ERCC5

Summary

ERCC5 (ERCC excision repair 5, endonuclease, HGNC:3437) is a protein-coding gene on chromosome 13q33.1, encoding DNA excision repair protein ERCC-5 (P28715). Single-stranded structure-specific DNA endonuclease involved in DNA excision repair.

This gene encodes a single-strand specific DNA endonuclease that makes the 3’ incision in DNA excision repair following UV-induced damage. The protein may also function in other cellular processes, including RNA polymerase II transcription, and transcription-coupled DNA repair. Mutations in this gene cause xeroderma pigmentosum complementation group G (XP-G), which is also referred to as xeroderma pigmentosum VII (XP7), a skin disorder characterized by hypersensitivity to UV light and increased susceptibility for skin cancer development following UV exposure. Some patients also develop Cockayne syndrome, which is characterized by severe growth defects, cognitive disability, and cachexia. Read-through transcription exists between this gene and the neighboring upstream BIVM (basic, immunoglobulin-like variable motif containing) gene.

Source: NCBI Gene 2073 — RefSeq curated summary.

At a glance

• Gene–disease (curated): xeroderma pigmentosum group G (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 20 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 118
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity dosage sensitivity unlikely
• MANE Select transcript: NM_000123

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3437
Approved symbol	ERCC5
Name	ERCC excision repair 5, endonuclease
Location	13q33.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134899
Ensembl biotype	protein_coding
OMIM	133530
Entrez	2073

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 9 retained_intron, 5 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000375954, ENST00000375958, ENST00000472151, ENST00000472247, ENST00000481099, ENST00000535557, ENST00000651002, ENST00000651055, ENST00000651281, ENST00000651387, ENST00000651470, ENST00000652225, ENST00000652613, ENST00000682632, ENST00000682869, ENST00000683246, ENST00000683642, ENST00000684184, ENST00000872814, ENST00000958785, ENST00000958786

RefSeq mRNA: 1 — MANE Select: NM_000123 NM_000123

CCDS: CCDS32004

Canonical transcript exons

ENST00000652225 — 15 exons

Exon	Start	End
ENSE00000000198	102846032	102846354
ENSE00000000199	102875307	102875995
ENSE00001468989	102873259	102873343
ENSE00003476881	102872198	102872398
ENSE00003481581	102853757	102853872
ENSE00003489189	102866262	102866381
ENSE00003514433	102854288	102854374
ENSE00003524230	102856052	102856112
ENSE00003574188	102861507	102861714
ENSE00003613399	102866632	102866845
ENSE00003626169	102852118	102852293
ENSE00003648689	102868113	102868257
ENSE00003653565	102865667	102865911
ENSE00003659293	102862030	102863103
ENSE00003691741	102858275	102858418

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.8650 / max 258.6420, expressed in 1812 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135934	18.6284	1800
135931	2.6714	1348
135932	2.0515	1108
135930	1.4202	982
135933	0.7416	440
135935	0.3519	151

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.64	gold quality
calcaneal tendon	UBERON:0003701	95.44	gold quality
body of pancreas	UBERON:0001150	94.88	gold quality
skin of leg	UBERON:0001511	94.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.84	gold quality
lower esophagus mucosa	UBERON:0035834	94.79	gold quality
skin of abdomen	UBERON:0001416	94.72	gold quality
right lobe of liver	UBERON:0001114	94.69	gold quality
adenohypophysis	UBERON:0002196	94.52	gold quality
right lung	UBERON:0002167	94.47	gold quality
mucosa of transverse colon	UBERON:0004991	94.41	gold quality
tibial nerve	UBERON:0001323	94.39	gold quality
mucosa of stomach	UBERON:0001199	94.31	gold quality
rectum	UBERON:0001052	94.04	gold quality
left lobe of thyroid gland	UBERON:0001120	93.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.81	gold quality
sural nerve	UBERON:0015488	93.73	gold quality
minor salivary gland	UBERON:0001830	93.72	gold quality
metanephros cortex	UBERON:0010533	93.71	gold quality
transverse colon	UBERON:0001157	93.68	gold quality
left ovary	UBERON:0002119	93.62	gold quality
cerebellar hemisphere	UBERON:0002245	93.52	gold quality
right lobe of thyroid gland	UBERON:0001119	93.49	gold quality
right ovary	UBERON:0002118	93.31	gold quality
cerebellar cortex	UBERON:0002129	93.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.19	gold quality
right uterine tube	UBERON:0001302	93.08	gold quality
right adrenal gland cortex	UBERON:0035827	93.03	gold quality
leukocyte	CL:0000738	92.80	gold quality
monocyte	CL:0000576	92.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPG, E2F1, YY1

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 40 (dosage sensitivity unlikely). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• results show that XPG endonuclease has distinct requirements for binding and cleaving DNA substrates (PMID:12644470)
• Results suggest that the Cockayne syndrome phenotype results from C-terminal truncations in the XPG (xeroderma pigmentosum) gene in mice and humans. (PMID:15082767)
• XPG expression in solid tumors may be a useful marker to predict their sensitivity to irofulven. (PMID:15328203)
• A short region of XPGC has been defined as necessary for TFIIH interaction and stable recruitment to sites of UV damage. (PMID:15572672)
• the N-terminal portion of the spacer region is particularly important for nucleotide excision repair progression by mediating the XPG-TFIIH interaction and XPG substrate specificity (PMID:15590680)
• XPG suppresses UV-induced apoptosis via its endonuclease function. (PMID:16167068)
• The XPG binds transcription-sized DNA bubbles through two domains not required for incision and functionally interacts with Cockayne Syndrome Group B on these bubbles to stimulate its ATPase activity. (PMID:16246722)
• potential implication of the XPG Asp1104His polymorphism in the occurrence of chromosomal translocations associated with specific subtypes of sarcomas (PMID:16646069)
• XPG forms a stable complex with TFIIH, which is active in transcription and nucleotide excision repair (PMID:17466625)
• SNPs associated with prognosis of lung cancer was mapped to ERCC5. (PMID:17855454)
• CEBPG regulates ERCC5 expression and this regulation is modified by E2F1/YY1 interactions. (PMID:17893230)
• molecular basis of disease caused by TFIIH and XPG mutations [review] (PMID:18077223)
• During nucleotide excision repair of DNA, the recruitment of Pol delta is associated with release of XPG and replication protein A (RPA). (PMID:18079701)
• patients treated with first-line oxaliplatin/fluoropyrimidine harboring both XPG C/C and XPA A/G or A/A profiles have a longer survival and TTP. (PMID:18204222)
• These findings offer evidence of the association between polymorphisms [ XPG Asp1104Asp (GG) and XPD Asn312Asn (AA)] and decreased risk for cervical carcinoma or cervical squamous cell carcinoma. (PMID:19096231)
• the polymorphic status of XPG His46His was associated with susceptibility of chemotherapy in advanced non-small cell lung carcinoma (PMID:19157633)
• the combination of high BRCA1 and low XPG expression increases the risk of shorter survival in early non-small-cell lung cancer (PMID:19289372)
• the ERCC5 mutation may contribute to development of gastric and colorectal carcinomas with MSI (PMID:19404856)
• Results showed that polymorphism in XPG His46His was associated with a decreased treatment response, but was not statistically significant. (PMID:19430706)
• Genetic polymorphisms in ERCC5 is associated with Laryngeal cancer risk associated with smoking and alcohol consumption. (PMID:19444904)
• PTGS2 and ERCC5 were associated with stomach cancer risk in a Chinese population. (PMID:19661089)
• There was significant difference in the frequency of the His/His variant genotype between cases and controls indicating a probable role of XPG in host viral interactions. (PMID:19693700)
• BRG1 stimulates the recruitment of XPG and PCNA to successfully culminate the nucleotide excision repair. (PMID:19740755)
• Polymorphisms in the ERCC5 gene is associated with with breast cancer and this association was more pronounced in women with lengthy estrogen exposure. (PMID:20183911)
• rs751402 A allele and rs2296147 T allele are associated with higher Allele-specific expression of ERCC5 T allele transcript at rs1047768 in normal human bronchial epithelial cells. (PMID:20233728)
• XPC and XPG polymorphisms do not independently affect the susceptibility to hepatocellular carcinoma, but the joint effect of C allele of XPC Lys939Gln and female sex may modify the risk. (PMID:20460046)
• XPG gene expression can be influenced by an epigenetic mechanism. Restoration of NER activity through XPG gene transfer or treatment with demethylating agents restored sensitivity to nemorubicin. (PMID:20868484)
• ERCC5 codon 1104 and ERCC2 codon 751 polymorphisms are independent prognostic factors in patients with cutaneous melanoma. (PMID:21390047)
• This meta-analysis suggests that XPG Asp1104His polymorphism is not associated with increased breast cancer risk. (PMID:21424776)
• The XPC, ERCC2 and ERCC5 variants don’t affect the tumors stage and grade. (PMID:21426550)
• novel function for XPG in S phase that is, at least in part, performed coordinately with WRN, and which may contribute to the severity of the phenotypes that occur upon loss of XPG. (PMID:21558802)
• Statistically significant increased risk of prostate cancer was observed on individuals that possess the His/His genotype of Asp 1104His of XPG. (PMID:21670956)
• These findings suggest that genetic variation in ERCC5 may not affect the risk of SCCHN, although rs4150351 C variant genotypes were associated with an increased expression of ERCC5 mRNA and nonsignificantly decreased risk of SCCHN (PMID:22108238)
• XPG Asp1104His polymorphism might contribute to the identification of patients with increased risk for colorectal carcinoma (PMID:22213216)
• study provided statistical evidence that the XPG rs873601 SNP, which has an effect on the gene expression in a recessive manner, was associated with risk for gastric cancer among an Eastern Chinese population. (PMID:22371296)
• Single nucleotide polymorphisms (SNPs) of OGG1, XRCC1, ERCC5, and XRCC4 were significantly associated with the overall survival in patients with hepatitis B virus-associated hepatocellular carcinoma. (PMID:22659345)
• XPG endonuclease promotes DNA breaks and DNA demethylation at promoters allowing the recruitment of CTCF and gene looping, which is further stabilized by XPF. (PMID:22771116)
• Down-regulating XPG in epithelial ovarian cancer cells resulted in reduced cell growth and increased susceptibility to cisplatin. (PMID:22781116)
• it is unlikely that the ERCC5 Asp1104His polymorphism may contribute to individual susceptibility to cancer risk (PMID:22815677)
• These findings suggested that ERCC5 polymorphisms may contribute to risk of ESCC in Eastern Chinese populations (PMID:22848513)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bivm	ENSDARG00000061409
mus_musculus	Ercc5	ENSMUSG00000026048
mus_musculus	Bivm	ENSMUSG00000041684
rattus_norvegicus	Ercc5	ENSRNOG00000022812
rattus_norvegicus	Bivm	ENSRNOG00000022894

Paralogs (1): BIVM (ENSG00000134897)

Protein

Protein identifiers

DNA excision repair protein ERCC-5 — P28715 (reviewed: P28715)

Alternative names: DNA repair protein complementing XP-G cells, Xeroderma pigmentosum group G-complementing protein

All UniProt accessions (5): A0A090HNM7, A0A494C0S2, P28715, A0A494C113, F2Z2A1

UniProt curated annotations — full annotation on UniProt →

Function. Single-stranded structure-specific DNA endonuclease involved in DNA excision repair. Makes the 3’incision in DNA nucleotide excision repair (NER). Binds and bends DNA repair bubble substrate and breaks base stacking at the single-strand/double-strand DNA junction of the DNA bubble. Plays a role in base excision repair (BER) by promoting the binding of DNA glycosylase NTHL1 to its substrate and increasing NTHL1 catalytic activity that removes oxidized pyrimidines from DNA. Involved in transcription-coupled nucleotide excision repair (TCR) which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Functions during the initial step of TCR in cooperation with ERCC6/CSB to recognized stalled RNA polymerase II. Also, stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity. Required for DNA replication fork maintenance and preservation of genomic stability. Involved in homologous recombination repair (HRR) induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 to the damaged DNA site. In TFIIH stimulates the 5’-3’ helicase activity of XPD/ERCC2 and the DNA translocase activity of XPB/ERCC3. During HRR, binds to the replication fork with high specificity and stabilizes it. Also, acts upstream of HRR, to promote the release of BRCA1 from DNA.

Subunit / interactions. Monomer. Homodimer. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51. Within the complex, interacts with BRCA2 and PALB2. Interacts with RNA polymerase II. Interacts (via C-terminus) with ERCC6/CSB; the interaction stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity. May form a complex composed of RNA polymerase II, ERCC6/CSB and ERCC5/XPG which associates with the DNA repair bubble during transcription-coupled nucleotide excision repair. Interacts with BRCA1; the interaction promotes the release of BRCA1 from DNA. Interacts with PCNA. Interacts with NTHL1; the interaction stimulates NTHL1 activity and NTHL1 binding to its DNA substrate.

Subcellular location. Nucleus. Chromosome.

Disease relevance. Xeroderma pigmentosum complementation group G (XP-G) [MIM:278780] 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. Some XP-G patients present features of Cockayne syndrome, cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex. The disease is caused by variants affecting the gene represented in this entry. Cerebro-oculo-facio-skeletal syndrome 3 (COFS3) [MIM:616570] A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.

Domain organisation. Both nuclear localization signals 1 and 2 act as a monopartite signal which binds to the high affinity site on KPNA2/importin-alpha. Both the spacer region (also known as the recognition (R) domain) and C-terminal domain are required for stable binding to the DNA repair bubble. However, both domains are dispensable for incision of DNA bubble structures.

Induction. Induced by replication stress caused by DNA double-strand breaks (DBS).

Miscellaneous. Includes a cryptic exon found in intron 6.

Similarity. Belongs to the XPG/RAD2 endonuclease family. XPG subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P28715-1	1	yes
P28715-2	2
P28715-3	3

RefSeq proteins (1): NP_000114* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001044	XPG/Rad2_eukaryotes	Family
IPR006084	XPG/Rad2	Family
IPR006085	XPG_DNA_repair_N	Domain
IPR006086	XPG-I_dom	Domain
IPR008918	HhH2	Conserved_site
IPR019974	XPG_CS	Conserved_site
IPR029060	PIN-like_dom_sf	Homologous_superfamily
IPR036279	5-3_exonuclease_C_sf	Homologous_superfamily

Pfam: PF00752, PF00867

UniProt features (102 total): sequence variant 25, helix 17, region of interest 16, strand 10, sequence conflict 8, binding site 7, compositionally biased region 4, mutagenesis site 4, modified residue 3, splice variant 3, short sequence motif 2, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6VBH	X-RAY DIFFRACTION	2
5EKF	X-RAY DIFFRACTION	2
6TUS	X-RAY DIFFRACTION	2.5
5EKG	X-RAY DIFFRACTION	2.8
6TUR	X-RAY DIFFRACTION	2.9
6TUX	X-RAY DIFFRACTION	3.1
9PD3	ELECTRON MICROSCOPY	3.3
9PD4	ELECTRON MICROSCOPY	3.4
6TUW	X-RAY DIFFRACTION	3.5
9PD5	ELECTRON MICROSCOPY	5.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28715-F1	57.91	0.13

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (7): 30; 77; 789; 791; 810; 812; 861

Post-translational modifications (3): 8, 384, 705

Mutagenesis-validated functional residues (4):

Position	Phenotype
67–68	slight reduction in endonuclease activity. increased affinity for bubble dna.
955–956	reduced protein stability, two-fold decrease in 15-nt bubble dna incision activity and smaller decrease in y dna incisio
978	reduced protein stability, two-fold decrease in 15-nt bubble dna incision activity and smaller decrease in y dna incisio
981	reduced protein stability, two-fold decrease in 15-nt bubble dna incision activity and smaller decrease in y dna incisio

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
R-HSA-6782135	Dual incision in TC-NER

MSigDB gene sets: 429 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_RESPONSE_TO_UV_C, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_TRANSCRIPTION_COUPLED_NUCLEOTIDE_EXCISION_REPAIR, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, KAUFFMANN_DNA_REPAIR_GENES, GOCC_NUCLEAR_REPLICATION_FORK, GOBP_NUCLEOTIDE_EXCISION_REPAIR, MUELLER_PLURINET, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOBP_RESPONSE_TO_UV, GOBP_DNA_DAMAGE_RESPONSE, GOBP_RESPONSE_TO_RADIATION

GO Biological Process (10): double-strand break repair via homologous recombination (GO:0000724), transcription-coupled nucleotide-excision repair (GO:0006283), base-excision repair, AP site formation (GO:0006285), nucleotide-excision repair (GO:0006289), response to UV (GO:0009411), response to UV-C (GO:0010225), negative regulation of apoptotic process (GO:0043066), DNA repair (GO:0006281), DNA recombination (GO:0006310), DNA damage response (GO:0006974)

GO Molecular Function (17): bubble DNA binding (GO:0000405), RNA polymerase II complex binding (GO:0000993), damaged DNA binding (GO:0003684), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), endonuclease activity (GO:0004519), DNA endonuclease activity (GO:0004520), enzyme activator activity (GO:0008047), hydrolase activity, acting on ester bonds (GO:0016788), protein homodimerization activity (GO:0042803), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872), DNA binding (GO:0003677), catalytic activity (GO:0003824), nuclease activity (GO:0004518), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleotide-excision repair complex (GO:0000109), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), protein-containing complex (GO:0032991), DNA replication factor A complex (GO:0005662)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	2
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	3
DNA binding	3
catalytic activity	2
binding	2
nuclear protein-containing complex	2
recombinational repair	1
double-strand break repair	1
nucleotide-excision repair	1
base-excision repair	1
DNA repair	1
response to light stimulus	1
response to UV	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
DNA damage response	1
cellular response to stress	1
DNA secondary structure binding	1
RNA polymerase core enzyme binding	1
nuclease activity	1
endonuclease activity	1
DNA nuclease activity	1
enzyme regulator activity	1
molecular function activator activity	1
hydrolase activity	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
nucleic acid binding	1
molecular_function	1
catalytic activity, acting on a nucleic acid	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membraneless organelle	1
cellular_component	1
nuclear replisome	1

Protein interactions and networks

STRING

2586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERCC5	ERCC2	P18074	974
ERCC5	ERCC1	P07992	973
ERCC5	ERCC4	Q92889	973
ERCC5	ERCC6	Q03468	966
ERCC5	ERCC3	P19447	962
ERCC5	XPA	P23025	959
ERCC5	ERCC8	Q13216	908
ERCC5	RAD23B	P54727	814
ERCC5	XRCC1	P18887	808
ERCC5	BRCA2	P51587	751
ERCC5	BRCA1	P38398	740
ERCC5	ATM	Q13315	706
ERCC5	CCNH	P51946	687
ERCC5	FAM120B	Q96EK7	673
ERCC5	FAM120C	Q9NX05	668

IntAct

73 interactions, top by confidence:

A	B	Type	Score
CCNH	ERCC2	psi-mi:“MI:0914”(association)	0.750
ERCC5	BRAF	psi-mi:“MI:0915”(physical association)	0.550
ERCC5	BRAF	psi-mi:“MI:2364”(proximity)	0.550
BRAF	ERCC5	psi-mi:“MI:0915”(physical association)	0.550
GADD45A	ERCC5	psi-mi:“MI:0407”(direct interaction)	0.540
GADD45A	ERCC5	psi-mi:“MI:0915”(physical association)	0.540
ERCC3	BCR	psi-mi:“MI:0914”(association)	0.530
HSPB1	ERCC5	psi-mi:“MI:0915”(physical association)	0.370
Kifbp	TPM1	psi-mi:“MI:0914”(association)	0.350
Tpx2		psi-mi:“MI:0914”(association)	0.350
Ndc80	SMCHD1	psi-mi:“MI:0914”(association)	0.350
GTF2H5	GTF2H3	psi-mi:“MI:0914”(association)	0.350
TGS1	SEPTIN10	psi-mi:“MI:0914”(association)	0.350
LRPPRC	HSPA8	psi-mi:“MI:0914”(association)	0.350
CDK7	SEC16A	psi-mi:“MI:0914”(association)	0.350
rep	VWA8	psi-mi:“MI:0914”(association)	0.350
CDK7	ACACB	psi-mi:“MI:0914”(association)	0.350
CDC7	ERCC1	psi-mi:“MI:0914”(association)	0.350
CDK7	ERCC1	psi-mi:“MI:0914”(association)	0.350
ERCC3	DNAJA2	psi-mi:“MI:0914”(association)	0.350
ERCC5	CSNK2A2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
MNAT1	MPO	psi-mi:“MI:0914”(association)	0.350
CDK7	A2M	psi-mi:“MI:0914”(association)	0.350
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350
CDK7	TAF4	psi-mi:“MI:2364”(proximity)	0.270
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (90): ERCC5 (Affinity Capture-MS), DTL (Co-localization), ERCC5 (Two-hybrid), ERCC5 (Affinity Capture-MS), ERCC5 (Affinity Capture-MS), ERCC5 (Affinity Capture-MS), ERCC5 (Affinity Capture-MS), ERCC5 (Affinity Capture-MS), ERCC5 (Affinity Capture-MS), BRCA2 (Affinity Capture-Western), PALB2 (Affinity Capture-Western), RAD51 (Affinity Capture-Western), ERCC5 (Affinity Capture-Western), ERCC5 (Affinity Capture-Western), ERCC5 (Affinity Capture-Western)

ESM2 similar proteins: A0A3Q2TTB3, A0JMR6, A4IIA7, F4JNY0, F6RRD7, I3XHK1, O60934, O88622, P14629, P28715, P79457, Q08DZ8, Q12789, Q17RS7, Q1LWH4, Q28I29, Q32PL8, Q3B7T1, Q4R7Q1, Q5FWP4, Q5M954, Q5QJC2, Q5RA37, Q5RCV3, Q5ZIN2, Q66J91, Q6GQV7, Q6NVF4, Q6P1E7, Q6P1H6, Q6P256, Q6P7W5, Q76CY8, Q7TP65, Q86W56, Q8BMI4, Q8C0W1, Q8C5W4, Q8GT06, Q8IXW5

Diamond homologs: A0B9M7, A0RU95, A1CJ75, A1D8A4, A2SQC6, A3FPN7, A3MY15, A4HFE4, A4I2L4, A5UL52, A7AX58, A8M9L3, A8NQC2, A9A4B0, B0E412, B0XZ33, B2VTT3, B3MDA3, B3NP61, B4GIM3, B4HTA1, B4LM90, B4MR84, B4P5U9, B4QIG6, B5DUR8, B6AFP1, B6QT52, B7G7Y7, B8AMS4, B8GIA0, B8MNF2, B8NV37, C5FZT5, C5GPA7, C5JVG7, C7Z125, C9ZKW4, D3BN56, D3TQJ5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ERCC5	“up-regulates quantity by stabilization”	ERCC2	binding
RAD23B	“up-regulates activity”	ERCC5	binding
ERCC5	up-regulates	Nucleotide-excision_repair

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 78 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	7	48.4×	6e-09
RNA Pol II CTD phosphorylation and interaction with CE	7	48.4×	6e-09
mRNA Capping	7	45.2×	6e-09
Formation of the Early Elongation Complex	7	39.9×	1e-08
Formation of the HIV-1 Early Elongation Complex	7	39.9×	1e-08
RNA Polymerase I Transcription Termination	7	38.7×	1e-08
Global Genome Nucleotide Excision Repair (GG-NER)	5	38.7×	3e-06
Formation of Incision Complex in GG-NER	8	34.4×	6e-09

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	7	38.9×	2e-07
transcription initiation at RNA polymerase II promoter	7	38.0×	2e-07
response to oxidative stress	5	9.5×	9e-03
mRNA splicing, via spliceosome	7	9.3×	2e-03
DNA repair	8	7.4×	2e-03
transcription by RNA polymerase II	7	7.2×	7e-03
protein stabilization	7	6.8×	8e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

20 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	10
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1710518	GRCh37/hg19 13q11-34(chr13:19253848-115108937)x3	Pathogenic
977918	NM_000123.3:c.89-?_528+?del	Likely pathogenic

SpliceAI

2707 predictions. Top by Δscore:

Variant	Effect	Δscore
13:102852210:C:A	acceptor_gain	1.0000
13:102856050:A:AG	acceptor_gain	1.0000
13:102856051:G:GA	acceptor_gain	1.0000
13:102858269:TTACA:T	acceptor_loss	1.0000
13:102858270:TACA:T	acceptor_loss	1.0000
13:102858272:CA:C	acceptor_loss	1.0000
13:102858273:A:AG	acceptor_gain	1.0000
13:102858273:A:C	acceptor_loss	1.0000
13:102858274:G:GC	acceptor_gain	1.0000
13:102858274:G:GG	acceptor_gain	1.0000
13:102858274:GGA:G	acceptor_gain	1.0000
13:102858274:GGAA:G	acceptor_gain	1.0000
13:102858414:CAGAG:C	donor_loss	1.0000
13:102858416:G:GT	donor_gain	1.0000
13:102858416:GAG:G	donor_gain	1.0000
13:102858417:AG:A	donor_loss	1.0000
13:102858417:AGGTG:A	donor_loss	1.0000
13:102858418:GGT:G	donor_loss	1.0000
13:102858419:GT:G	donor_loss	1.0000
13:102858420:T:G	donor_loss	1.0000
13:102858434:G:GG	donor_gain	1.0000
13:102861498:T:A	acceptor_gain	1.0000
13:102861503:TTAG:T	acceptor_loss	1.0000
13:102861504:TA:T	acceptor_loss	1.0000
13:102861504:TAG:T	acceptor_loss	1.0000
13:102861505:A:AG	acceptor_gain	1.0000
13:102861505:A:AT	acceptor_loss	1.0000
13:102861505:AG:A	acceptor_gain	1.0000
13:102861506:G:GA	acceptor_gain	1.0000
13:102861506:G:GT	acceptor_gain	1.0000

AlphaMissense

7825 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:102866636:T:C	L775P	0.999
13:102866752:T:A	W814R	0.999
13:102866752:T:C	W814R	0.999
13:102866758:T:C	F816L	0.999
13:102866760:T:A	F816L	0.999
13:102866760:T:G	F816L	0.999
13:102868157:A:C	S860R	0.999
13:102868159:T:A	S860R	0.999
13:102868159:T:G	S860R	0.999
13:102846285:T:A	W7R	0.998
13:102846285:T:C	W7R	0.998
13:102846349:C:A	A28D	0.998
13:102852244:C:A	P72H	0.998
13:102852253:T:A	V75E	0.998
13:102852281:G:C	K84N	0.998
13:102852281:G:T	K84N	0.998
13:102866376:A:C	S772R	0.998
13:102866378:C:A	S772R	0.998
13:102866378:C:G	S772R	0.998
13:102866702:T:C	L797P	0.998
13:102866732:T:A	I807N	0.998
13:102866743:A:C	S811R	0.998
13:102866745:T:A	S811R	0.998
13:102866745:T:G	S811R	0.998
13:102866774:T:A	V821D	0.998
13:102872367:T:A	W950R	0.998
13:102872367:T:C	W950R	0.998
13:102852123:A:C	S32R	0.997
13:102852125:C:A	S32R	0.997
13:102852125:C:G	S32R	0.997

dbSNP variants (sampled 300 via entrez): RS1000051436 (13:102864123 CAACCA>C), RS1000180881 (13:102845059 C>T), RS1000230732 (13:102851544 C>T), RS1000452046 (13:102851145 C>G), RS1000699796 (13:102845367 G>A), RS1000717439 (13:102847291 G>A), RS1000797132 (13:102857972 A>G), RS1001157741 (13:102869692 A>G), RS1001166656 (13:102872813 C>T), RS1001234786 (13:102850050 T>A), RS1001260938 (13:102871613 A>G), RS1001401405 (13:102856624 T>G), RS1001441983 (13:102869468 C>T), RS1001455939 (13:102849832 A>G), RS1001548523 (13:102874431 A>G)

Disease associations

OMIM: gene MIM:133530 | disease phenotypes: MIM:616570

GenCC curated gene-disease

Disease	Classification	Inheritance
xeroderma pigmentosum group G	Definitive	Autosomal recessive
cerebrooculofacioskeletal syndrome 3	Strong	Autosomal recessive
COFS syndrome	Supportive	Autosomal recessive
xeroderma pigmentosum-Cockayne syndrome complex	Supportive	Autosomal recessive
xeroderma pigmentosum	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
xeroderma pigmentosum group G	Definitive	AR

Mondo (6): hereditary neoplastic syndrome (MONDO:0015356), cerebrooculofacioskeletal syndrome 3 (MONDO:0014696), xeroderma pigmentosum group G (MONDO:0010216), COFS syndrome (MONDO:0008926), xeroderma pigmentosum-Cockayne syndrome complex (MONDO:0016354), xeroderma pigmentosum (MONDO:0019600)

Orphanet (1): Inherited cancer-predisposing syndrome (Orphanet:140162)

HPO phenotypes

118 total (30 of 118 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000135	Hypogonadism
HP:0000164	Abnormality of the dentition
HP:0000175	Cleft palate
HP:0000232	Everted lower lip vermilion
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000491	Keratitis
HP:0000498	Blepharitis
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000524	Conjunctival telangiectasia
HP:0000568	Microphthalmia
HP:0000613	Photophobia
HP:0000621	Entropion
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000651	Diplopia
HP:0000656	Ectropion
HP:0000958	Dry skin
HP:0000962	Hyperkeratosis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST009391_484	Metabolite levels	7.000000e-06
GCST009391_684	Metabolite levels	2.000000e-06
GCST009676_11	Urinary calcium excretion	4.000000e-06
GCST010241_215	Apolipoprotein A1 levels	1.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010389	phosphatidylcholine 40:6 measurement
EFO:0008529	kynurenine measurement
EFO:0004838	calcium measurement
EFO:0004614	apolipoprotein A 1 measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D014983	Xeroderma Pigmentosum	C04.834.867; C16.131.831.936; C16.320.850.970; C17.800.600.925; C17.800.621.936; C17.800.804.936; C17.800.827.970; C18.452.284.975
C565035	Cerebrooculofacioskeletal Syndrome 3 (supp.)
C562593	Xeroderma Pigmentosum, Complementation Group G (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4736 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17655	Efficacy	3	platinum	Ovarian Neoplasms

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17655	ERCC5	3	3.75	1	platinum
rs1047768	ERCC5		0.00	0
rs751402	ERCC5		0.00	0
rs2094258	ERCC5		0.00	0
rs2296147	ERCC5		0.00	0
rs873601	ERCC5		0.00	0

ChEMBL bioactivities

104 potent at pChembl≥5 of 122 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.64	IC50	0.023	nM	CHEMBL361962
10.55	IC50	0.028	nM	CHEMBL361011
10.21	IC50	0.062	nM	CHEMBL359533
10.21	IC50	0.061	nM	CHEMBL183133
10.00	IC50	0.101	nM	CHEMBL361350
9.89	IC50	0.128	nM	CHEMBL182381
9.87	IC50	0.136	nM	CHEMBL364591
9.84	IC50	0.145	nM	CHEMBL183792
9.80	IC50	0.16	nM	CHEMBL183852
9.80	IC50	0.157	nM	CHEMBL362842
9.73	IC50	0.185	nM	CHEMBL182687
9.70	IC50	0.202	nM	CHEMBL183062
9.67	IC50	0.215	nM	CHEMBL185325
9.65	IC50	0.226	nM	CHEMBL181962
9.64	IC50	0.23	nM	CHEMBL359747
9.59	IC50	0.258	nM	CHEMBL360615
9.59	IC50	0.257	nM	CHEMBL181766
9.56	IC50	0.276	nM	CHEMBL183539
9.54	IC50	0.292	nM	CHEMBL361546
9.48	IC50	0.327	nM	CHEMBL180566
9.26	IC50	0.55	nM	CHEMBL185322
9.26	IC50	0.556	nM	CHEMBL182077
8.70	IC50	2	nM	CHEMBL182974
8.52	IC50	3.04	nM	CHEMBL182519
8.40	IC50	3.99	nM	CHEMBL181709
8.34	IC50	4.62	nM	CHEMBL181637
8.07	IC50	8.45	nM	CHEMBL362205
7.52	IC50	30.2	nM	CHEMBL181907
6.51	IC50	310	nM	CHEMBL182756
6.30	IC50	500	nM	CHEMBL5766648
6.30	IC50	500	nM	CHEMBL5766532
6.30	IC50	500	nM	CHEMBL5791956
6.30	IC50	500	nM	CHEMBL5984295
6.24	IC50	570	nM	CHEMBL182748
6.05	IC50	900	nM	CHEMBL361960
6.01	IC50	980	nM	CHEMBL183027
5.95	IC50	1130	nM	CHEMBL188067
5.85	IC50	1400	nM	CHEMBL361460
5.82	IC50	1500	nM	CHEMBL5925060
5.82	IC50	1500	nM	CHEMBL5999214
5.82	IC50	1500	nM	CHEMBL5973687
5.82	IC50	1500	nM	CHEMBL5966172
5.82	IC50	1500	nM	CHEMBL5963461
5.82	IC50	1500	nM	CHEMBL5927933
5.82	IC50	1500	nM	CHEMBL5944915
5.82	IC50	1500	nM	CHEMBL5791956
5.82	IC50	1500	nM	CHEMBL6056114
5.82	IC50	1500	nM	CHEMBL5925873
5.82	IC50	1500	nM	CHEMBL5761467
5.82	IC50	1500	nM	CHEMBL5849549

PubChem BioAssay actives

47 with measured affinity, of 64 total; 47 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-hydroxy-7-phenyl-1H-thieno[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	<0.0001	uM
7-(benzenesulfonyl)-3-hydroxy-1H-thieno[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	<0.0001	uM
3-hydroxy-1H-[1]benzothiolo[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0001	uM
3-hydroxy-7-(4-phenylphenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0001	uM
7-benzyl-3-hydroxy-1H-furo[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0001	uM
3-hydroxy-1H-thieno[2,3-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0001	uM
3-hydroxy-5-methyl-1H-thieno[2,3-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0001	uM
3-hydroxy-7-(4-methylphenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0001	uM
3-hydroxy-5,6,7,8-tetrahydro-1H-[1]benzothiolo[2,3-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0002	uM
3-hydroxy-6-phenyl-1H-thieno[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0002	uM
4-[3-[(3-hydroxy-2,4-dioxothieno[3,2-d]pyrimidin-1-yl)methyl]phenyl]benzamide	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0002	uM
3-hydroxy-7-(3-methoxyphenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0002	uM
3-hydroxy-1H-quinazoline-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0002	uM
5-chloro-3-hydroxy-1H-quinazoline-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0002	uM
3-hydroxy-7-(4-methoxyphenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0002	uM
3-hydroxy-1H-[1]benzofuro[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0003	uM
6-tert-butyl-3-hydroxy-1H-thieno[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0003	uM
1-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-3-hydroxythieno[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0003	uM
3-hydroxy-7-phenyl-1H-furo[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0003	uM
7-(4-bromophenyl)-3-hydroxy-1H-furo[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0003	uM
1-[(3-bromophenyl)methyl]-3-hydroxythieno[3,2-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0006	uM
N-[3-[3-[(3-hydroxy-2,4-dioxothieno[3,2-d]pyrimidin-1-yl)methyl]phenyl]phenyl]acetamide	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0006	uM
1-benzyl-3-hydroxythieno[2,3-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0020	uM
3-hydroxy-1-[(7-methoxy-1,3-benzodioxol-5-yl)methyl]-5-methylthieno[2,3-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0030	uM
1-benzyl-3-hydroxy-5-methylthieno[2,3-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0040	uM
3-hydroxy-1,5-dimethylthieno[2,3-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0046	uM
3-hydroxy-1-(4-methoxyphenyl)-5-methylthieno[2,3-d]pyrimidine-2,4-dione	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0084	uM
4-[3-[(3-hydroxy-7-methyl-2,4-dioxothieno[3,2-d]pyrimidin-1-yl)methyl]phenyl]benzamide	241035: Inhibitory concentration against the xeroderma pigmentosum G	ic50	0.0302	uM
2,4-dioxo-4-[5-[4-(trifluoromethoxy)phenyl]thiophen-2-yl]butanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	0.3100	uM
4-[2-chloro-5-(4-methoxyphenyl)phenyl]-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	0.5700	uM
4-[5-(4-chloro-3-fluorophenyl)thiophen-2-yl]-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	0.9000	uM
4-[5-(4-chlorophenyl)furan-2-yl]-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	0.9800	uM
4-(2-chloro-5-phenylphenyl)-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	1.1300	uM
4-[5-(4-ethoxyphenyl)furan-2-yl]-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	1.4000	uM
4-[3-(4-methoxyphenyl)phenyl]-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	1.5900	uM
2,4-dioxo-4-(4-phenylphenyl)butanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	1.6000	uM
4-[2-chloro-4-(4-chlorophenyl)phenyl]-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	1.7700	uM
2,4-dioxo-4-(5-phenylfuran-2-yl)butanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	1.8100	uM
4-[5-(2-chlorophenyl)furan-2-yl]-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	1.8500	uM
2,4-dioxo-4-(5-phenylthiophen-2-yl)butanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	1.8500	uM
2,4-dioxo-4-(4-phenoxyphenyl)butanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	1.8700	uM
2,4-dioxo-4-[5-(trifluoromethyl)thiophen-2-yl]butanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	2.3200	uM
4-[5-(4-tert-butylphenyl)furan-2-yl]-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	3.1300	uM
2,4-dioxo-4-(3-phenylphenyl)butanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	3.2400	uM
2,4-dioxo-4-(3-phenoxyphenyl)butanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	5.4400	uM
4-(2,5-dichlorophenyl)-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	7.0000	uM
4-(2,4-dichlorophenyl)-2,4-dioxobutanoic acid	240742: Concentration required for 50% inhibition of Xeroderma pigmentosum G	ic50	9.8500	uM

CTD chemical–gene interactions

57 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases mutagenesis	4
Cisplatin	increases reaction, decreases reaction, decreases response to substance, increases expression, increases phosphorylation	3
Valproic Acid	affects cotreatment, increases expression, affects expression	3
bisphenol A	increases expression, affects response to substance	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance	2
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	2
Pesticides	increases response to substance, decreases expression	2
Cadmium Chloride	decreases expression, affects cotreatment	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
lead acetate	affects cotreatment, decreases expression	1
titanium dioxide	increases expression	1
IMOL S-140	decreases expression	1
sulforaphane	increases expression	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
4-hydroxy-2-nonenal	decreases expression	1
coumarin	decreases phosphorylation	1
cisplatin-DNA adduct	decreases abundance	1
phenethyl isothiocyanate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
benzo(a)pyrene diolepoxide I	increases expression	1
seocalcitol	decreases expression	1
Y 27632	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one	decreases reaction, decreases response to substance, increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5739076	Binding	Enzymatic IC50 Assays: FEN1, EXO1 or XPG enzyme was incubated with compound or vehicle (DMSO) and the FAM-labeled DNA oligomer substrate in a microtiter plate. The stop buffer contains EDTA to stop the enzymatic reaction. The plate is read	Dihydrothieno[3,2-b]pyridine compounds

Cellosaurus cell lines

45 cell lines: 25 finite cell line, 13 transformed cell line, 6 cancer cell line, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0N73	AG08806	Transformed cell line	Male
CVCL_0N74	AG08807	Finite cell line	Male
CVCL_1F56	XPH103BE LCL	Transformed cell line	Female
CVCL_1F62	XPH104BE LCL	Transformed cell line	Male
CVCL_2570	LB81	Transformed cell line	Female
CVCL_2572	XP125LO LCL	Transformed cell line	Female
CVCL_B8FJ	Abcam HCT 116 ERCC5 KO	Cancer cell line	Male
CVCL_B8VF	Abcam MCF-7 ERCC5 KO	Cancer cell line	Female
CVCL_B9HS	Abcam A-549 ERCC5 KO	Cancer cell line	Male
CVCL_E1WC	HAP1 ERCC5 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

39 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05159752	PHASE2	UNKNOWN	A Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Xeroderma Pigmentosum (XP)
NCT05370235	PHASE2	UNKNOWN	A Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Xeroderma Pigmentosum C and V
NCT04500548	PHASE1	WITHDRAWN	Testing the Combination of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) in Children, Adolescent, and Young Adult Patients With Relapsed/Refractory Cancers That Have an Increased Number of Genetic Changes, The 3CI Study
NCT00001813	Not specified	COMPLETED	Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy
NCT00046189	Not specified	COMPLETED	Cancer Risk in Carriers of the Gene for Xeroderma Pigmentosum
NCT00555633	Not specified	COMPLETED	Use of an SPF30 Sunscreen and an After-sun-lotion in Skin Cancer Risk Patients
NCT01123694	Not specified	UNKNOWN	Xeroderma Pigmentosum Patient Experiences
NCT03445052	Not specified	COMPLETED	XPAND Trial: Enhancing XP Photoprotection Activities - New Directions
NCT05484570	Not specified	RECRUITING	Natural History Study for DNA Repair Disorders
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT00001496	Not specified	COMPLETED	Establishment of Normal Breast Epithelial Cell Lines From Patients at High Risk for Breast Cancer
NCT00001898	Not specified	COMPLETED	Microarray Analysis for Human Genetic Disease
NCT00026884	Not specified	RECRUITING	Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease
NCT02289326	Not specified	COMPLETED	Biomarker Monitoring in TP53 Mutation Carriers
NCT02958462	Not specified	RECRUITING	Pre-myeloid Cancer and Bone Marrow Failure Clinic Study
NCT03160274	Not specified	RECRUITING	Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
NCT03426878	Not specified	COMPLETED	Cancer Health Assessments Reaching Many
NCT03857594	Not specified	ACTIVE_NOT_RECRUITING	Integrative Sequencing In Germline and Hereditary Tumours
NCT03973450	Not specified	UNKNOWN	Epidemiology of Pituitary Tumours: Prevalence of Associated Neoplasia
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04261972	Not specified	ACTIVE_NOT_RECRUITING	Cell-free DNA in Hereditary And High-Risk Malignancies 1
NCT04494945	Not specified	RECRUITING	Identifying and Caring for Individuals With Inherited Cancer Syndrome
NCT04541654	Not specified	RECRUITING	Li-Fraumeni & TP53 (LiFT UP): Understanding and Progress
NCT04763915	Not specified	ACTIVE_NOT_RECRUITING	Improving Care After Inherited Cancer Testing
NCT05562778	Not specified	RECRUITING	Chatbot to Maximize Hereditary Cancer Genetic Risk Assessment
NCT05664867	Not specified	RECRUITING	Implementation of Population Cancer Genetic Services in Federally Qualified Health Centers (FQHC)
NCT05721326	Not specified	COMPLETED	Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition
NCT06096688	Not specified	RECRUITING	Discovering New Targets for Colorectal and Endometrial Cancer Risk Reduction
NCT06654466	Not specified	RECRUITING	Closing the GAPS: Guideline Adherence, Prevention and Surveillance in Hereditary Cancer
NCT06708429	Not specified	RECRUITING	Lynch Syndrome X-Talk of Enteral Mucosa With Immune System
NCT06726642	Not specified	RECRUITING	CfDNA in Hereditary And High-risk Malignancies 2
NCT06914726	Not specified	ENROLLING_BY_INVITATION	Patient Centered Clinical Decision Support for Hereditary Cancer Syndromes
NCT06927947	Not specified	RECRUITING	Navigation Interventions to Improve Cascade Genetic Testing Among Relatives of Patients With Hereditary Cancer Syndromes
NCT06999954	Not specified	RECRUITING	Shwachman-Diamond Syndrome Global Patient Survey and Partnering Platform
NCT07052266	Not specified	RECRUITING	Trial of Combined Obstetric Carrier Screening and Hereditary Cancer Screening
NCT07195071	Not specified	RECRUITING	Feasibility Trial of Combination of Obstetrical Carrier Screening and Hereditary Cancer Screening
NCT07378423	Not specified	RECRUITING	Questionnaire on Congenital Cancer Signs Through Self-Assessment
NCT07381985	Not specified	ENROLLING_BY_INVITATION	Strategy for Management of Patients With Hereditary Cancer Syndromes (HCS) in a Rural Environment
NCT07542405	Not specified	NOT_YET_RECRUITING	A Web-Based Program (Kindred) to Improve the Understanding of Genetic Cancer Risk and Cancer Genetic Testing in African American Families