GAL3ST2

Chr 2

galactose-3-O-sulfotransferase 2

Also known as: GAL3ST-2, GP3ST

The protein encoded by this gene is a galactose-3-O-sulfotransferase that catalyzes the transfer of sulfate groups to terminal beta-galactosyl residues in oligosaccharides, participating in the sulfation of various glycan structures including those found in mucins and cancer antigens. Mutations in GAL3ST2 cause autosomal recessive intellectual disability with early-onset seizures and distinctive dysmorphic features. The gene shows very low constraint against loss-of-function variants (LOEUF 1.89), suggesting tolerance to protein-truncating changes in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
103
P/LP submissions
1%
P/LP missense
1.89
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryGAL3ST2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
101 unique Pathogenic / Likely Pathogenic· 108 VUS of 222 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.89LOEUF
pLI 0.000
Z-score -1.07
OE 1.36 (0.891.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.05Z-score
OE missense 1.01 (0.901.13)
219 obs / 216.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.36 (0.891.89)
00.351.4
Missense OE1.01 (0.901.13)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 14 / 10.3Missense obs/exp: 219 / 216.8Syn Z: 0.77
DN
0.6455th %ile
GOF
0.6930th %ile
LOF
0.2872th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction 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

222 submitted variants in ClinVar

Classification Summary

Pathogenic88
Likely Pathogenic13
VUS108
Likely Benign7
Benign3
Conflicting1
88
Pathogenic
13
Likely Pathogenic
108
VUS
7
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
88
0
88
Likely Pathogenic
0
1
12
0
13
VUS
0
86
22
0
108
Likely Benign
0
6
1
0
7
Benign
0
0
3
0
3
Conflicting
1
Total0931260220

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

View in ClinVar →

Protein Context — Lollipop Plot

GAL3ST2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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