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 DNA repair-dependent chromatin remodeling; positive regulation of protein localization; and protein ubiquitination. Located in several cellular components, including early endosome; lysosome; and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.78

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in DTX3L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

888 rare PASS variants

Rare truncating (LoF)

1 in 1,300

104 rare PASS variants

Rare synonymous (reference)

1 in 220

311 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DTX3L. 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 1,400
South Asian	~43k	1 in 59	1 in 1,700
Remaining (unassigned)	~30k	1 in 77	1 in 1,800
European (Finnish)	~27k	1 in 140	1 in 640
Admixed American	~22k	1 in 61	1 in 1,700
African / African American	~21k	1 in 67	1 in 1,300
East Asian	~20k	1 in 64	1 in 1,700
Ashkenazi Jewish	~13k	1 in 320	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 67	≈ 1 in 2,900

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