ST6GAL1

Chr 3

ST6 beta-galactoside alpha-2,6-sialyltransferase 1

ENSG00000073849 UniProt: P15907 OMIM: 109675

Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates. In B lymphocytes, generates neuraminidase-sensitive lymphocyte cell-surface differentiation antigens, such as CDw75, HB-6 and CD76 (PubMed:1730763). Sialylates complex-type N-glycans attached on the fragment crystallizable (Fc) of IgGs conferring anti-inflammatory effector functions. Preferentially monosialylates the alpha(1->3) mannose antenna of Fc glycoforms with subsequent disialylation occurring at a much slower rate

OMIM Research

OMIM 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

0.57

LOEUF

—

Mechanism

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.234

Z-score 2.78

OE 0.25 (0.12–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.15Z-score

OE missense 0.78 (0.69–0.89)

177 obs / 225.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.25 (0.12–0.57)

0≤0.351.4

Missense OE?0.78 (0.69–0.89)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 4 / 16.0Missense obs/exp: 177 / 225.7Syn Z: 0.43

Background carrier burden — how many people carry a rare variant somewhere in ST6GAL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 180

458 rare PASS variants

Rare truncating (LoF)

1 in 4,000

55 rare PASS variants

Rare synonymous (reference)

1 in 140

205 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ST6GAL1. 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 240	1 in 3,800
South Asian	~43k	1 in 200	1 in 6,900
Remaining (unassigned)	~30k	1 in 190	1 in 4,300
European (Finnish)	~27k	1 in 1,100	≈ 1 in 27,000
Admixed American	~22k	1 in 190	≈ 1 in 22,000
African / African American	~21k	1 in 140	1 in 3,900
East Asian	~20k	1 in 170	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 670	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 220	≈ 1 in 2,700

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 ↓