ST8SIA4

Chr 5

ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4

Also known as: PST, PST1, SIAT8-D, SIAT8D, ST8SIA-IV, ST8SiaIV

NCBI Gene: 7903ENSG00000113532UniProt: Q92187

The protein encoded by this gene catalyzes the polycondensation of alpha-2,8-linked sialic acid required for the synthesis of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). The encoded protein, which is a member of glycosyltransferase family 29, is a type II membrane protein that may be present in the Golgi apparatus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

56
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ST8SIA4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 35 VUS of 56 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.
0.90LOEUF
pLI 0.000
Z-score 1.86
OE 0.50 (0.29–0.90)
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.
1.74Z-score
OE missense 0.65 (0.56–0.75)
125 obs / 193.0 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.0.50 (0.29–0.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.56–0.75)
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.1.13
0≤1.21.6
LoF obs/exp: 8 / 16.0Missense obs/exp: 125 / 193.0Syn Z: -0.86

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic2
VUS35
Likely Benign1
18
Pathogenic
2
Likely Pathogenic
35
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
2
0
2
VUS
0
29
6
0
35
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total02927056

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

View in ClinVar →

Protein Context — Lollipop Plot

ST8SIA4 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Upregulation of miR-181c inhibits chemoresistance by targeting ST8SIA4 in chronic myelocytic leukemia.
Zhao L et al.·Oncotarget
2016
Identification of a buried β-strand as a novel disease-related motif in the human polysialyltransferases.
Hatanaka R et al.·J Biol Chem
2024
Altered volume of thalamic nuclei and genetic expression in first-episode psychotic patients, and their association with childhood adversity.
Elvira UKA et al.·Prog Neuropsychopharmacol Biol Psychiatry
2025Cohort
Modification of sialylation is associated with multidrug resistance in human acute myeloid leukemia.
Ma H et al.·Oncogene
2015
α-2,8-Sialyltransferase Is Involved in the Development of Multidrug Resistance via PI3K/Akt Pathway in Human Chronic Myeloid Leukemia.
Zhang X et al.·IUBMB Life
2015
Glycation Interferes with the Expression of Sialyltransferases and Leads to Increased Polysialylation in Glioblastoma Cells.
Schildhauer P et al.·Cells
2023
Integrating WGCNA and SVM-RFE identifies hub molecular biomarkers driving ischemic stroke progression.
Zhang Y et al.·Neurol Res
2025
A New Insight into the Study of Neural Cell Adhesion Molecule (NCAM) Polysialylation Inhibition Incorporated the Molecular Docking Models into the NMR Spectroscopy of a Crucial Peptide-Ligand Interaction.
Huang RB et al.·Biomolecules
2025Functional
Encore: Genetic Association Interaction Network centrality pipeline and application to SLE exome data.
Davis NA et al.·Genet Epidemiol
2013
iGWAS: Integrative Genome-Wide Association Studies of Genetic and Genomic Data for Disease Susceptibility Using Mediation Analysis.
Huang YT et al.·Genet Epidemiol
2015
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