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: 6487 ENSG00000126091 UniProt: Q11203 OMIM: 606494

The protein is a sialyltransferase that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates in the Golgi apparatus. Mutations cause autosomal recessive developmental and epileptic encephalopathy 15 and intellectual developmental disorder, autosomal recessive 12. The pathogenic mechanism involves dominant-negative effects disrupting normal protein function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.622 OMIM phenotypes

Clinical Summary— ST3GAL3

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · ARModerate

Moderate evidence — consider for supplementary testing

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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

24 unique Pathogenic / Likely Pathogenic· 157 VUS of 415 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.003

Z-score 3.00

OE 0.36 (0.21–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.50Z-score

OE missense 0.74 (0.65–0.83)

188 obs / 255.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.62)

0≤0.351.4

Missense OE?0.74 (0.65–0.83)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 9 / 25.3Missense obs/exp: 188 / 255.4Syn Z: 0.27

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongST3GAL3-related intellectual developmental disorderOTHERAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6550th %ile

GOF

0.4875th %ile

LOF

0.2582th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

415 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic13

VUS157

Likely Benign181

Benign24

Conflicting20

Pathogenic

Likely Pathogenic

157

VUS

181

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	8	2	1	0	11
Likely Pathogenic	11	1	1	0	13
VUS	4	135	13	5	157
Likely Benign	0	5	92	84	181
Benign	0	2	22	0	24
Conflicting	—				20
Total	23	145	129	89	406

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap ST3GAL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →