DTL

denticleless E3 ubiquitin protein ligase homolog, the group of WD repeat domain containing|MicroRNA protein coding host genes|DDB1 and CUL4 associated factors

Basic information

Region (hg38): 1:212035553-212107400

Links

ENSG00000143476 ∙ NCBI:51514 ∙ OMIM:610617 ∙ HGNC:30288 ∙ Uniprot:Q9NZJ0 ∙ 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 DTL gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DTL 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	1	3
missense			22	2		24
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	22	4	1

Variants in DTL

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

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

Position	Type	Phenotype	Significance	ClinVar
1-212035901-A-G		not specified	Uncertain significance (Oct 20, 2023)
1-212043027-G-A			Likely benign (Feb 01, 2023)
1-212043044-G-C		not specified	Uncertain significance (Aug 16, 2022)
1-212043115-T-A		not specified	Uncertain significance (Nov 18, 2022)
1-212044752-T-G		not specified	Likely benign (Dec 19, 2023)
1-212047174-G-A		not specified	Uncertain significance (Dec 15, 2022)
1-212064996-G-C		not specified	Uncertain significance (Oct 06, 2022)
1-212065019-C-T		not specified	Uncertain significance (Dec 19, 2023)
1-212066855-A-T		not specified	Uncertain significance (Mar 02, 2023)
1-212068629-G-A		not specified	Uncertain significance (Dec 16, 2023)
1-212068674-T-A		not specified	Uncertain significance (Jan 09, 2024)
1-212068700-C-T		not specified	Uncertain significance (Jun 02, 2024)
1-212072205-A-G		not specified	Uncertain significance (Nov 11, 2024)
1-212078197-A-G		not specified	Uncertain significance (Oct 08, 2024)
1-212078228-C-T		not specified	Uncertain significance (Nov 12, 2021)
1-212078239-T-C		not specified	Uncertain significance (Jan 06, 2023)
1-212080704-G-A			Likely benign (Feb 01, 2023)
1-212100303-G-A		not specified	Uncertain significance (Oct 06, 2024)
1-212100383-C-T		not specified	Uncertain significance (Nov 10, 2022)
1-212100397-T-G		not specified	Uncertain significance (Aug 15, 2023)
1-212100411-C-G		not specified	Uncertain significance (Nov 12, 2021)
1-212100487-G-A		not specified	Uncertain significance (Dec 13, 2023)
1-212100542-C-T		not specified	Uncertain significance (Jan 24, 2024)
1-212100549-C-T		not specified	Uncertain significance (Oct 17, 2023)
1-212100555-C-T		not specified	Uncertain significance (Jun 18, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DTL	protein_coding	protein_coding	ENST00000366991	15	71824

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00330	0.997	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	291	390	0.747	0.0000196	4741
Missense in Polyphen		55	96.97	0.56718		1189
Synonymous	-0.486	152	145	1.05	0.00000782	1426
Loss of Function	4.03	12	39.2	0.306	0.00000204	460

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000133	0.000114
Middle Eastern	0.000218	0.000217
South Asian	0.000272	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), FBH1, KMT5A and SDE2 (PubMed:16861906, PubMed:16949367, PubMed:16964240, PubMed:17085480, PubMed:18703516, PubMed:18794347, PubMed:18794348, PubMed:19332548, PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613, PubMed:27906959). CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication (PubMed:16861906, PubMed:16949367, PubMed:17085480). CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing (PubMed:18794348, PubMed:19332548). KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration (PubMed:23478445). Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA- dependent translesion DNA synthesis (PubMed:20129063, PubMed:23478441, PubMed:23478445, PubMed:23677613). {ECO:0000269|PubMed:16861906, ECO:0000269|PubMed:16949367, ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:17085480, ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:18794348, ECO:0000269|PubMed:19332548, ECO:0000269|PubMed:20129063, ECO:0000269|PubMed:23478441, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:23677613, ECO:0000269|PubMed:27906959}.
• Pathway: DNA Repair;Post-translational protein modification;Metabolism of proteins;Neddylation;Recognition of DNA damage by PCNA-containing replication complex;DNA Damage Bypass (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.623
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.41

Haploinsufficiency Scores

• pHI: 0.773
• hipred: Y
• hipred_score: 0.602
• ghis: 0.612

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dtl
• Phenotype: immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: dtl
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: flat

Gene ontology

• Biological process: protein polyubiquitination;DNA replication;ubiquitin-dependent protein catabolic process;protein monoubiquitination;cellular response to DNA damage stimulus;response to UV;positive regulation of G2/M transition of mitotic cell cycle;translesion synthesis;DNA damage response, detection of DNA damage;post-translational protein modification;positive regulation of protein catabolic process;regulation of cell cycle;signal transduction involved in G2 DNA damage checkpoint
• Cellular component: nucleus;nucleoplasm;chromosome;nucleolus;centrosome;cytosol;Cul4A-RING E3 ubiquitin ligase complex;Cul4B-RING E3 ubiquitin ligase complex;nuclear membrane;Cul4-RING E3 ubiquitin ligase complex
• Molecular function: ubiquitin-protein transferase activity;protein binding