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…

Primary Disease Associations & Inheritance

Arthrogryposis, impaired intellectual development, and seizuresMIM #615553

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Arthrogryposis, impaired intellectual development, and seizures; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in SLC35A3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

465 rare PASS variants

Rare truncating (LoF)

1 in 610

91 rare PASS variants

Rare synonymous (reference)

1 in 250

174 rare PASS variants

Rare missense and truncating variants are carried at similar rates in SLC35A3; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 1,100
South Asian	~43k	1 in 140	1 in 440
Remaining (unassigned)	~30k	1 in 160	1 in 390
European (Finnish)	~27k	1 in 590	1 in 2,400
Admixed American	~22k	1 in 110	1 in 900
African / African American	~21k	1 in 160	1 in 1,100
East Asian	~20k	1 in 160	1 in 1,100
Ashkenazi Jewish	~13k	1 in 970	≈ 1 in 4,200
Middle Eastern	~2,884	1 in 210	≈ 1 in 2,700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 7 coding exons well covered in gnomAD exomes; exons 3, 5, 7, 8 marginal. Genomes: all 7.? see exons ↓