ST3GAL3

Chr 1AR

ST3 beta-galactoside alpha-2,3-sialyltransferase 3

Also known as: DEE15, EIEE15, MRT12, SIAT6, ST3GALII, ST3Gal III, ST3GalIII, ST3N

NCBI Gene: 6487 ENSG00000126091 UniProt: Q11203 OMIM: 606494

The protein is a sialyltransferase that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates in the Golgi apparatus. Mutations cause autosomal recessive developmental and epileptic encephalopathy 15 and intellectual developmental disorder, autosomal recessive 12. The pathogenic mechanism involves dominant-negative effects disrupting normal protein function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to galactose-containing substrates. The encoded protein is normally found in the Golgi apparatus but can be proteolytically processed to a soluble form. This protein is a member of glycosyltransferase family 29. Mutations in this gene have been associated with a form of autosomal recessive nonsymdromic cognitive disability as well as infantile epileptic encephalopathy. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 15MIM #615006

Intellectual developmental disorder, autosomal recessive 12MIM #611090

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · complex neurodevelopmental disorder · AR · ClinGen 2020

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.62

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.003

Z-score 3.00

OE 0.36 (0.21–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.50Z-score

OE missense 0.74 (0.65–0.83)

188 obs / 255.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.21–0.62)

0≤0.351.4

Missense OE?0.74 (0.65–0.83)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 9 / 25.3Missense obs/exp: 188 / 255.4Syn Z: 0.27

Background carrier burden — how many people carry a rare variant somewhere in ST3GAL3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 76

645 rare PASS variants

Rare truncating (LoF)

1 in 190

107 rare PASS variants

Rare synonymous (reference)

1 in 180

256 rare PASS variants

Rare missense and truncating variants are carried at similar rates in ST3GAL3; this gene does not show strong loss-of-function constraint by this measure. 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 81	1 in 420
South Asian	~43k	1 in 78	1 in 370
Remaining (unassigned)	~30k	1 in 89	1 in 1,100
European (Finnish)	~27k	1 in 230	1 in 520
Admixed American	~22k	1 in 85	1 in 1,700
African / African American	~21k	1 in 51	1 in 280
East Asian	~20k	1 in 170	1 in 570
Ashkenazi Jewish	~13k	1 in 190	1 in 440
Middle Eastern	~2,884	1 in 95	1 in 490

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓