CCNH

Summary

CCNH (cyclin H, HGNC:1594) is a protein-coding gene on chromosome 5q14.3, encoding Cyclin-H (P51946). Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. It is a common-essential gene (DepMap: required in 98.7% of cancer cell lines).

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with CDK7 kinase and ring finger protein MAT1. The kinase complex is able to phosphorylate CDK2 and CDC2 kinases, thus functions as a CDK-activating kinase (CAK). This cyclin and its kinase partner are components of TFIIH, as well as RNA polymerase II protein complexes. They participate in two different transcriptional regulation processes, suggesting an important link between basal transcription control and the cell cycle machinery. A pseudogene of this gene is found on chromosome 4. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 902 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 1,456 total — 187 pathogenic, 72 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes — 28 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1594
Approved symbol	CCNH
Name	cyclin H
Location	5q14.3
Locus type	gene with protein product
Status	Approved
Aliases	p34, p37, CycH
Ensembl gene	ENSG00000134480
Ensembl biotype	protein_coding
OMIM	601953
Entrez	902

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 11 protein_coding, 4 retained_intron, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000256897, ENST00000504115, ENST00000504878, ENST00000505230, ENST00000505587, ENST00000508855, ENST00000510020, ENST00000510921, ENST00000511207, ENST00000513499, ENST00000607486, ENST00000645953, ENST00000646883, ENST00000713562, ENST00000888806, ENST00000888807, ENST00000888808, ENST00000888809, ENST00000939483, ENST00000962232, ENST00000962233

RefSeq mRNA: 5 — MANE Select: NM_001239 NM_001199189, NM_001239, NM_001363539, NM_001364075, NM_001364076

CCDS: CCDS4064, CCDS87309

Canonical transcript exons

ENST00000256897 — 9 exons

Exon	Start	End
ENSE00003487375	87401702	87401772
ENSE00003535360	87404844	87405007
ENSE00003579207	87407976	87408186
ENSE00003596209	87409290	87409363
ENSE00003634048	87399394	87399505
ENSE00003644157	87395044	87395104
ENSE00003644466	87411224	87411346
ENSE00004020326	87394274	87394484
ENSE00004020327	87412678	87412930

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 97.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.6676 / max 564.0431, expressed in 1812 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62429	34.7856	1808
62428	2.9456	1319
62427	1.4210	503
62426	0.7612	213
62432	0.4940	247
62425	0.2602	111

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.41	gold quality
left testis	UBERON:0004533	96.92	gold quality
right testis	UBERON:0004534	96.65	gold quality
ventricular zone	UBERON:0003053	96.60	gold quality
colonic epithelium	UBERON:0000397	96.24	gold quality
testis	UBERON:0000473	96.24	gold quality
omental fat pad	UBERON:0010414	95.97	gold quality
peritoneum	UBERON:0002358	95.93	gold quality
ganglionic eminence	UBERON:0004023	95.93	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.78	gold quality
adenohypophysis	UBERON:0002196	95.71	gold quality
cortical plate	UBERON:0005343	95.34	gold quality
right lung	UBERON:0002167	94.99	gold quality
sperm	CL:0000019	94.89	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.60	gold quality
tibial nerve	UBERON:0001323	94.55	gold quality
male germ cell	CL:0000015	94.51	gold quality
cerebellar hemisphere	UBERON:0002245	94.39	gold quality
tibial artery	UBERON:0007610	94.32	gold quality
cerebellar cortex	UBERON:0002129	94.31	gold quality
popliteal artery	UBERON:0002250	94.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.29	gold quality
bone marrow cell	CL:0002092	94.23	gold quality
pituitary gland	UBERON:0000007	94.23	gold quality
adipose tissue	UBERON:0001013	94.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.10	gold quality
adrenal tissue	UBERON:0018303	94.07	gold quality
left uterine tube	UBERON:0001303	94.06	gold quality
left lobe of thyroid gland	UBERON:0001120	94.00	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	29.62
E-CURD-122	yes	20.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting CCNH, 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-1277-5P	100.00	73.95	5056
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-4693-5P	97.35	67.02	1234
HSA-MIR-8069	97.05	66.79	718

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 19)

• The cyclin H/cdk7/Mat1 kinase activity is regulated by CK2 phosphorylation of cyclin H. (PMID:12140753)
• Confocal microscopy revealed the co-localization of PKC-iota with CAK/cdk7 in both the cytoplasm and nucleus of U-373 MG glioma cells, supporting its role in cell signaling (PMID:15695176)
• In response to ATRA, PML/RARalpha is dissociated from CAK, leading to MAT1 degradation, G1 arrest, and decreased CAK phosphorylation of PML/RARalpha (PMID:16935935)
• Retinoic-acid-induced RAR-CAK signaling events appear to proceed intrinsically during granulocytic development of normal primitive hematopoietic cells. ALDH-governed RA availability may mediate this process by initiating RAR-CAK signaling. (PMID:17628022)
• These results suggested that genetic variants in CAK genes, Cdk7, cyclin H, MAT1, might modulate the risk of lung cancer in a gene-gene interaction mode, which consist to the biochemical interaction of corresponding proteins. (PMID:17707548)
• Our study demonstrates the independent prognostic value of cyclin H expression in diffuse large B-cell lymphoma and proposes its use as a prognostic marker. (PMID:18400256)
• TFIIH changes subunit composition in response to DNA damage. The CAK is released from the core during nucleotide excision repair (NER). (PMID:18614043)
• The expression of cyclin H and CDK7 protein in proliferating hemangiomas was significantly higher than that in involuting hemangiomas and normal skin tissues. (PMID:18950027)
• High Cyclin H is associated with gastrointestinal stromal tumours. (PMID:20598140)
• CCNH and CDK7 may play an important role in the tumorigenesis and development of esophageal squamous cell carcinoma. (PMID:23456497)
• When considering all thyroid cancer (DTC) cases, only rs2230641 (CCNH) was associated with DTC risk. (PMID:23982724)
• SNPs in CCNH and ABCG2 can modulate the development of severe oxaliplatin-induced peripheral neuropathy. (PMID:24351404)
• Hemodynamic forces modulate EC proliferative phenotype through the miR-23b/CAK/cyclin H pathway. (PMID:24855060)
• Our results indicated that CCNH/CDK7-CtBP2 axis may augment ESCC cell migration, and targeting the interaction of both may provide a novel therapeutic target of esophageal squamous cell carcinoma . (PMID:25820824)
• Expressions of components of the CAK complex, CDK7, MAT1, and Cyclin H are elevated in breast cancer. (PMID:27301701)
• Genetic polymorphisms in cyclin H gene are associated with oxaliplatin-induced acute peripheral neuropathy in South Indian digestive tract cancer patients. (PMID:29936608)
• Cyclins B1, T1, and H differ in their molecular mode of interaction with cytomegalovirus protein kinase pUL97 (PMID:30782840)
• Cyclin H Regulates Lung Cancer Progression as a Carcinoma Inducer. (PMID:33777168)
• Cytomegalovirus cyclin-dependent kinase ortholog vCDK/pUL97 undergoes regulatory interaction with human cyclin H and CDK7 to codetermine viral replication efficiency. (PMID:37591314)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccnh	ENSDARG00000007657
mus_musculus	Ccnh	ENSMUSG00000021548
rattus_norvegicus	Ccnh	ENSRNOG00000031656
drosophila_melanogaster	CycH	FBGN0022936
drosophila_melanogaster	CycT	FBGN0025455
caenorhabditis_elegans		WBGENE00000507
caenorhabditis_elegans		WBGENE00000508
caenorhabditis_elegans		WBGENE00021714

Paralogs (6): CCNT2 (ENSG00000082258), CCNK (ENSG00000090061), CCNT1 (ENSG00000129315), CCNL1 (ENSG00000163660), CCNL2 (ENSG00000221978), CCNQ (ENSG00000262919)

Protein

Protein identifiers

Cyclin-H — P51946 (reviewed: P51946)

Alternative names: MO15-associated protein, p34, p37

All UniProt accessions (5): A0A2R8Y4K6, A0A2R8YEM2, P51946, D6RG18, D6RHI7

UniProt curated annotations — full annotation on UniProt →

Function. Regulates CDK7, the catalytic subunit of the CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle.

Subunit / interactions. Associates primarily with CDK7 and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor.

Subcellular location. Nucleus.

Similarity. Belongs to the cyclin family. Cyclin C subfamily.

RefSeq proteins (5): NP_001186118, NP_001230, NP_001350468, NP_001351004, NP_001351005 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR027081	CyclinH/Ccl1	Family
IPR031658	Cyclin_C_2	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR043198	Cyclin/Ssn8	Family

Pfam: PF00134, PF16899

UniProt features (40 total): helix 18, turn 5, modified residue 5, sequence variant 4, mutagenesis site 2, strand 2, compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

47 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8P79	ELECTRON MICROSCOPY	1.7
8P77	ELECTRON MICROSCOPY	1.8
8ORM	ELECTRON MICROSCOPY	1.9
8P6V	ELECTRON MICROSCOPY	1.9
8P6W	ELECTRON MICROSCOPY	1.9
8P6X	ELECTRON MICROSCOPY	1.9
8P6Y	ELECTRON MICROSCOPY	1.9
8P72	ELECTRON MICROSCOPY	1.9
8P78	ELECTRON MICROSCOPY	1.9
8PLZ	ELECTRON MICROSCOPY	1.9
8P70	ELECTRON MICROSCOPY	2
8P71	ELECTRON MICROSCOPY	2
8P73	ELECTRON MICROSCOPY	2
8P75	ELECTRON MICROSCOPY	2
8P76	ELECTRON MICROSCOPY	2
8P6Z	ELECTRON MICROSCOPY	2.1
8PYR	X-RAY DIFFRACTION	2.15
8P74	ELECTRON MICROSCOPY	2.2
8S0T	ELECTRON MICROSCOPY	2.3
9HIY	ELECTRON MICROSCOPY	2.3
8S0R	ELECTRON MICROSCOPY	2.4
9I9K	ELECTRON MICROSCOPY	2.4
9QJN	ELECTRON MICROSCOPY	2.4
7B5O	ELECTRON MICROSCOPY	2.5
7B5Q	ELECTRON MICROSCOPY	2.5
9QCV	ELECTRON MICROSCOPY	2.5
1JKW	X-RAY DIFFRACTION	2.6
1KXU	X-RAY DIFFRACTION	2.6
9HIX	ELECTRON MICROSCOPY	2.6
9HJ0	ELECTRON MICROSCOPY	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51946-F1	86.26	0.70

Antibody-complex structures (SAbDab): 1 — 8PYR

Functional residue map

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

Post-translational modifications (5): 5, 132, 304, 315, 322

Mutagenesis-validated functional residues (2):

Position	Phenotype
5	no effect on the transcriptional activity of the reconstituted tfiih complex.
304	no effect on the transcriptional activity of the reconstituted tfiih complex.

Function

Pathways and Gene Ontology

Reactome pathways

61 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-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-69202	Cyclin E associated events during G1/S transition
R-HSA-69231	Cyclin D associated events in G1
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
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

MSigDB gene sets: 232 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KYNG_DNA_DAMAGE_DN, KAUFFMANN_DNA_REPAIR_GENES, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, GOBP_NUCLEOTIDE_EXCISION_REPAIR, REACTOME_HIV_INFECTION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, BIOCARTA_PTC1_PATHWAY, GROSS_HYPOXIA_VIA_HIF1A_UP, GOBP_PROTEIN_STABILIZATION, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (5): regulation of transcription by RNA polymerase II (GO:0006357), transcription initiation at RNA polymerase II promoter (GO:0006367), protein stabilization (GO:0050821), regulation of G1/S transition of mitotic cell cycle (GO:2000045), DNA-templated transcription (GO:0006351)

GO Molecular Function (4): kinase activity (GO:0016301), cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538), protein binding (GO:0005515), RNA polymerase II general transcription initiation factor activity (GO:0016251)

GO Cellular Component (8): cyclin-dependent protein kinase holoenzyme complex (GO:0000307), transcription factor TFIIH core complex (GO:0000439), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFIIH holo complex (GO:0005675), CAK-ERCC2 complex (GO:0070516), transcription factor TFIIK complex (GO:0070985)

Reactome top-level categories

Rollup of top-13 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
Late Phase of HIV Life Cycle	1
Tat-mediated elongation of the HIV-1 transcript	1
Negative epigenetic regulation of rRNA expression	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
RNA Polymerase II Transcription	1
Nucleotide Excision Repair	1
Transcriptional Regulation by TP53	1
G1/S Transition	1
G1 Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
RNA polymerase II transcription regulator complex	3
regulation of DNA-templated transcription	1
DNA-templated transcription initiation	1
regulation of protein stability	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
gene expression	1
RNA biosynthetic process	1
transferase activity, transferring phosphorus-containing groups	1
cyclin-dependent protein serine/threonine kinase activity	1
cyclin-dependent protein kinase regulator activity	1
binding	1
general transcription initiation factor activity	1
serine/threonine protein kinase complex	1
germ cell nucleus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
transcription factor TFIIH core complex	1
RNA polymerase II, holoenzyme	1
nuclear cyclin-dependent protein kinase holoenzyme complex	1
carboxy-terminal domain protein kinase complex	1
nuclear protein-containing complex	1
transcription factor TFIIH holo complex	1

Protein interactions and networks

STRING

1720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNH	CDK7	P50613	999
CCNH	MNAT1	P51948	998
CCNH	ERCC3	P19447	996
CCNH	ERCC2	P18074	988
CCNH	GTF2H1	P32780	964
CCNH	GTF2H4	Q92759	959
CCNH	GTF2H5	Q6ZYL4	935
CCNH	CDK2	P24941	915
CCNH	CDK20	Q8IZL9	907
CCNH	GTF2H2	Q13888	906
CCNH	GTF2H3	Q13889	902
CCNH	CDK8	P49336	900
CCNH	CCNT1	O60563	891
CCNH	CDK9	P50750	883
CCNH	CCNA1	P78396	865

IntAct

202 interactions, top by confidence:

A	B	Type	Score
CDK7	CCNH	psi-mi:“MI:0914”(association)	0.950
CCNH	CDK7	psi-mi:“MI:0915”(physical association)	0.950
CDK7	ERCC2	psi-mi:“MI:0914”(association)	0.890
CCNH	GOLGA2	psi-mi:“MI:0915”(physical association)	0.870
GOLGA2	CCNH	psi-mi:“MI:0915”(physical association)	0.870
CDK2	CCNH	psi-mi:“MI:0915”(physical association)	0.860
CCNH	CDK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.860
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
CCNH	ERCC3	psi-mi:“MI:0914”(association)	0.850
GTF2H1	CDK7	psi-mi:“MI:0915”(physical association)	0.820
PSMA1	CCNH	psi-mi:“MI:0915”(physical association)	0.780
CCNH	DUSP12	psi-mi:“MI:0915”(physical association)	0.780
CCNH	PSMA1	psi-mi:“MI:0915”(physical association)	0.780
DUSP12	CCNH	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (194): GOLGA2 (Two-hybrid), SFN (Two-hybrid), PSMA1 (Two-hybrid), PPFIA1 (Two-hybrid), CALCOCO2 (Two-hybrid), NDC80 (Two-hybrid), SSSCA1 (Two-hybrid), DUSP12 (Two-hybrid), CCDC33 (Two-hybrid), CCDC170 (Two-hybrid), SSX2IP (Two-hybrid), KLC3 (Two-hybrid), CCNH (Affinity Capture-MS), CCNH (Affinity Capture-MS), ERCC2 (Affinity Capture-MS)

ESM2 similar proteins: A1C7R6, A1CQB4, A2QQA2, A2QQE8, A3LPX1, A4RD79, A6RQZ9, A7E7B3, B0XQB9, C8VDQ4, G0SAK8, O59748, O74627, P0C654, P47821, P51946, P51947, P93411, Q01317, Q0CV29, Q0D1J4, Q0UPL5, Q10D80, Q1EAW8, Q2GSV2, Q2GVK1, Q2U2J1, Q2UDB2, Q3ZBL9, Q4P101, Q4R7U4, Q4WTA6, Q4WZT9, Q503D6, Q5BBA8, Q5BD89, Q61458, Q6BYF8, Q6CAC7, Q6CP20

Diamond homologs: A1C7R6, A3LPX1, A4RD79, O94503, P47821, P51946, P51947, P93411, Q0CV29, Q1EAW8, Q2GVK1, Q2UDB2, Q4R7U4, Q4WZT9, Q5A4H9, Q5BBA8, Q6BYF8, Q6CAC7, Q6CP20, Q6FJE8, Q75AX7, Q9C1M4, Q9FJK7, Q9HE63, P24863, P25008, P39947, P55168, Q16JA2, Q28F72, Q29AI1, Q3ZBL9, Q3ZCK5, Q4KLA0, Q62447, Q7QB13, Q86KE7, Q9FJK6, F1QMB9, O74627

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CCNH	“form complex”	“CAK complex”	binding
“CKM complex”	“down-regulates activity”	CCNH	phosphorylation
CDK8	down-regulates	CCNH	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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	9	53.2×	8e-12
RNA Pol II CTD phosphorylation and interaction with CE	9	53.2×	8e-12
Global Genome Nucleotide Excision Repair (GG-NER)	8	53.0×	5e-11
mRNA Capping	9	49.6×	1e-11
Formation of the Early Elongation Complex	9	43.8×	1e-11
Formation of the HIV-1 Early Elongation Complex	9	43.8×	1e-11
RNA Polymerase I Transcription Termination	9	42.6×	2e-11
Formation of Incision Complex in GG-NER	11	40.5×	9e-13

GO biological processes:

GO term	Partners	Fold	FDR
nucleotide-excision repair	10	46.1×	8e-12
transcription initiation at RNA polymerase II promoter	8	36.1×	2e-08
G1/S transition of mitotic cell cycle	7	16.9×	3e-05
transcription by RNA polymerase II	11	9.3×	6e-06
DNA repair	10	7.7×	8e-05
cell division	11	6.1×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1456 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	187
Likely pathogenic	72
Uncertain significance	538
Likely benign	511
Benign	43

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012514	NM_002890.3(RASA1):c.2925+1G>T	Pathogenic
1033551	NM_002890.3(RASA1):c.2532_2533delinsATTTGA (p.Asn844fs)	Pathogenic
1045761	NM_002890.3(RASA1):c.2366G>A (p.Arg789Gln)	Pathogenic
1068659	NM_002890.3(RASA1):c.1926dup (p.Val643fs)	Pathogenic
1069799	NM_002890.3(RASA1):c.3050del (p.Gly1017fs)	Pathogenic
1072333	NM_002890.3(RASA1):c.2920del (p.Asn976fs)	Pathogenic
1172579	NM_002890.3(RASA1):c.1980_1981dup (p.Lys661fs)	Pathogenic
1172580	NM_002890.3(RASA1):c.543G>A (p.Trp181Ter)	Pathogenic
1172581	NM_002890.3(RASA1):c.768C>A (p.Tyr256Ter)	Pathogenic
1200888	NM_002890.3(RASA1):c.2422C>T (p.Gln808Ter)	Pathogenic
1302016	NM_002890.3(RASA1):c.1460del (p.Gly487fs)	Pathogenic
1316663	NM_002890.3(RASA1):c.1870C>T (p.Gln624Ter)	Pathogenic
1331016	NM_002890.3(RASA1):c.2216_2217del (p.Tyr739fs)	Pathogenic
1357848	NM_002890.3(RASA1):c.1984_1988del (p.Thr662fs)	Pathogenic
1364501	NM_002890.3(RASA1):c.2648_2655del (p.His883fs)	Pathogenic
1374513	NM_002890.3(RASA1):c.2390del (p.Thr796_Leu797insTer)	Pathogenic
1395909	NM_002890.3(RASA1):c.2891_2894del (p.Lys964fs)	Pathogenic
1451642	NM_002890.3(RASA1):c.2329_2330del (p.Glu777fs)	Pathogenic
1454971	NM_002890.3(RASA1):c.1319del (p.Pro440fs)	Pathogenic
1458184	NM_002890.3(RASA1):c.1336C>T (p.Gln446Ter)	Pathogenic
1459034	NM_002890.3(RASA1):c.617_621del (p.Ile206fs)	Pathogenic
1459752	NM_002890.3(RASA1):c.2534_2535insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNTTTTTGAGACGGAGTCTCGCTCTGTCGCCCAGGTCGGACTGCGGACTGCAGTGGCGCAATCTCGGCTCACTGTGAACACTAATTT (p.Leu845delinsPhePhePhePhePhePhePheXaaXaaXaaXaaPheTer)	Pathogenic
146291	GRCh38/hg38 5q14.3(chr5:87191898-89957449)x1	Pathogenic
151699	GRCh38/hg38 5q14.3(chr5:86658611-87608243)x1	Pathogenic
1524107	NM_002890.3(RASA1):c.828+5G>T	Pathogenic
15996	NM_002890.3(RASA1):c.1193G>T (p.Arg398Leu)	Pathogenic
15997	NM_002890.3(RASA1):c.1198A>G (p.Lys400Glu)	Pathogenic
16000	NM_002890.3(RASA1):c.1619G>A (p.Cys540Tyr)	Pathogenic
16001	NM_002890.3(RASA1):c.853C>T (p.Arg285Ter)	Pathogenic
16002	NM_002890.3(RASA1):c.829-9G>A	Pathogenic

SpliceAI

5323 predictions. Top by Δscore:

Variant	Effect	Δscore
5:87331344:CTAG:C	acceptor_loss	1.0000
5:87331345:TAGG:T	acceptor_loss	1.0000
5:87331346:A:AG	acceptor_gain	1.0000
5:87331346:AG:A	acceptor_gain	1.0000
5:87331346:AGGT:A	acceptor_gain	1.0000
5:87331346:AGGTG:A	acceptor_gain	1.0000
5:87331347:G:A	acceptor_gain	1.0000
5:87331347:G:GT	acceptor_gain	1.0000
5:87331347:GGT:G	acceptor_gain	1.0000
5:87331347:GGTG:G	acceptor_gain	1.0000
5:87331347:GGTGG:G	acceptor_gain	1.0000
5:87331405:G:T	donor_gain	1.0000
5:87331499:AGG:A	donor_loss	1.0000
5:87331501:G:GG	donor_gain	1.0000
5:87331501:GTA:G	donor_loss	1.0000
5:87331502:T:A	donor_loss	1.0000
5:87332505:A:AG	acceptor_gain	1.0000
5:87332506:G:GG	acceptor_gain	1.0000
5:87333256:AT:A	acceptor_gain	1.0000
5:87333257:T:TA	acceptor_gain	1.0000
5:87333265:A:AG	acceptor_gain	1.0000
5:87333266:G:GG	acceptor_gain	1.0000
5:87333266:GCCA:G	acceptor_gain	1.0000
5:87337972:A:AG	acceptor_gain	1.0000
5:87337973:G:GG	acceptor_gain	1.0000
5:87337973:GTTT:G	acceptor_gain	1.0000
5:87338092:G:GA	donor_loss	1.0000
5:87338093:TAAGT:T	donor_loss	1.0000
5:87341322:G:GG	donor_gain	1.0000
5:87346669:AAGAT:A	acceptor_gain	1.0000

AlphaMissense

2138 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:87408033:G:C	F156L	1.000
5:87408033:G:T	F156L	1.000
5:87408035:A:G	F156L	1.000
5:87408159:T:A	K114N	1.000
5:87408159:T:G	K114N	1.000
5:87408160:T:A	K114I	1.000
5:87404895:G:T	A213D	0.999
5:87407996:C:G	G169R	0.999
5:87408028:A:G	L158P	0.999
5:87408028:A:T	L158H	0.999
5:87408040:A:G	L154P	0.999
5:87408061:T:A	E147V	0.999
5:87408061:T:G	E147A	0.999
5:87408147:G:C	F118L	0.999
5:87408147:G:T	F118L	0.999
5:87408149:A:G	F118L	0.999
5:87408161:T:C	K114E	0.999
5:87408166:G:T	A112D	0.999
5:87408177:A:C	C108W	0.999
5:87408178:C:T	C108Y	0.999
5:87408179:A:G	C108R	0.999
5:87409338:C:G	R89P	0.999
5:87409356:G:T	A83D	0.999
5:87411228:A:T	V79D	0.999
5:87412764:A:G	W11R	0.999
5:87412764:A:T	W11R	0.999
5:87408052:A:G	L150P	0.998
5:87408061:T:C	E147G	0.998
5:87408073:A:C	I143R	0.998
5:87408073:A:T	I143K	0.998

dbSNP variants (sampled 300 via entrez): RS1000000194 (5:87393269 C>G,T), RS1000035296 (5:87332782 A>G,T), RS1000084742 (5:87403615 C>CA), RS1000119777 (5:87347379 G>A,T), RS1000123902 (5:87314405 G>A,C), RS1000125560 (5:87378098 T>G), RS1000139410 (5:87331770 A>C,T), RS1000158306 (5:87323455 G>A,C), RS1000192507 (5:87351682 CCTGA>C), RS1000224192 (5:87374351 T>C), RS1000324352 (5:87357887 T>C), RS1000359888 (5:87333855 C>G), RS1000412441 (5:87318675 C>G,T), RS1000424382 (5:87373778 A>G), RS1000426497 (5:87407297 G>A)

Disease associations

OMIM: gene MIM:601953 | disease phenotypes: MIM:608354, MIM:608355, MIM:605462, MIM:149000, MIM:602089, MIM:314580, MIM:187300

GenCC curated gene-disease

Mondo (11): capillary malformation-arteriovenous malformation syndrome (MONDO:0012016), capillary malformation-arteriovenous malformation 1 (MONDO:0020783), basal cell carcinoma, susceptibility to, 1 (MONDO:0011556), angioosteohypertrophic syndrome (MONDO:0007864), vascular malformation (MONDO:0024291), capillary infantile hemangioma (MONDO:0011191), breast ductal adenocarcinoma (MONDO:0005590), capillary malformation (MONDO:0016231), Wieacker-Wolff syndrome (MONDO:0010758), hereditary hemorrhagic telangiectasia (MONDO:0019180), hydrops fetalis (MONDO:0015193)

Orphanet (12): Capillary malformation-arteriovenous malformation (Orphanet:137667), RASA1-related capillary malformation-arteriovenous malformation (Orphanet:693907), OBSOLETE: Angioosteohypertrophic syndrome (Orphanet:2346), Capillary-lymphatic-venous malformation with segmental distribution (Orphanet:90308), Rare capillary malformation (Orphanet:211247), Wieacker-Wolff syndrome (Orphanet:3454), X-linked intellectual disability, Miles-Carpenter type (Orphanet:85283), Hereditary hemorrhagic telangiectasia (Orphanet:774), Hydrops fetalis (Orphanet:1041), Parkes Weber syndrome (Orphanet:90307), NON RARE IN EUROPE: Infantile capillary hemangioma (Orphanet:464293), OBSOLETE: Familial capillary hemangioma (Orphanet:91415)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001789	Hydrops fetalis

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001850_35	Major depressive disorder	4.000000e-06
GCST002886_1	Prostate cancer aggressiveness	6.000000e-09
GCST005023_52	Initial pursuit acceleration	4.000000e-06
GCST005081_4	Bipolar disorder lithium response (continuous) or schizophrenia	5.000000e-09
GCST006976_19	Macular thickness	5.000000e-24
GCST007094_60	Diastolic blood pressure	3.000000e-08
GCST007096_162	Pulse pressure	6.000000e-06
GCST007099_220	Systolic blood pressure	7.000000e-11
GCST010988_96	Adult body size	1.000000e-09
GCST012047_12	Fasting glucose	4.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006999	cancer aggressiveness measurement
EFO:0007000	Gleason score measurement
EFO:0008434	initial pursuit acceleration
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D015160	Hydrops Fetalis	C12.050.703.277.060.480; C15.378.295.480; C15.378.420.826.100.350; C16.300.060.480; C16.320.365.826.100.350; C20.306.480; C23.888.277.395
D007715	Klippel-Trenaunay-Weber Syndrome	C14.907.077.410
D013683	Telangiectasia, Hereditary Hemorrhagic	C14.907.454.900; C14.907.823.780; C15.378.463.515.900; C16.131.240.850.968
D054079	Vascular Malformations	C14.240.850; C16.131.240.850
C564254	Capillary Malformation-Arteriovenous Malformation (supp.)
C535860	Hemangioma, capillary infantile (supp.)
C536703	Wieacker syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2111288 (PROTEIN COMPLEX), CHEMBL2165 (SINGLE PROTEIN), CHEMBL3038473 (PROTEIN COMPLEX), CHEMBL4523632 (PROTEIN COMPLEX), CHEMBL5483181 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

28 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 57,798 (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
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL4594350	ADAGRASIB	4	2,814
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL3904602	LEROCICLIB	3	1,012
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL2347597	ASNUCICLIB	2	100
CHEMBL3655762	CYC-065	2	388
CHEMBL4067549	ULECACICLIB	2	41
CHEMBL4442620	RONICICLIB	2	367
CHEMBL445813	AT-7519	2	2,614
CHEMBL5095102	INIXACICLIB	2	9
CHEMBL5199065	ISTISOCICLIB	2	21
CHEMBL564829	MILCICLIB	2	821
CHEMBL1944698	ZOTIRACICLIB	2	2,915
CHEMBL3115681	NARAZACICLIB	2	287
CHEMBL4297488	CT-7001	2	379
CHEMBL4462530	ZEMIRCICLIB	2	429
CHEMBL1230607	PHA-793887	1	299
CHEMBL296468	BMS-387032	1
CHEMBL3545083	RGB-286638	1
CHEMBL4754493	BTX-A51	1
CHEMBL488436	AZD-5438	1
CHEMBL5090754	SY-5609	1
CHEMBL258805	SU-9516	1
CHEMBL3128043	PF-03758309	1
CHEMBL4225966	SEL-120 FREE BASE	1

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2230641	CCNH		0.00	0

Binding affinities (BindingDB)

54 measured of 149 human assays (150 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
28-dimethylphosphoryl-11-methyl-25-(trifluoromethyl)-4,11,16,21,23,26-hexazapentacyclo[20.3.1.15,9.116,20.02,6]octacosa-1(26),2,5,7,9(28),22,24-heptaen-10-one	IC50	1 nM	US-20250109156: INDOLE-CONTAINING MACROCYCLIC COMPOUNDS AND USES THEREOF
(20S)-28-dimethylphosphoryl-25-(trifluoromethyl)-4,11,16,21,23,26-hexazapentacyclo[20.3.1.15,9.116,20.02,6]octacosa-1(26),2,5,7,9(28),22,24-heptaen-10-one	IC50	1.2 nM	US-20250109156: INDOLE-CONTAINING MACROCYCLIC COMPOUNDS AND USES THEREOF
(1S)-28-dimethylphosphoryl-6-(trifluoromethyl)-2,4,10,17,22,29-hexazapentacyclo[20.4.1.13,7.111,15.08,12]nonacosa-3,5,7(29),8,11,13,15(28)-heptaen-16-one	IC50	1.4 nM	US-20250109156: INDOLE-CONTAINING MACROCYCLIC COMPOUNDS AND USES THEREOF
(21S)-29-dimethylphosphoryl-26-(trifluoromethyl)-10-oxa-4,17,22,24,27-pentazapentacyclo[21.3.1.15,9.117,21.02,6]nonacosa-1(27),2,5,7,9(29),23,25-heptaene	IC50	1.6 nM	US-20250109156: INDOLE-CONTAINING MACROCYCLIC COMPOUNDS AND USES THEREOF
(19R)-24-(trifluoromethyl)-4,11,16,20,22,25-hexazapentacyclo[19.3.1.15,9.116,19.02,6]heptacosa-1(25),2,5,7,9(27),21,23-heptaen-10-one	IC50	4.58 nM	US-20250145632: Pyrimidine Heterocyclic Compound, Preparation Method Thereof and use Thereof in Medicine
3-[5-(morpholin-4-ylmethyl)-1H-indol-2-yl]-1H-indazole-6-carbonitrile	IC50	11 nM
[(6R)-6-methyl-2-[(2-methyl-1H-imidazol-5-yl)methylamino]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-7-yl]-[(3S,4S)-1-methyl-3-phenylpiperidin-4-yl]methanone	IC50	11 nM	WO-2022064009: CYCLIN-DEPENDENT KINASE 7 (CDK7) NON-COVALENT INHIBITORS
(20R)-25-(trifluoromethyl)-14-oxa-4,11,17,21,23,26-hexazapentacyclo[20.3.1.15,9.117,20.02,6]octacosa-1(26),2,5,7,9(28),22,24-heptaen-10-one	IC50	11 nM	US-20250145632: Pyrimidine Heterocyclic Compound, Preparation Method Thereof and use Thereof in Medicine
4-{3-[5-(piperidin-1-ylmethyl)-1H-indol-2-yl]-1H-indazol-6-yl}-1,2-thiazole	IC50	18 nM
4-({2-[6-(1H-pyrazol-4-yl)-1H-indazol-3-yl]-1H-indol-5-yl}methyl)morpholine	IC50	25 nM
4-({2-[6-(1H-pyrazol-5-yl)-1H-indazol-3-yl]-1H-indol-5-yl}methyl)morpholine	IC50	34 nM
GP0210	IC50	40 nM
(5-{3-[5-(piperidin-1-ylmethyl)-1H-indol-2-yl]-1H-indazol-6-yl}-1H-1,2,3-triazol-4-yl)methanol	IC50	56 nM
3-[5-(piperidin-1-ylmethyl)-1H-indol-2-yl]-6-(1H-1,2,3-triazol-1-yl)-1H-indazole	IC50	57 nM
(2R)-2-({4-[(3-chlorophenyl)amino]-8-(propan-2-yl)pyrazolo[1,5-a][1,3,5]triazin-2-yl}amino)-3-methylbutan-1-ol	IC50	60 nM
(E)-N-[4-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]phenyl]-4-(dimethylamino)but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[4-[3-[(2S)-1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]phenyl]-4-(dimethylamino)but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[3-[4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]phenyl]phenyl]butanamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[6-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-3-pyridinyl]-4-(dimethylamino)but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[3-[3-fluoro-4-(prop-2-enoylamino)phenyl]phenyl]propanamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[4-fluoro-3-[3-fluoro-4-(prop-2-enoylamino)phenyl]phenyl]propanamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[3-[5-(prop-2-enoylamino)-2-pyridinyl]phenyl]propanamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[3-[3-fluoro-4-(prop-2-enoylamino)phenyl]phenyl]-3-methylbutanamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[4-[3-[1-[(5-cyclopentyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-fluorophenyl]-4-(dimethylamino)but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[4-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-fluorophenyl]-4-pyrrolidin-1-ylbut-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[5-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-6-fluoro-2-pyridinyl]-4-morpholin-4-ylbut-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[5-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-3-pyridinyl]-4-morpholin-4-ylbut-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[5-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-3-fluoro-2-pyridinyl]-4-morpholin-4-ylbut-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[6-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-fluoro-3-pyridinyl]-4-(3-fluoropyrrolidin-1-yl)but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[5-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-pyridinyl]-4-imidazol-1-ylbut-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[5-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-pyridinyl]-4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[5-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-pyridinyl]-4-[(2S,4S)-4-fluoro-2-(methoxymethyl)pyrrolidin-1-yl]but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-4-(3-cyanopyrrolidin-1-yl)-N-[5-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-pyridinyl]but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[4-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-fluorophenyl]-4-[(3S)-3-fluoropyrrolidin-1-yl]but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
methyl (2S)-1-[(E)-4-[[5-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-pyridinyl]amino]-4-oxobut-2-enyl]pyrrolidine-2-carboxylate	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-4-[(2S)-2-(cyanomethyl)pyrrolidin-1-yl]-N-[5-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]-2-pyridinyl]but-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
(E)-N-[6-[3-[1-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-1-oxopropan-2-yl]phenyl]pyrazin-2-yl]-4-pyrrolidin-1-ylbut-2-enamide	IC50	62.5 nM	US-11174232: Substituted heterocyclyl derivatives as CDK inhibitors
[5-(3-{5-[(4-fluoropiperidin-1-yl)methyl]-1H-indol-2-yl}-1H-indazol-6-yl)-1H-1,2,3-triazol-4-yl]methanol	IC50	180 nM
(2R)-2-{[4-(benzylamino)-7-(propan-2-yl)imidazo[1,2-a][1,2,4]triazin-2-yl]amino}butan-1-ol	IC50	220 nM
(2R)-2-[[6-(benzylamino)-9-isopropyl-purin-2-yl]amino]butan-1-ol	KD	260 nM
[5-(3-{5-[(4-fluoropiperidin-1-yl)methyl]-1H-indol-2-yl}-1H-indazol-6-yl)-1H-1,2,3-triazol-4-yl]methanamine	IC50	300 nM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[4-(prop-2-enoylamino)anilino]-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazole-5-carboxamide	IC50	300 nM	US-10870651: Inhibitors of cyclin-dependent kinase 7 (CDK7)
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-3-[[4-(prop-2-enoylamino)benzoyl]amino]spiro[1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazole-6,1’-cyclohexane]-5-carboxamide	IC50	300 nM	US-10870651: Inhibitors of cyclin-dependent kinase 7 (CDK7)
2-methoxy-4-{3-[5-(piperidin-1-ylmethyl)-1H-indol-2-yl]-1H-indazol-6-yl}phenol	IC50	310 nM
6-(5-methyl-1H-1,2,3-triazol-1-yl)-3-[5-(piperidin-1-ylmethyl)-1H-indol-2-yl]-1H-indazole	IC50	420 nM
3-[5-(piperidin-1-ylmethyl)-1H-indol-2-yl]-6-(2H-1,2,3-triazol-2-yl)-1H-indazole	IC50	480 nM
3-[5-(morpholin-4-ylmethyl)-1H-indol-2-yl]-1H-indazole-6-carboxamide	IC50	1300 nM
3-[5-(piperidin-1-ylmethyl)-1H-indol-2-yl]-6-(1H-pyrazol-1-yl)-1H-indazole	IC50	2300 nM
2-{3-[5-(piperidin-1-ylmethyl)-1H-indol-2-yl]-1H-indazol-6-yl}-1,3-thiazole	IC50	4000 nM
N-methyl-3-[5-(morpholin-4-ylmethyl)-1H-indol-2-yl]-1H-indazole-6-carboxamide	IC50	4900 nM

ChEMBL bioactivities

983 potent at pChembl≥5 of 1064 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Kd	0.03	nM	CHEMBL5088381
10.22	Kd	0.06	nM	CHEMBL5080711
10.22	Kd	0.06	nM	CHEMBL6144858
10.15	Kd	0.07	nM	CHEMBL4791134
10.15	Kd	0.07	nM	SY-5609
10.10	Kd	0.08	nM	CHEMBL4786592
10.10	Kd	0.08	nM	CHEMBL4782954
10.05	Kd	0.09	nM	CHEMBL5083688
10.00	Kd	0.1	nM	CHEMBL4779443
10.00	Kd	0.1	nM	CHEMBL4790490
9.96	Kd	0.11	nM	SY-5609
9.92	Kd	0.12	nM	CHEMBL6143916
9.85	Kd	0.14	nM	CHEMBL6152747
9.82	Kd	0.15	nM	CHEMBL4786320
9.82	Kd	0.15	nM	CHEMBL4798916
9.80	Kd	0.16	nM	CHEMBL6149443
9.74	Kd	0.18	nM	CHEMBL6144731
9.68	Kd	0.21	nM	CHEMBL4786555
9.48	Kd	0.33	nM	CHEMBL4555799
9.47	Kd	0.34	nM	CHEMBL4786843
9.40	Kd	0.4	nM	CHEMBL4800180
9.34	IC50	0.46	nM	SELICICLIB
9.21	IC50	0.623	nM	QUIZARTINIB
9.21	IC50	0.623	nM	CHEMBL3683258
9.00	IC50	0.996	nM	CHEMBL256570
9.00	IC50	0.996	nM	CHEMBL3683258
8.89	IC50	1.3	nM	ADAGRASIB
8.89	IC50	1.3	nM	BTX-A51
8.77	Ki	1.7	nM	CHEMBL5573062
8.70	IC50	2	nM	RGB-286638
8.68	Ki	2.1	nM	CHEMBL5571052
8.66	Ki	2.2	nM	CHEMBL5571158
8.66	Ki	2.2	nM	CHEMBL5612622
8.64	IC50	2.3	nM	SY-5609
8.60	IC50	2.5	nM	SY-5609
8.55	Ki	2.8	nM	CHEMBL5570901
8.54	Ki	2.9	nM	CHEMBL5573958
8.52	IC50	3	nM	ZOTIRACICLIB
8.52	IC50	3	nM	CHEMBL5573062
8.52	Ki	3	nM	CHEMBL5569632
8.49	Ki	3.2	nM	CT-7001
8.47	Ki	3.4	nM	CHEMBL5573301
8.46	Kd	3.5	nM	CHEMBL6161045
8.43	IC50	3.7	nM	CHEMBL5589668
8.42	Ki	3.8	nM	CHEMBL5594541
8.40	EC50	4	nM	CHEMBL4436535
8.34	IC50	4.6	nM	CHEMBL6152747
8.25	IC50	5.6	nM	CHEMBL5612636
8.21	IC50	6.1	nM	CHEMBL5574236
8.21	IC50	6.1	nM	CHEMBL5573301

PubChem BioAssay actives

557 with measured affinity, of 1354 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[6-(3,5-dimethyl-1,2-oxazol-4-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-N-[(3S)-piperidin-3-yl]-5-(trifluoromethyl)pyrimidin-2-amine;hydrochloride	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	<0.0001	uM
4-[6-(3,5-dimethyl-1,2-oxazol-4-yl)-1H-indol-3-yl]-N-[(3S)-piperidin-3-yl]-5-(trifluoromethyl)pyrimidin-2-amine	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
4-(7-dimethylphosphoryl-1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]-5-(trifluoromethyl)pyrimidin-2-amine	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
3-[5-ethyl-2-[[(3S)-piperidin-3-yl]amino]pyrimidin-4-yl]-7-methylsulfonyl-1H-indole-6-carbonitrile	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
7-methylsulfonyl-3-[2-[[(3S)-piperidin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]-1H-indole-6-carbonitrile	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
4-(6-methylsulfonyl-1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]-5-(trifluoromethyl)pyrimidin-2-amine	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
7-dimethylphosphoryl-3-[2-[[(3S)-6,6-dimethylpiperidin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]-1H-indole-6-carbonitrile	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
7-dimethylphosphoryl-3-[2-[[(3S)-5,5-dimethylpiperidin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]-1H-indole-6-carbonitrile	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
4-(7-methylsulfonyl-1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]-5-(trifluoromethyl)pyrimidin-2-amine	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
4-(1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]-5-(trifluoromethyl)pyrimidin-2-amine	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
3-[2-[[(3S)-piperidin-3-yl]amino]-5-(trifluoromethyl)pyrimidin-4-yl]-1H-indole-6-carbonitrile	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0001	uM
N-[(3S)-5,5-dimethylpiperidin-3-yl]-4-(1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0002	uM
N-[(3S)-6,6-dimethylpiperidin-3-yl]-4-(1H-indol-3-yl)-5-(trifluoromethyl)pyrimidin-2-amine	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0003	uM
5-chloro-4-(1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]pyrimidin-2-amine	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0003	uM
5-ethyl-4-(1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]pyrimidin-2-amine	1820461: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay	kd	0.0004	uM
(2R)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]butan-1-ol	1868068: Inhibition of CDK7/Cyclin H (unknown origin)	ic50	0.0005	uM
4-N-[5-chloro-4-[5-(cyclopropylmethyl)-1-methylpyrazol-4-yl]pyrimidin-2-yl]cyclohexane-1,4-diamine	1868068: Inhibition of CDK7/Cyclin H (unknown origin)	ic50	0.0013	uM
Adagrasib	1853202: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) in leukemia cells	ic50	0.0013	uM
22-propan-2-ylspiro[10-oxa-2,18,20,24,25,26-hexazatetracyclo[17.6.1.04,9.021,25]hexacosa-1(26),4,6,8,19,21,23-heptaene-16,3’-azetidine]	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0017	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	1317365: Inhibition of CDK7/cyclin H (unknown origin)	ic50	0.0020	uM
23-propan-2-ylspiro[10-oxa-2,19,21,25,26,27-hexazatetracyclo[18.6.1.04,9.022,26]heptacosa-1(27),4,6,8,20,22,24-heptaene-17,4’-piperidine]	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0021	uM
N-[(1R)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[[4-(prop-2-enoylamino)benzoyl]amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	2125276: Inhibition of recombinant GST-tagged CDK7/CycH/MAT1 (unknown origin) extracted from baculo-virus infected Sf9 insect cells assessed as inhibition constant using ATP containing 32P measured after 15 mins by Beckman liquid scintillation counter analysis	ki	0.0022	uM
(12R)-22-propan-2-ylspiro[10-oxa-2,18,20,24,25,26-hexazatetracyclo[17.6.1.04,9.021,25]hexacosa-1(26),4,6,8,19,21,23-heptaene-16,4’-piperidine]-12-ol	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0022	uM
(3S,4S)-4-[(20-propan-2-yl-10-oxa-2,16,18,22,23,24-hexazatetracyclo[15.6.1.04,9.019,23]tetracosa-1(24),4,6,8,17,19,21-heptaen-16-yl)methyl]pyrrolidin-3-ol	2107679: Inhibition of recombinant human His-tagged CDK7/cyclin H/MNAT1 expressed in baculovirus expression system using histone H1 as substrate preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo reagent based microplate reader assay	ki	0.0028	uM
12-methoxy-22-propan-2-ylspiro[10-oxa-2,18,20,24,25,26-hexazatetracyclo[17.6.1.04,9.021,25]hexacosa-1(26),4,6,8,19,21,23-heptaene-16,4’-piperidine]	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0029	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	1317353: Inhibition of recombinant human full length C-terminal His6-tagged CDK7/cyclin H/N-terminal GST-tagged MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 substrate peptide	ic50	0.0030	uM
(12S)-22-propan-2-ylspiro[10-oxa-2,18,20,24,25,26-hexazatetracyclo[17.6.1.04,9.021,25]hexacosa-1(26),4,6,8,19,21,23-heptaene-16,4’-piperidine]-12-ol	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0030	uM
(3R,4R)-4-[[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]methyl]piperidin-3-ol	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0032	uM
22-propan-2-ylspiro[10-oxa-2,18,20,24,25,26-hexazatetracyclo[17.6.1.04,9.021,25]hexacosa-1(26),4,6,8,19,21,23-heptaene-16,4’-piperidine]	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0034	uM
7-methyl-22-propan-2-ylspiro[10-oxa-2,8,18,20,24,25,26-heptazatetracyclo[17.6.1.04,9.021,25]hexacosa-1(26),4(9),5,7,19,21,23-heptaene-16,4’-piperidine]	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ic50	0.0037	uM
20-propan-2-ylspiro[2,16,18,22,23,24-hexazatetracyclo[15.6.1.04,9.019,23]tetracosa-1(24),4,6,8,17,19,21-heptaene-14,4’-piperidine]	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0038	uM
N-[(1S,3R)-3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]cyclohexyl]-5-[[(E)-4-(dimethylamino)but-2-enoyl]amino]pyridine-2-carboxamide	1609458: Competitive irreversible inhibition of CDK7/cyclinH/MAT1 (unknown origin)	ec50	0.0040	uM
4-N-[5-[[(1S)-2-(dimethylamino)-1-phenylethyl]carbamoyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-1-N-[4-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-4-oxobutyl]benzene-1,4-dicarboxamide	2125279: Inhibition of CDK7/CycH/MNAT1 (unknown origin) assessed as change in TR-FRET ratio using Cdk7/9tide as substrate and ATP by in vitro Adapta Eu kinase assay	ic50	0.0056	uM
4-(7-dimethylphosphoryl-1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]thieno[3,2-d]pyrimidin-2-amine	2092594: Inhibition of human His-tagged CDK7/cyclin H/MNAT1 expressed in baculovirus infected insect cells preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0061	uM
4-N-[5-[[(1S)-2-(dimethylamino)-1-phenylethyl]carbamoyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-1-N-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethyl]benzene-1,4-dicarboxamide	2125279: Inhibition of CDK7/CycH/MNAT1 (unknown origin) assessed as change in TR-FRET ratio using Cdk7/9tide as substrate and ATP by in vitro Adapta Eu kinase assay	ic50	0.0064	uM
7-dimethylphosphoryl-3-[2-[[(3S,5S)-5-fluoropiperidin-3-yl]amino]thieno[3,2-d]pyrimidin-4-yl]-1H-indole-6-carbonitrile	2092594: Inhibition of human His-tagged CDK7/cyclin H/MNAT1 expressed in baculovirus infected insect cells preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0065	uM
4-N-[5-[[(1S)-2-(dimethylamino)-1-phenylethyl]carbamoyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-1-N-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethyl]benzene-1,4-dicarboxamide	2125279: Inhibition of CDK7/CycH/MNAT1 (unknown origin) assessed as change in TR-FRET ratio using Cdk7/9tide as substrate and ATP by in vitro Adapta Eu kinase assay	ic50	0.0067	uM
N-[(1R)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[[4-(propanoylamino)benzoyl]amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	2125278: Inhibition of CDK7/CycH/MAT1 (unknown origin)	ic50	0.0068	uM
4-N-[5-[[(1S)-2-(dimethylamino)-1-phenylethyl]carbamoyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-1-N-[5-[2-(2,4-dioxocyclohexyl)-1,3-dioxoisoindol-4-yl]pent-4-ynyl]benzene-1,4-dicarboxamide	2125279: Inhibition of CDK7/CycH/MNAT1 (unknown origin) assessed as change in TR-FRET ratio using Cdk7/9tide as substrate and ATP by in vitro Adapta Eu kinase assay	ic50	0.0069	uM
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	1651611: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) pre incubated up to 60 mins followed by substrate and ATP addition	ic50	0.0070	uM
7-dimethylphosphoryl-3-[2-[[(3S,5S)-5-methylpiperidin-3-yl]amino]thieno[3,2-d]pyrimidin-4-yl]-1H-indole-6-carbonitrile	2092594: Inhibition of human His-tagged CDK7/cyclin H/MNAT1 expressed in baculovirus infected insect cells preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0072	uM
4-(7-dimethylphosphoryl-4-fluoro-1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]thieno[3,2-d]pyrimidin-2-amine	2092594: Inhibition of human His-tagged CDK7/cyclin H/MNAT1 expressed in baculovirus infected insect cells preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0073	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[3-[[4-(prop-2-enoylamino)benzoyl]amino]anilino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	1651611: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) pre incubated up to 60 mins followed by substrate and ATP addition	ic50	0.0076	uM
4-N-[5-[[(1S)-2-(dimethylamino)-1-phenylethyl]carbamoyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-1-N-[2-[2-[3-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-3-oxopropoxy]ethoxy]ethyl]benzene-1,4-dicarboxamide	2125279: Inhibition of CDK7/CycH/MNAT1 (unknown origin) assessed as change in TR-FRET ratio using Cdk7/9tide as substrate and ATP by in vitro Adapta Eu kinase assay	ic50	0.0076	uM
8-fluoro-20-propan-2-ylspiro[2,16,18,22,23,24-hexazatetracyclo[15.6.1.04,9.019,23]tetracosa-1(24),4(9),5,7,17,19,21-heptaene-14,4’-piperidine]	2104174: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ic50	0.0076	uM
4-N-[5-[[(1S)-2-(dimethylamino)-1-phenylethyl]carbamoyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-1-N-[8-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]amino]-2-oxoethyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-8-oxooctyl]benzene-1,4-dicarboxamide	2125279: Inhibition of CDK7/CycH/MNAT1 (unknown origin) assessed as change in TR-FRET ratio using Cdk7/9tide as substrate and ATP by in vitro Adapta Eu kinase assay	ic50	0.0078	uM
4-N-[5-[[(1S)-2-(dimethylamino)-1-phenylethyl]carbamoyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-1-N-[6-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-6-oxohexyl]benzene-1,4-dicarboxamide	2125279: Inhibition of CDK7/CycH/MNAT1 (unknown origin) assessed as change in TR-FRET ratio using Cdk7/9tide as substrate and ATP by in vitro Adapta Eu kinase assay	ic50	0.0081	uM
1-N-[5-[[5-[4-[(1S)-1-[[(2S,4R)-1-[(2S)-2-acetamido-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-2-carbonyl]amino]ethyl]phenyl]-1,3-thiazole-4-carbonyl]amino]pentyl]-4-N-[5-[[(1S)-2-(dimethylamino)-1-phenylethyl]carbamoyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]benzene-1,4-dicarboxamide	2125279: Inhibition of CDK7/CycH/MNAT1 (unknown origin) assessed as change in TR-FRET ratio using Cdk7/9tide as substrate and ATP by in vitro Adapta Eu kinase assay	ic50	0.0086	uM
4-N-[5-[[(1S)-2-(dimethylamino)-1-phenylethyl]carbamoyl]-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-3-yl]-1-N-[3-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-3-oxopropyl]benzene-1,4-dicarboxamide	2125279: Inhibition of CDK7/CycH/MNAT1 (unknown origin) assessed as change in TR-FRET ratio using Cdk7/9tide as substrate and ATP by in vitro Adapta Eu kinase assay	ic50	0.0087	uM
4-(7-dimethylphosphoryl-5-fluoro-1H-indol-3-yl)-N-[(3S)-piperidin-3-yl]thieno[3,2-d]pyrimidin-2-amine	2092594: Inhibition of human His-tagged CDK7/cyclin H/MNAT1 expressed in baculovirus infected insect cells preincubated for 10 mins followed by substrate and ATP addition and measured after 60 mins by ADP-Glo kinase assay	ic50	0.0087	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
bisphenol A	increases expression, affects cotreatment	2
Arsenic Trioxide	decreases expression, increases expression	2
Carbamazepine	affects expression	2
Tretinoin	affects binding, decreases reaction, increases phosphorylation, decreases activity	2
aristolochic acid I	decreases expression	1
LL202 flavonoid	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
naringenin	affects cotreatment, increases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	increases expression	1
CPG-oligonucleotide	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
pyrimidifen	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
pyrachlostrobin	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Antimycin A	increases expression	1
Arecoline	decreases expression	1
Benzo(a)pyrene	affects methylation	1

ChEMBL screening assays

348 unique, capped per target: 346 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004615	Binding	Inhibition of CDK7/cyclinH by IMAP florescence polarization assay	A diaminocyclohexyl analog of SNS-032 with improved permeability and bioavailability properties. — Bioorg Med Chem Lett
CHEMBL5724508	Functional	Biochemical CDK7 assay (KIapp) ( CDK7 catalyzed, ATP-dependent, phosphorylation of a peptide substrate derived from RNA Pol II (CDK7/9-tide). Coupled via lactate dehydrogenase (LDH) and pyruvate kinase (PK) to lactate and NAD+ production, w	Data for DCP probe JNJ-3738

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04999618	PHASE4	COMPLETED	A New Approach in Laser Surgery Using the Regenerative Solution in Children Diagnosed With Vascular Pathology
NCT02389959	PHASE4	COMPLETED	Intranasal Bevacizumab for HHT-Related Epistaxis
NCT07285005	PHASE3	NOT_YET_RECRUITING	A Study to Investigate Efficacy and Safety of KP-001 Compared With Placebo in Patients Aged ≥2 Years With Common VM, Common LM, or KTS/CLOVES Syndrome
NCT02384122	PHASE3	COMPLETED	Efficacy of Octreotide on Blood and Iron Requirements in Patients With Anemia Due to Angiodysplasias
NCT02638389	PHASE3	RECRUITING	Efficacy and Safety of Sirolimus in Vascular Anomalies That Are Refractory to Standard Care
NCT03110783	PHASE3	COMPLETED	Bioseal Dural Sealing Study BIOS-14-001
NCT03987152	PHASE3	UNKNOWN	Treatment of Congenital Vascular Malformations Using Sirolimus: Improving Quality of Life
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT02764411	PHASE3	TERMINATED	Onreltea (Brimonidine) Gel In Pediatric Patients With Capillary Malformations
NCT00004654	PHASE3	COMPLETED	Phase III Randomized, Placebo-Controlled, Crossover Study of Soy Protein Isolate for Hereditary Hemorrhagic Telangiectasia
NCT00355108	PHASE3	COMPLETED	ATERO : A Randomised Study With Tranexamic Acid in Epistaxis of Rendu Osler Syndrome
NCT01031992	PHASE3	COMPLETED	Tranexamic Acid and Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
NCT02963129	PHASE3	UNKNOWN	Treatment of Nasal Staphylococcus Aureus Colonization in Patients With HHT
NCT03227263	PHASE3	COMPLETED	BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT).
NCT04113187	PHASE3	COMPLETED	Propranolol for Epistaxis in Hereditary Hemorrhagic Telangiectasia Patients
NCT06789913	PHASE2	RECRUITING	A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation
NCT02509468	PHASE2	COMPLETED	suPERficial Slow-flow Vascular malFORMations Treated With sirolimUS
NCT02754960	PHASE2	WITHDRAWN	Efficacy Study of Thalidomide in Gastrointestinal Vascular Malformation Related Bleeding
NCT02883023	PHASE2	UNKNOWN	Electrosclerotherapy for Capillary Malformations
NCT03972592	PHASE2	COMPLETED	Topical Sirolimus in Cutaneous Lymphatic Malformations
NCT05983159	PHASE2	RECRUITING	A Trial of Targeted Therapies for Patients With Slow-Flow or Fast-Flow Vascular Malformations
NCT06788314	PHASE2	RECRUITING	A Study of Enalapril in Treatment of Venous Malformations
NCT07037238	PHASE2	RECRUITING	An Open-Label, Single-Arm Exploratory Clinical Study of Everolimus for the Treatment of Vascular Malformations
NCT07477548	PHASE2	NOT_YET_RECRUITING	A Study to Evaluate the Efficacy and Safety of Everolimus in Patients With Teratment-refractory Vascular Anomalies
NCT07579962	PHASE2	NOT_YET_RECRUITING	Treatment of Low-flow Vascular Malformations With Bleomycin Electrosclerotherapy (BEST)
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00004327	PHASE2	COMPLETED	Phase II Pilot Study of Octreotide, a Somatostatin Octapeptide Analog, for Gastrointestinal Hemorrhage in Hormone-Refractory Hereditary Hemorrhagic Telangiectasia and Senile Ectasia
NCT00375622	PHASE2	COMPLETED	Anti-Estrogen Therapy for Hereditary Hemorrhagic Telangiectasia A Double-Blind Placebo-Controlled Clinical Trial
NCT00389935	PHASE2	COMPLETED	Thalidomide Reduces Arteriovenous Malformation Related Gastrointestinal Bleeding
NCT01314274	PHASE2	COMPLETED	Intranasal Submucosal Bevacizumab for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
NCT01397695	PHASE2	COMPLETED	Topical Bevacizumab for the Management of Recurrent Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)
NCT01402531	PHASE2	COMPLETED	Submucosal Bevacizumab for the Management of Recurrent Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)
NCT01408030	PHASE2	COMPLETED	North American Study of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
NCT01485224	PHASE2	COMPLETED	Efficacy of Thalidomide in the Treatment of Hereditary Hemorrhagic Telangiectasia
NCT02204371	PHASE2	TERMINATED	Evaluation of Pazopanib on Bleeding in Subjects With Hereditary Haemorrhagic Telangiectasia
NCT02484716	PHASE2	COMPLETED	Efficacy of a Timolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) - (TEMPO)
NCT02874326	PHASE2	UNKNOWN	Octreotide in Patients With GI Bleeding Due to Rendu-Osler-Weber
NCT03397004	PHASE2	COMPLETED	Doxycycline for Hereditary Hemorrhagic Telangiectasia
NCT03910244	PHASE2	COMPLETED	Pomalidomide for the Treatment of Bleeding in HHT