ST3GAL5

Chr 2AR

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

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

NCBI Gene: 8869 ENSG00000115525 UniProt: Q9UNP4 OMIM: 604402

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.761 OMIM phenotype

Clinical Summary— ST3GAL5

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Gene-Disease Validity (ClinGen)

GM3 synthase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

53 unique Pathogenic / Likely Pathogenic· 199 VUS of 511 total submissions

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GeneReview available — ST3GAL5

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.001

Z-score 2.35

OE 0.42 (0.24–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.05Z-score

OE missense 0.80 (0.70–0.91)

168 obs / 210.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.24–0.76)

0≤0.351.4

Missense OE?0.80 (0.70–0.91)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 8 / 19.1Missense obs/exp: 168 / 210.9Syn Z: 1.23

ClinVar Variant Classifications

511 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34

Likely Pathogenic19

VUS199

Likely Benign206

Benign25

Conflicting22

Pathogenic

Likely Pathogenic

199

VUS

206

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	31	1	2	0	34
Likely Pathogenic	14	4	1	0	19
VUS	2	155	39	3	199
Likely Benign	0	3	90	113	206
Benign	0	2	23	0	25
Conflicting	—				22
Total	47	165	155	116	505

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap ST3GAL5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →