DTX3L

Chr 3

deltex E3 ubiquitin ligase 3L

Also known as: BBAP, RNF143

NCBI Gene: 151636 ENSG00000163840 UniProt: Q8TDB6 OMIM: 613143

DTX3L encodes an E3 ubiquitin ligase that monoubiquitinates histones and functions in DNA damage repair and interferon-mediated antiviral responses, working in association with PARP9. The gene is not well-established as a cause of human disease, as loss-of-function variants appear to be well-tolerated based on population genetic data showing minimal constraint against such variants. Current evidence does not support DTX3L mutations as a cause of pediatric neurological disorders.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including STAT family protein binding activity; histone H4K91 ubiquitin ligase activity; and protein ADP-ribosyltransferase-substrate adaptor activity. Involved in several processes, including positive regulation of protein localization; protein ubiquitination; and regulation of macromolecule metabolic process. Located in several cellular components, including early endosome; lysosome; and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.78

Clinical Summary— DTX3L

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.000

Z-score 2.42

OE 0.49 (0.32–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.33Z-score

OE missense 0.95 (0.87–1.04)

366 obs / 384.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.32–0.78)

0≤0.351.4

Missense OE?0.95 (0.87–1.04)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 13 / 26.4Missense obs/exp: 366 / 384.2Syn Z: 0.66

This gene — mechanism propensity

0.6839th %ile

GOF

0.5170th %ile

LOF

0.2091th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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.