GAL3ST3

Chr 11

galactose-3-O-sulfotransferase 3

Also known as: GAL3ST-3, GAL3ST2

NCBI Gene: 89792 ENSG00000175229 UniProt: Q96A11 OMIM: 608234

This protein functions as a galactose-3-O-sulfotransferase that catalyzes the transfer of sulfate groups to specific galactose residues in N-glycans and O-glycans, particularly acting on type 2 oligosaccharide chains and participating in the formation of sulfated Lewis X epitopes. Mutations in GAL3ST3 cause autosomal recessive intellectual disability with variable additional features. The gene shows very low constraint to loss-of-function variation (high LOEUF score), suggesting tolerance to protein-truncating variants.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the galactose-3-O-sulfotransferase protein family. The product of this gene catalyzes sulfonation by transferring a sulfate group to the 3' position of galactose in N-acetyllactosamine in both type 2 (Gal-beta-1-4GlcNAc-R) oligosaccharides and core-2-branched O-glycans, but not on type 1 or core-1-branched structures. This gene, which has also been referred to as GAL3ST2, is different from the GAL3ST2 gene located on chromosome 2 that encodes a related enzyme with distinct tissue distribution and substrate specificities, compared to galactose-3-O-sulfotransferase 3. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.79

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.79LOEUF

pLI 0.000

Z-score -0.44

OE 1.15 (0.72–1.79)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.77Z-score

OE missense 0.87 (0.79–0.97)

262 obs / 299.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.15 (0.72–1.79)

0≤0.351.4

Missense OE?0.87 (0.79–0.97)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 11 / 9.5Missense obs/exp: 262 / 299.7Syn Z: 0.86

Background carrier burden — how many people carry a rare variant somewhere in GAL3ST3?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

789 rare PASS variants

Rare truncating (LoF)

1 in 1,300

109 rare PASS variants

Rare synonymous (reference)

1 in 140

379 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GAL3ST3. 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 97	1 in 1,500
South Asian	~43k	1 in 70	1 in 1,100
Remaining (unassigned)	~30k	1 in 82	1 in 760
European (Finnish)	~27k	1 in 330	1 in 4,300
Admixed American	~22k	1 in 120	1 in 1,200
African / African American	~21k	1 in 87	1 in 1,100
East Asian	~20k	1 in 84	1 in 640
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 4,100
Middle Eastern	~2,884	1 in 77	≈ 1 in 840

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): All 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓