ST8SIA6

Chr 10

ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 6

Also known as: SIA8F, SIAT8-F, SIAT8F, ST8SIA-VI, ST8SiaVI

NCBI Gene: 338596 ENSG00000148488 UniProt: P61647 OMIM: 610139

This gene encodes an alpha-2,8-sialyltransferase that adds sialic acid residues to O-glycans, with the minimal acceptor substrate being NeuAc-alpha-2,3(6)-Gal sequences. Pathogenic variants cause autosomal recessive intellectual developmental disorder with seizures, hypotonia, and brain abnormalities. The gene is not highly constrained against loss-of-function variants, consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the glycosyltransferase 29 protein family. Members of this protein family synthesize sialylglycoconjugates. Sialylation may contribute to multidrug resistance in cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.57

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.57LOEUF

pLI 0.000

Z-score -0.03

OE 1.01 (0.67–1.57)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.43Z-score

OE missense 1.09 (0.97–1.23)

199 obs / 182.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.01 (0.67–1.57)

0≤0.351.4

Missense OE?1.09 (0.97–1.23)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 14 / 13.9Missense obs/exp: 199 / 182.6Syn Z: -1.15

Background carrier burden — how many people carry a rare variant somewhere in ST8SIA6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

502 rare PASS variants

Rare truncating (LoF)

1 in 1,100

106 rare PASS variants

Rare synonymous (reference)

1 in 170

212 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ST8SIA6. 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 170	1 in 1,300
South Asian	~43k	1 in 120	1 in 300
Remaining (unassigned)	~30k	1 in 88	1 in 840
European (Finnish)	~27k	1 in 430	none seen
Admixed American	~22k	1 in 55	1 in 720
African / African American	~21k	1 in 92	1 in 1,700
East Asian	~20k	1 in 110	1 in 820
Ashkenazi Jewish	~13k	1 in 460	1 in 1,200
Middle Eastern	~2,884	1 in 140	≈ 1 in 1,400

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): 5 of 8 coding exons well covered in gnomAD exomes; exon 1 poorly covered; exons 2, 4 marginal. Genomes: all 8.? see exons ↓