DTX3L

deltex E3 ubiquitin ligase 3L, the group of Ring finger proteins

Basic information

Region (hg38): 3:122564338-122575203

Links

ENSG00000163840 ∙ NCBI:151636 ∙ OMIM:613143 ∙ HGNC:30323 ∙ Uniprot:Q8TDB6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DTX3L gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DTX3L gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2		2
missense			48	6	1	55
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	48	8	1

Variants in DTX3L

This is a list of pathogenic ClinVar variants found in the DTX3L region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-122564438-C-T		not specified	Likely benign (Jan 23, 2025)
3-122564482-G-A		not specified	Uncertain significance (Jul 27, 2021)
3-122564516-C-A		not specified	Uncertain significance (Mar 01, 2024)
3-122564521-G-C		not specified	Uncertain significance (Aug 12, 2022)
3-122564527-A-C		not specified	Uncertain significance (Feb 28, 2023)
3-122564529-T-C		not specified	Uncertain significance (Mar 30, 2024)
3-122564592-G-T		not specified	Uncertain significance (Jan 19, 2022)
3-122565870-G-C		not specified	Uncertain significance (Jan 10, 2022)
3-122565905-C-T			Likely benign (Jul 15, 2018)
3-122565961-C-T		not specified	Likely benign (Jun 12, 2023)
3-122565979-C-T		not specified	Uncertain significance (May 02, 2024)
3-122565993-C-G		not specified	Uncertain significance (Jul 14, 2022)
3-122566006-C-T		not specified	Uncertain significance (Jun 18, 2021)
3-122566039-T-C		not specified	Uncertain significance (Feb 14, 2023)
3-122568538-A-G		not specified	Uncertain significance (Jul 12, 2023)
3-122568594-G-A		not specified	Likely benign (Jul 25, 2024)
3-122568670-A-G		not specified	Uncertain significance (Apr 24, 2023)
3-122568700-C-T		not specified	Likely benign (May 18, 2022)
3-122568723-A-G		not specified	Uncertain significance (Feb 27, 2024)
3-122568736-G-C		not specified	Uncertain significance (Mar 01, 2025)
3-122568762-C-T		not specified	Uncertain significance (Nov 17, 2022)
3-122568841-C-T		not specified	Uncertain significance (Jun 21, 2021)
3-122568853-A-G		not specified	Uncertain significance (Oct 03, 2024)
3-122568892-A-G		not specified	Uncertain significance (Mar 07, 2023)
3-122568910-T-C		not specified	Uncertain significance (Sep 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DTX3L	protein_coding	protein_coding	ENST00000296161	5	10966

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000527	0.993	125735	0	12	125747	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.330	366	384	0.953	0.0000184	4880
Missense in Polyphen		63	70.991	0.88743		915
Synonymous	0.655	135	145	0.931	0.00000743	1389
Loss of Function	2.42	13	26.4	0.493	0.00000127	371

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000530	0.0000527
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: E3 ubiquitin-protein ligase which, in association with ADP-ribosyltransferase PARP9, plays a role in DNA damage repair and in interferon-mediated antiviral responses (PubMed:12670957, PubMed:19818714, PubMed:26479788, PubMed:23230272). Monoubiquitinates several histones, including histone H2A, H2B, H3 and H4 (PubMed:28525742). In response to DNA damage, mediates monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1) (PubMed:19818714). The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 'Lys-20' methylation (H4K20me) (PubMed:19818714). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). By monoubiquitinating histone H2B HIST1H2BH/H2BJ and thereby promoting chromatin remodeling, positively regulates STAT1-dependent interferon- stimulated gene transcription and thus STAT1-mediated control of viral replication (PubMed:26479788). Independently of its catalytic activity, promotes the sorting of chemokine receptor CXCR4 from early endosome to lysosome following CXCL12 stimulation by reducing E3 ligase ITCH activity and thus ITCH-mediated ubiquitination of endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:24790097). In addition, required for the recruitment of HGS and STAM to early endosomes (PubMed:24790097). In association with PARP9, plays a role in antiviral responses by mediating 'Lys-48'-linked ubiquitination of encephalomyocarditis virus (EMCV) and human rhinovirus (HRV) C3 proteases and thus promoting their proteosomal-mediated degradation (PubMed:26479788). {ECO:0000269|PubMed:12670957, ECO:0000269|PubMed:19818714, ECO:0000269|PubMed:23230272, ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:26479788, ECO:0000269|PubMed:28525742}.
• Pathway: Notch signaling pathway - Homo sapiens (human);Notch Signaling Pathway;Notch Signaling Pathway;Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.0605

Intolerance Scores

• loftool: 0.794
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.43

Haploinsufficiency Scores

• pHI: 0.0337
• hipred: N
• hipred_score: 0.172
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.427

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dtx3l

Gene ontology

• Biological process: protein polyubiquitination;positive regulation of defense response to virus by host;double-strand break repair;ubiquitin-dependent protein catabolic process;cellular response to DNA damage stimulus;Notch signaling pathway;endosome to lysosome transport;histone monoubiquitination;protein transport;positive regulation of protein binding;histone H2A ubiquitination;histone H2B ubiquitination;positive regulation of chromatin binding;innate immune response;positive regulation of transcription, DNA-templated;negative regulation of ubiquitin-protein transferase activity;defense response to virus;protein autoubiquitination;protein K48-linked ubiquitination;positive regulation of protein localization to nucleus;positive regulation of NAD+ ADP-ribosyltransferase activity;positive regulation of protein localization to early endosome;positive regulation of receptor catabolic process;positive regulation of double-strand break repair via nonhomologous end joining
• Cellular component: nucleus;nucleoplasm;cytoplasm;lysosome;lysosomal membrane;early endosome;cytosol;early endosome membrane;protein-containing complex
• Molecular function: ubiquitin-protein transferase activity;enzyme inhibitor activity;protein binding;enzyme activator activity;enzyme binding;histone binding;ubiquitin-like protein ligase binding;metal ion binding;STAT family protein binding