ST6GALNAC4

Chr 9

ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 4

Also known as: IV, SIAT3-C, SIAT3C, SIAT7-D, SIAT7D, ST6GALNACIV, ST6GalNAc

NCBI Gene: 27090 ENSG00000136840 UniProt: Q9H4F1 OMIM: 606378

The encoded sialyltransferase catalyzes the transfer of sialic acid from CMP-sialic acid to GalNAc residues on glycoproteins and glycolipids, forming alpha-2,6-linkages and producing branched disialyl structures essential for proper glycosylation. The extremely low pLI score and elevated LOEUF score indicate this gene is highly tolerant to loss-of-function mutations, suggesting haploinsufficiency is unlikely to cause disease. No specific diseases associated with ST6GALNAC4 mutations are established based on the provided information.

OMIM ResearchSummary from RefSeq, UniProt

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 prefers glycoproteins rather than glycolipids as substrates and shows restricted substrate specificity, utilizing only the trisaccharide sequence Neu5Ac-alpha-2,3-Gal-beta-1,3-GalNAc. In addition, it is involved in the synthesis of ganglioside GD1A from GM1B. 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. Transcript variants encoding different isoforms have been found for this gene. Readthrough transcripts exist for this gene and the downstream ST6GALNAC6 gene. [provided by RefSeq, Jan 2022]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.39LOEUF

pLI 0.000

Z-score 0.54

OE 0.84 (0.53–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.76Z-score

OE missense 0.85 (0.75–0.96)

174 obs / 204.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.53–1.39)

0≤0.351.4

Missense OE?0.85 (0.75–0.96)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 11 / 13.1Missense obs/exp: 174 / 204.7Syn Z: 0.41

Background carrier burden — how many people carry a rare variant somewhere in ST6GALNAC4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

390 rare PASS variants

Rare truncating (LoF)

1 in 2,500

53 rare PASS variants

Rare synonymous (reference)

1 in 150

168 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ST6GALNAC4. 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 5,100
South Asian	~43k	1 in 130	1 in 8,600
Remaining (unassigned)	~30k	1 in 120	1 in 6,000
European (Finnish)	~27k	1 in 690	1 in 3,200
Admixed American	~22k	1 in 190	1 in 1,200
African / African American	~21k	1 in 170	1 in 3,600
East Asian	~20k	1 in 110	1 in 2,000
Ashkenazi Jewish	~13k	1 in 300	none seen
Middle Eastern	~2,884	1 in 98	≈ 1 in 2,900

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓