
ClinVar variants
40
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC35A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 73 VUS of 291 total submissions
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.80LOEUF
pLI 0.003
Z-score 2.17
OE 0.42 (0.24–0.80)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.42Z-score
OE missense 0.68 (0.58–0.80)
109 obs / 159.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.24–0.80)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.58–0.80)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 7 / 16.5Missense obs/exp: 109 / 159.3Syn Z: 0.74

ClinVar Variant Classifications

291 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic8
VUS73
Likely Benign146
Benign30
Conflicting2
32
Pathogenic
8
Likely Pathogenic
73
VUS
146
Likely Benign
30
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
18
0
32
Likely Pathogenic
6
0
2
0
8
VUS
1
55
13
4
73
Likely Benign
0
4
47
95
146
Benign
0
1
29
0
30
Conflicting
—2
Total216010999291

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC35A3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Arthrogryposis, impaired intellectual development, and seizures

MIM #615553

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Structural Characterization of Glycoprotein Glycans and Glycosaminoglycans of Brain Tissues in Slc35a3-Knockout Mice.
Hirose I et al.·Int J Mol Sci
2026
Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis.
Lu S et al.·Sci Rep
2024🔓 Open Access
The glycosylation defect in solute carrier SLC35A2/SLC35A3 double knockout cells is rescued by SLC35A2-SLC35A3 and SLC35A3-SLC35A2 hybrids.
Wiertelak W et al.·FEBS Lett
2023
Mice lacking nucleotide sugar transporter SLC35A3 exhibit lethal chondrodysplasia with vertebral anomalies and impaired glycosaminoglycan biosynthesis.
Saito S et al.·PLoS One
2023🔓 Open Access
Association of genotypes at rs438228855 in bovine SLC35A3 receptor gene of Pakistani cattle with the susceptibility to develop complex vertebral malformation.
Rafiq A et al.·Reprod Domest Anim
2023
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools