ST3GAL3

Chr 1AR

ST3 beta-galactoside alpha-2,3-sialyltransferase 3

Also known as: DEE15, EIEE15, MRT12, SIAT6, ST3GALII, ST3Gal III, ST3GalIII, ST3N

NCBI Gene: 6487ENSG00000126091UniProt: Q11203

The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Mutations in this gene have been associated with a form of autosomal recessive nonsymdromic cognitive disability as well as infantile epileptic encephalopathy. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 15MIM #615006
AR
Intellectual developmental disorder, autosomal recessive 12MIM #611090
AR
423
ClinVar variants
34
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ST3GAL3
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 Pathogenic / Likely Pathogenic· 164 VUS of 423 total submissions

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.
0.62LOEUF
pLI 0.003
Z-score 3.00
OE 0.36 (0.21–0.62)
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.
1.50Z-score
OE missense 0.74 (0.65–0.83)
188 obs / 255.4 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.0.36 (0.21–0.62)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.65–0.83)
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.0.97
0≤1.21.6
LoF obs/exp: 9 / 25.3Missense obs/exp: 188 / 255.4Syn Z: 0.27

ClinVar Variant Classifications

423 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic15
VUS164
Likely Benign181
Benign24
Conflicting20
19
Pathogenic
15
Likely Pathogenic
164
VUS
181
Likely Benign
24
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
2
13
0
19
Likely Pathogenic
9
1
5
0
15
VUS
4
134
21
5
164
Likely Benign
0
5
92
84
181
Benign
0
2
22
0
24
Conflicting
—20
Total1714415389423

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

View in ClinVar →

Protein Context — Lollipop Plot

ST3GAL3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ST3GAL3-related intellectual developmental disorder

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 15

MIM #615006

Molecular basis of disorder known

Autosomal recessive

Intellectual developmental disorder, autosomal recessive 12

MIM #611090

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Attenuation of Sialylation Augments Antitumor Immunity and Improves Response to Immunotherapy in Ovarian Cancer.
Cao K et al.·Cancer Res
2023
The epilepsy phenotype of ST3GAL3-related developmental and epileptic encephalopathy.
Whitney R et al.·Epilepsia Open
2023Review
Clinical report and genetic analysis of a Chinese patient with developmental and epileptic encephalopathy associated with novel biallelic variants in the ST3GAL3 gene.
Hu J et al.·Mol Genet Genomic Med
2024Review
Phenotype of ST3GAL3 deficient patients: A case and review of the literature.
Khamirani HJ et al.·Eur J Med Genet
2021Review
A novel nonsense and inactivating variant of ST3GAL3 in two infant siblings suffering severe epilepsy and expressing circulating CA19.9.
Indellicato R et al.·Glycobiology
2020
alpha2,3 sialic acid processing enzymes expression in gastric cancer tissues reveals that ST3Gal3 but not Neu3 are associated with Lauren's classification, angiolymphatic invasion and histological grade.
Quirino MWL et al.·Eur J Histochem
2022
A novel variant of ST3GAL3 causes non-syndromic autosomal recessive intellectual disability in Iranian patients.
Farajollahi Z et al.·J Gene Med
2020Case report
A patient-specific induced pluripotent stem cell model for West syndrome caused by ST3GAL3 deficiency.
van Diepen L et al.·Eur J Hum Genet
2018Functional
Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion.
Guerrero PE et al.·Int J Mol Sci
2020
Exploring the genetic etiology of drug-resistant epilepsy: incorporation of exome sequencing into practice.
Mahdiannasser M et al.·Acta Neurol Belg
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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