ST3GAL5

Chr 2AR

ST3 beta-galactoside alpha-2,3-sialyltransferase 5

Also known as: SATI, SIAT9, SIATGM3S, SPDRS, ST3Gal V, ST3GalV

NCBI Gene: 8869ENSG00000115525UniProt: Q9UNP4

Ganglioside GM3 is known to participate in the induction of cell differentiation, modulation of cell proliferation, maintenance of fibroblast morphology, signal transduction, and integrin-mediated cell adhesion. The protein encoded by this gene is a type II membrane protein which catalyzes the formation of GM3 using lactosylceramide as the substrate. The encoded protein is a member of glycosyltransferase family 29 and may be localized to the Golgi apparatus. Mutation in this gene has been associated with Amish infantile epilepsy syndrome. Transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Salt and pepper developmental regression syndromeMIM #609056
AR
100
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ST3GAL5
🧬
Gene-Disease Validity (ClinGen)
GM3 synthase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 54 VUS of 100 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.
0.76LOEUF
pLI 0.001
Z-score 2.35
OE 0.42 (0.24–0.76)
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.
1.05Z-score
OE missense 0.80 (0.70–0.91)
168 obs / 210.9 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 (0.24–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.70–0.91)
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.0.82
0≤1.21.6
LoF obs/exp: 8 / 19.1Missense obs/exp: 168 / 210.9Syn Z: 1.23

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic6
VUS54
Likely Benign22
Benign2
Conflicting11
5
Pathogenic
6
Likely Pathogenic
54
VUS
22
Likely Benign
2
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
2
2
2
0
6
VUS
0
33
19
2
54
Likely Benign
0
0
6
16
22
Benign
0
0
2
0
2
Conflicting
—11
Total2353418100

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

View in ClinVar →

Protein Context — Lollipop Plot

ST3GAL5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ST3GAL5-related Amish infantile epilepsy syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Salt and pepper developmental regression syndrome

MIM #609056

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of a novel ST3GAL5 variant in a Chinese boy with GM3 synthase deficiency and literature review of variants in the ST3GAL5 gene.
Mu D et al.·Orphanet J Rare Dis
2024Review
Identification and Functional Characterization of ST3GAL5 and ST8SIA1 Variants in Patients with Thyroid-Associated Ophthalmopathy.
Park HJ et al.·Yonsei Med J
2017Cohort
GM3 synthase deficiency in non-Amish patients.
Heide S et al.·Genet Med
2022Cohort
Rescue of GM3 synthase deficiency by spatially controlled, rAAV-mediated ST3GAL5 delivery.
Yang H et al.·JCI Insight
2023
Identification and validation of sialyltransferase ST3Gal5 in bladder cancer through bioinformatics and experimental analysis.
Jian Y et al.·Int Immunopharmacol
2024
Homeostatic and pathogenic roles of the GM3 ganglioside.
Inokuchi JI et al.·FEBS J
2022Review
Whole Exome Sequencing Reveals a Novel Homozygous Variant in the Ganglioside Biosynthetic Enzyme, ST3GAL5 Gene in a Saudi Family Causing Salt and Pepper Syndrome.
Abdulkareem AA et al.·Genes (Basel)
2023Case report
Ganglioside GM3 Synthase Deficiency in Mouse Models and Human Patients.
Inamori KI et al.·Int J Mol Sci
2022Review
Diseases of ganglioside biosynthesis: An expanding group of congenital disorders of glycosylation.
Trinchera M et al.·Mol Genet Metab
2018Review
Total loss of GM3 synthase activity by a normally processed enzyme in a novel variant and in all ST3GAL5 variants reported to cause a distinct congenital disorder of glycosylation.
Indellicato R et al.·Glycobiology
2019
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