DDB1

damage specific DNA binding protein 1, the group of Nucleotide excision repair

Basic information

Region (hg38): 11:61299450-61342596

Links

ENSG00000167986 ∙ NCBI:1642 ∙ OMIM:600045 ∙ HGNC:2717 ∙ Uniprot:Q16531 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• White-Kernohan syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
White-Kernohan syndrome	AD	General	Among other findings, the condition can include vesicoureteral reflux, and awareness may allow preventative measures and management related to sequelae of these anomalies	Craniofacial; Genitourinary; Musculoskeletal; Neurologic; Renal	33743206

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DDB1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DDB1 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		2	45	2		49
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	2	5
non coding			1			1
Total	0	2	47	2	2

Variants in DDB1

This is a list of pathogenic ClinVar variants found in the DDB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-61300140-T-C			Uncertain significance (Apr 21, 2023)
11-61300154-C-G		not specified	Uncertain significance (Apr 09, 2024)
11-61300815-G-T		not specified	Uncertain significance (Jan 30, 2024)
11-61300822-A-G		not specified	Uncertain significance (Feb 14, 2023)
11-61300877-C-G		not specified	Uncertain significance (May 06, 2024)
11-61302302-C-T			Uncertain significance (Sep 28, 2022)
11-61302335-C-T			Uncertain significance (Sep 22, 2022)
11-61302620-T-C		DDB1-related disorder	Uncertain significance (Aug 02, 2023)
11-61302681-T-C			Uncertain significance (Jan 12, 2021)
11-61302684-C-T		not specified	Uncertain significance (Jun 16, 2024)
11-61303086-C-A		White-Kernohan syndrome	Uncertain significance (Sep 28, 2022)
11-61304014-T-C		White-Kernohan syndrome	Uncertain significance (Nov 29, 2022)
11-61304025-T-C		not specified	Uncertain significance (Feb 02, 2024)
11-61304038-G-T		DDB1-related disorder	Likely benign (Jul 03, 2023)
11-61304043-G-T		not specified	Uncertain significance (Apr 23, 2024)
11-61308984-G-A			Uncertain significance (Jan 01, 2023)
11-61308997-T-C			Uncertain significance (Jul 28, 2022)
11-61309012-C-T		White-Kernohan syndrome	Uncertain significance (Apr 04, 2024)
11-61309037-G-A			Benign (May 18, 2018)
11-61309039-C-T		not specified	Uncertain significance (Jan 23, 2024)
11-61309066-T-C		Syndromic intellectual disability	Uncertain significance (Feb 02, 2022)
11-61310316-T-C		not specified	Uncertain significance (Mar 18, 2024)
11-61310318-A-G		White-Kernohan syndrome	Uncertain significance (Jan 13, 2023)
11-61310416-A-G			Benign (May 18, 2018)
11-61311785-T-G			Uncertain significance (Nov 07, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DDB1	protein_coding	protein_coding	ENST00000301764	27	43146

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000207	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.89	313	669	0.468	0.0000392	7509
Missense in Polyphen		60	247.72	0.24221		2877
Synonymous	-0.593	276	264	1.05	0.0000164	2218
Loss of Function	6.19	8	59.5	0.134	0.00000300	688

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for DNA repair. Binds to DDB2 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 a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. The functional specificity of the DCX E3 ubiquitin- protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) 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. DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-binding by XPC and promote NER. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. DCX(ERCC8) (the CSA complex) plays a role in transcription-coupled repair (TCR). May also play a role in ubiquitination of CDKN1B/p27kip when associated with CUL4 and SKP2. {ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:14739464, ECO:0000269|PubMed:15448697, ECO:0000269|PubMed:15882621, ECO:0000269|PubMed:16260596, ECO:0000269|PubMed:16407242, ECO:0000269|PubMed:16407252, ECO:0000269|PubMed:16473935, ECO:0000269|PubMed:16482215, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:16940174, ECO:0000269|PubMed:17041588, ECO:0000269|PubMed:17079684, ECO:0000269|PubMed:18332868, ECO:0000269|PubMed:18381890, ECO:0000269|PubMed:18593899, ECO:0000269|PubMed:19966799, ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:25043012, ECO:0000269|PubMed:25108355}.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);DNA Repair;Post-translational protein modification;Metabolism of proteins;Neddylation;Recognition of DNA damage by PCNA-containing replication complex;DNA Damage Bypass;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);Formation of TC-NER Pre-Incision Complex;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.271
• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.72

Haploinsufficiency Scores

• pHI: 0.375
• hipred: Y
• hipred_score: 0.783
• ghis: 0.623

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.983

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ddb1
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system 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); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Zebrafish Information Network

• Gene name: ddb1
• Affected structure: cranial cartilage
• Phenotype tag: abnormal
• Phenotype quality: hypoplastic

Gene ontology

• Biological process: nucleotide-excision repair, DNA damage recognition;DNA repair;transcription-coupled nucleotide-excision repair;nucleotide-excision repair;nucleotide-excision repair, preincision complex stabilization;nucleotide-excision repair, preincision complex assembly;nucleotide-excision repair, DNA incision, 5'-to lesion;ubiquitin-dependent protein catabolic process;cellular response to DNA damage stimulus;proteasomal protein catabolic process;viral process;Wnt signaling pathway;protein ubiquitination;nucleotide-excision repair, DNA incision;histone H2A monoubiquitination;DNA damage response, detection of DNA damage;negative regulation of apoptotic process;proteasome-mediated ubiquitin-dependent protein catabolic process;post-translational protein modification;positive regulation of viral genome replication;positive regulation of protein catabolic process;positive regulation by virus of viral protein levels in host cell;interaction with symbiont;global genome nucleotide-excision repair;UV-damage excision repair;regulation of mitotic cell cycle phase transition;positive regulation of viral release from host cell
• Cellular component: nuclear chromosome, telomeric region;extracellular space;nucleus;nucleoplasm;cytoplasm;Cul4A-RING E3 ubiquitin ligase complex;Cul4B-RING E3 ubiquitin ligase complex;protein-containing complex;extracellular exosome;Cul4-RING E3 ubiquitin ligase complex
• Molecular function: DNA binding;damaged DNA binding;protein binding;protein binding, bridging;protein-containing complex binding;WD40-repeat domain binding;cullin family protein binding