ERCC3

Summary

ERCC3 (ERCC excision repair 3, TFIIH core complex helicase subunit, HGNC:3435) is a protein-coding gene on chromosome 2q14.3, encoding General transcription and DNA repair factor IIH helicase/translocase subunit XPB (P19447). ATP-dependent 3’-5’ DNA helicase/translocase. It is a common-essential gene (DepMap: required in 98.0% of cancer cell lines).

This gene encodes an ATP-dependent DNA helicase that functions in nucleotide excision repair. The encoded protein is a subunit of basal transcription factor 2 (TFIIH) and, therefore, also functions in class II transcription. Mutations in this gene are associated with Xeroderma pigmentosum B, Cockayne’s syndrome, and trichothiodystrophy. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2071 — RefSeq curated summary.

At a glance

• Gene–disease (curated): xeroderma pigmentosum group B (Definitive, ClinGen) — +6 more curated relationships
• Clinical variants (ClinVar): 689 total — 38 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 166
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• Cancer dependency (DepMap): dependent in 98.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000122

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3435
Approved symbol	ERCC3
Name	ERCC excision repair 3, TFIIH core complex helicase subunit
Location	2q14.3
Locus type	gene with protein product
Status	Approved
Aliases	XPB, BTF2, RAD25, Ssl2
Ensembl gene	ENSG00000163161
Ensembl biotype	protein_coding
OMIM	133510
Entrez	2071

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 10 protein_coding, 9 nonsense_mediated_decay, 8 retained_intron

ENST00000285398, ENST00000426778, ENST00000445889, ENST00000456257, ENST00000460485, ENST00000462306, ENST00000490062, ENST00000491292, ENST00000494464, ENST00000642308, ENST00000642972, ENST00000643982, ENST00000644317, ENST00000645233, ENST00000645467, ENST00000645504, ENST00000645736, ENST00000646042, ENST00000646654, ENST00000647169, ENST00000647496, ENST00000890189, ENST00000890190, ENST00000918332, ENST00000918333, ENST00000918334, ENST00000958089

RefSeq mRNA: 3 — MANE Select: NM_000122 NM_000122, NM_001303416, NM_001303418

CCDS: CCDS2144

Canonical transcript exons

ENST00000285398 — 15 exons

Exon	Start	End
ENSE00003458629	127259296	127259448
ENSE00003469206	127280447	127280631
ENSE00003471901	127289689	127289824
ENSE00003494503	127257290	127257727
ENSE00003506890	127288660	127288864
ENSE00003527924	127261228	127261346
ENSE00003552276	127286703	127287017
ENSE00003587081	127272865	127272961
ENSE00003603136	127289337	127289501
ENSE00003610308	127290224	127290273
ENSE00003644834	127292610	127292846
ENSE00003685512	127271336	127271453
ENSE00003691753	127293513	127293718
ENSE00003694078	127279173	127279375
ENSE00003823736	127294054	127294144

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 95.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.1791 / max 188.4298, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30516	18.7108	1813
30515	2.4683	1346

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	95.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.58	gold quality
cerebellar hemisphere	UBERON:0002245	94.56	gold quality
right uterine tube	UBERON:0001302	94.47	gold quality
cerebellar cortex	UBERON:0002129	94.45	gold quality
mucosa of stomach	UBERON:0001199	94.07	gold quality
cortical plate	UBERON:0005343	93.25	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.21	gold quality
granulocyte	CL:0000094	93.16	gold quality
cerebellum	UBERON:0002037	93.06	gold quality
ganglionic eminence	UBERON:0004023	93.03	gold quality
body of uterus	UBERON:0009853	92.97	gold quality
adenohypophysis	UBERON:0002196	92.93	gold quality
tibial nerve	UBERON:0001323	92.80	gold quality
endocervix	UBERON:0000458	92.75	gold quality
ventricular zone	UBERON:0003053	92.61	gold quality
right frontal lobe	UBERON:0002810	92.37	gold quality
right ovary	UBERON:0002118	92.25	gold quality
left ovary	UBERON:0002119	92.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.09	gold quality
pituitary gland	UBERON:0000007	92.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.05	gold quality
lower esophagus	UBERON:0013473	92.03	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.00	gold quality
ectocervix	UBERON:0012249	91.69	gold quality
left uterine tube	UBERON:0001303	91.66	gold quality
right adrenal gland cortex	UBERON:0035827	91.29	gold quality
skin of leg	UBERON:0001511	91.26	gold quality
right coronary artery	UBERON:0001625	91.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, BCLAF1, FUBP1, HMGB2, NR1H2, SP1, TBP, TP53, VDR, YBX1

miRNA regulators (miRDB)

17 targeting ERCC3, 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-4533	100.00	69.48	2758
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-548AS-3P	99.12	69.12	2294

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 98.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• p52 mediates function within the transcription/repair factor TFIIH. (PMID:12080057)
• Reduced level of the repair/transcription factor TFIIH in trichothiodystrophy. (PMID:12393803)
• TFIIH from trichothiodystrophy patients, but not from xeroderma pigmentosum patients, exhibit a significant in vitro basal transcription defect in addition to a reduced intercellular concentration. (PMID:12820975)
• High XRB mRNA levels is associated with Clear cell tumors of epithelial ovarian cancer (PMID:14614013)
• identification of a new, evolutionarily conserved, core TFIIH subunit is essential for our understanding of TFIIH function in transcription, DNA repair and human disease (PMID:15220921)
• Reduced expression of ERCC3 was correlated with esophageal cancer progression (PMID:15375507)
• data support an additional role for XPB in promoting the incision of the damaged DNA fragment and reveal a point of nucleotide excision repair regulation on TFIIH without interference in its transcription activity (PMID:15549133)
• Single Nucleotide Polymorphism in the ERCC3 is associated with lung cancer (PMID:16835333)
• XPB could inhibit the proliferation of hepatoma cells and had a positive effect on the expression of p53 and p21(waf1/cip1) but a negative effect on c-myc. (PMID:16914395)
• mechanism in which the helicase activity of XPB is not used for the opening and repair of damaged DNA, which is instead only driven by its ATPase activity, in combination with the helicase activity of XPD (PMID:17466626)
• Multiple proteins both known and unknown to interact with RAD52 were identified by the “dual-tagging” proteomic method. (PMID:19338310)
• Single Nucleotide Polimorphisms in VEGF and ERCC3 were associated with alterations in White Blood Cells and WBC subtype counts in workers exposed to benzene, even at relatively low levels of exposure below 1 ppm. (PMID:19773279)
• Results show that a deficiency in functional XPB paradoxically renders cells more sensitive to the genotoxic effects of oxidative stress while reducing the cytotoxic effects. (PMID:19840190)
• TFIIH core subunit p89, but not other subunits of TFIIH, associates with the centrosomes and the adjacent parts of the mitotic spindle during mitosis. (PMID:20208140)
• The C1D gene has been identified as one of the major genes whose expression is significantly upregulated by restoring XPB function. (PMID:20530579)
• results demonstrated that a) XP-G/CS mutations affect the disassembly state of TFIIH resulting in the dissociation of CAK, but not XPD from core TFIIH (PMID:20543986)
• The phosphorylation of the androgen receptor by TFIIH directs the ubiquitin/proteasome process. (PMID:21157430)
• These results suggest that TFIIH mediated cDNA degradation is a nuclear host defense against retroviral infection. (PMID:21167544)
• These results indicated that persistent HBV infection might trigger NER impairment in part through upregulation of miR-192, which suppressed the levels of ERCC3 and ERCC4. (PMID:21672525)
• high expression of ERCC1, XPB and ILF3 was observed in human epithelial ovarian cancer (PMID:21971700)
• Phenotype-specific adverse effects of XPD mutations on human prenatal development implicate impairment of TFIIH-mediated functions in placenta. (PMID:22234153)
• reduction in ERCC3 by siRNA interference in human melanocytes in vitro reduced their tyrosinase production ability (PMID:22615732)
• XPB and XPD helicases differentially regulate TFIIH compositional change during nucleotide excision repair. (PMID:23083890)
• results identify the ARCH domain of XPD as a platform for the recruitment of CAK and as a molecular switch that might control TFIIH composition and play a role in conversion of TFIIH from a factor active in transcription to a factor involved in DNA repair (PMID:23382212)
• The crystal structure of the C-terminal half of the XPB subunit of TFIIH (residues 494-782) is reported, containing XPB helicase domain (HD)2 and a C-terminal extension which shares structural similarity with RIG-I. (PMID:23385459)
• findings suggest that benzene exposure may be associated with hypermethylation in ERCC3, and that genetic variants in EPHX1 may play an important role in epigenetic changes and hematotoxicity among benzene-exposed workers (PMID:23797950)
• XPB and XPD enrichment at G4 motifs characterizes specific signaling pathways and regulatory pathways associated with specific cancers (PMID:24609361)
• Transcriptional differences found between various TFIIH subunit variants participate in the phenotypic variability observed among xeroderma pigmentosum, XP associated with Cockayne syndrome, and trichothiodystrophy individuals. (PMID:25620205)
• Data did not find any association between ERCC2 or ERCC3 gene polymorphisms and the development of osteosarcoma. (PMID:27051024)
• An essential role of MYC-ERCC3 interactions in PDAC. (PMID:27384421)
• similar to tumors arising in the background of homologous repair defects, mutations in nucleotide excision repair genes such as ERCC3 could constitute potential therapeutic targets in a subset of hereditary breast cancers. (PMID:27655433)
• significant interactions between ERCC2 (Lys751Gln) and ERCC3 (7122 A>G) genotypes polymorphism and cadmium exposure in association with nasal polyposis disease (PMID:27838878)
• Study shows that: mRNA synthesis is sensitive to the inhibition of the ATPase activity of XPB; mRNA synthesis accommodates the depletion of XPB; XPB-depleted TFIIH participates in mRNA synthesis, and finally, XPB ATPase overcomes transcription initiation block imposed by its helicase motifs. (PMID:28157507)
• We found that the T allele of ERCC2-rs1799793 and the A allele of ERCC3-rs4150441, interaction between rs1799793 and rs4150441, and haplotype containing the rs1799793T and rs11615-T alleles were all associated with increased osteosarcoma risk (PMID:28474168)
• results reveal a previously unknown role for transcription factor IIH in ATR kinase activation in non-replicating, non-cycling cells (PMID:28592488)
• This study demonstrates that CpG-specific DNA methylation in the ERCC3 promoter region may be involved in benzene-induced epigenetic modification and it may contribute to benzene-induced hematotoxicity. (PMID:28813025)
• Spironolactone-induced degradation of the TFIIH core complex XPB subunit suppresses NF-kappaB and AP-1 signalling, preventing inflammation in pulmonary hypertension. (PMID:29036418)
• Reduced protein expression levels of DNA excision repair protein ERCC-3 (ERCC3) and XPA nucleotide excision repair protein (XPA) were associated with an increased risk of squamous cell carcinoma of head and neck (SCCHN). (PMID:29528139)
• Reduced mRNA expression levels of XPB were associated with an increased risk of the head and neck squamous cell carcinomas in a Chinese population. (PMID:31832883)
• Microtubule associated protein 9 inhibits liver tumorigenesis by suppressing ERCC3. (PMID:32151798)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ercc3	ENSDARG00000002402
mus_musculus	Ercc3	ENSMUSG00000024382
rattus_norvegicus	Ercc3	ENSRNOG00000013180
drosophila_melanogaster	hay	FBGN0001179
caenorhabditis_elegans		WBGENE00013441

Protein

Protein identifiers

General transcription and DNA repair factor IIH helicase/translocase subunit XPB — P19447 (reviewed: P19447)

Alternative names: Basic transcription factor 2 89 kDa subunit, DNA 3’-5’ helicase/translocase XPB, DNA excision repair protein ERCC-3, DNA repair protein complementing XP-B cells, TFIIH basal transcription factor complex 89 kDa subunit, Xeroderma pigmentosum group B-complementing protein

All UniProt accessions (11): A0A2R8Y4R8, A0A2R8Y5H0, A0A2R8Y5L2, A0A2R8Y681, A0A2R8Y6W8, A0A2R8Y762, A0A2R8YES7, A0A2R8YFS3, P19447, F2Z2V4, H7C309

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent 3’-5’ DNA helicase/translocase. Binds dsDNA rather than ssDNA, unzipping it in a translocase rather than classical helicase activity. Component of the general transcription and DNA repair factor IIH (TFIIH) core complex. When complexed to CDK-activating kinase (CAK), involved in RNA transcription by RNA polymerase II. The ATPase activity of XPB/ERCC3, but not its helicase activity, is required for DNA opening; it may wrap around the damaged DNA wedging it open, causing localized melting that allows XPD/ERCC2 helicase to anchor. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. The ATP-dependent helicase activity of XPB/ERCC3 is required for promoter opening and promoter escape. In transcription pre-initiation complexes induces and propagates a DNA twist to open DNA. Also involved in transcription-coupled nucleotide excision repair (NER) of damaged DNA. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The structure of the TFIIH transcription complex differs from the NER-TFIIH complex; large movements by XPD/ERCC2 and XPB/ERCC3 are stabilized by XPA. XPA retains XPB/ERCC3 at the 5’ end of a DNA bubble (mimicking DNA damage).

Subunit / interactions. Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with PUF60. Interacts with ATF7IP. Interacts with KAT2A; leading to KAT2A recruitment to promoters and acetylation of histones. Part of TBP-based Pol II pre-initiation complex (PIC), in which Pol II core assembles with general transcription factors and other specific initiation factors including GTF2E1, GTF2E2, GTF2F1, GTF2F2, TCEA1, ERCC2, ERCC3, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2A1, GTF2A2, GTF2B and TBP; this large multi-subunit PIC complex mediates DNA unwinding and targets Pol II core to the transcription start site where the first phosphodiester bond forms. (Microbial infection) Interacts with Epstein-Barr virus EBNA2.

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylation on Ser-751 by CK2 controls the 5’-excision activity of ERCC1-XPF endonuclease; phosphorylated protein inhibits the excision activity and thus NER. Dephosphorylation reactivates the 5’-excision step. Phosphorylation has no effect on transcription or the 3’-5’ helicase activity.

Disease relevance. Xeroderma pigmentosum complementation group B (XP-B) [MIM:610651] 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-B patients present features of Cockayne syndrome, including 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. Trichothiodystrophy 2, photosensitive (TTD2) [MIM:616390] A form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phosphorylation on Ser-751 by CK2 controls the 5’-excision activity of ERCC1-XPF endonuclease; phosphorylated protein inhibits the excision activity and thus NER. ATPase activity is stimulated by TFIIH subunit p52 (GTF2H4). DNA translocase activity by this subunit in TFIIH is stimulated by XPA, ERCC5/XPG and XFP plus ERCC1; translocase activity is sensitive to triptolide which targets this enzyme.

Miscellaneous. The TFIIH core complex from patient XP11BE (a patient with XP/CS who has a C-terminal splice-site frameshift from residue 741 in this protein) reconstitutes in vitro transcription about 30% less well than wild-type but does not restore NER in vitro or in vivo. The XP11BE TFIIH complex has all the subunits in the same stoichiometry as wild-type. Purified mutant protein has very weak 3’-5’ helicase and ATPase activities. In another paper the mutant protein has wild-type 3’-5’ helicase activity. The mutation is recessive to wild-type. XPB/ERCC3 is not phosphorylated in vitro in this mutant, and does not restore transcription in XPB/ERCC3-defective cells. Conventional DNA helicases unwind DNA by binding to a ssDNA overhang of dsDNA and then translocating on this strand with cycles of ATP binding and hydrolysis to ‘unzip’ the dsDNA. XPB/ERCC3 is believed to be an unconventional DNA helicase principally because it translocates in a 3’-5’ direction along dsDNA instead of ssDNA, thus it is referred to as a DNA translocase.

Similarity. Belongs to the helicase family. RAD25/XPB subfamily.

RefSeq proteins (3): NP_000113, NP_001290345, NP_001290347 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001161	XPB/Ssl2	Family
IPR001650	Helicase_C-like	Domain
IPR006935	Helicase/UvrB_N	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032438	ERCC3_RAD25_C	Domain
IPR032830	XPB/Ssl2_N	Domain
IPR050615	ATP-dep_DNA_Helicase	Family

Pfam: PF04851, PF13625, PF16203

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (99 total): helix 33, strand 31, sequence variant 7, turn 7, mutagenesis site 6, binding site 3, compositionally biased region 3, domain 2, modified residue 2, region of interest 2, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

52 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4ERN	X-RAY DIFFRACTION	1.8
7NVV	ELECTRON MICROSCOPY	2.9
28JM	ELECTRON MICROSCOPY	3.29
7EGB	ELECTRON MICROSCOPY	3.3
8EBU	ELECTRON MICROSCOPY	3.3
9PD3	ELECTRON MICROSCOPY	3.3
28JS	ELECTRON MICROSCOPY	3.32
9PD4	ELECTRON MICROSCOPY	3.4
6RO4	ELECTRON MICROSCOPY	3.5
7AD8	ELECTRON MICROSCOPY	3.5
9XYU	ELECTRON MICROSCOPY	3.5
28KE	ELECTRON MICROSCOPY	3.6
8EBX	ELECTRON MICROSCOPY	3.6
8EBY	ELECTRON MICROSCOPY	3.6
6NMI	ELECTRON MICROSCOPY	3.7
7EGC	ELECTRON MICROSCOPY	3.9
7NVX	ELECTRON MICROSCOPY	3.9
8EBT	ELECTRON MICROSCOPY	3.9
28JV	ELECTRON MICROSCOPY	3.91
8BVW	ELECTRON MICROSCOPY	4
8EBS	ELECTRON MICROSCOPY	4
7ENA	ELECTRON MICROSCOPY	4.07
8BYQ	ELECTRON MICROSCOPY	4.1
7ENC	ELECTRON MICROSCOPY	4.13
8GXS	ELECTRON MICROSCOPY	4.16
7NVW	ELECTRON MICROSCOPY	4.3
9PCP	ELECTRON MICROSCOPY	4.3
5OF4	ELECTRON MICROSCOPY	4.4
6O9M	ELECTRON MICROSCOPY	4.4
7NVR	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19447-F1	76.34	0.30

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 (3): 340–347; 642; 645

Post-translational modifications (2): 686, 751

Mutagenesis-validated functional residues (6):

Position	Phenotype
346	dominant-negative effect on transcription and ner, induces chromatin collapse, probably has no atpase activity. no trans
469	very low 3’-5’ helicase activity, wild-type atpase activity, opens damaged dna, nearly wild-type ner activity in vivo, 5
638	very low 3’-5’ helicase activity, wild-type atpase activity, wild-type damaged dna removal, 80% decreased transcription
751	restores ner in xpb/ercc3-defective cells, does not inhibit 5’-incision by ercc1-xpf, wild-type transcription and helica
751	does not restore ner in xpb/ercc3-defective cells, inhibits 5’-incision by ercc1-xpf, wild-type transcription and helica
782	impairs protein folding.

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-113418	Formation of the Early Elongation Complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158	Formation of the HIV-1 Early Elongation Complex
R-HSA-167160	RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
R-HSA-167161	HIV Transcription Initiation
R-HSA-167162	RNA Polymerase II HIV Promoter Escape
R-HSA-167172	Transcription of the HIV genome
R-HSA-167200	Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167246	Tat-mediated elongation of the HIV-1 transcript
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5696395	Formation of Incision Complex in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-72086	mRNA Capping
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-73776	RNA Polymerase II Promoter Escape
R-HSA-73779	RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
R-HSA-73863	RNA Polymerase I Transcription Termination
R-HSA-75953	RNA Polymerase II Transcription Initiation
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-76042	RNA Polymerase II Transcription Initiation And Promoter Clearance
R-HSA-77075	RNA Pol II CTD phosphorylation and interaction with CE

MSigDB gene sets: 531 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_CHROMOSOME_ORGANIZATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_TRANSCRIPTION_COUPLED_NUCLEOTIDE_EXCISION_REPAIR, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GEORGES_CELL_CYCLE_MIR192_TARGETS, GOBP_NEUROGENESIS, KAUFFMANN_DNA_REPAIR_GENES, MODULE_229, GOBP_UV_PROTECTION, PUJANA_CHEK2_PCC_NETWORK, GOBP_DNA_CONFORMATION_CHANGE, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_NUCLEOTIDE_EXCISION_REPAIR

GO Biological Process (17): DNA topological change (GO:0006265), DNA repair (GO:0006281), transcription-coupled nucleotide-excision repair (GO:0006283), nucleotide-excision repair (GO:0006289), transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367), transcription elongation by RNA polymerase II (GO:0006368), apoptotic process (GO:0006915), response to oxidative stress (GO:0006979), intracellular protein localization (GO:0008104), response to UV (GO:0009411), UV protection (GO:0009650), hair cell differentiation (GO:0035315), positive regulation of apoptotic process (GO:0043065), embryonic organ development (GO:0048568), regulation of mitotic cell cycle phase transition (GO:1901990), DNA damage response (GO:0006974)

GO Molecular Function (12): DNA binding (GO:0003677), damaged DNA binding (GO:0003684), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), 3’-5’ DNA helicase activity (GO:0043138), promoter-specific chromatin binding (GO:1990841), nucleotide binding (GO:0000166), DNA helicase activity (GO:0003678), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787), isomerase activity (GO:0016853)

GO Cellular Component (7): nucleotide-excision repair factor 3 complex (GO:0000112), transcription factor TFIIH core complex (GO:0000439), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIID complex (GO:0005669), transcription factor TFIIH holo complex (GO:0005675), transcription preinitiation complex (GO:0097550)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Transcription of the HIV genome	4
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	3
RNA Polymerase II Transcription Elongation	2
HIV Transcription Elongation	2
Global Genome Nucleotide Excision Repair (GG-NER)	2
Late Phase of HIV Life Cycle	1
Tat-mediated elongation of the HIV-1 transcript	1
Negative epigenetic regulation of rRNA expression	1
RNA Polymerase II Transcription	1
Nucleotide Excision Repair	1
Transcriptional Regulation by TP53	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulator complex	3
DNA metabolic process	2
transcription by RNA polymerase II	2
ATP-dependent activity	2
catalytic activity	2
transcription factor TFIIH core complex	2
RNA polymerase II, holoenzyme	2
DNA conformation change	1
DNA damage response	1
nucleotide-excision repair	1
DNA repair	1
DNA-templated transcription	1
DNA-templated transcription initiation	1
DNA-templated transcription elongation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to stress	1
macromolecule localization	1
response to light stimulus	1
response to UV	1
epidermal cell differentiation	1
neuron differentiation	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
embryo development	1
animal organ development	1
regulation of mitotic cell cycle	1
mitotic cell cycle phase transition	1
regulation of cell cycle phase transition	1
cellular response to stress	1
nucleic acid binding	1
DNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
DNA helicase activity	1
chromatin binding	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

2735 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERCC3	ERCC2	P18074	999
ERCC3	GTF2H5	Q6ZYL4	999
ERCC3	GTF2H4	Q92759	998
ERCC3	GTF2H1	P32780	998
ERCC3	GTF2H2	Q13888	998
ERCC3	XPA	P23025	998
ERCC3	CCNH	P51946	996
ERCC3	GTF2H3	Q13889	996
ERCC3	CDK7	P50613	991
ERCC3	ERCC1	P07992	988
ERCC3	ERCC4	Q92889	968
ERCC3	ERCC5	P28715	962
ERCC3	A0A090J7P6	A0A090J7P6	954
ERCC3	GTF2B	Q00403	950
ERCC3	PUF60	Q9UHX1	947

IntAct

144 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CCNH	ERCC3	psi-mi:“MI:0914”(association)	0.850
GTF2H5	ERCC3	psi-mi:“MI:0915”(physical association)	0.800
ERCC3	GTF2H1	psi-mi:“MI:0914”(association)	0.790
CCNH	ERCC2	psi-mi:“MI:0915”(physical association)	0.750
CETN2	SFI1	psi-mi:“MI:0914”(association)	0.740
ERCC3	XIAP	psi-mi:“MI:0915”(physical association)	0.670
XIAP	ERCC3	psi-mi:“MI:0915”(physical association)	0.670
ERCC3	ERCC2	psi-mi:“MI:0915”(physical association)	0.670
ERCC2	ERCC3	psi-mi:“MI:0915”(physical association)	0.670
ERCC3	ERCC2	psi-mi:“MI:0914”(association)	0.670
ERCC3	TRIM27	psi-mi:“MI:0915”(physical association)	0.670
KPNA3	ERCC3	psi-mi:“MI:0915”(physical association)	0.670
TRIM27	ERCC3	psi-mi:“MI:0915”(physical association)	0.670
GTF2H5	ERCC2	psi-mi:“MI:0914”(association)	0.650
POLR2C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
GTF2H3	ERCC3	psi-mi:“MI:0914”(association)	0.640
MNAT1	ERCC2	psi-mi:“MI:0914”(association)	0.640
FGL1	LCMT2	psi-mi:“MI:0914”(association)	0.640
ERCC3	XPC	psi-mi:“MI:0407”(direct interaction)	0.590
XPC	ERCC3	psi-mi:“MI:0407”(direct interaction)	0.590
ERCC3	Psmc5	psi-mi:“MI:0915”(physical association)	0.580
Psmc5	ERCC3	psi-mi:“MI:0915”(physical association)	0.580

BioGRID (340): ERCC3 (Two-hybrid), CEP70 (Two-hybrid), ERCC3 (Affinity Capture-RNA), BCR (Reconstituted Complex), MCF2 (Reconstituted Complex), CDC42 (Reconstituted Complex), BCR (Affinity Capture-Western), GTF2H1 (Affinity Capture-Western), ERCC3 (Affinity Capture-MS), ERCC3 (Affinity Capture-MS), ERCC3 (Affinity Capture-MS), GTF2H1 (Co-fractionation), GTF2H2C (Co-fractionation), GTF2H2 (Co-fractionation), GTF2H2C_2 (Co-fractionation)

ESM2 similar proteins: A0JN86, A2AHJ4, A2APV2, A2AQW0, A9JRL3, B3DK16, O08874, O35099, P0CF52, P19447, P23798, P25916, P32866, P35226, P35227, P49135, Q07139, Q1JPS1, Q1RMT1, Q21029, Q28H21, Q2YDF9, Q32KX7, Q3UK78, Q4QR06, Q5R8L2, Q5RA62, Q5SDR3, Q5ZKK7, Q640D5, Q6DD21, Q6DLV9, Q6GN16, Q6RI45, Q6ZN16, Q7T3E6, Q7Z569, Q7ZYZ7, Q86SE9, Q8BPM2

Diamond homologs: A6WE36, A9CRJ7, C4V922, O53873, P19447, P49135, Q02870, Q1RMT1, Q38861, Q4G005, Q580W5, Q5RA62, Q5V5F7, Q5ZKK7, Q60HG1, Q6E6J3, Q7ZVV1, Q8SSK1, Q971U1, Q9FUG4, Q9HPZ2, O00835, O13768, Q00578, Q381F9

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ERCC3	“form complex”	TFIIH	binding
CDK7	“down-regulates quantity by destabilization”	ERCC3	phosphorylation
FBXL18	“down-regulates quantity by destabilization”	ERCC3	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	ERCC3	polyubiquitination
ERCC2	up-regulates	ERCC3	binding
CSNK2A1	“down-regulates activity”	ERCC3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 112 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	11	59.0×	3e-15
RNA Pol II CTD phosphorylation and interaction with CE	11	59.0×	3e-15
mRNA Capping	11	55.1×	5e-15
Formation of the Early Elongation Complex	11	48.6×	1e-14
Formation of the HIV-1 Early Elongation Complex	11	48.6×	1e-14
HIV Transcription Elongation	10	44.2×	3e-13
Global Genome Nucleotide Excision Repair (GG-NER)	7	42.1×	3e-09
Formation of Incision Complex in GG-NER	12	40.1×	1e-14

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	11	42.6×	9e-13
transcription initiation at RNA polymerase II promoter	8	30.3×	5e-08
positive regulation of miRNA transcription	5	14.7×	4e-03
positive regulation of transcription initiation by RNA polymerase II	5	13.7×	4e-03
transcription by RNA polymerase II	14	10.0×	5e-08
DNA repair	10	6.5×	7e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — CESC, MEL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	38
Likely pathogenic	15
Uncertain significance	276
Likely benign	245
Benign	36

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071982	NM_000122.2(ERCC3):c.862del (p.Glu288fs)	Pathogenic
1322831	NM_000122.2(ERCC3):c.1385_1386del (p.His461_Cys462insTer)	Pathogenic
1456206	NM_000122.2(ERCC3):c.659_660insA (p.Ser221fs)	Pathogenic
16582	NM_000122.2(ERCC3):c.2218-6C>A	Pathogenic
16583	NM_000122.2(ERCC3):c.296T>C (p.Phe99Ser)	Pathogenic
16584	NM_000122.2(ERCC3):c.355A>C (p.Thr119Pro)	Pathogenic
16585	NM_000122.2(ERCC3):c.1273C>T (p.Arg425Ter)	Pathogenic
16586	NM_000122.2(ERCC3):c.809_810del (p.Ser269_Phe270insTer)	Pathogenic
16588	NM_000122.2(ERCC3):c.1633C>T (p.Gln545Ter)	Pathogenic
16589	NM_000122.2(ERCC3):c.471+1G>A	Pathogenic
1913053	NM_000122.2(ERCC3):c.973C>T (p.Arg325Ter)	Pathogenic
1973296	NM_000122.2(ERCC3):c.579_580insT (p.Ile194fs)	Pathogenic
2020402	NM_000122.2(ERCC3):c.174del (p.Lys59fs)	Pathogenic
2030008	NM_000122.2(ERCC3):c.731del (p.Ile244fs)	Pathogenic
2032305	NM_000122.2(ERCC3):c.1771C>T (p.Gln591Ter)	Pathogenic
2123844	NM_000122.2(ERCC3):c.568C>T (p.Gln190Ter)	Pathogenic
2169501	NM_000122.2(ERCC3):c.1129C>T (p.Gln377Ter)	Pathogenic
2171512	NM_000122.2(ERCC3):c.1337dup (p.Pro447fs)	Pathogenic
2696647	NM_000122.2(ERCC3):c.229del (p.Trp77fs)	Pathogenic
2717993	NM_000122.2(ERCC3):c.133C>T (p.Gln45Ter)	Pathogenic
2755393	NM_000122.2(ERCC3):c.338dup (p.His114fs)	Pathogenic
2762837	NM_000122.2(ERCC3):c.1685_1686del (p.Ala562fs)	Pathogenic
2787734	NM_000122.2(ERCC3):c.146C>G (p.Ser49Ter)	Pathogenic
2816957	NM_000122.2(ERCC3):c.832G>T (p.Glu278Ter)	Pathogenic
2829712	NM_000122.2(ERCC3):c.363C>G (p.Tyr121Ter)	Pathogenic
2832554	NM_000122.2(ERCC3):c.971del (p.Leu324fs)	Pathogenic
2982186	NM_000122.2(ERCC3):c.576_583del (p.Val193fs)	Pathogenic
3247457	NC_000002.11:g.(?128046216)(128051657_?)del	Pathogenic
3255224	NM_000122.2(ERCC3):c.760C>T (p.Gln254Ter)	Pathogenic
3630007	NM_000122.2(ERCC3):c.1841C>A (p.Ser614Ter)	Pathogenic

SpliceAI

1991 predictions. Top by Δscore:

Variant	Effect	Δscore
2:127259294:A:AC	donor_gain	1.0000
2:127259294:AC:A	donor_gain	1.0000
2:127259294:ACCTG:A	donor_loss	1.0000
2:127259295:C:CA	donor_gain	1.0000
2:127259295:CC:C	donor_gain	1.0000
2:127259295:CCT:C	donor_gain	1.0000
2:127259295:CCTG:C	donor_gain	1.0000
2:127259295:CCTGG:C	donor_gain	1.0000
2:127259445:TCAC:T	acceptor_gain	1.0000
2:127259446:CAC:C	acceptor_gain	1.0000
2:127259446:CACC:C	acceptor_gain	1.0000
2:127272962:C:CC	acceptor_gain	1.0000
2:127279167:TCTTA:T	donor_loss	1.0000
2:127279168:CTTAC:C	donor_loss	1.0000
2:127279169:TTAC:T	donor_loss	1.0000
2:127279170:TACT:T	donor_loss	1.0000
2:127279171:A:AC	donor_gain	1.0000
2:127279171:ACTT:A	donor_loss	1.0000
2:127279172:C:CC	donor_gain	1.0000
2:127279172:C:CG	donor_loss	1.0000
2:127279243:T:TA	donor_gain	1.0000
2:127279371:CAGAC:C	acceptor_gain	1.0000
2:127279372:AGAC:A	acceptor_gain	1.0000
2:127279372:AGACC:A	acceptor_loss	1.0000
2:127279373:GAC:G	acceptor_gain	1.0000
2:127279373:GACCT:G	acceptor_loss	1.0000
2:127279374:AC:A	acceptor_gain	1.0000
2:127279374:ACC:A	acceptor_loss	1.0000
2:127279375:CC:C	acceptor_gain	1.0000
2:127279375:CCTGT:C	acceptor_loss	1.0000

AlphaMissense

5176 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:127259366:A:T	V716D	1.000
2:127259378:A:G	L712P	1.000
2:127261231:G:C	F687L	1.000
2:127261231:G:T	F687L	1.000
2:127261233:A:G	F687L	1.000
2:127261242:C:G	G684R	1.000
2:127261253:A:C	L680W	1.000
2:127261253:A:G	L680S	1.000
2:127261255:G:C	F679L	1.000
2:127261255:G:T	F679L	1.000
2:127261256:A:C	F679C	1.000
2:127261256:A:G	F679S	1.000
2:127261257:A:G	F679L	1.000
2:127261257:A:T	F679I	1.000
2:127261286:T:A	E669V	1.000
2:127261287:C:T	E669K	1.000
2:127261292:G:A	T667I	1.000
2:127261301:G:A	S664F	1.000
2:127261301:G:T	S664Y	1.000
2:127261302:A:G	S664P	1.000
2:127261307:A:C	L662R	1.000
2:127261307:A:G	L662P	1.000
2:127261307:A:T	L662Q	1.000
2:127261311:A:G	S661P	1.000
2:127261314:A:C	Y660D	1.000
2:127261315:G:C	F659L	1.000
2:127261315:G:T	F659L	1.000
2:127261317:A:G	F659L	1.000
2:127261322:G:T	A657D	1.000
2:127271350:A:G	L644P	1.000

dbSNP variants (sampled 300 via entrez): RS1000118663 (2:127257068 AAC>A), RS1000225636 (2:127268750 C>T), RS1000226031 (2:127286249 C>A), RS1000235391 (2:127269673 G>A,C), RS1000240074 (2:127256829 T>C), RS1000258542 (2:127285983 A>T), RS1000363729 (2:127263752 G>A,C), RS1000491983 (2:127273743 C>A,G), RS1000606436 (2:127273506 T>C), RS1000660055 (2:127261476 A>C), RS1000811142 (2:127267569 G>C), RS1000814889 (2:127280015 T>C), RS1000908184 (2:127267180 T>C,G), RS1000962059 (2:127261658 G>A), RS1000962855 (2:127287109 A>G)

Disease associations

OMIM: gene MIM:133510 | disease phenotypes: MIM:278700, MIM:610651, MIM:616390, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
xeroderma pigmentosum group B	Definitive	Autosomal recessive
trichothiodystrophy 2, photosensitive	Definitive	Autosomal recessive
trichothiodystrophy 1, photosensitive	Strong	Autosomal recessive
xeroderma pigmentosum-Cockayne syndrome complex	Supportive	Autosomal recessive
trichothiodystrophy	Supportive	Autosomal recessive
xeroderma pigmentosum	Supportive	Autosomal recessive
hereditary breast carcinoma	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
xeroderma pigmentosum group B	Definitive	AR

Mondo (9): xeroderma pigmentosum (MONDO:0019600), xeroderma pigmentosum group B (MONDO:0012531), trichothiodystrophy 2, photosensitive (MONDO:0014615), ovarian cancer (MONDO:0008170), hereditary neoplastic syndrome (MONDO:0015356), hereditary breast carcinoma (MONDO:0016419), trichothiodystrophy 1, photosensitive (MONDO:0011125), xeroderma pigmentosum-Cockayne syndrome complex (MONDO:0016354), trichothiodystrophy (MONDO:0018053)

Orphanet (5): Xeroderma pigmentosum (Orphanet:910), Trichothiodystrophy (Orphanet:33364), Rare ovarian cancer (Orphanet:213500), Inherited cancer-predisposing syndrome (Orphanet:140162), OBSOLETE: Xeroderma pigmentosum complementation group B (Orphanet:276252)

HPO phenotypes

166 total (30 of 166 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000133	Gonadal dysgenesis
HP:0000135	Hypogonadism
HP:0000164	Abnormality of the dentition
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000320	Bird-like facies
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000482	Microcornea
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000491	Keratitis
HP:0000498	Blepharitis
HP:0000509	Conjunctivitis
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000524	Conjunctival telangiectasia
HP:0000545	Myopia
HP:0000546	Retinal degeneration
HP:0000565	Esotropia
HP:0000568	Microphthalmia
HP:0000580	Pigmentary retinopathy

GWAS associations

0 associations (top):

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
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
C562840	Breast Cancer, Familial (supp.)
C562590	Xeroderma Pigmentosum, Complementation Group B (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523193 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3738948	Efficacy	3	Platinum compounds	Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3738948	ERCC3	3	2.25	1	Platinum compounds

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	increases expression, affects cotreatment	2
Benzene	affects expression, affects response to substance	2
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
IMOL S-140	decreases expression	1
beta-lapachone	decreases expression	1
o,p’-DDT	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
riccardin D	decreases expression	1
6-OH-BDE-47	decreases expression	1
1-(3-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-3-(4-(bis(2-chloroethyl)amino)phenyl)urea	increases response to substance	1
Bortezomib	increases response to substance	1
Acetaminophen	increases expression	1
Arsenic	decreases expression	1
Benzo(a)pyrene	increases expression	1
Chelating Agents	decreases expression, affects binding	1
Copper	decreases expression, affects binding	1
Dihydroxyacetone	increases expression	1
Doxorubicin	decreases expression	1
Lead	affects expression	1
Menthol	increases expression	1
Pentachlorophenol	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quartz	decreases expression	1
Tretinoin	decreases expression	1
Vitamin E	increases expression	1
Zearalenone	increases expression	1
Asbestos, Amphibole	increases expression	1
Sodium Selenite	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4385229	ADMET	Inhibition of XBP ATPase activity in human HeLa cell nuclear extracts	NQO1-Selective Activated Prodrug of Triptolide: Synthesis and Antihepatocellular Carcinoma Activity Evaluation. — ACS Med Chem Lett

Cellosaurus cell lines

26 cell lines: 15 finite cell line, 11 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1F28	XPCSH4BA	Finite cell line	Female
CVCL_1F29	XPCSH5BA	Finite cell line	Male
CVCL_1F81	GM21149	Transformed cell line	Male
CVCL_1F82	GM21150	Transformed cell line	Female
CVCL_L460	XP11BE LCL	Transformed cell line	Female
CVCL_L461	XPH134BE	Finite cell line	Female
CVCL_L462	XPH134BE LCL	Transformed cell line	Female
CVCL_L463	XPH135BE LCL	Transformed cell line	Male
CVCL_U690	XP11BE	Finite cell line	Female
CVCL_V271	XPCS1BA	Finite cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	PHASE3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	PHASE3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer
NCT00003644	PHASE3	COMPLETED	Carboplatin Plus Paclitaxel With or Without Continued Low-Dose Paclitaxel in Treating Patients With Early-Stage Ovarian Cancer