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 UniProt: Q92186

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.

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]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in ST8SIA2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

408 rare PASS variants

Rare truncating (LoF)

1 in 6,600

43 rare PASS variants

Rare synonymous (reference)

1 in 150

218 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ST8SIA2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 4,600
South Asian	~43k	1 in 180	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 110	≈ 1 in 30,000
European (Finnish)	~27k	1 in 310	1 in 5,300
Admixed American	~22k	1 in 110	none seen
African / African American	~21k	1 in 160	≈ 1 in 6,700
East Asian	~20k	1 in 170	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 1,600	none seen
Middle Eastern	~2,884	1 in 180	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓