ART4

Chr 12

ADP-ribosyltransferase 4 (inactive) (Dombrock blood group)

Also known as: ARTC4, CD297, DO, DO/ART4, DOK1

NCBI Gene: 420 ENSG00000111339 UniProt: Q9ULX3 OMIM: 110600

This protein contains a mono-ADP-ribosylation motif and is anchored to the erythrocyte membrane where it carries antigens of the Dombrock blood group system, though its enzymatic activity has not been demonstrated. Mutations cause Dombrock blood group variants with autosomal inheritance, some of which can lead to adverse transfusion reactions. The gene shows low constraint against loss-of-function variants, consistent with its primary role in blood group antigen presentation rather than essential cellular functions.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that contains a mono-ADP-ribosylation (ART) motif. It is a member of the ADP-ribosyltransferase gene family but enzymatic activity has not been demonstrated experimentally. Antigens of the Dombrock blood group system are located on the gene product, which is glycosylphosphatidylinosotol-anchored to the erythrocyte membrane. Allelic variants, some of which lead to adverse transfusion reactions, are known. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

[Blood group, Dombrock]MIM #616060

Active trials

—

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.07

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — ART4

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.002

Z-score 1.41

OE 0.54 (0.30–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.14Z-score

OE missense 1.03 (0.91–1.17)

168 obs / 162.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.54 (0.30–1.07)

0≤0.351.4

Missense OE?1.03 (0.91–1.17)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 6 / 11.0Missense obs/exp: 168 / 162.8Syn Z: -0.68

Background carrier burden — how many people carry a rare variant somewhere in ART4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 95

394 rare PASS variants

Rare truncating (LoF)

1 in 1,200

45 rare PASS variants

Rare synonymous (reference)

1 in 450

162 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ART4. 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 120	1 in 2,100
South Asian	~43k	1 in 100	1 in 750
Remaining (unassigned)	~30k	1 in 82	1 in 820
European (Finnish)	~27k	1 in 3,000	≈ 1 in 13,000
Admixed American	~22k	1 in 130	≈ 1 in 4,500
African / African American	~21k	1 in 140	1 in 3,300
East Asian	~20k	1 in 140	1 in 2,000
Ashkenazi Jewish	~13k	1 in 580	none seen
Middle Eastern	~2,884	1 in 140	none seen

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