ST8SIA3

Chr 18

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

Also known as: SIAT8C, ST8SiaIII

NCBI Gene: 51046 ENSG00000177511 UniProt: O43173

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.

ResearchSummary from RefSeq, UniProt

Enables alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity and identical protein binding activity. Involved in several processes, including N-glycan processing; ganglioside biosynthetic process; and sialylation. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Jun 2026]

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

0.41

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.859

Z-score 3.14

OE 0.13 (0.05–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.47Z-score

OE missense 0.71 (0.63–0.82)

150 obs / 210.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.05–0.41)

0≤0.351.4

Missense OE?0.71 (0.63–0.82)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 2 / 15.2Missense obs/exp: 150 / 210.0Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in ST8SIA3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

387 rare PASS variants

Rare truncating (LoF)

1 in 6,100

47 rare PASS variants

Rare synonymous (reference)

1 in 200

190 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ST8SIA3. 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 200	1 in 7,200
South Asian	~43k	1 in 160	1 in 6,100
Remaining (unassigned)	~30k	1 in 230	≈ 1 in 15,000
European (Finnish)	~27k	1 in 900	1 in 2,200
Admixed American	~22k	1 in 160	1 in 2,800
African / African American	~21k	1 in 350	≈ 1 in 9,300
East Asian	~20k	1 in 380	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 500	none seen
Middle Eastern	~2,884	≈ 1 in 580	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 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓