A4GALT

Chr 22

alpha 1,4-galactosyltransferase (P1PK blood group)

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

NCBI Gene: 53947ENSG00000128274UniProt: Q9NPC4

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]

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
188
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— A4GALT
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
188 total variants — no pathogenic classifications of 188 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.19Z-score
OE missense 1.03 (0.93–1.15)
241 obs / 233.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.95 (0.55–1.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.93–1.15)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.12
0≤1.21.6
LoF obs/exp: 8 / 8.5Missense obs/exp: 241 / 233.0Syn Z: -0.99

ClinVar Variant Classifications

188 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

A4GALT · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

[Blood group, P1Pk system, p phenotype]

MIM #111400

Molecular basis of disorder known

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

MIM #111400

Molecular basis of disorder known

NOR polyagglutination syndrome

MIM #111400

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CRISPR/Cas9-mediated suppression of A4GALT rescues endothelial cell dysfunction in a fabry disease vasculopathy model derived from human induced pluripotent stem cells.
Shin YJ et al.·Atherosclerosis
2024Functional
CRISPR/Cas9-mediated A4GALT suppression rescues Fabry disease phenotypes in a kidney organoid model.
Cui S et al.·Transl Res
2023Functional
Application of a simplified PCR-SSP method to detect A4GALT*01 and A4GALT*02 typing among Thai blood donors.
Amphonritthisak P et al.·Transfus Clin Biol
2023
Novel A4GALT Variants Cause Rare p Phenotype and Recurrent Pregnancy Loss in a Chinese Individual.
Li G et al.·Am J Med Genet A
2025Case report
The differential expression of the blood group P(1) -A4GALT and P(2) -A4GALT alleles is stimulated by the transcription factor early growth response 1.
Yeh CC et al.·Transfusion
2018
Two Thai Burmese descendants with A4GALT*01N.21, p phenotype, and anti-PP1Pk.
Intharanut K et al.·Immunohematology
2020Case report
Allele-selective RUNX1 binding regulates P1 blood group status by transcriptional control of A4GALT.
Westman JS et al.·Blood
2018
Large deletions involving the regulatory upstream regions of A4GALT give rise to principally novel P1PK-null alleles.
Westman JS et al.·Transfusion
2014
Naturally occurring anti-PP1P(K) in a Chinese individual with p phenotype: A case based on compound heterozygosity including one novel allele.
Liang S et al.·Transfusion
2022Case report
Homozygosity for a novel A4GALT allele resulting in the rare p phenotype in an Indian blood donor.
Tilley LA et al.·Vox Sang
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools