ST8SIA2

Chr 15

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

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

NCBI Gene: 8128 ENSG00000140557 OMIM: 602546

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a type II membrane protein that is thought to catalyze the transfer of sialic acid from CMP-sialic acid to N-linked oligosaccharides and glycoproteins. The encoded protein may be found in the Golgi apparatus and may be involved in the production of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). This protein is a member of glycosyltransferase family 29. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.65

Clinical Summary— ST8SIA2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

40 VUS of 49 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?

0.65LOEUF

pLI 0.058

Z-score 2.57

OE 0.31 (0.16–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.50Z-score

OE missense 0.72 (0.63–0.82)

160 obs / 223.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.16–0.65)

0≤0.351.4

Missense OE?0.72 (0.63–0.82)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 5 / 16.2Missense obs/exp: 160 / 223.3Syn Z: -1.28

This gene — mechanism propensity

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

49 submitted variants in ClinVar

ClinVar

Classification Summary

VUS40

Likely Benign5

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	40	0	0	40
Likely Benign	1	0	1	3	5
Benign	0	0	0	1	1
Total	1	40	1	4	46

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

View in ClinVar →

44 pathogenic / likely-pathogenic (of 46) ClinVar copy-number / structural variants overlap ST8SIA2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →