DDB2

damage specific DNA binding protein 2, the group of Nucleotide excision repair|WD repeat domain containing|Xeroderma pigmentosum complementation groups

Basic information

Region (hg38): 11:47214465-47239217

Links

ENSG00000134574 ∙ NCBI:1643 ∙ OMIM:600811 ∙ HGNC:2718 ∙ Uniprot:Q92466 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• xeroderma pigmentosum group E (Definitive), mode of inheritance: AR
• xeroderma pigmentosum group E (Strong), mode of inheritance: AR
• xeroderma pigmentosum group E (Strong), mode of inheritance: AR
• xeroderma pigmentosum (Supportive), mode of inheritance: AR
• xeroderma pigmentosum group E (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Xeroderma pigmentosum, group E	AR	Dermatologic; Oncologic	Skin lesions can be treated (and possibly prevented in some cases) with a variety of methods, depending on the specific type of lesion; Sun/UV exposure (and other agents, such as tobacco smoke) should be avoided; Periodic surveillance (primarily related to skin manifestations, as well as other sequelae) can be beneficial	Dermatologic; Oncologic; Ophthalmologic	3175673; 3339259; 8798680; 10447254; 20301571

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DDB2 gene.

• not provided (3 variants)
• Xeroderma pigmentosum, group E (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDB2 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			4	13	1	18
missense		1	30	3	1	35
nonsense	4					4
start loss						0
frameshift		2				2
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region			4	2		6
non coding			14	9	17	40
Total	5	5	51	25	19

Highest pathogenic variant AF is 0.0000395

Variants in DDB2

This is a list of pathogenic ClinVar variants found in the DDB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-47214602-AAG-A			Benign (Sep 24, 2019)
11-47214743-A-G			Benign (Jan 10, 2019)
11-47214747-A-G			Benign (Jan 10, 2019)
11-47214854-C-G			Benign (Jan 10, 2019)
11-47214868-C-T			Likely benign (Jun 12, 2019)
11-47214879-G-T			Likely benign (Jun 12, 2019)
11-47214994-A-G		Xeroderma pigmentosum, group E	Uncertain significance (Jan 12, 2018)
11-47215014-T-G		Xeroderma pigmentosum, group E	Uncertain significance (Jan 13, 2018)
11-47215017-G-A		Xeroderma pigmentosum, group E	Benign (Feb 28, 2019)
11-47215017-G-C		Xeroderma pigmentosum, group E	Uncertain significance (Apr 27, 2017)
11-47215081-A-G		Xeroderma pigmentosum, group E	Uncertain significance (Jan 13, 2018)
11-47215101-G-A		Xeroderma pigmentosum, group E	Uncertain significance (Jan 12, 2018)
11-47215106-G-C		Xeroderma pigmentosum	Uncertain significance (Jun 14, 2016)
11-47215187-A-G			Likely benign (Jan 19, 2018)
11-47215188-C-T		Xeroderma pigmentosum, group E	Uncertain significance (Apr 15, 2021)
11-47215193-C-A			Likely benign (May 19, 2018)
11-47215195-G-A		Xeroderma pigmentosum • Inborn genetic diseases • Xeroderma pigmentosum, group E	Conflicting classifications of pathogenicity (Jan 02, 2024)
11-47215219-T-TG		Xeroderma pigmentosum, group E	Likely pathogenic (Mar 21, 2024)
11-47215236-G-T		Ovarian cancer	Benign (Jan 01, 2022)
11-47215239-A-G		Inborn genetic diseases	Uncertain significance (Jun 22, 2021)
11-47215268-T-G		Xeroderma pigmentosum, group E • not specified • Xeroderma pigmentosum	Conflicting classifications of pathogenicity (Mar 29, 2023)
11-47216129-T-C			Benign (Jan 10, 2019)
11-47216252-T-G		not specified	Likely benign (Dec 10, 2020)
11-47216270-C-T		not specified	Likely benign (Jun 01, 2023)
11-47216328-C-T			Likely benign (Nov 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDB2	protein_coding	protein_coding	ENST00000256996	10	24275

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000740	0.980	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	187	240	0.779	0.0000138	2809
Missense in Polyphen		47	87.942	0.53444		1065
Synonymous	0.495	88	94.1	0.935	0.00000579	829
Loss of Function	2.11	12	22.9	0.523	0.00000138	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.000647	0.000647
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.000272	0.000272
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for DNA repair. Binds to DDB1 to form the UV- damaged DNA-binding protein complex (the UV-DDB complex). The UV- DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also appears to function as the substrate recognition module for the DCX (DDB1- CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB1-CUL4- ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair. The DDB1-CUL4-ROC1 complex also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. Isoform D1 and isoform D2 inhibit UV-damaged DNA repair. {ECO:0000269|PubMed:10882109, ECO:0000269|PubMed:11278856, ECO:0000269|PubMed:11705987, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:12944386, ECO:0000269|PubMed:14751237, ECO:0000269|PubMed:15882621, ECO:0000269|PubMed:16260596, ECO:0000269|PubMed:16473935, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:9892649}.
• Disease: DISEASE: Xeroderma pigmentosum complementation group E (XP-E) [MIM:278740]: An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. XP-E patients show a mild phenotype with minimal or no neurologic features. {ECO:0000269|PubMed:8798680}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Non-small cell lung cancer - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Nucleotide excision repair - Homo sapiens (human);Melanoma - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Breast cancer - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);miRNA Regulation of DNA Damage Response;TP53 Regulates Transcription of DNA Repair Genes;miRNA regulation of p53 pathway in prostate cancer;Endometrial cancer;Chromosomal and microsatellite instability in colorectal cancer;DNA Damage Response;DNA Repair;Gene expression (Transcription);Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;TP53 Regulates Transcription of DNA Repair Genes;Neddylation;Ub-specific processing proteases;Deubiquitination;Transcriptional Regulation by TP53;Direct p53 effectors;DNA Damage Recognition in GG-NER;Formation of Incision Complex in GG-NER;Dual Incision in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.399

Intolerance Scores

• loftool: 0.693
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.66

Haploinsufficiency Scores

• pHI: 0.166
• hipred: Y
• hipred_score: 0.756
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ddb2
• Phenotype: neoplasm; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); growth/size/body region phenotype; cellular phenotype

Gene ontology

• Biological process: protein polyubiquitination;nucleotide-excision repair, DNA damage recognition;DNA repair;nucleotide-excision repair;pyrimidine dimer repair;nucleotide-excision repair, preincision complex stabilization;nucleotide-excision repair, preincision complex assembly;nucleotide-excision repair, DNA incision, 5'-to lesion;response to UV;response to UV-B;protein deubiquitination;nucleotide-excision repair, DNA incision;histone H2A monoubiquitination;post-translational protein modification;protein autoubiquitination;global genome nucleotide-excision repair;UV-damage excision repair
• Cellular component: nucleoplasm;cell junction;Cul4B-RING E3 ubiquitin ligase complex;protein-containing complex;Cul4-RING E3 ubiquitin ligase complex
• Molecular function: DNA binding;damaged DNA binding;ubiquitin-protein transferase activity;protein binding;protein-containing complex binding