ART4

Chr 12

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

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

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.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

[Blood group, Dombrock]MIM #616060
0
Active trials
1
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.07
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryART4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.002
Z-score 1.41
OE 0.54 (0.301.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.14Z-score
OE missense 1.03 (0.911.17)
168 obs / 162.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.54 (0.301.07)
00.351.4
Missense OE1.03 (0.911.17)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 6 / 11.0Missense obs/exp: 168 / 162.8Syn Z: -0.68
DN
0.7036th %ile
GOF
0.6442th %ile
LOF
0.1796th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ART4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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