ST3GAL5

Chr 2AR

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

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

This gene encodes a glycosyltransferase that catalyzes the formation of ganglioside GM3 from lactosylceramide, with GM3 participating in cell differentiation, proliferation control, and signal transduction. Mutations cause salt and pepper developmental regression syndrome (also known as Amish infantile epilepsy syndrome) through autosomal recessive inheritance. The pathogenic mechanism involves disrupted ganglioside biosynthesis leading to neurodegeneration and epilepsy.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.761 OMIM phenotype
Clinical SummaryST3GAL5
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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.
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ClinVar Variants
19 unique Pathogenic / Likely Pathogenic· 101 VUS of 200 total submissions
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GeneReview available — ST3GAL5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.76LOEUF
pLI 0.001
Z-score 2.35
OE 0.42 (0.240.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.05Z-score
OE missense 0.80 (0.700.91)
168 obs / 210.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.240.76)
00.351.4
Missense OE0.80 (0.700.91)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 8 / 19.1Missense obs/exp: 168 / 210.9Syn Z: 1.23

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic5
VUS101
Likely Benign60
Benign16
Conflicting4
14
Pathogenic
5
Likely Pathogenic
101
VUS
60
Likely Benign
16
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
4
0
14
Likely Pathogenic
5
0
0
0
5
VUS
1
85
15
0
101
Likely Benign
0
0
22
38
60
Benign
0
0
16
0
16
Conflicting
4
Total16855738200

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.

3D Protein StructureAlphaFold

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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