ERCC1

Summary

ERCC1 (ERCC excision repair 1, endonuclease non-catalytic subunit, HGNC:3433) is a protein-coding gene on chromosome 19q13.32, encoding DNA excision repair protein ERCC-1 (P07992). Non-catalytic component of a structure-specific DNA repair endonuclease responsible for the 5’-incision during DNA repair. In precision oncology, ERCC1 Expression confers sensitivity to Cisplatin in Bladder Carcinoma (CIViC Level B); 6 further curated variant–drug associations are listed below.

The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5’ incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand.

Source: NCBI Gene 2067 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebrooculofacioskeletal syndrome 4 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 288 total — 7 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 107
• Druggable target: yes
• Precision-oncology evidence (CIViC): 7 curated variant–drug associations
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001983

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3433
Approved symbol	ERCC1
Name	ERCC excision repair 1, endonuclease non-catalytic subunit
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	RAD10
Ensembl gene	ENSG00000012061
Ensembl biotype	protein_coding
OMIM	126380
Entrez	2067

Gene structure

Transcript identifiers

Ensembl transcripts: 72 — 66 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000013807, ENST00000300853, ENST00000340192, ENST00000423698, ENST00000587888, ENST00000588300, ENST00000588738, ENST00000589165, ENST00000589214, ENST00000589381, ENST00000590701, ENST00000591636, ENST00000592023, ENST00000592083, ENST00000592410, ENST00000592444, ENST00000592905, ENST00000710953, ENST00000899224, ENST00000899225, ENST00000899226, ENST00000899227, ENST00000899228, ENST00000899229, ENST00000899230, ENST00000899231, ENST00000899232, ENST00000899233, ENST00000899234, ENST00000899235, ENST00000899236, ENST00000899237, ENST00000899238, ENST00000899239, ENST00000899240, ENST00000899241, ENST00000899242, ENST00000917574, ENST00000917575, ENST00000917576, ENST00000917577, ENST00000917578, ENST00000917579, ENST00000969023, ENST00000969024, ENST00000969025, ENST00000969026, ENST00000969027, ENST00000969028, ENST00000969029, ENST00000969030, ENST00000969031, ENST00000969032, ENST00000969033, ENST00000969034, ENST00000969035, ENST00000969036, ENST00000969037, ENST00000969038, ENST00000969039, ENST00000969040, ENST00000969041, ENST00000969042, ENST00000969043, ENST00000969044, ENST00000969045, ENST00000969046, ENST00000969047, ENST00000969048, ENST00000969049, ENST00000969050, ENST00000969051

RefSeq mRNA: 15 — MANE Select: NM_001983 NM_001166049, NM_001369408, NM_001369409, NM_001369410, NM_001369411, NM_001369412, NM_001369413, NM_001369414, NM_001369415, NM_001369416, NM_001369417, NM_001369418, NM_001369419, NM_001983, NM_202001

CCDS: CCDS12662, CCDS12663, CCDS54279

Canonical transcript exons

ENST00000300853 — 10 exons

Exon	Start	End
ENSE00002906515	45423781	45423917
ENSE00003595521	45416821	45416897
ENSE00003613980	45419098	45419197
ENSE00003666935	45421178	45421393
ENSE00003693538	45423270	45423381
ENSE00003786484	45413963	45414034
ENSE00003787259	45414861	45414960
ENSE00003787919	45420324	45420427
ENSE00003788626	45413677	45413745
ENSE00003903321	45407334	45409725

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 86.3376 / max 499.6035, expressed in 1823 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181506	47.4592	1813
181504	22.0262	1738
181505	9.2326	1703
181502	1.9483	1126
181514	1.8525	767
181508	1.7219	755
181503	0.5775	307
181527	0.5449	315
181526	0.3732	204
181512	0.1536	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.49	gold quality
parotid gland	UBERON:0001831	97.21	gold quality
right atrium auricular region	UBERON:0006631	97.17	gold quality
heart left ventricle	UBERON:0002084	96.76	gold quality
cardiac ventricle	UBERON:0002082	96.66	gold quality
cardiac atrium	UBERON:0002081	96.35	gold quality
ganglionic eminence	UBERON:0004023	96.26	gold quality
heart	UBERON:0000948	96.09	gold quality
left ovary	UBERON:0002119	95.91	gold quality
ventricular zone	UBERON:0003053	95.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.80	gold quality
right ovary	UBERON:0002118	95.61	gold quality
stromal cell of endometrium	CL:0002255	95.47	gold quality
ascending aorta	UBERON:0001496	95.37	gold quality
adenohypophysis	UBERON:0002196	95.30	gold quality
thoracic aorta	UBERON:0001515	95.29	gold quality
heart right ventricle	UBERON:0002080	95.29	gold quality
right uterine tube	UBERON:0001302	95.27	gold quality
endocervix	UBERON:0000458	95.22	gold quality
saliva-secreting gland	UBERON:0001044	95.21	gold quality
body of uterus	UBERON:0009853	95.21	gold quality
ectocervix	UBERON:0012249	95.21	gold quality
gastrocnemius	UBERON:0001388	95.18	gold quality
skin of abdomen	UBERON:0001416	95.14	gold quality
skin of leg	UBERON:0001511	95.05	gold quality
left uterine tube	UBERON:0001303	94.97	gold quality
muscle of leg	UBERON:0001383	94.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.94	gold quality
minor salivary gland	UBERON:0001830	94.91	gold quality
pituitary gland	UBERON:0000007	94.75	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.14
E-MTAB-7303	no	604.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CREBBP, E2F1, FOS, GATA1, HMGA2, JUN, KAT5, MZF1, SNAI1

miRNA regulators (miRDB)

69 targeting ERCC1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Lactacystin enhances cisplatin sensitivity in resistant human ovarian cancer cell lines via inhibition of DNA repair and ERCC-1 expression. (PMID:11936875)
• Inter-individual variation, seasonal variation and close correlation of OGG1 and ERCC1 mRNA levels in full blood (PMID:12189194)
• Epidermal growth factor and ionizing radiation up-regulate the DNA repair genes XRCC1 and ERCC1 in DU145 and LNCaP prostate carcinoma through MAPK signaling. (PMID:12643788)
• The results show a significant association between BCC and the A-allele of a polymorphism in ERCCI exon4 (Odds ratio 12;95% Confidence Interval 1.17-124; p(chi2, two-side) = 0.019) and to a lesser extent with XPD exon6 (p = 0.06). (PMID:12645871)
• ERCC1 gene is a useful independent prognostic tumor marker in patients with early stage non-small-cell lung cancer. (PMID:12800797)
• Data reveal an unanticipated involvement of the ERCC1/XPF NER endonuclease in the regulation of telomere integrity. (PMID:14690602)
• the ternary complex of hRad52 and XPF/ERCC1 is the active species that processes recombination intermediates generated during the repair of DNA double strand breaks and in homology-dependent gene targeting events. (PMID:14734547)
• XPA, ERCC1 and XPF DNA repair protein expression is reduced in testis neoplasms (PMID:15095299)
• ERCC1 has a role as a nucleotide excision repair protein involved in the repair of therapeutic radiation-induced DNA damage (PMID:15173087)
• the ERCC1 C8092A polymorphism may have a role in progression of non-small cell lung cancer (PMID:15297394)
• This alternate transcript is ubiquitous in human tissues and cancer cell lines, but is absent in mouse and thus does not appear to be cancer related. (PMID:15688021)
• High ERCC1 gene expression is associated with chemotherapy resistance in esophageal cancer (PMID:15788669)
• Overexpression of ERCC1 is associated with liver fibrogenesis and cancer and could be related to the well recognized resistance of HCC to chemotherapeutics. (PMID:15922480)
• The XPF binding sites of ERCC1 were located in helices H1 and H3 and in the C-terminal region, similar to the involved surface of XPF. (PMID:15932882)
• A nuclear magnetic resonance examination of the DNA binding site. (PMID:16034668)
• XPF-ERCC1 recognizes a branched DNA substrate by binding the two ssDNA arms with the two HhH2 domains of XPF and ERCC1 and by binding the 5’-ssDNA arm with the central domain of ERCC1. (PMID:16076955)
• The half-life of ERCC1 protein in a testis tumor cell line was not significantly different to that in a prostate cancer cell line. These results suggest that constitutive levels of these DNA repair proteins are controlled at the level of translation. (PMID:16315315)
• The ERCC1 domain folds properly only in the presence of the XPF domain, which implies a role for XPF as a scaffold for the folding of ERCC1. (PMID:16338413)
• Low variant A-allele frequency of ERCC1 G19007A in the Chinese population may suggest that the genetic contribution to cancer risk differs substantially between ethnic groups. (PMID:16341770)
• These results suggest that the ERCC1 8092C>A polymorphism may be related to the occurrence of childhood ALL in a Chinese population. (PMID:16723154)
• The conflicting information regarding the ERCC1 codon 118 polymorphism might be explained by the coexistence of major confounding factors(smoking or diet), which might mask the relatively minor gene effect associated with a single genetic polymorphism. (PMID:16899630)
• ERCC1 expression may results in chemoresistance. (PMID:17064812)
• data indicated that ERCC1 mRNA level is associated with CDDP, BCNU & VCR cytotoxicity, while ERCC2 expression is associated with BCNU cytotoxicity in gliomas; however, there was no association between ERCC1, ERCC2 SNP and chemotherapy drug response (PMID:17151930)
• results of the study indicate that ERCC1 may predict survival in bladder cancer treated by platinum-based therapy (PMID:17229776)
• ERCC1 deficiency is associated with cerebro-oculo-facio-skeletal syndrome with a mild defect in nucleotide excision repair and severe developmental failure (PMID:17273966)
• Our findings suggest that the C19007T ERCC1 polymorphism is unlikely to play an important role in epithelial ovarian or endometrial cancer in Korean women. (PMID:17314486)
• variant genotypes of the rs3212948 C allele were associated with significantly decreased risk of lung cancer (PMID:17502833)
• meta-analysis suggests that the ERCC1 C8092A and T19007C polymorphisms had no association to cancer risk (PMID:17522621)
• the benefit of adjuvant cisplatin-based chemotherapy was more profound in patients with low ERCC1 expression. (PMID:17534174)
• ERCC1 has a role in head and neck squamous cell carcinomaresponse to Cisplatin-based induction chemotherapy (PMID:17606717)
• Identification of two distinct interaction surfaces of ERCC1 that mediate XPA and DNA binding. (PMID:17720715)
• The XPF HhH homodimer has a larger interaction interface, aromatic stacking interactions, and additional hydrogen bond contacts as compared to the XPF/ERCC1 HhH complex, which accounts for its higher stability (PMID:17912758)
• Patients with ERCC1-negative tumors appear to have significantly better response to platinum-based chemotherapy compared to patients with ERCC1-positive tumors;the TT genotype seems to be favorable toward better response to platinum-based chemotherapy. (PMID:17961161)
• ERCC1 expression could be useful in identifying patients who may benefit from platinum-containing treatments. (PMID:17987380)
• These results implicate the XPF-ERCC1 complex in initiating interstrand cross-links (ICL) repair by unhooking the ICL, which simultaneously induces a double strand break at a stalled fork. (PMID:18006494)
• ERCC1 expression was identified as a positive prognostic marker in resected non-small cell lung cancer (PMID:18036700)
• Upregulation of ERCC1 and XPD protein expression was associated with resistance process to platinum-based chemotherapy in advanced epithelial ovarian cancer (PMID:18081788)
• in our study ERCC1 was not associated with any clinical characteristic of colorectal cancer (PMID:18204222)
• The previously identified haplotype of ERCC1 and its present polymorphisms are not associated with an increased risk for colorectal cancer. (PMID:18289367)
• Significantly lower ERCC1 expression is associated with prostate cancer (PMID:18332046)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ercc1	ENSDARG00000031680
mus_musculus	Ercc1	ENSMUSG00000003549
rattus_norvegicus	Ercc1	ENSRNOG00000017839
drosophila_melanogaster	Ercc1	FBGN0028434
caenorhabditis_elegans	ercc-1	WBGENE00008665

Protein

Protein identifiers

DNA excision repair protein ERCC-1 — P07992 (reviewed: P07992)

All UniProt accessions (10): P07992, A0AA34QVL1, K7EJL2, K7EJW9, K7EK97, K7EMT9, K7EP14, K7ER60, K7ER89, K7ES46

UniProt curated annotations — full annotation on UniProt →

Function. Non-catalytic component of a structure-specific DNA repair endonuclease responsible for the 5’-incision during DNA repair. Responsible, in conjunction with SLX4, for the first step in the repair of interstrand cross-links (ICL). Participates in the processing of anaphase bridge-generating DNA structures, which consist in incompletely processed DNA lesions arising during S or G2 phase, and can result in cytokinesis failure. Also required for homology-directed repair (HDR) of DNA double-strand breaks, in conjunction with SLX4. Not functional in the nucleotide excision repair pathway. Not functional in the nucleotide excision repair pathway. Not functional in the nucleotide excision repair pathway.

Subunit / interactions. Heterodimer composed of ERCC1 isoform 1 and ERCC4/XPF. Interacts with USP45. Does not interact with ERCC4/XPF. Does not interact with ERCC4/XPF. Does not interact with ERCC4/XPF.

Subcellular location. Nucleus Cytoplasm. Nucleus Nucleus Nucleus.

Post-translational modifications. Ubiquitinated with both ‘Lys-48’ and ‘Lys-63’ linkages. Deubiquitinated by USP45.

Disease relevance. Cerebro-oculo-facio-skeletal syndrome 4 (COFS4) [MIM:610758] 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.

Similarity. Belongs to the ERCC1/RAD10/SWI10 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P07992-1	1, 202	yes
P07992-2	2, 203
P07992-3	3, 201
P07992-4	4, 204

RefSeq proteins (15): NP_001159521, NP_001356337, NP_001356338, NP_001356339, NP_001356340, NP_001356341, NP_001356342, NP_001356343, NP_001356344, NP_001356345, NP_001356346, NP_001356347, NP_001356348, NP_001974, NP_973730 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004579	ERCC1/RAD10/SWI10	Family
IPR010994	RuvA_2-like	Homologous_superfamily
IPR011335	Restrct_endonuc-II-like	Homologous_superfamily
IPR047260	ERCC1-like_central_dom	Domain

Pfam: PF03834, PF14520

UniProt features (42 total): helix 11, strand 10, mutagenesis site 6, splice variant 3, cross-link 3, sequence variant 2, region of interest 2, chain 1, DNA-binding region 1, sequence conflict 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
2A1I	X-RAY DIFFRACTION	1.9
2A1J	X-RAY DIFFRACTION	2.7
9QEC	ELECTRON MICROSCOPY	2.9
9QED	ELECTRON MICROSCOPY	3.2
9PD3	ELECTRON MICROSCOPY	3.3
9PD4	ELECTRON MICROSCOPY	3.4
9QEE	ELECTRON MICROSCOPY	3.4
6SXA	ELECTRON MICROSCOPY	3.6
9PCP	ELECTRON MICROSCOPY	4.3
6SXB	ELECTRON MICROSCOPY	7.9
1Z00	SOLUTION NMR
2JNW	SOLUTION NMR
2JPD	SOLUTION NMR
2MUT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07992-F1	77.48	0.52

Functional residue map

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

Post-translational modifications (4): 1, 21, 37, 243

Mutagenesis-validated functional residues (6):

Position	Phenotype
221	impaired interaction with ercc4.
223	impaired interaction with ercc4.
224	impaired interaction with ercc4.
225	impaired interaction with ercc4.
227	impaired interaction with ercc4.
228	impaired interaction with ercc4.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
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
R-HSA-6783310	Fanconi Anemia Pathway

MSigDB gene sets: 586 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOMF_ENDONUCLEASE_ACTIVITY, GOBP_TELOMERE_CAPPING, GOBP_CELLULAR_RESPONSE_TO_UV, GOBP_B_CELL_ACTIVATION, GOMF_NUCLEASE_ACTIVITY, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_GROWTH, GOBP_OOGENESIS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP

GO Biological Process (35): pyrimidine dimer repair by nucleotide-excision repair (GO:0000720), DNA repair (GO:0006281), nucleotide-excision repair (GO:0006289), double-strand break repair via nonhomologous end joining (GO:0006303), mitotic recombination (GO:0006312), obsolete syncytium formation (GO:0006949), response to oxidative stress (GO:0006979), spermatogenesis (GO:0007283), cell population proliferation (GO:0008283), determination of adult lifespan (GO:0008340), male gonad development (GO:0008584), UV protection (GO:0009650), response to X-ray (GO:0010165), negative regulation of telomere maintenance (GO:0032205), post-embryonic hemopoiesis (GO:0035166), multicellular organism growth (GO:0035264), interstrand cross-link repair (GO:0036297), isotype switching (GO:0045190), insulin-like growth factor receptor signaling pathway (GO:0048009), oogenesis (GO:0048477), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), telomeric DNA-containing double minutes formation (GO:0061819), UV-damage excision repair (GO:0070914), replicative senescence (GO:0090399), t-circle formation (GO:0090656), positive regulation of t-circle formation (GO:1904431), negative regulation of protection from non-homologous end joining at telomere (GO:1905765), telomere maintenance (GO:0000723), double-strand break repair (GO:0006302), DNA recombination (GO:0006310), DNA damage response (GO:0006974), germ cell development (GO:0007281), regulation of telomere maintenance (GO:0032204), cell development (GO:0048468), chromosome organization (GO:0051276)

GO Molecular Function (8): TFIID-class transcription factor complex binding (GO:0001094), damaged DNA binding (GO:0003684), single-stranded DNA binding (GO:0003697), promoter-specific chromatin binding (GO:1990841), single-stranded DNA endonuclease activity (GO:0000014), DNA binding (GO:0003677), protein binding (GO:0005515), 3’ overhang single-stranded DNA endonuclease activity (GO:1990599)

GO Cellular Component (7): nucleotide-excision repair complex (GO:0000109), nucleotide-excision repair factor 1 complex (GO:0000110), chromosome, telomeric region (GO:0000781), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), ERCC4-ERCC1 complex (GO:0070522), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Global Genome Nucleotide Excision Repair (GG-NER)	2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1
DNA Repair	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA repair	2
multicellular organismal process	2
DNA binding	2
nucleotide-excision repair complex	2
cellular anatomical structure	2
nucleotide-excision repair	1
pyrimidine dimer repair	1
DNA metabolic process	1
DNA damage response	1
double-strand break repair	1
DNA recombination	1
response to stress	1
developmental process involved in reproduction	1
male gamete generation	1
cellular process	1
gonad development	1
development of primary male sexual characteristics	1
response to UV	1
response to ionizing radiation	1
telomere maintenance	1
regulation of telomere maintenance	1
negative regulation of DNA metabolic process	1
negative regulation of chromosome organization	1
post-embryonic development	1
hemopoiesis	1
developmental growth	1
somatic recombination of immunoglobulin genes involved in immune response	1
B cell activation involved in immune response	1
cell surface receptor protein tyrosine kinase signaling pathway	1
germ cell development	1
female gamete generation	1
RNA polymerase II general transcription initiation factor binding	1
chromatin binding	1
DNA endonuclease activity	1
hydrolase activity, acting on ester bonds	1
nucleic acid binding	1
binding	1
single-stranded DNA endonuclease activity	1
nuclear protein-containing complex	1
chromosomal region	1

Protein interactions and networks

STRING

1821 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERCC1	XPA	P23025	999
ERCC1	ERCC4	Q92889	999
ERCC1	SLX4	Q8IY92	998
ERCC1	ERCC2	P18074	993
ERCC1	ERCC3	P19447	988
ERCC1	RAD23B	P54727	984
ERCC1	SLX1A	Q9BQ83	980
ERCC1	MUS81	Q96NY9	974
ERCC1	ERCC5	P28715	973
ERCC1	XRCC1	P18887	946
ERCC1	XPC	Q01831	945
ERCC1	A0A090J7P6	A0A090J7P6	940
ERCC1	FEN1	P39748	939
ERCC1	RAD52	P43351	935
ERCC1	ERCC6	Q03468	927

IntAct

92 interactions, top by confidence:

A	B	Type	Score
ERCC1	XPA	psi-mi:“MI:0915”(physical association)	0.930
XPA	ERCC1	psi-mi:“MI:0915”(physical association)	0.930
XPA	ERCC1	psi-mi:“MI:0914”(association)	0.930
XPA	ERCC1	psi-mi:“MI:0407”(direct interaction)	0.930
ERCC4	ERCC1	psi-mi:“MI:0915”(physical association)	0.880
ERCC1	ERCC4	psi-mi:“MI:0915”(physical association)	0.880
ERCC1	ERCC4	psi-mi:“MI:0407”(direct interaction)	0.880
UBL7	ERCC1	psi-mi:“MI:0915”(physical association)	0.670
ERCC1	VPS37B	psi-mi:“MI:0915”(physical association)	0.670
ERCC1	UBL7	psi-mi:“MI:0915”(physical association)	0.670
VPS37B	ERCC1	psi-mi:“MI:0915”(physical association)	0.670
SLX4	ERCC1	psi-mi:“MI:0914”(association)	0.640
ERCC1	SLX4	psi-mi:“MI:0915”(physical association)	0.640
ERCC1	SLX4	psi-mi:“MI:0403”(colocalization)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640

BioGRID (172): MKRN3 (Two-hybrid), VPS37B (Two-hybrid), TRMT2B (Two-hybrid), USHBP1 (Two-hybrid), UBL7 (Two-hybrid), SLX4IP (Affinity Capture-MS), ERCC4 (Affinity Capture-MS), SLX4 (Affinity Capture-MS), ERCC1 (Affinity Capture-MS), ERCC1 (Affinity Capture-MS), UBL7 (Two-hybrid), ERCC1 (Affinity Capture-Western), UHRF1 (Affinity Capture-Western), ERCC1 (Reconstituted Complex), ACAT1 (Co-fractionation)

ESM2 similar proteins: A1L3K1, A2AFS3, A5PKD9, A6QQ60, A8MYP8, B5DFI8, B5DFK7, G3MWR8, O35217, O73884, P07992, P0C7P0, P28686, P42642, P48801, Q01134, Q08DW9, Q2HJ19, Q3SZB3, Q4R766, Q5EA46, Q5M8M2, Q5R890, Q5TH74, Q5XIJ5, Q5ZIN0, Q5ZJB7, Q63750, Q67FW5, Q6DD70, Q6GL10, Q6GV29, Q6PCB6, Q6UXG2, Q7RTP6, Q7Z6J6, Q86XW9, Q8CJ19, Q8N2K0, Q8N5X7

Diamond homologs: P06838, P07903, P07992, Q06182, Q9MA98, Q1LZ75, Q55GG6

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ERCC1	“form complex”	ERCC4/ERCC1	binding
RAD23B	“up-regulates activity”	ERCC1	binding
ERCC1	up-regulates	Nucleotide-excision_repair

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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
Homology Directed Repair	6	57.9×	1e-07
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	6	57.9×	1e-07
DNA Double-Strand Break Repair	6	46.5×	3e-07
Nonhomologous End-Joining (NHEJ)	5	26.2×	5e-05
G2/M Checkpoints	6	25.2×	7e-06
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	5	22.9×	9e-05
DNA Repair	7	21.5×	2e-06
G2/M DNA damage checkpoint	5	18.8×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair via nonhomologous end joining	5	51.4×	7e-06
double-strand break repair	5	24.8×	2e-04
double-strand break repair via homologous recombination	5	19.0×	3e-04
DNA repair	10	15.6×	2e-07
ubiquitin-dependent protein catabolic process	5	9.1×	5e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	8
Uncertain significance	110
Likely benign	86
Benign	35

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1322828	NM_001983.4(ERCC1):c.121C>T (p.Arg41Ter)	Pathogenic
16777	NM_001983.4(ERCC1):c.472C>T (p.Gln158Ter)	Pathogenic
16778	NM_001983.4(ERCC1):c.693C>G (p.Phe231Leu)	Pathogenic
3342960	NM_001983.4(ERCC1):c.109A>T (p.Lys37Ter)	Pathogenic
4731585	NM_001983.4(ERCC1):c.208G>T (p.Glu70Ter)	Pathogenic
489383	NM_001983.4(ERCC1):c.525+2T>C	Pathogenic
981245	NM_001983.4(ERCC1):c.321+61_525+132del	Pathogenic
1208249	NM_001983.4(ERCC1):c.703-2A>G	Likely pathogenic
1501659	NM_001983.4(ERCC1):c.526-1G>A	Likely pathogenic
1683582	NM_001983.4(ERCC1):c.231del (p.Thr78fs)	Likely pathogenic
225348	NM_001983.4(ERCC1):c.184G>T (p.Glu62Ter)	Likely pathogenic
3391184	NM_001983.4(ERCC1):c.23dup (p.Val10fs)	Likely pathogenic
3659772	NM_001983.4(ERCC1):c.525+1G>A	Likely pathogenic
444475	NM_001983.4(ERCC1):c.155C>A (p.Ser52Ter)	Likely pathogenic
808600	NM_001983.4(ERCC1):c.199C>T (p.Gln67Ter)	Likely pathogenic

SpliceAI

2200 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45413675:A:AC	donor_gain	1.0000
19:45413676:C:CC	donor_gain	1.0000
19:45413676:CTTT:C	donor_gain	1.0000
19:45413742:GAGA:G	acceptor_gain	1.0000
19:45413746:C:CC	acceptor_gain	1.0000
19:45413956:T:TA	donor_gain	1.0000
19:45413961:A:AC	donor_gain	1.0000
19:45413961:ACT:A	donor_gain	1.0000
19:45413962:C:CC	donor_gain	1.0000
19:45413962:CT:C	donor_gain	1.0000
19:45413962:CTC:C	donor_gain	1.0000
19:45414855:CCTCA:C	donor_loss	1.0000
19:45414856:CTCA:C	donor_loss	1.0000
19:45414857:TCA:T	donor_loss	1.0000
19:45414858:CA:C	donor_loss	1.0000
19:45414859:A:AC	donor_gain	1.0000
19:45414859:AC:A	donor_gain	1.0000
19:45414860:C:CA	donor_loss	1.0000
19:45414860:C:CC	donor_gain	1.0000
19:45414860:CC:C	donor_gain	1.0000
19:45414872:AGT:A	donor_gain	1.0000
19:45414874:T:TA	donor_gain	1.0000
19:45414956:CGGGG:C	acceptor_gain	1.0000
19:45414961:C:CC	acceptor_gain	1.0000
19:45414970:CAGGA:C	acceptor_gain	1.0000
19:45416815:TCTCA:T	donor_loss	1.0000
19:45416816:CTCAC:C	donor_loss	1.0000
19:45416817:TCACC:T	donor_loss	1.0000
19:45416818:CAC:C	donor_loss	1.0000
19:45416820:C:CA	donor_loss	1.0000

AlphaMissense

1901 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45414003:A:T	V245D	1.000
19:45413677:T:A	K281N	0.999
19:45413677:T:G	K281N	0.999
19:45413678:T:A	K281I	0.999
19:45420329:G:C	F140L	0.999
19:45420329:G:T	F140L	0.999
19:45420331:A:G	F140L	0.999
19:45421178:C:A	Q107H	0.999
19:45421178:C:G	Q107H	0.999
19:45413679:T:C	K281E	0.998
19:45413687:C:T	G278D	0.998
19:45413693:C:T	G276D	0.998
19:45413979:A:G	L253P	0.998
19:45413979:A:T	L253H	0.998
19:45414021:A:G	L239P	0.998
19:45414924:C:A	K213N	0.998
19:45414924:C:G	K213N	0.998
19:45414937:A:G	L209P	0.998
19:45414946:C:T	G206E	0.998
19:45414947:C:A	G206W	0.998
19:45420336:G:T	A138D	0.998
19:45420419:A:C	N110K	0.998
19:45420419:A:T	N110K	0.998
19:45421191:A:T	V103E	0.998
19:45409715:A:G	L285P	0.997
19:45413679:T:G	K281Q	0.997
19:45413708:A:G	L271P	0.997
19:45414950:C:G	A205P	0.997
19:45419117:A:G	L169P	0.997
19:45419120:A:T	V168D	0.997

dbSNP variants (sampled 300 via entrez): RS1000157911 (19:45443867 C>G,T), RS1000158783 (19:45432973 G>A,T), RS1000197486 (19:45440766 C>T), RS1000277094 (19:45433205 C>T), RS1000427158 (19:45415864 A>T), RS1000612252 (19:45443617 G>A,C), RS1000620541 (19:45444012 A>G,T), RS1000703093 (19:45421840 C>T), RS1000737808 (19:45428571 G>A,C), RS1000749260 (19:45444279 G>C), RS1000865793 (19:45422723 C>G,T), RS1000878432 (19:45445319 T>G), RS1000883614 (19:45438297 G>A), RS1000947583 (19:45451579 A>G), RS1000964609 (19:45450198 C>T)

Disease associations

OMIM: gene MIM:126380 | disease phenotypes: MIM:610758

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebrooculofacioskeletal syndrome 4	Definitive	Autosomal recessive
COFS syndrome	Supportive	Autosomal recessive
Cockayne syndrome type 2	Supportive	Autosomal recessive

Mondo (6): cerebrooculofacioskeletal syndrome 4 (MONDO:0012554), Cockayne syndrome (MONDO:0016006), premature menopause (MONDO:0001119), skin sensitivity to sun (MONDO:0005434), COFS syndrome (MONDO:0008926), Cockayne syndrome type 2 (MONDO:0019570)

Orphanet (1): Cockayne syndrome (Orphanet:191)

HPO phenotypes

107 total (30 of 107 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000026	Male hypogonadism
HP:0000028	Cryptorchidism
HP:0000078	Abnormality of the genital system
HP:0000135	Hypogonadism
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000303	Mandibular prognathia
HP:0000322	Short philtrum
HP:0000331	Short chin
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000479	Abnormal retinal morphology
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000505	Visual impairment
HP:0000509	Conjunctivitis
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000528	Anophthalmia
HP:0000554	Uveitis
HP:0000568	Microphthalmia

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005950_15	Body mass index x sex x age interaction (4df test)	2.000000e-10
GCST005951_56	Body mass index	1.000000e-06
GCST005952_8	Body mass index (age>50)	9.000000e-12
GCST005954_4	Body mass index x age interaction	2.000000e-07
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97
GCST008551_25	Simvastatin-induced myopathy	9.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003057	Cockayne Syndrome	C05.116.099.343.250; C10.574.500.362; C16.131.077.250; C16.320.240.562; C16.320.400.200; C18.452.284.250
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500
C565184	Cerebrooculofacioskeletal Syndrome 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3883316 (PROTEIN COMPLEX)

Clinical evidence (CIViC)

Drug × variant × indication: 7 predictive associations from 7 curated evidence items; also 3 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
ERCC1 Expression	Cisplatin	Bladder Carcinoma	Sensitivity/Response	CIViC B	EID809
ERCC1 Underexpression	Gemcitabine + Carboplatin	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID10142
ERCC1 Underexpression	Platinum Compound	Epithelial Ovarian Cancer	Sensitivity/Response	CIViC B	EID10146
ERCC1 Underexpression	Platinum Compound	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID6430
ERCC1 Underexpression	Cisplatin + Gemcitabine	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID6431
ERCC1 Underexpression	Cisplatin	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID6433
ERCC1 Expression	Paclitaxel + Cisplatin + Gemcitabine	Bladder Carcinoma		CIViC B	EID6438

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

PharmGKB clinical annotations

28 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11615	Toxicity	3	cisplatin;cyclophosphamide	Ovarian Neoplasms
rs11615	Toxicity	3	cisplatin;doxorubicin	Mucositis;Osteosarcoma
rs11615	Efficacy	3	cisplatin	Neoplasm of esophagus;Ovarian Neoplasms;Stomach Neoplasms
rs11615	Efficacy	3	cisplatin;gemcitabine	Non-Small Cell Lung Carcinoma
rs11615	Efficacy	3	cisplatin	Pancreatic Neoplasms
rs11615	Efficacy	3	capecitabine;radiotherapy	Rectal Neoplasms
rs11615	Toxicity	3	docetaxel	Breast Neoplasms
rs11615	Toxicity	3	fluorouracil;leucovorin;oxaliplatin	Colonic Neoplasms
rs11615	Toxicity	3	cyclophosphamide;doxorubicin;fluorouracil	Breast Neoplasms
rs11615	Efficacy	3	fluorouracil;leucovorin;oxaliplatin	Colorectal Neoplasms
rs11615	Toxicity	3	bleomycin;cisplatin;etoposide	Febrile neutropenia;Testicular Neoplasms
rs11615	Toxicity	3	cisplatin	Drug Toxicity
rs11615	Toxicity	3	carboplatin;cisplatin;oxaliplatin;platinum;Platinum compounds	Neoplasms
rs2298881	Efficacy	3	fluorouracil;Platinum compounds;radiotherapy	Stomach Neoplasms
rs2336219	Efficacy	3	cisplatin	Ovarian Neoplasms
rs3212980	Efficacy	3	cisplatin	Ovarian Neoplasms
rs3212986	Toxicity	3	paclitaxel	Breast Neoplasms
rs3212986	Toxicity	3	docetaxel	Breast Neoplasms
rs3212986	Efficacy	3	granisetron;palonosetron	Nausea;Neoplasms;Vomiting
rs3212986	Toxicity	3	cyclophosphamide;doxorubicin;fluorouracil	Breast Neoplasms
rs3212986	Toxicity	3	bleomycin;cisplatin;etoposide	Testicular Neoplasms;Vomiting
rs3212986	Toxicity	3	cisplatin	Neoplasms
rs3212986	Efficacy	4	Platinum compounds	Non-Small Cell Lung Carcinoma;Ovarian Neoplasms
rs3212986	Efficacy	4	cisplatin	Neoplasm of esophagus;Ovarian Neoplasms;Stomach Neoplasms
rs3212986	Efficacy	3	Platinum compounds	Ovarian Neoplasms
rs3212986	Efficacy	3	cisplatin;gemcitabine	Mesothelioma
rs3212986	Toxicity	3	doxorubicin	Infectious disease;Leukopenia;Osteosarcoma
rs735482	Efficacy	3	thalidomide	Multiple Myeloma

PharmGKB variants

10 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11615	ERCC1	3	3.75	13	carboplatin;cisplatin;oxaliplatin;platinum;Platinum compounds;docetaxel;cisplatin;fluorouracil;leucovorin;oxaliplatin;cisplatin;cyclophosphamide;cyclophosphamide;doxorubicin;fluorouracil;bleomycin;cisplatin;etoposide;capecitabine;radiotherapy;cisplatin;doxorubicin;cisplatin;gemcitabine
rs735482	ERCC1, POLR1G, PPP1R13L	3	2.00	1	thalidomide
rs3212948	ERCC1		0.00	0
rs3212986	ERCC1, POLR1G, PPP1R13L	3	4.00	11	cisplatin;Platinum compounds;docetaxel;paclitaxel;cisplatin;gemcitabine;bleomycin;cisplatin;etoposide;cyclophosphamide;doxorubicin;fluorouracil;granisetron;palonosetron;doxorubicin
rs3212935	ERCC1		0.00	0
rs2298881	ERCC1	3	2.50	1	fluorouracil;Platinum compounds;radiotherapy
rs2336219	ERCC1	3	0.00	1	cisplatin
rs3212980	ERCC1	3	0.00	1	cisplatin
rs3212964	ERCC1		0.00	0
rs3212961	ERCC1		0.00	0

ChEMBL bioactivities

62 potent at pChembl≥5 of 88 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.07	Kd	85	nM	CHEMBL4759590
7.00	Kd	100	nM	CHEMBL4470176
6.85	Kd	140	nM	CHEMBL463783
6.48	IC50	330	nM	CHEMBL4470176
6.31	IC50	490	nM	CHEMBL4759590
6.30	IC50	500	nM	CHEMBL3617281
6.22	IC50	600	nM	CHEMBL3617209
6.22	IC50	600	nM	CHEMBL3617205
6.20	IC50	630	nM	CHEMBL3617002
6.16	IC50	700	nM	CHEMBL3617284
6.16	IC50	700	nM	CHEMBL3617207
6.13	IC50	740	nM	CHEMBL3617018
6.10	IC50	800	nM	CHEMBL3617014
6.10	IC50	800	nM	CHEMBL3617001
6.10	IC50	800	nM	CHEMBL3617286
6.10	IC50	800	nM	CHEMBL3617283
6.10	IC50	800	nM	CHEMBL3617282
6.05	IC50	900	nM	CHEMBL3616993
6.00	IC50	1000	nM	CHEMBL3617013
6.00	IC50	1000	nM	CHEMBL3617000
6.00	IC50	1000	nM	CHEMBL3617285
6.00	IC50	1000	nM	CHEMBL223338
5.96	IC50	1100	nM	CHEMBL3617016
5.85	IC50	1400	nM	CHEMBL3617007
5.82	IC50	1500	nM	CHEMBL3617203
5.82	IC50	1500	nM	CHEMBL182381
5.80	IC50	1600	nM	CHEMBL3617015
5.80	IC50	1600	nM	CHEMBL3617004
5.80	IC50	1600	nM	CHEMBL3616994
5.77	IC50	1700	nM	CHEMBL3617287
5.75	IC50	1800	nM	CHEMBL3616999
5.75	IC50	1800	nM	CHEMBL361011
5.73	IC50	1860	nM	CHEMBL463783
5.70	IC50	2000	nM	CHEMBL3616991
5.58	IC50	2600	nM	CHEMBL3617003
5.57	IC50	2700	nM	CHEMBL3617206
5.54	IC50	2900	nM	CHEMBL3617017
5.54	IC50	2900	nM	CHEMBL181653
5.46	Kd	3500	nM	CHEMBL2443225
5.41	IC50	3900	nM	CHEMBL440562
5.41	IC50	3900	nM	CHEMBL3617197
5.41	IC50	3900	nM	CHEMBL361350
5.40	IC50	4000	nM	CHEMBL3617008
5.40	Kd	4000	nM	CHEMBL3617205
5.39	IC50	4100	nM	CHEMBL3617020
5.38	IC50	4200	nM	CHEMBL216874
5.34	IC50	4600	nM	CHEMBL3617208
5.32	IC50	4800	nM	CHEMBL3617019
5.28	IC50	5200	nM	CHEMBL3617023
5.24	IC50	5800	nM	CHEMBL3617012

PubChem BioAssay actives

62 with measured affinity, of 129 total; 50 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
6-chloro-9-[3-[[4-[2-(dimethylamino)ethyl]piperazin-1-yl]methyl]-4-hydroxyanilino]acridin-2-ol	1704038: Binding affinity to His-tagged human ERCC1-XPF expressed in Escherichia coli BL21 (DE3) cells by steady-state fluorescence assay	kd	0.0850	uM
4-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[[4-[2-(dimethylamino)ethyl]piperazin-1-yl]methyl]phenol	1516751: Binding affinity to human His6-tagged ERCC1-XPF expressed in Escherichia coli BL21 (DE3) by spectrofluorimetric method	kd	0.1000	uM
4-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(4-methylpiperazin-1-yl)methyl]phenol	1704038: Binding affinity to His-tagged human ERCC1-XPF expressed in Escherichia coli BL21 (DE3) cells by steady-state fluorescence assay	kd	0.1400	uM
5-hydroxy-N-(3-methylbutyl)-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.5000	uM
5-hydroxy-N-methyl-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.6000	uM
N-butan-2-yl-5-hydroxy-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.6000	uM
2-(2,4-dichlorophenyl)-N-[(3,4-dihydroxyphenyl)methyl]acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.6300	uM
5-hydroxy-N-(2-hydroxyethyl)-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.7000	uM
5-hydroxy-6-oxo-N-pyridin-3-yl-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.7000	uM
N-[(2,4-dichlorophenyl)methyl]-2-(3,4-dihydroxyphenyl)acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.7400	uM
2-(2-chlorophenyl)-N-[(3,4-dihydroxyphenyl)methyl]acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.8000	uM
2-(2,4-dichlorophenyl)-N-[(3,4-dihydroxyphenyl)methyl]-N-methylacetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.8000	uM
N-(2-acetamidoethyl)-5-hydroxy-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.8000	uM
N-(4-fluorophenyl)-5-hydroxy-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.8000	uM
5-hydroxy-N-(3-methylbutyl)-2-[4-(morpholin-4-ylmethyl)phenyl]-6-oxo-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.8000	uM
2-anilino-N-[(3,4-dihydroxyphenyl)methyl]acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	0.9000	uM
2-(4-chlorophenyl)-N-[(3,4-dihydroxyphenyl)methyl]acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.0000	uM
2-(2,4-dichlorophenyl)-1-(6,7-dihydroxy-3,4-dihydro-1H-isoquinolin-2-yl)ethanone	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.0000	uM
5-hydroxy-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.0000	uM
5-hydroxy-N-(2-morpholin-4-ylethyl)-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.0000	uM
2-(2,4-dichlorophenyl)-N-[(2-fluoro-4,5-dihydroxyphenyl)methyl]acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.1000	uM
2-cyclohexyl-N-[(3,4-dihydroxyphenyl)methyl]acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.4000	uM
3-hydroxy-6-phenyl-1H-pyrimidine-2,4-dione	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.5000	uM
3-hydroxy-7-(4-methylphenyl)-1H-furo[3,2-d]pyrimidine-2,4-dione	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.5000	uM
2-anilino-N-(3,4-dihydroxyphenyl)acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.6000	uM
N-[(3,4-dihydroxyphenyl)methyl]-1-phenylcyclohexane-1-carboxamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.6000	uM
N-[(2-chloro-3,4-dihydroxyphenyl)methyl]-2-(2,4-dichlorophenyl)acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.6000	uM
2-[4-[(dimethylamino)methyl]phenyl]-5-hydroxy-N-(3-methylbutyl)-6-oxo-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.7000	uM
3-hydroxy-7-phenyl-1H-thieno[3,2-d]pyrimidine-2,4-dione	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.8000	uM
N-[(3,4-dihydroxyphenyl)methyl]-2-phenylpropanamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	1.8000	uM
2-anilino-N-[(E)-(3,4-dihydroxyphenyl)methylideneamino]acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	2.0000	uM
N-[(3,4-dihydroxyphenyl)methyl]-2-(4-methoxyphenyl)acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	2.6000	uM
5-hydroxy-6-oxo-N-propyl-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	2.7000	uM
1-(2,4-dichlorophenyl)-N-[(3,4-dihydroxyphenyl)methyl]methanesulfonamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	2.9000	uM
5-hydroxy-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxylic acid	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	2.9000	uM
5-(4-fluorophenyl)-3-hydroxy-1H-pyridin-2-one	1247666: Binding affinity to ERCC1-XPF (unknown origin) by SPR assay	kd	3.5000	uM
7-anilino-3-hydroxy-1H-quinazoline-2,4-dione	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	3.9000	uM
5-hydroxy-6-oxo-2-phenyl-1H-pyrimidine-4-carboxylic acid	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	3.9000	uM
3-hydroxy-1H-thieno[2,3-d]pyrimidine-2,4-dione	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	3.9000	uM
2-(3-cyanophenyl)-N-[(3,4-dihydroxyphenyl)methyl]acetamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	4.0000	uM
1-[(4-chlorophenyl)methyl]-3-[(3,4-dihydroxyphenyl)methyl]imidazolidin-2-one	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	4.1000	uM
N-[(4-fluorophenyl)methyl]-5-hydroxy-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	4.2000	uM
5-hydroxy-4-(pyrrolidine-1-carbonyl)-2-thiophen-2-yl-1H-pyrimidin-6-one	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	4.6000	uM
1-(4-chlorophenyl)-3-[(3,4-dihydroxyphenyl)methyl]urea	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	4.8000	uM
3-hydroxy-5-(3-pyrazol-1-ylphenyl)-1H-pyridin-2-one	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	5.2000	uM
N-[(3,4-dihydroxyphenyl)methyl]-1-[(4-fluorophenyl)methyl]piperidine-4-carboxamide	1247658: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	5.8000	uM
N-(3-hydroxy-2,4-dioxo-1H-quinazolin-8-yl)acetamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	6.1000	uM
5-hydroxy-N-(3-methylbutyl)-6-oxo-2-piperidin-2-yl-1H-pyrimidine-4-carboxamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	6.3000	uM
N-(3-hydroxy-2,4-dioxo-1H-quinazolin-7-yl)acetamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	6.4000	uM
N-(3-hydroxy-2,4-dioxo-1H-quinazolin-6-yl)acetamide	1247798: Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	ic50	6.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	increases expression, increases response to substance, affects binding, affects expression, decreases expression (+6 more)	19
Oxaliplatin	affects cotreatment, affects response to substance, increases expression	7
Fluorouracil	affects cotreatment, decreases expression, affects response to substance, increases response to substance	7
Benzo(a)pyrene	decreases reaction, affects expression, decreases expression, increases expression, affects response to substance (+1 more)	5
sodium arsenite	affects cotreatment, increases expression, decreases expression	4
Arsenic	affects expression, decreases expression, increases expression, affects cotreatment	4
Cadmium Chloride	decreases expression, affects cotreatment, increases activity, increases methylation, increases expression (+1 more)	4
Curcumin	decreases reaction, increases expression, decreases expression, increases response to substance	3
Valproic Acid	affects cotreatment, decreases expression, affects expression	3
cobaltous chloride	decreases expression	2
Decitabine	decreases expression, decreases reaction	2
Air Pollutants	increases abundance, increases oxidation, increases expression, affects cotreatment	2
Camptothecin	decreases expression, increases expression, increases reaction	2
Tobacco Smoke Pollution	affects response to substance, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, affects response to substance	2
TAK-243	increases sumoylation	1
myristicin	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
pirinixic acid	affects binding, decreases expression, increases activity	1
methylselenic acid	increases expression	1
quercitrin	decreases expression	1
trichostatin A	decreases expression, decreases reaction, increases expression	1
beta-lapachone	increases expression	1
sodium bichromate	decreases expression	1
quinoline yellow	increases expression	1
tanshinone	decreases expression, decreases reaction	1
3-aminobenzamide	decreases reaction, increases expression, decreases expression	1
3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz(a)anthracene	increases expression	1
cupric chloride	increases expression	1

ChEMBL screening assays

28 unique, capped per target: 28 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3619484	Binding	Inhibition of ERCC1-XPF (unknown origin) by high-throughput fluorescence based in-vitro endonuclease assay	N-Hydroxyimides and hydroxypyrimidinones as inhibitors of the DNA repair complex ERCC1-XPF. — Bioorg Med Chem Lett

Cellosaurus cell lines

10 cell lines: 5 cancer cell line, 5 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2MS	Abcam A-549 ERCC1 KO	Cancer cell line	Male
CVCL_D7PK	Ubigene A-549 ERCC1 KO	Cancer cell line	Male
CVCL_DB99	173TOR	Finite cell line	Male
CVCL_E0CU	Ubigene HeLa ERCC1 KO	Cancer cell line	Female
CVCL_KT53	HeLa SilenciX ERCC1	Cancer cell line	Female
CVCL_SM32	HAP1 ERCC1 (-)	Cancer cell line	Male
CVCL_ZP21	165TOR	Finite cell line	Male
CVCL_ZP22	XP202DC	Finite cell line	Female
CVCL_ZP23	174TOR	Finite cell line	Female
CVCL_ZP67	CS20LO	Finite cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT01142154	PHASE1/PHASE2	COMPLETED	Pharmacokinetics and Safety Study of Single and Multiple Oral Doses Prodarsan™ in Patients With Cockayne Syndrome
NCT00001813	Not specified	COMPLETED	Examination of Clinical and Laboratory Abnormalities in Patients With Defective DNA Repair: Xeroderma Pigmentosum, Cockayne Syndrome, or Trichothiodystrophy
NCT00985413	Not specified	TERMINATED	Observational Study to Assess Natural History in Cockayne Syndrome Patients
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03044210	Not specified	TERMINATED	Metabolic Study of Cockayne Syndrome
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT05484570	Not specified	RECRUITING	Natural History Study for DNA Repair Disorders
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency