ST8SIA2

Chr 15

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

Also known as: HsT19690, SIAT8-B, SIAT8B, ST8SIA-II, ST8SiaII, STX

The enzyme catalyzes the transfer of sialic acid to produce polysialic acid on neural cell adhesion molecule (NCAM1) and other glycoproteins, supporting neurite outgrowth and influencing oligodendrocyte differentiation and myelin integrity. Mutations cause autosomal recessive intellectual disability with seizures and language delay, affecting neurodevelopment in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.651), consistent with its role in critical neurodevelopmental processes.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.65
Clinical SummaryST8SIA2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.65LOEUF
pLI 0.058
Z-score 2.57
OE 0.31 (0.160.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.50Z-score
OE missense 0.72 (0.630.82)
160 obs / 223.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.160.65)
00.351.4
Missense OE0.72 (0.630.82)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 5 / 16.2Missense obs/exp: 160 / 223.3Syn Z: -1.28
DN
0.6550th %ile
GOF
0.4974th %ile
LOF
0.2776th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ST8SIA2 · 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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