ST8SIA3

Chr 18

ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 3

Also known as: SIAT8C, ST8SiaIII

This highly constrained gene encodes a sialyltransferase that catalyzes the transfer of sialic acid to form oligosialic and polysialic acid modifications on N-linked glycoproteins and glycolipids, particularly in the striatum where it regulates protein distribution in lipid rafts. Mutations cause autosomal recessive intellectual disability with seizures and spasticity, typically presenting in early childhood. The gene shows strong intolerance to loss-of-function variants (pLI 0.86, LOEUF 0.41), suggesting haploinsufficiency is not well tolerated.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
66
P/LP submissions
0%
P/LP missense
0.41
LOEUF
Mechanism
Clinical SummaryST8SIA3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
64 unique Pathogenic / Likely Pathogenic· 41 VUS of 106 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.859
Z-score 3.14
OE 0.13 (0.050.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.47Z-score
OE missense 0.71 (0.630.82)
150 obs / 210.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.050.41)
00.351.4
Missense OE0.71 (0.630.82)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 2 / 15.2Missense obs/exp: 150 / 210.0Syn Z: 0.17

ClinVar Variant Classifications

106 submitted variants in ClinVar

Classification Summary

Pathogenic62
Likely Pathogenic2
VUS41
62
Pathogenic
2
Likely Pathogenic
41
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
62
0
62
Likely Pathogenic
0
0
2
0
2
VUS
0
37
4
0
41
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total037680105

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

View in ClinVar →

Protein Context — Lollipop Plot

ST8SIA3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC