ERCC2

Summary

ERCC2 (ERCC excision repair 2, TFIIH core complex helicase subunit, HGNC:3434) is a protein-coding gene on chromosome 19q13.32, encoding General transcription and DNA repair factor IIH helicase subunit XPD (P18074). ATP-dependent 5’-3’ DNA helicase. In precision oncology, ERCC2 K751Q confers sensitivity to Paclitaxel + Carboplatin in Lung Non-small Cell Carcinoma (CIViC Level B); 1 further curated variant–drug associations are listed below. It is a common-essential gene (DepMap: required in 94.8% of cancer cell lines).

The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2068 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex hereditary spastic paraplegia (Definitive, ClinGen) — +9 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 2,812 total — 96 pathogenic, 97 likely-pathogenic
• Phenotypes (HPO): 230
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 94.8% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity dosage sensitivity unlikely
• MANE Select transcript: NM_000400

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3434
Approved symbol	ERCC2
Name	ERCC excision repair 2, TFIIH core complex helicase subunit
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	MAG, EM9, MGC102762, MGC126218, MGC126219
Ensembl gene	ENSG00000104884
Ensembl biotype	protein_coding
OMIM	126340
Entrez	2068

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 14 protein_coding, 8 retained_intron, 5 nonsense_mediated_decay

ENST00000391941, ENST00000391942, ENST00000391944, ENST00000391945, ENST00000485403, ENST00000586131, ENST00000586441, ENST00000586737, ENST00000586856, ENST00000587376, ENST00000588652, ENST00000591309, ENST00000646507, ENST00000682414, ENST00000682508, ENST00000684218, ENST00000684264, ENST00000684407, ENST00000684458, ENST00000684468, ENST00000891924, ENST00000891925, ENST00000891926, ENST00000891927, ENST00000913227, ENST00000913228, ENST00000965097

RefSeq mRNA: 2 — MANE Select: NM_000400 NM_000400, NM_001130867

CCDS: CCDS33049, CCDS46112

Canonical transcript exons

ENST00000391945 — 23 exons

Exon	Start	End
ENSE00000712881	45369070	45369147
ENSE00000712883	45368930	45368992
ENSE00000712888	45364424	45364547
ENSE00000712891	45363743	45363911
ENSE00000712894	45361524	45361642
ENSE00002812654	45349837	45351721
ENSE00003459564	45355665	45355728
ENSE00003485462	45357630	45357699
ENSE00003526094	45364838	45364954
ENSE00003555914	45353242	45353334
ENSE00003582081	45357270	45357371
ENSE00003590405	45352746	45352816
ENSE00003611088	45370133	45370232
ENSE00003612056	45368630	45368743
ENSE00003612951	45352506	45352649
ENSE00003628958	45357474	45357543
ENSE00003636052	45353083	45353155
ENSE00003641442	45364235	45364331
ENSE00003690867	45354730	45354851
ENSE00003786171	45363986	45364119
ENSE00003786327	45365042	45365158
ENSE00003787289	45352209	45352352
ENSE00004472052	45370536	45370573

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 92.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.9091 / max 81.2498, expressed in 1677 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181493	6.9091	1677

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	92.30	gold quality
right adrenal gland	UBERON:0001233	88.17	gold quality
left adrenal gland	UBERON:0001234	87.48	gold quality
ganglionic eminence	UBERON:0004023	87.41	gold quality
right adrenal gland cortex	UBERON:0035827	87.41	gold quality
left adrenal gland cortex	UBERON:0035825	87.40	gold quality
ventricular zone	UBERON:0003053	86.55	gold quality
right testis	UBERON:0004534	86.10	gold quality
left testis	UBERON:0004533	85.99	gold quality
adrenal cortex	UBERON:0001235	85.80	gold quality
prefrontal cortex	UBERON:0000451	85.55	gold quality
adrenal gland	UBERON:0002369	85.30	gold quality
right frontal lobe	UBERON:0002810	85.23	gold quality
granulocyte	CL:0000094	84.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.94	gold quality
cortical plate	UBERON:0005343	84.55	gold quality
adenohypophysis	UBERON:0002196	84.43	gold quality
body of uterus	UBERON:0009853	84.11	gold quality
testis	UBERON:0000473	84.07	gold quality
right lobe of thyroid gland	UBERON:0001119	84.04	gold quality
cingulate cortex	UBERON:0003027	84.01	gold quality
right ovary	UBERON:0002118	84.00	gold quality
anterior cingulate cortex	UBERON:0009835	83.95	gold quality
pituitary gland	UBERON:0000007	83.78	gold quality
apex of heart	UBERON:0002098	83.61	gold quality
gastrocnemius	UBERON:0001388	83.59	gold quality
muscle of leg	UBERON:0001383	83.47	gold quality
lower esophagus mucosa	UBERON:0035834	83.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.19	gold quality
left uterine tube	UBERON:0001303	83.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.17

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
BAX	Activation
BCL2	Repression
CDKN1A	Activation
CPD	Unknown
E2F1	Unknown
LAMTOR5	Repression
TP53	Activation
XPA	Unknown

Upstream regulators (CollecTRI, top): HIF1A, NR1H2, TP53, YBX1

miRNA regulators (miRDB)

12 targeting ERCC2, 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-22-3P	99.93	68.13	917
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-3622B-3P	96.82	66.36	988

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 40 (dosage sensitivity unlikely). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 94.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. (PMID:11751380)
• we investigated the association between the repair phenotype of ultraviolet (UV)-induced damage and genotypes of three DNA repair genes, XPC and XPD [involved in nucleotide excision repair (NER)] and XRCC1 [involved in base excision repair (BER)]. (PMID:11872635)
• Polymorphisms in XPD protein is associated with risk of primary lung cancer (PMID:11891028)
• The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk. (PMID:11960912)
• Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population. (PMID:12124811)
• polymorphism and risk of lung cancer in a Chinese population (PMID:12151350)
• XPD overexpression in SK-MG-4 cells leads to cisplatin resistance without affecting the nucleotide excision repair activity or UV light sensitivity of the cell. (PMID:12359753)
• The genotype distribution of the XPD gene does not indicate a role for base excision repair in the development of therapy-related acute myeloblastic leukemia (PMID:12393447)
• ERCC2/XPD gene polymorphisms and cancer risk. Review. (PMID:12435843)
• XPD protein levels correlate with resistance to alkylating agents in human tumor cell lines (PMID:12451985)
• Structural and functional characterization of the human DNA repair helicase XPD (PMID:12458209)
• the XPD variant alleles may be associated with an increased frequency of smoking-related p53 mutations in lung tumors, presumably due to reduced DNA repair proficiency. (PMID:12552590)
• Findings indicate that the Asp312Asn and Lys751Gln polymorphisms in the XPD locus are associated with the risk of lung Squamous Cell Carcinoma (SCC) but not lung adenocarcinoma or esophageal SCC in this Chinese population. (PMID:12579497)
• 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)
• Cumulative cigarette smoking plays an important role in altering the direction and magnitude of the associations between the XRCC1 and ERCC2 polymorphisms and lung cancer risk. (PMID:12692111)
• The Asp312Asn and Lys751Gln polymorphisms in the XPD gene may alter DNA repair capacity. The hypothesis that these 2 XPD polymorphisms are associated with risk of lung cancer was confirmed in a large hospital-based, case-control study among Chinese. (PMID:12740916)
• DNA repair gene XPD may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions (PMID:12749816)
• Basal transcription defect discriminates between xeroderma pigmentosum and trichothiodystrophy in XPD patients. (PMID:12820975)
• XPD polymorphisms is associated with breast cancer (PMID:15090466)
• Patients with nonmelanoma skin cancer who have the variant XPD Gln allele are increased risk of developing second primary cancer. (PMID:15298945)
• XPD codon 751 glutamine variant protects against myeloid cell death after chemotherapy. (PMID:15339847)
• effect of XPD codon 751 and 312 polymorphisms on the risk of esophageal squamous cell carcinoma (PMID:15381366)
• The role of a genetic polymorphism of the XPD gene in risk for colorectal cancer was investigated. (PMID:15679883)
• An associative interaction between XPD protein and CCND1 genetic polymorphisms, tobacco exposure, and cancer risk. (PMID:15754315)
• relationship between genetic polymorphism of XRCC1 and ERCC2 and DNA damage in polycyclic aromatic hydrocarbon exposed workers; no significant associations between G23591A and A35931C polymorphisms of ERCC2 were found (PMID:15764301)
• XPD single nucleotide polymorphisms mediate susceptibility to cutaneous basal cell carcinoma (PMID:15776433)
• Polymorphisms in ERCC2 are associated with the development of oligodendrogliomas (PMID:15834925)
• The combined effect of ERCC2 Asp(312)Asn and ERCC4 Ser(835)Ser genotypes might be associated with breast cancer risk in Korean women (PMID:15886521)
• A review of the possible relationship between ERCC2 polymorphisms, reduced DNA repair and increased cancer risk. (PMID:16054878)
• results provide further evidence for a role of XPD in the etiology of melanoma (PMID:16258177)
• Polymorphisms of the DNA repair genes XPD is associated with breast cancer (PMID:16319991)
• Results show that the XPD gene polymorphism could be a genetic risk modifier for smoking-related pancreatic cancer. (PMID:16458430)
• the XPD 751Gln allele may have a role in development of esophageal adenocarcinoma (PMID:16571649)
• For XPD, both alleles were lost with a similar frequency (PMID:16646069)
• results suggest that the polymorphic variants of these NER genes do not contribute to the risk of developing AD. (PMID:16806697)
• Single Nucleotide Polymorphism in the ERCC2 is associated with lung cancer (PMID:16835333)
• identification of polymorphisms in lung carcinoma of never smokers (PMID:16865671)
• Xeroderma pigmentosum group D (XPD Lys751Gln) polymorphism may be an important marker in the prediction of clinical outcome to chemo-radiotherapy in resected gastric cancer patients. (PMID:17009404)
• the XPD codon 751 glutamine-encoding variant significantly associates with risk of developing AML with a chromosome 5q deletion or a chromosome 7q deletion, but not with any other commonly recurring cytogenetic lesion (PMID:17023576)
• ERCC2 codon 751 Lys/Lys genotype is significantly associated with arsenic-induced premalignant hyperkeratosis. (PMID:17050553)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ercc2	ENSDARG00000021985
mus_musculus	Ercc2	ENSMUSG00000030400
rattus_norvegicus	Ercc2	ENSRNOG00000017753
drosophila_melanogaster	Xpd	FBGN0261850
caenorhabditis_elegans		WBGENE00021752

Paralogs (3): DDX11 (ENSG00000013573), BRIP1 (ENSG00000136492), RTEL1 (ENSG00000258366)

Protein

Protein identifiers

General transcription and DNA repair factor IIH helicase subunit XPD — P18074 (reviewed: P18074)

Alternative names: Basic transcription factor 2 80 kDa subunit, CXPD, DNA 5’-3’ helicase XPD, DNA excision repair protein ERCC-2, DNA repair protein complementing XP-D cells, TFIIH basal transcription factor complex 80 kDa subunit, Xeroderma pigmentosum group D-complementing protein

All UniProt accessions (10): P18074, A0A804HK53, A0A804HK75, A0A804HL97, A8MX75, B4E0F6, E7EVE9, K7EIT8, K7EKF3, K7ENL1

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent 5’-3’ DNA helicase. Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, not absolutely essential for minimal transcription in vitro. Required for transcription-coupled nucleotide excision repair (NER) of damaged DNA; recognizes damaged bases. Sequestered in chromatin on UV-damaged DNA. When complexed to CDK-activating kinase (CAK), involved in transcription by RNA polymerase II. 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 ATP-dependent helicase activity of XPD/ERCC2 is required for DNA opening. Involved in DNA lesion verification. 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. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. XPD/ERCC2 acts by forming a bridge between CAK and the core-TFIIH complex. 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 which allow this subunit to contact ssDNA. Involved in the regulation of vitamin-D receptor activity. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation. Might have a role in aging process and could play a causative role in the generation of skin cancers.

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 GTF2H2 (p44) which stimulates the 5’-3’ helicase activity of this subunit. Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5. Interacts with CIAO1 and CIAO2B; the interaction WITH CIAO2B is direct. Interacts with ATF7IP. Interacts directly with MMS19. 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. Cytoplasm. Cytoskeleton. Spindle.

Post-translational modifications. ISGylated.

Disease relevance. Xeroderma pigmentosum complementation group D (XP-D) [MIM:278730] 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-D 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 1, photosensitive (TTD1) [MIM:601675] 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. TTD1 patients manifest cutaneous photosensitivity. The disease is caused by variants affecting the gene represented in this entry. Cerebro-oculo-facio-skeletal syndrome 2 (COFS2) [MIM:610756] 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.

Activity regulation. Interaction with GTF2H2 (p44) results in stimulation of the 5’-3’ helicase activity of this subunit. DNA unwinding by this subunit in TFIIH is stimulated 4-fold by XPA and 20-fold by ERCC5/XPG.

Cofactor. Binds 1 [4Fe-4S] cluster.

Domain organisation. Interacts with GTF2H2/p44 via the C-terminus of this protein; mutations in the C-terminal region of XPD do not alter its helicase activity, but prevent its interaction with and helicase stimulation by GTF2H2/p44.

Similarity. Belongs to the helicase family. RAD3/XPD subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P18074-1	1	yes
P18074-2	2

RefSeq proteins (2): NP_000391, NP_001124339 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001945	RAD3/XPD	Family
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
IPR006554	Helicase-like_DEXD_c2	Domain
IPR006555	ATP-dep_Helicase_C	Domain
IPR010614	RAD3-like_helicase_DEAD	Domain
IPR010643	HBB	Domain
IPR013020	Rad3/Chl1-like	Family
IPR014013	Helic_SF1/SF2_ATP-bd_DinG/Rad3	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR045028	DinG/Rad3-like	Family

Pfam: PF06733, PF06777, PF13307

Enzyme classification (BRENDA):

• EC 3.6.4.12 — DNA helicase (BRENDA: 0 organisms, 0 substrates, 0 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (130 total): sequence variant 40, helix 34, strand 26, turn 12, binding site 5, mutagenesis site 5, splice variant 3, short sequence motif 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

51 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6TUN	X-RAY DIFFRACTION	2.07
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
7LBM	ELECTRON MICROSCOPY	4.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18074-F1	87.74	0.53

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 (5): 42–49; 116; 134; 155; 190

Mutagenesis-validated functional residues (5):

Position	Phenotype
48	decreased transcriptional activity of the reconstituted tfiih complex. damaged dna opening by tfiih is impeded. loss of
190	reduced iron-sulfur-binding. iron-sulfur-binding is further decreased in absence of mms19.
192	does not restore nucleotide excision repair (ner) in deficient cells, does not bind uv damaged dna, tfiih is able to tra
196	restores <5% nucleotide excision repair (ner) in deficient cells, does not bind uv damaged dna, tfiih is able to transcr
675	no longer interacts with gtf2h2/p44, has 5’-3’ helicase activity.

Function

Pathways and Gene Ontology

Reactome pathways

30 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-2564830	Cytosolic iron-sulfur cluster assembly
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: 921 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_SPINAL_CORD_DEVELOPMENT, REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_RIBOSOME_BIOGENESIS, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_MYELOID_CELL_DEVELOPMENT

GO Biological Process (39): maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), response to hypoxia (GO:0001666), in utero embryonic development (GO:0001701), transcription-coupled nucleotide-excision repair (GO:0006283), nucleotide-excision repair (GO:0006289), regulation of transcription by RNA polymerase II (GO:0006357), transcription elongation by RNA polymerase I (GO:0006362), transcription by RNA polymerase II (GO:0006366), transcription initiation at RNA polymerase II promoter (GO:0006367), apoptotic process (GO:0006915), response to oxidative stress (GO:0006979), chromosome segregation (GO:0007059), determination of adult lifespan (GO:0008340), UV protection (GO:0009650), post-embryonic development (GO:0009791), spinal cord development (GO:0021510), extracellular matrix organization (GO:0030198), bone mineralization (GO:0030282), central nervous system myelin formation (GO:0032289), multicellular organism growth (GO:0035264), hair cell differentiation (GO:0035315), embryonic cleavage (GO:0040016), erythrocyte maturation (GO:0043249), positive regulation of mitotic recombination (GO:0045951), insulin-like growth factor receptor signaling pathway (GO:0048009), embryonic organ development (GO:0048568), hair follicle maturation (GO:0048820), hematopoietic stem cell differentiation (GO:0060218), hematopoietic stem cell proliferation (GO:0071425), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), regulation of mitotic cell cycle phase transition (GO:1901990), nucleobase-containing compound metabolic process (GO:0006139), DNA repair (GO:0006281), DNA-templated transcription (GO:0006351), DNA damage response (GO:0006974), response to UV (GO:0009411), hair cycle process (GO:0022405), ribosomal small subunit biogenesis (GO:0042274), skin development (GO:0043588)

GO Molecular Function (17): DNA helicase activity (GO:0003678), damaged DNA binding (GO:0003684), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), protein-macromolecule adaptor activity (GO:0030674), 5’-3’ DNA helicase activity (GO:0043139), metal ion binding (GO:0046872), 4 iron, 4 sulfur cluster binding (GO:0051539), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), DNA binding (GO:0003677), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides (GO:0016818), isomerase activity (GO:0016853), iron-sulfur cluster binding (GO:0051536)

GO Cellular Component (11): 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), cytoplasm (GO:0005737), spindle (GO:0005819), cytosol (GO:0005829), CAK-ERCC2 complex (GO:0070516), MMXD complex (GO:0071817), cytoskeleton (GO:0005856)

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
Metabolism	1
Negative epigenetic regulation of rRNA expression	1
RNA Polymerase II Transcription	1
Nucleotide Excision Repair	1
Transcriptional Regulation by TP53	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
multicellular organismal process	3
RNA polymerase II transcription regulator complex	3
cellular anatomical structure	3
response to stress	2
transcription by RNA polymerase II	2
ATP-dependent activity	2
binding	2
catalytic activity	2
RNA polymerase II, holoenzyme	2
intracellular membraneless organelle	2
maturation of SSU-rRNA	1
response to decreased oxygen levels	1
chordate embryonic development	1
nucleotide-excision repair	1
DNA repair	1
regulation of DNA-templated transcription	1
DNA-templated transcription elongation	1
transcription by RNA polymerase I	1
DNA-templated transcription	1
DNA-templated transcription initiation	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell cycle process	1
response to UV	1
multicellular organism development	1
central nervous system development	1
anatomical structure development	1
extracellular structure organization	1
external encapsulating structure organization	1
ossification	1
biomineral tissue development	1
central nervous system myelination	1
myelin assembly	1
developmental growth	1
helicase activity	1
ATP-dependent activity, acting on DNA	1
DNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1

Protein interactions and networks

STRING

2481 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERCC2	ERCC3	P19447	999
ERCC2	GTF2H5	Q6ZYL4	999
ERCC2	XPA	P23025	998
ERCC2	GTF2H4	Q92759	997
ERCC2	GTF2H1	P32780	997
ERCC2	GTF2H2	Q13888	997
ERCC2	GTF2H3	Q13889	995
ERCC2	CDK7	P50613	994
ERCC2	ERCC1	P07992	993
ERCC2	CCNH	P51946	988
ERCC2	ERCC4	Q92889	976
ERCC2	ERCC5	P28715	974
ERCC2	XRCC1	P18887	972
ERCC2	A0A090J7P6	A0A090J7P6	962
ERCC2	RAD23B	P54727	953

IntAct

114 interactions, top by confidence:

A	B	Type	Score
MMS19	CIAO1	psi-mi:“MI:0915”(physical association)	0.910
MMS19	CIAO1	psi-mi:“MI:0914”(association)	0.910
CDK7	ERCC2	psi-mi:“MI:0914”(association)	0.890
CCNH	ERCC2	psi-mi:“MI:0915”(physical association)	0.750
CCNH	ERCC2	psi-mi:“MI:0914”(association)	0.750
CETN2	SFI1	psi-mi:“MI:0914”(association)	0.740
MMS19	ERCC2	psi-mi:“MI:0915”(physical association)	0.690
MMS19	ERCC2	psi-mi:“MI:0914”(association)	0.690
MMS19	ERCC2	psi-mi:“MI:0407”(direct interaction)	0.690
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
GTF2H5	ERCC2	psi-mi:“MI:0914”(association)	0.650
MNAT1	ERCC2	psi-mi:“MI:0914”(association)	0.640
GTF2H2	ERCC2	psi-mi:“MI:0914”(association)	0.620
GTF2H2	ERCC2	psi-mi:“MI:0915”(physical association)	0.620
ERCC2	CIAO1	psi-mi:“MI:0914”(association)	0.590
CIAO2B	ERCC2	psi-mi:“MI:0407”(direct interaction)	0.590
CIAO1	ERCC2	psi-mi:“MI:0407”(direct interaction)	0.590

BioGRID (151): GTF2H2C_2 (Two-hybrid), ERCC2 (Affinity Capture-MS), ERCC2 (Affinity Capture-Western), ERCC2 (Affinity Capture-MS), ERCC2 (Affinity Capture-MS), ERCC2 (Affinity Capture-MS), CTPS1 (Co-fractionation), ERCC2 (Co-fractionation), ERCC2 (Co-fractionation), ERCC2 (Co-fractionation), ERCC2 (Co-fractionation), ERCC2 (Co-fractionation), ERCC2 (Affinity Capture-MS), ERCC2 (Affinity Capture-MS), ERCC2 (Affinity Capture-MS)

ESM2 similar proteins: A1CJ34, A1CRW7, A1D4S4, A1D8E4, A2Q8L1, A2QY22, A4R1J7, A6QLJ0, A8MPP1, E7F8F4, F1R345, F4JWP9, O08811, O62621, P06839, P0CR38, P0CR39, P11498, P18074, P24785, P26659, P45437, Q01320, Q0CUU1, Q0US25, Q1DY01, Q1E5T3, Q295E6, Q29RK2, Q2HB00, Q2U587, Q2URM9, Q4WK80, Q55G81, Q5BGR9, Q5E9H5, Q60452, Q6E6J3, Q6Z9U7, Q8K224

Diamond homologs: A6QLJ0, O08811, P06839, P18074, P26659, Q55G81, Q60452, Q8W4M7, Q58352

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
ERCC5	“up-regulates quantity by stabilization”	ERCC2	binding
ERCC2	“form complex”	TFIIH	binding
ERCC2	up-regulates	ERCC3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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	10	70.3×	2e-14
RNA Pol II CTD phosphorylation and interaction with CE	10	70.3×	2e-14
mRNA Capping	10	65.6×	2e-14
Global Genome Nucleotide Excision Repair (GG-NER)	8	63.0×	5e-12
Formation of the Early Elongation Complex	10	57.9×	3e-14
Formation of the HIV-1 Early Elongation Complex	10	57.9×	3e-14
HIV Transcription Elongation	9	52.1×	1e-12
RNA Polymerase I Transcription Termination	9	50.6×	2e-12

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	11	60.2×	2e-14
transcription initiation at RNA polymerase II promoter	9	48.1×	7e-11
transcription by RNA polymerase II	10	10.1×	1e-05
DNA repair	11	10.0×	3e-06
protein stabilization	9	8.6×	2e-04

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

ERCC2 functions as a DNA repair gene involved in separating the double helix via 5’-3’ helicase activity. It forms a part of the transcription factor II Human (TFIIH) complex and is ATP-dependent. The TFIIH complex is known to be involved in the nucleotide excision repair pathway (NER) which can repair DNA damage caused by chemotherapeutic treatment and basal transcription. ERCC2 variants have been observed in a variety of cancers. A number of studies have suggested ERCC2 variants can act as biomarkers to predict response to neoadjuvant treatment, and cancer prognosis. Additionally the Lys751Gln polymorphism has been observed to increase risk in a number of cancer types; however, results have been conflicting.

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — BLCA.

Clinical variants and AI predictions

ClinVar

2812 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	96
Likely pathogenic	97
Uncertain significance	1170
Likely benign	1176
Benign	76

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013171	NM_000400.4(ERCC2):c.820A>T (p.Lys274Ter)	Pathogenic
1176083	NM_000400.4(ERCC2):c.2009del (p.Gly670fs)	Pathogenic
1176084	NM_000400.4(ERCC2):c.139G>A (p.Gly47Arg)	Pathogenic
120188	NM_002361.4(MAG):c.1288T>G (p.Cys430Gly)	Pathogenic
1319436	NM_000400.4(ERCC2):c.1984C>T (p.Gln662Ter)	Pathogenic
1320616	NM_000400.4(ERCC2):c.898G>T (p.Glu300Ter)	Pathogenic
1322829	NM_000400.4(ERCC2):c.591_594del (p.Arg196_Tyr197insTer)	Pathogenic
1358482	NM_000400.4(ERCC2):c.1917C>A (p.Tyr639Ter)	Pathogenic
1363277	NM_000400.4(ERCC2):c.1867dup (p.Val623fs)	Pathogenic
1375106	NM_000400.4(ERCC2):c.580del (p.Ala195fs)	Pathogenic
1389326	NM_000400.4(ERCC2):c.614dup (p.Val206fs)	Pathogenic
1452293	NM_000400.4(ERCC2):c.1025G>A (p.Trp342Ter)	Pathogenic
1455083	NM_000400.4(ERCC2):c.1354C>T (p.Gln452Ter)	Pathogenic
1456616	NC_000019.9:g.(?45871868)(45873798_?)del	Pathogenic
1478560	NM_002361.4(MAG):c.719dup (p.Val241fs)	Pathogenic
16780	NM_000400.4(ERCC2):c.2176C>T (p.Gln726Ter)	Pathogenic
16783	NM_000400.4(ERCC2):c.1621A>C (p.Ser541Arg)	Pathogenic
16784	NM_000400.4(ERCC2):c.335G>A (p.Arg112His)	Pathogenic
16790	NM_000400.4(ERCC2):c.1745_1747delinsTTTCGG (p.Glu582_Lys583delinsValSerGlu)	Pathogenic
16791	NM_000400.4(ERCC2):c.1454T>C (p.Leu485Pro)	Pathogenic
16792	NM_000400.4(ERCC2):c.2164C>T (p.Arg722Trp)	Pathogenic
1685773	NM_000400.4(ERCC2):c.851del (p.Glu284fs)	Pathogenic
1705268	NM_000400.4(ERCC2):c.2191-1G>A	Pathogenic
2007717	NM_000400.4(ERCC2):c.854_866del (p.Tyr285fs)	Pathogenic
2024178	NM_000400.4(ERCC2):c.828_831del (p.Asp277fs)	Pathogenic
2025036	NC_000019.10:g.45369069CT[2]	Pathogenic
2029830	NM_000400.4(ERCC2):c.1398del (p.Tyr467fs)	Pathogenic
2079745	NM_000400.4(ERCC2):c.1230C>A (p.Tyr410Ter)	Pathogenic
2088636	NM_000400.4(ERCC2):c.2041_2046+9delinsATGAGCA	Pathogenic
218187	NM_002361.4(MAG):c.399C>G (p.Ser133Arg)	Pathogenic

SpliceAI

5727 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35293224:G:GG	donor_gain	1.0000
19:35295384:A:AG	acceptor_gain	1.0000
19:35295384:AGC:A	acceptor_gain	1.0000
19:35295385:G:GG	acceptor_gain	1.0000
19:35295385:GCG:G	acceptor_gain	1.0000
19:35295905:G:GT	donor_gain	1.0000
19:35295978:GTCA:G	donor_gain	1.0000
19:35295982:G:GG	donor_gain	1.0000
19:35299841:G:GT	donor_gain	1.0000
19:35299849:GT:G	donor_gain	1.0000
19:35300137:C:CA	acceptor_gain	1.0000
19:35300138:G:A	acceptor_gain	1.0000
19:35300144:TAG:T	acceptor_loss	1.0000
19:35300145:A:AG	acceptor_gain	1.0000
19:35300145:AGACC:A	acceptor_loss	1.0000
19:35300146:G:GA	acceptor_gain	1.0000
19:35300146:G:GC	acceptor_loss	1.0000
19:35300374:G:GT	donor_gain	1.0000
19:35300403:GT:G	donor_gain	1.0000
19:35300405:G:GG	donor_gain	1.0000
19:35302442:CCGCA:C	acceptor_loss	1.0000
19:35302446:A:AG	acceptor_gain	1.0000
19:35302446:AGAT:A	acceptor_gain	1.0000
19:35302447:G:GA	acceptor_gain	1.0000
19:35302447:GA:G	acceptor_gain	1.0000
19:35302447:GAT:G	acceptor_gain	1.0000
19:35302447:GATG:G	acceptor_gain	1.0000
19:35302447:GATGC:G	acceptor_gain	1.0000
19:35302641:A:T	donor_gain	1.0000
19:35302704:GGAGT:G	donor_gain	1.0000

AlphaMissense

4945 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45352311:C:A	W696C	1.000
19:45352311:C:G	W696C	1.000
19:45352313:A:G	W696R	1.000
19:45352313:A:T	W696R	1.000
19:45352510:T:A	D681V	1.000
19:45352511:C:G	D681H	1.000
19:45352513:G:T	A680D	1.000
19:45352528:C:T	G675D	1.000
19:45352534:T:A	D673V	1.000
19:45352535:C:G	D673H	1.000
19:45352546:C:A	R669M	1.000
19:45352555:C:G	R666P	1.000
19:45352556:G:A	R666W	1.000
19:45352558:C:A	G665V	1.000
19:45352558:C:T	G665D	1.000
19:45352559:C:A	G665C	1.000
19:45352559:C:G	G665R	1.000
19:45352563:A:C	C663W	1.000
19:45352564:C:T	C663Y	1.000
19:45352565:A:G	C663R	1.000
19:45352566:C:A	Q662H	1.000
19:45352566:C:G	Q662H	1.000
19:45352570:G:T	A661D	1.000
19:45352571:C:G	A661P	1.000
19:45352574:C:G	A660P	1.000
19:45352579:C:G	R658P	1.000
19:45352580:G:T	R658S	1.000
19:45352585:G:T	A656D	1.000
19:45352590:G:C	F654L	1.000
19:45352590:G:T	F654L	1.000

dbSNP variants (sampled 300 via entrez): RS1000022619 (19:45350114 G>A,C), RS1000046663 (19:45358466 C>T), RS1000211330 (19:45358198 C>A,G,T), RS1000348573 (19:45368475 G>A), RS1000392057 (19:45362397 G>A), RS1000515533 (19:45355981 G>A), RS1000657922 (19:45355431 C>A,T), RS1000761424 (19:45362615 C>A,T), RS1001052182 (19:45359308 G>A), RS1001208168 (19:45368429 G>T), RS1001245726 (19:45365116 G>C), RS1001320541 (19:45359743 A>C), RS1001388599 (19:45363277 C>T), RS1001639820 (19:45368098 T>C), RS1001715821 (19:45353478 C>G)

Disease associations

OMIM: gene MIM:126340 | disease phenotypes: MIM:278730, MIM:601675, MIM:610756, MIM:278700, MIM:616680, MIM:217990, MIM:167000, MIM:312080, MIM:214150, MIM:109800, MIM:266600, MIM:278720, MIM:303350, MIM:119530, MIM:116200

GenCC curated gene-disease

Disease	Classification	Inheritance
xeroderma pigmentosum group D	Definitive	Autosomal recessive
trichothiodystrophy 1, photosensitive	Definitive	Autosomal recessive
cerebrooculofacioskeletal syndrome 2	Definitive	Autosomal recessive
hereditary spastic paraplegia 75	Strong	Autosomal recessive
complex hereditary spastic paraplegia	Strong	Autosomal recessive
sarcoma	Moderate	Autosomal recessive
COFS syndrome	Supportive	Autosomal recessive
xeroderma pigmentosum-Cockayne syndrome complex	Supportive	Autosomal recessive
trichothiodystrophy	Supportive	Autosomal recessive
xeroderma pigmentosum	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
complex hereditary spastic paraplegia	Definitive	AR
xeroderma pigmentosum group D	Definitive	AR

Mondo (24): xeroderma pigmentosum group D (MONDO:0010212), trichothiodystrophy 1, photosensitive (MONDO:0011125), cerebrooculofacioskeletal syndrome 2 (MONDO:0012553), xeroderma pigmentosum (MONDO:0019600), hereditary spastic paraplegia 75 (MONDO:0014729), corpus callosum, agenesis of (MONDO:0009022), trichothiodystrophy (MONDO:0018053), ovarian cancer (MONDO:0008170), leukodystrophy (MONDO:0019046), cerebrooculofacioskeletal syndrome 1 (MONDO:0008955), hepatoblastoma (MONDO:0018666), hypotrichosis simplex (MONDO:0018914), hereditary neoplastic syndrome (MONDO:0015356), urinary bladder cancer (MONDO:0001187), inflammatory bowel disease 1 (MONDO:0009960)

Orphanet (15): Trichothiodystrophy (Orphanet:33364), Xeroderma pigmentosum (Orphanet:910), Autosomal recessive spastic paraplegia type 75 (Orphanet:459056), Isolated corpus callosum agenesis (Orphanet:200), Rare ovarian cancer (Orphanet:213500), Leukodystrophy (Orphanet:68356), Hepatoblastoma (Orphanet:449), Hypotrichosis simplex (Orphanet:55654), Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary spastic paraplegia (Orphanet:685), Craniopharyngioma (Orphanet:54595), OBSOLETE: Xeroderma pigmentosum complementation group D (Orphanet:276258), PIBIDS syndrome (Orphanet:670), NON RARE IN EUROPE: Bladder cancer (Orphanet:157980), OBSOLETE: Xeroderma pigmentosum complementation group C (Orphanet:276255)

HPO phenotypes

230 total (30 of 230 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000054	Micropenis
HP:0000133	Gonadal dysgenesis
HP:0000135	Hypogonadism
HP:0000164	Abnormality of the dentition
HP:0000207	Triangular mouth
HP:0000232	Everted lower lip vermilion
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:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000444	Convex nasal ridge
HP:0000448	Prominent nose
HP:0000470	Short neck
HP:0000482	Microcornea
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000490	Deeply set eye

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001721_1	Lung Cancer (DNA repair capacity)	9.000000e-07
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1.000000e-97
GCST012034_11	Sleep (1/2-day periodicity)	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D061085	Agenesis of Corpus Callosum	C10.500.034; C16.131.666.034; C23.300.008
D002386	Cataract	C11.510.245
D003397	Craniopharyngioma	C04.557.465.625.200; C04.557.580.625.200
D018197	Hepatoblastoma	C04.557.435.380
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
D012509	Sarcoma	C04.557.450.795
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820
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
C565185	Cerebrooculofacioskeletal Syndrome 2 (supp.)
C537160	Hypotrichosis simplex (supp.)
C566121	Orofacial Cleft 1 (supp.)
C567886	Xeroderma Pigmentosum, Complementation Group C (supp.)
C562591	Xeroderma Pigmentosum, Complementation Group D (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105743 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 125,410 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL535	SUNITINIB	4	79,020
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL3137331	DEFACTINIB	3	1,229
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL564829	MILCICLIB	2	821
CHEMBL1084546	PF-00562271	1	399
CHEMBL1230607	PHA-793887	1	299
CHEMBL1908397	KW-2449	1	622
CHEMBL296468	BMS-387032	1	2,075
CHEMBL3128043	PF-03758309	1	233
CHEMBL3544932	TAK-901	1	557
CHEMBL3545083	RGB-286638	1	551
CHEMBL3545085	XL-228	1	936

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
ERCC2 K751Q	Paclitaxel + Carboplatin	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID677
ERCC2 K751Q	Cisplatin	Osteosarcoma	Resistance	CIViC B	EID676

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

PharmGKB clinical annotations

15 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1052555	Efficacy	3	Platinum compounds	Non-Small Cell Lung Carcinoma
rs13181	Efficacy,Toxicity	3	fluorouracil;leucovorin;oxaliplatin	Colorectal Neoplasms
rs13181	Toxicity	3	Platinum compounds	Non-Small Cell Lung Carcinoma
rs13181	Toxicity	3	bleomycin;cisplatin;etoposide	Alopecia;Testicular Neoplasms
rs13181	Toxicity	3	cisplatin;doxorubicin;methotrexate	Nephrotoxicity;Osteosarcoma
rs13181	Toxicity	4	docetaxel	Breast Neoplasms
rs13181	Efficacy	3	cisplatin;gemcitabine	Mesothelioma
rs13181	Efficacy	3	cisplatin;oxaliplatin;platinum;Platinum compounds	Colorectal Neoplasms;Neoplasm of esophagus;Osteosarcoma;Ovarian Neoplasms;Pancreatic Neoplasms
rs1799793	Toxicity	3	Platinum compounds	Non-Small Cell Lung Carcinoma
rs1799793	Toxicity	3	bleomycin;cisplatin;etoposide	Anemia;Testicular Neoplasms
rs1799793	Toxicity	3	Platinum compounds	Non-Small Cell Lung Carcinoma;Pneumonitis
rs1799793	Toxicity	3	Platinum compounds	adverse events;Non-Small Cell Lung Carcinoma
rs1799793	Efficacy,Toxicity	4	Platinum compounds	Neoplasms
rs238406	Toxicity	3	bleomycin;cisplatin;etoposide	Leukopenia;Testicular Neoplasms
rs50872	Toxicity	3	Platinum compounds	Non-Small Cell Lung Carcinoma

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs13181	ERCC2, KLC3	3	4.75	7	cisplatin;oxaliplatin;platinum;Platinum compounds;cisplatin;gemcitabine;fluorouracil;leucovorin;oxaliplatin;bleomycin;cisplatin;etoposide;cisplatin;doxorubicin;methotrexate;Platinum compounds;docetaxel
rs238406	ERCC2	3	3.00	1	bleomycin;cisplatin;etoposide
rs1052555	ERCC2	3	5.00	1	Platinum compounds
rs1799793	ERCC2	3	4.50	5	Platinum compounds;bleomycin;cisplatin;etoposide
rs50872	ERCC2	3	3.50	1	Platinum compounds
rs3810366	ERCC2		0.00	0

ChEMBL bioactivities

17 potent at pChembl≥5 of 21 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	Kd	2	nM	PF-03758309
8.00	Kd	10	nM	PHA-793887
6.87	Kd	134	nM	DANUSERTIB
6.75	Kd	179.7	nM	CHEMBL3752910
6.70	ED50	198.6	nM	CHEMBL3752910
6.61	Kd	246	nM	TAK-901
6.50	Kd	319	nM	ZOTIRACICLIB
6.48	Kd	329	nM	MILCICLIB
6.34	Kd	456	nM	RGB-286638
6.25	Kd	560	nM	DINACICLIB
6.04	Kd	921	nM	ALVOCIDIB
6.02	Kd	953	nM	XL-228
5.96	Kd	1108	nM	BMS-387032
5.91	Kd	1225	nM	SUNITINIB
5.65	Kd	2259	nM	DEFACTINIB
5.58	Kd	2637	nM	PF-00562271
5.50	Kd	3131	nM	KW-2449

PubChem BioAssay actives

17 with measured affinity, of 245 total; 17 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
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0020	uM
N-[6,6-dimethyl-5-(1-methylpiperidine-4-carbonyl)-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-3-methylbutanamide	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0100	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1340	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148330: Binding affinity to human ERCC2 incubated for 45 mins by Kinobead based pull down assay	kd	0.1797	uM
5-(3-ethylsulfonylphenyl)-3,8-dimethyl-N-(1-methylpiperidin-4-yl)-9H-pyrido[2,3-b]indole-7-carboxamide	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2460	uM
(16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3190	uM
N,1,4,4-tetramethyl-8-[4-(4-methylpiperazin-1-yl)anilino]-5H-pyrazolo[4,5-h]quinazoline-3-carboxamide	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3290	uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4560	uM
2-[(2S)-1-[3-ethyl-7-[(1-oxidopyridin-1-ium-3-yl)methylamino]pyrazolo[1,5-a]pyrimidin-5-yl]piperidin-2-yl]ethanol	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.5600	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.9210	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.9530	uM
N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]piperidine-4-carboxamide	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1080	uM
Sunitinib	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.2250	uM
N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.2590	uM
N-methyl-N-[3-[[[2-[(2-oxo-1,3-dihydroindol-5-yl)amino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]methyl]-2-pyridinyl]methanesulfonamide	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.6370	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	3.1310	uM
(2R)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]butan-1-ol	1424996: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	12.0220	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	decreases activity, decreases methylation, increases expression, increases response to substance, decreases expression (+5 more)	10
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases reaction, decreases expression (+1 more)	6
Oxaliplatin	affects cotreatment, affects response to substance, increases expression	4
Cisplatin	decreases reaction, increases response to substance, decreases expression, decreases response to substance	3
Doxorubicin	affects response to substance, decreases expression, increases expression, affects expression	2
Fluorouracil	affects cotreatment, affects response to substance	2
Pesticides	affects response to substance, decreases methylation	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
apocarotenal	decreases expression	1
lasiocarpine	decreases expression	1
myristicin	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases expression	1
lead acetate	affects cotreatment, decreases expression	1
quercitrin	decreases expression	1
trichostatin A	decreases expression, decreases reaction, increases abundance	1
beta-lapachone	decreases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
chromous chloride	affects cotreatment, decreases expression	1
cobaltous chloride	decreases expression	1
chromic oxide	affects cotreatment, decreases expression	1
zinc chromate	decreases expression, increases abundance	1
1,10-phenanthroline	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
butylparaben	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991709	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

99 cell lines: 79 finite cell line, 19 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_2560	XP8BR LCL	Transformed cell line	Male
CVCL_3815	XP17BE	Finite cell line	Male
CVCL_4Z76	TTD2BR	Finite cell line	Female
CVCL_4Z77	TTD1BEL	Finite cell line	Male
CVCL_4Z78	TTD2GL	Finite cell line	Female
CVCL_C1LM	KMUGMCi003-A	Induced pluripotent stem cell	Female
CVCL_F505	XP6BE(SV)	Transformed cell line	Female
CVCL_F508	GM15877	Transformed cell line	Female
CVCL_F599	XP6BE	Finite cell line	Female
CVCL_J996	XP2NE	Finite cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03144206	PHASE4	ACTIVE_NOT_RECRUITING	Hyperbaric Oxygen Therapy for Soft Tissue Sarcoma Pilot Study
NCT03244020	PHASE4	ENROLLING_BY_INVITATION	LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology
NCT04033081	PHASE4	ACTIVE_NOT_RECRUITING	Registry of Sarcoma Patients Treated With Permanently Implantable LDR CivaSheet®
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
NCT00001300	PHASE3	COMPLETED	A Randomized Study of the Effect of Adjuvant Chemotherapy With Doxorubicin and Ifosfamide With Mesna in the Treatment of High-Grade Adult Extremity Soft Tissue Sarcoma
NCT00002459	PHASE3	COMPLETED	Radiation Therapy or No Further Treatment Following Surgery in Treating Patients With Cancer of the Uterus
NCT00002516	PHASE3	UNKNOWN	Combination Chemotherapy Plus Surgery and Radiation Therapy in Treating Patients With Ewing’s Sarcoma
NCT00002539	PHASE3	COMPLETED	Combination Chemotherapy and Surgery With or Without G-CSF in Treating Patients With Osteosarcoma
NCT00002546	PHASE3	COMPLETED	Radiation Therapy Compared With Combination Chemotherapy in Treating Patients With Cancer of the Uterus
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002898	PHASE3	COMPLETED	Surgery Followed by Chemotherapy in Treating Young Patients With Soft Tissue Sarcoma
NCT00002985	PHASE3	COMPLETED	Doxorubicin in Treating Patients With AIDS-Related Kaposi’s Sarcoma
NCT00002995	PHASE3	COMPLETED	Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma
NCT00003052	PHASE3	COMPLETED	Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma