A4GALT

Chr 22

alpha 1,4-galactosyltransferase (P1PK blood group)

Also known as: A14GALT, A4GALT1, Gb3S, P(k), P1, P1PK, PK

NCBI Gene: 53947 ENSG00000128274 UniProt: Q9NPC4 OMIM: 607922

This glycosyltransferase catalyzes the transfer of galactose to lactosylceramide to form globotriaosylceramide and synthesizes antigens of the P1PK blood group system. Mutations cause P1Pk blood group phenotypes and NOR polyagglutination syndrome, which are inherited in an autosomal recessive pattern. The gene shows low constraint to loss-of-function variation, consistent with primarily hematologic rather than severe developmental phenotypes.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene catalyzes the transfer of galactose to lactosylceramide to form globotriaosylceramide, which has been identified as the P(k) antigen of the P blood group system. This protein, a type II membrane protein found in the Golgi, is also required for the synthesis of the bacterial verotoxins receptor. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Blood group, P1Pk system, p phenotype]MIM #111400

[Blood group, P1Pk system, P(2) phenotype]MIM #111400

NOR polyagglutination syndromeMIM #111400

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · A4GALT-related congenital disorder of glycosylation · AR · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.65

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.65LOEUF

pLI 0.000

Z-score 0.15

OE 0.95 (0.55–1.65)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.19Z-score

OE missense 1.03 (0.93–1.15)

241 obs / 233.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.95 (0.55–1.65)

0≤0.351.4

Missense OE?1.03 (0.93–1.15)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 8 / 8.5Missense obs/exp: 241 / 233.0Syn Z: -0.99

Background carrier burden — how many people carry a rare variant somewhere in A4GALT?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

541 rare PASS variants

Rare truncating (LoF)

1 in 330

114 rare PASS variants

Rare synonymous (reference)

1 in 160

273 rare PASS variants

Rare missense and truncating variants are carried at similar rates in A4GALT; 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 160	1 in 260
South Asian	~43k	1 in 110	1 in 510
Remaining (unassigned)	~30k	1 in 89	1 in 300
European (Finnish)	~27k	1 in 370	1 in 2,900
Admixed American	~22k	1 in 99	1 in 630
African / African American	~21k	1 in 130	1 in 200
East Asian	~20k	1 in 140	1 in 380
Ashkenazi Jewish	~13k	1 in 440	1 in 980
Middle Eastern	~2,884	1 in 78	1 in 420

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