CCNT2

Summary

CCNT2 (cyclin T2, HGNC:1600) is a protein-coding gene on chromosome 2q21.3, encoding Cyclin-T2 (O60583). Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin T) complex, also called positive transcription elongation factor B (P-TEFB), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the CTD (carboxy-terminal dom….

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 and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb complex containing this cyclin was reported to interact with, and act as a negative regulator of human immunodeficiency virus type 1 (HIV-1) Tat protein. A pseudogene of this gene is found on chromosome 1. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 905 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 81 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_058241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1600
Approved symbol	CCNT2
Name	cyclin T2
Location	2q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000082258
Ensembl biotype	protein_coding
OMIM	603862
Entrez	905

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000264157, ENST00000295238, ENST00000417175, ENST00000419781, ENST00000438691, ENST00000446247, ENST00000452521, ENST00000452839, ENST00000464932, ENST00000475094, ENST00000922066

RefSeq mRNA: 4 — MANE Select: NM_058241 NM_001241, NM_001320748, NM_001320749, NM_058241

CCDS: CCDS2174, CCDS2175

Canonical transcript exons

ENST00000264157 — 9 exons

Exon	Start	End
ENSE00001386482	134953230	134959342
ENSE00003461128	134947736	134947899
ENSE00003477476	134936841	134936969
ENSE00003490235	134919810	134919891
ENSE00003607271	134946101	134946146
ENSE00003648904	134952641	134952711
ENSE00003657278	134918822	134919012
ENSE00003660489	134942612	134942674
ENSE00003667063	134939002	134939062

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 94.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5906 / max 145.9400, expressed in 1804 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22630	17.5906	1804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	94.52	gold quality
calcaneal tendon	UBERON:0003701	93.45	gold quality
body of pancreas	UBERON:0001150	92.26	gold quality
visceral pleura	UBERON:0002401	91.83	gold quality
endothelial cell	CL:0000115	91.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.48	gold quality
monocyte	CL:0000576	91.05	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.01	gold quality
cortical plate	UBERON:0005343	90.97	gold quality
mononuclear cell	CL:0000842	90.83	gold quality
rectum	UBERON:0001052	90.77	gold quality
leukocyte	CL:0000738	90.42	gold quality
germinal epithelium of ovary	UBERON:0001304	90.42	gold quality
endometrium	UBERON:0001295	90.35	gold quality
tibia	UBERON:0000979	90.32	gold quality
left ovary	UBERON:0002119	90.29	gold quality
tibial nerve	UBERON:0001323	90.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.12	gold quality
ganglionic eminence	UBERON:0004023	90.08	gold quality
pleura	UBERON:0000977	90.05	gold quality
right ovary	UBERON:0002118	89.90	gold quality
cerebellar hemisphere	UBERON:0002245	89.67	gold quality
body of uterus	UBERON:0009853	89.59	gold quality
cerebellar cortex	UBERON:0002129	89.54	gold quality
tonsil	UBERON:0002372	89.39	gold quality
parietal pleura	UBERON:0002400	89.29	gold quality
gingival epithelium	UBERON:0001949	89.00	gold quality
embryo	UBERON:0000922	88.98	gold quality
ovary	UBERON:0000992	88.90	gold quality
corpus callosum	UBERON:0002336	88.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.80
E-MTAB-6379	no	961.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

281 targeting CCNT2, 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-4692	100.00	67.32	2066
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 10)

• Physical interaction between pRb and cdk9/cyclinT2 complex. (PMID:12037672)
• CycT2 not only contains two domains that target rna polymerase II but this substrate recognition is necessary for its transcriptional activity via DNA (PMID:15563843)
• Data strengthen the hypothesis that Cyclin T2a plays a role in muscle differentiation, and propose PKNalpha as a novel partner of Cyclin T2a in this process. (PMID:16331689)
• The results establish that cdk9/cyclin T2a-mediated coactivation of MyoD depends on serine 37 phosphorylation. (PMID:16841087)
• These results suggest that acetylation of CDK9 is an important posttranslational modification that is involved in regulating P-TEFb transcriptional elongation function. (PMID:17452463)
• TAF7 interacts with the transcription factors, TFIIH and P-TEFb, resulting in the inhibition of their Pol II CTD kinase activities (PMID:18391197)
• The tripartite protein-RNA complex formation between Hexim, Cyclin T and 7SK snRNA, was analyzed. (PMID:19883659)
• the release of P-TEFb from the 7SK snRNP led to increased synthesis of HEXIM1 but not HEXIM2 (PMID:24515107)
• miR-192 inhibits cell proliferation and induces G0/G1 cell cycle arrest in AML by regulating the expression of CCNT2. (PMID:28409330)
• MiRNA-188-5p alleviates the progression of osteosarcoma via target degrading CCNT2. (PMID:31957815)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccnt2b	ENSDARG00000036510
danio_rerio	ccnt2a	ENSDARG00000036685
mus_musculus	Ccnt2	ENSMUSG00000026349
rattus_norvegicus	Ccnt2	ENSRNOG00000017113
drosophila_melanogaster	CycT	FBGN0025455
caenorhabditis_elegans		WBGENE00000507
caenorhabditis_elegans		WBGENE00000508

Paralogs (6): CCNK (ENSG00000090061), CCNT1 (ENSG00000129315), CCNH (ENSG00000134480), CCNL1 (ENSG00000163660), CCNL2 (ENSG00000221978), CCNQ (ENSG00000262919)

Protein

Protein identifiers

Cyclin-T2 — O60583 (reviewed: O60583)

All UniProt accessions (6): O60583, C9JUL2, F2Z2C9, F8WDY7, H7BZ27, H7C411

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the cyclin-dependent kinase pair (CDK9/cyclin T) complex, also called positive transcription elongation factor B (P-TEFB), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the CTD (carboxy-terminal domain) of the large subunit of RNA polymerase II (RNAP II). The activity of this complex is regulated by binding with 7SK snRNA. Plays a role during muscle differentiation; P-TEFB complex interacts with MYOD1; this tripartite complex promotes the transcriptional activity of MYOD1 through its CDK9-mediated phosphorylation and binds the chromatin of promoters and enhancers of muscle-specific genes; this event correlates with hyperphosphorylation of the CTD domain of RNA pol II. In addition, enhances MYOD1-dependent transcription through interaction with PKN1. Involved in early embryo development. (Microbial infection) Promotes transcriptional activation of early and late herpes simplex virus 1/HHV-1 promoters.

Subunit / interactions. Interacts with CDK9 to form P-TEFb. Interacts with POLR2A (via the C-terminal domain (CTD)); mediates transcriptional activity. Interacts with HEXIM1; mediates formation of a tripartite complex with KPNA2. Interacts with HEXIM2. Interacts with PKN1; enhances MYOD1-dependent transcription. P-TEFB complex interacts with RB1; promotes phosphorylation of RB1. P-TEFB complex interacts with MYOD1; promotes the transcriptional activity of MYOD1 through its CDK9-mediated phosphorylation. Interacts with MDFI and MDFIC. Interacts with MON1B; down-regulates CCNT2-mediated activation of viral promoters during herpes simplex virus 1/HHV-1 infection. (Microbial infection) Interacts with HIV-2 and SIV Tat. Does not bind efficiently to the transactivation domain of the HIV-1 Tat.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus.

Tissue specificity. Ubiquitously expressed.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O60583-1	1, B	yes
O60583-2	2, A

RefSeq proteins (4): NP_001232, NP_001307677, NP_001307678, NP_490595* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006671	Cyclin_N	Domain
IPR013763	Cyclin-like_dom	Domain
IPR036915	Cyclin-like_sf	Homologous_superfamily
IPR043198	Cyclin/Ssn8	Family
IPR047321	CYCLIN_CCNT2_rpt1	Domain
IPR047322	CYCLIN_CCNT2_rpt2	Domain

Pfam: PF00134, PF21797

UniProt features (39 total): helix 15, compositionally biased region 9, region of interest 4, turn 3, modified residue 2, chain 1, domain 1, cross-link 1, splice variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2IVX	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60583-F1	59.93	0.30

Functional residue map

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

Post-translational modifications (3): 480, 601, 407

Mutagenesis-validated functional residues (1):

Position	Phenotype
260	activation of hiv-1 tat function.

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-112382	Formation of RNA Pol II elongation complex
R-HSA-167152	Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167287	HIV elongation arrest and recovery
R-HSA-167290	Pausing and recovery of HIV elongation
R-HSA-2173796	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-674695	RNA Polymerase II Pre-transcription Events
R-HSA-6796648	TP53 Regulates Transcription of DNA Repair Genes
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-75955	RNA Polymerase II Transcription Elongation
R-HSA-162582	Signal Transduction
R-HSA-162587	HIV Life Cycle
R-HSA-162599	Late Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
R-HSA-167172	Transcription of the HIV genome
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-212436	Generic Transcription Pathway
R-HSA-2173793	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006936	Signaling by TGFB family members
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 317 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_MUSCLE_TISSUE_DEVELOPMENT, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_REGULATION_OF_PHOSPHORYLATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, RACCACAR_AML_Q6, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, ATGTTAA_MIR302C, GOMF_KINASE_ACTIVATOR_ACTIVITY, REACTOME_HIV_INFECTION

GO Biological Process (12): regulation of cyclin-dependent protein serine/threonine kinase activity (GO:0000079), transcription by RNA polymerase II (GO:0006366), skeletal muscle tissue development (GO:0007519), early viral transcription (GO:0019085), late viral transcription (GO:0019086), positive regulation of DNA-templated transcription, elongation (GO:0032786), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), host-mediated activation of viral transcription (GO:0043923), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of muscle cell differentiation (GO:0051147), cell division (GO:0051301), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (8): transcription coactivator binding (GO:0001223), chromatin binding (GO:0003682), protein kinase binding (GO:0019901), cyclin-dependent protein serine/threonine kinase activator activity (GO:0061575), RNA polymerase binding (GO:0070063), 7SK snRNA binding (GO:0097322), protein binding (GO:0005515), cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cyclin/CDK positive transcription elongation factor complex (GO:0008024), perinuclear region of cytoplasm (GO:0048471), cyclin-dependent protein kinase holoenzyme complex (GO:0000307), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
RNA Polymerase II Transcription	4
Transcription of the HIV genome	3
Generic Transcription Pathway	2
RNA Polymerase II Transcription Elongation	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Transcriptional Regulation by TP53	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Late Phase of HIV Life Cycle	1
Signaling by TGFB family members	1
Signaling by TGF-beta Receptor Complex	1
Disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cyclin-dependent protein serine/threonine kinase activity	3
cellular anatomical structure	3
viral transcription	2
positive regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
binding	2
regulation of protein serine/threonine kinase activity	1
DNA-templated transcription	1
striated muscle tissue development	1
skeletal muscle organ development	1
DNA-templated transcription elongation	1
regulation of DNA-templated transcription elongation	1
transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
host-mediated perturbation of viral transcription	1
host-mediated activation of viral process	1
regulation of transcription by RNA polymerase II	1
muscle cell differentiation	1
regulation of cell differentiation	1
cellular process	1
regulation of DNA-templated transcription	1
transcription coregulator binding	1
kinase binding	1
cyclin-dependent protein serine/threonine kinase regulator activity	1
protein serine/threonine kinase activator activity	1
enzyme binding	1
snRNA binding	1
cyclin-dependent protein kinase regulator activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
transcription elongation factor complex	1
nuclear cyclin-dependent protein kinase holoenzyme complex	1
carboxy-terminal domain protein kinase complex	1
cytoplasm	1
serine/threonine protein kinase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCNT2	CDK9	P50750	999
CCNT2	HEXIM1	O94992	972
CCNT2	BRD4	O60885	953
CCNT2	AFF4	Q9UHB7	946
CCNT2	AFF1	P51825	916
CCNT2	LARP7	Q4G0J3	903
CCNT2	MEPCE	Q7L2J0	866
CCNT2	CCNT1	O60563	832
CCNT2	MLLT1	Q03111	830
CCNT2	ELL2	O00472	822
CCNT2	CCNH	P51946	791
CCNT2	HMGN3	Q15651	773
CCNT2	CCNK	O75909	747
CCNT2	ELL	P55199	735
CCNT2	POLR2A	P24928	735

IntAct

50 interactions, top by confidence:

A	B	Type	Score
CDK9	CCNT1	psi-mi:“MI:0914”(association)	0.980
HEXIM1	CCNT1	psi-mi:“MI:0914”(association)	0.930
CDK9	CCNT2	psi-mi:“MI:0915”(physical association)	0.910
LARP7	CCNT1	psi-mi:“MI:0914”(association)	0.850
HEXIM2	AHCYL1	psi-mi:“MI:0914”(association)	0.740
CDK9	AIP	psi-mi:“MI:0914”(association)	0.730
AFF4	ELL2	psi-mi:“MI:0914”(association)	0.730
MLLT1	ELL2	psi-mi:“MI:0914”(association)	0.640
ELL3	CCNT1	psi-mi:“MI:0914”(association)	0.640
MLLT3	ELL2	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
CDK6	CCNT1	psi-mi:“MI:0914”(association)	0.530

BioGRID (104): CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Co-fractionation), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS), CCNT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R6X6S3, A2AM29, A2BIL7, A6QP06, B5DE93, D2H526, E1BB50, F1QW93, O60293, O60563, O60583, O93383, P25992, P42568, Q03111, Q0VBM2, Q10728, Q14693, Q14AX6, Q1L8U8, Q1LVC2, Q24595, Q3MJK5, Q5ZK36, Q62901, Q640I9, Q69ZW3, Q6DD45, Q6P1G2, Q6P2L6, Q7YZA2, Q7ZX31, Q7ZXG4, Q80TZ9, Q8BRB7, Q8HXN7, Q8NDI1, Q8WYB5, Q90YL3, Q91ZP3

Diamond homologs: A3LPX1, F1QMB9, O60563, O60583, O74627, O75909, O88874, O96433, P24863, P47821, P55168, Q0E474, Q28F72, Q2QQS5, Q2RAC5, Q3ZCK5, Q4KLA0, Q52KE7, Q56YF8, Q5I0H5, Q5RD50, Q5ZJP9, Q62447, Q6GN15, Q6T8E9, Q6Z7H3, Q7TQK0, Q7ZVX0, Q8GYM6, Q8HXN7, Q8RWV3, Q96S94, Q9AS36, Q9C8P7, Q9FKE6, Q9JJA7, Q9QWV9, Q9R1Q2, Q9UK58, Q9XT26

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MiRNA-188-5p	“down-regulates quantity by destabilization”	CCNT2	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
Formation of RNA Pol II elongation complex	5	42.1×	1e-05
RNA Polymerase II Transcription Elongation	5	42.1×	1e-05
RNA Polymerase II Pre-transcription Events	6	35.9×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	5	50.1×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2071 predictions. Top by Δscore:

Variant	Effect	Δscore
2:134918990:GAGA:G	donor_gain	1.0000
2:134919011:GT:G	donor_gain	1.0000
2:134931680:A:T	donor_gain	1.0000
2:134936835:CTGCA:C	acceptor_loss	1.0000
2:134936836:TGCAG:T	acceptor_loss	1.0000
2:134936837:GCA:G	acceptor_loss	1.0000
2:134936838:CA:C	acceptor_loss	1.0000
2:134936839:A:AG	acceptor_gain	1.0000
2:134936839:AGATA:A	acceptor_loss	1.0000
2:134936840:G:C	acceptor_loss	1.0000
2:134936840:G:GG	acceptor_gain	1.0000
2:134936840:GA:G	acceptor_gain	1.0000
2:134936840:GATA:G	acceptor_gain	1.0000
2:134936965:GTGAT:G	donor_gain	1.0000
2:134936967:GAT:G	donor_gain	1.0000
2:134936970:G:GG	donor_gain	1.0000
2:134947689:T:G	acceptor_gain	1.0000
2:134952710:GG:G	donor_gain	1.0000
2:134952711:GG:G	donor_gain	1.0000
2:134954622:T:G	donor_gain	1.0000
2:134954622:T:TG	donor_gain	1.0000
2:134954635:G:GT	donor_gain	1.0000
2:134954636:A:T	donor_gain	1.0000
2:134919010:TGTG:T	donor_loss	0.9900
2:134919012:TGTAT:T	donor_loss	0.9900
2:134919013:G:GG	donor_gain	0.9900
2:134919013:GT:G	donor_loss	0.9900
2:134919014:TA:T	donor_loss	0.9900
2:134919135:G:T	donor_gain	0.9900
2:134934735:A:T	donor_gain	0.9900

AlphaMissense

4839 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:134918963:C:A	R37S	1.000
2:134918996:G:A	G48R	1.000
2:134918996:G:C	G48R	1.000
2:134918997:G:A	G48E	1.000
2:134919006:T:C	L51P	1.000
2:134919828:C:A	N59K	1.000
2:134919828:C:G	N59K	1.000
2:134919833:C:A	A61E	1.000
2:134936875:A:T	K92I	1.000
2:134936876:A:C	K92N	1.000
2:134936876:A:T	K92N	1.000
2:134939051:T:C	L140P	1.000
2:134942614:T:C	F145L	1.000
2:134942616:T:A	F145L	1.000
2:134942616:T:G	F145L	1.000
2:134942636:C:A	P152Q	1.000
2:134946137:C:A	A177D	1.000
2:134947744:T:C	L183P	1.000
2:134947787:T:G	C197W	1.000
2:134947791:T:C	C199R	1.000
2:134947792:G:A	C199Y	1.000
2:134947793:C:G	C199W	1.000
2:134947812:T:A	W206R	1.000
2:134947812:T:C	W206R	1.000
2:134947814:G:C	W206C	1.000
2:134947814:G:T	W206C	1.000
2:134947828:T:C	I211T	1.000
2:134947854:T:A	W220R	1.000
2:134947854:T:C	W220R	1.000
2:134947856:G:C	W220C	1.000

dbSNP variants (sampled 300 via entrez): RS1000009551 (2:134945850 G>A), RS1000034825 (2:134936627 C>T), RS1000159317 (2:134950016 G>C), RS1000192241 (2:134928506 G>A), RS1000311641 (2:134942878 A>G), RS1000388819 (2:134917778 A>C), RS1000390648 (2:134931023 C>T), RS1000401897 (2:134957244 A>G), RS1000423224 (2:134959671 T>A,C), RS1000463452 (2:134949810 G>GA,GT), RS1000473511 (2:134959422 C>A,G,T), RS1000501527 (2:134920183 A>C), RS1000520004 (2:134946368 A>C,G), RS1000527374 (2:134926842 T>C), RS1000644737 (2:134920708 A>G)

Disease associations

OMIM: gene MIM:603862 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): premature menopause (MONDO:0001119)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002875_17	Diisocyanate-induced asthma	6.000000e-07
GCST004902_42	Parkinson’s disease	8.000000e-24
GCST005951_43	Body mass index	5.000000e-09
GCST008159_39	Waist-to-hip ratio adjusted for BMI	8.000000e-06
GCST011122_37	Walking pace	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0004340	body mass index
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1293321 (SINGLE PROTEIN), CHEMBL4523631 (PROTEIN COMPLEX), CHEMBL5291961 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 16,215 (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
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL3905910	VORUCICLIB	2	856

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

ChEMBL bioactivities

19 potent at pChembl≥5 of 21 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.20	IC50	0.626	nM	VORUCICLIB
8.42	IC50	3.77	nM	STAUROSPORINE
8.40	Ki	4	nM	DINACICLIB
8.30	IC50	5	nM	CHEMBL5287128
8.30	IC50	5	nM	CHEMBL5202522
8.22	IC50	6	nM	CHEMBL5272545
8.15	IC50	7	nM	CHEMBL5290495
8.15	IC50	7	nM	CHEMBL5283233
8.10	IC50	8	nM	CHEMBL5288282
8.05	IC50	9	nM	CHEMBL5283615
7.58	Ki	26	nM	CHEMBL5195030
7.25	Kd	55.59	nM	CHEMBL5653589
7.20	ED50	63.17	nM	CHEMBL5653589
7.19	IC50	64	nM	KENPAULLONE
6.66	IC50	220	nM	CHEMBL1782168
6.62	IC50	240	nM	CHEMBL1782169
6.46	IC50	350	nM	CHEMBL215205
5.96	IC50	1100	nM	PALBOCICLIB
5.13	IC50	7400	nM	CHEMBL1782170

PubChem BioAssay actives

19 with measured affinity, of 31 total; 19 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
2-[2-chloro-4-(trifluoromethyl)phenyl]-5,7-dihydroxy-8-[(2R,3S)-2-(hydroxymethyl)-1-methylpyrrolidin-3-yl]chromen-4-one	1868094: Inhibition of CDK9/Cyclin T2 (unknown origin)	ic50	0.0006	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1531636: Inhibition of human CDK9/cyclin-T2 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate by [gamma-33P]-ATP assay	ic50	0.0038	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	1940565: Inhibition of CDK9/cyclin T (unknown origin) assessed as inhibition constant	ki	0.0040	uM
[4-amino-2-[[(2S)-2-bicyclo[2.2.1]heptanyl]amino]-1,3-thiazol-5-yl]-(2-nitrophenyl)methanone	1921460: Inhibition of CDK9/cyclin T (unknown origin)	ic50	0.0050	uM
(2R,3R)-3-[[2-[4-(cyclopropylsulfonimidoyl)anilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]butan-2-ol	1921460: Inhibition of CDK9/cyclin T (unknown origin)	ic50	0.0050	uM
2-[[[2-(1-hydroxybutan-2-ylamino)-9-propan-2-ylpurin-6-yl]amino]methyl]-4-methylphenol	1949421: Inhibition of CDK9/Cyclin T (unknown origin) using (YSPTSPS)3 peptide as substrate incubated for 30 mins in presence of gamma[33P]ATP by digital imaging analysis	ic50	0.0060	uM
2-[[[2-[(2-aminocyclohexyl)amino]-9-propan-2-ylpurin-6-yl]amino]methyl]-6-methoxyphenol	1949421: Inhibition of CDK9/Cyclin T (unknown origin) using (YSPTSPS)3 peptide as substrate incubated for 30 mins in presence of gamma[33P]ATP by digital imaging analysis	ic50	0.0070	uM
4-chloro-2-[[[2-[(3-hydroxy-3-methylbutyl)amino]-9-propan-2-ylpurin-6-yl]amino]methyl]phenol	1949421: Inhibition of CDK9/Cyclin T (unknown origin) using (YSPTSPS)3 peptide as substrate incubated for 30 mins in presence of gamma[33P]ATP by digital imaging analysis	ic50	0.0070	uM
2-[[[2-[(4-aminocyclohexyl)amino]-9-propan-2-ylpurin-6-yl]amino]methyl]-4-fluorophenol	1949421: Inhibition of CDK9/Cyclin T (unknown origin) using (YSPTSPS)3 peptide as substrate incubated for 30 mins in presence of gamma[33P]ATP by digital imaging analysis	ic50	0.0080	uM
2-[[[2-[(4-aminocyclohexyl)amino]-9-propan-2-ylpurin-6-yl]amino]methyl]-6-methoxyphenol	1949421: Inhibition of CDK9/Cyclin T (unknown origin) using (YSPTSPS)3 peptide as substrate incubated for 30 mins in presence of gamma[33P]ATP by digital imaging analysis	ic50	0.0090	uM
4-[(2,6-dichlorobenzoyl)amino]-N-piperidin-4-yl-1H-pyrazole-5-carboxamide	1940565: Inhibition of CDK9/cyclin T (unknown origin) assessed as inhibition constant	ki	0.0100	uM
6-(difluoromethyl)-8-[(1R,2R)-2-hydroxy-2-methylcyclopentyl]-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrido[2,3-d]pyrimidin-7-one	1940565: Inhibition of CDK9/cyclin T (unknown origin) assessed as inhibition constant	ki	0.0190	uM
(2S,3R)-3-[[6-[(4,6-dimethyl-3-pyridinyl)methylamino]-9-propan-2-ylpurin-2-yl]amino]pentan-2-ol	1940565: Inhibition of CDK9/cyclin T (unknown origin) assessed as inhibition constant	ki	0.0260	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148019: Binding affinity to human CCNT2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0556	uM
9-bromo-7,12-dihydro-5H-indolo[3,2-d][1]benzazepin-6-one	1924396: Inhibition of CDK9/Cyclin T (unknown origin)	ic50	0.0640	uM
8,14,18-triazatetracyclo[9.7.0.02,7.012,17]octadeca-1(11),2,4,6,12(17),13,15-heptaen-9-one	1924396: Inhibition of CDK9/Cyclin T (unknown origin)	ic50	0.2200	uM
14-benzyl-8,18-diaza-14-azoniatetracyclo[9.7.0.02,7.012,17]octadeca-1(11),2,4,6,12(17),13,15-heptaen-9-one bromide	1924396: Inhibition of CDK9/Cyclin T (unknown origin)	ic50	0.2400	uM
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	1921504: Inhibition of CDK9/cyclin T (unknown origin) using GST-CTD and gamma-32P-ATP as substrate incubated for 5 min by Differential scanning fluorimetry	ic50	0.3500	uM
14-hydroxy-8,14,18-triazatetracyclo[9.7.0.02,7.012,17]octadeca-1(11),2,4,6,12,15,17-heptaen-9-one	1924396: Inhibition of CDK9/Cyclin T (unknown origin)	ic50	7.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	affects methylation, increases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	affects sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentanal	decreases expression	1
polyhexamethyleneguanidine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
vanadium pentoxide	affects expression	1
chromium hexavalent ion	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

ChEMBL screening assays

16 unique, capped per target: 16 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4768774	Binding	Inhibition of cyclin T2 (unknown origin) at 0.5 uM	Optimization of 5-substituted thiazolyl ureas and 6-substituted imidazopyridines as potential HIV-1 latency reversing agents. — Eur J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SH50	HAP1 CCNT2 (-) 1	Cancer cell line	Male
CVCL_SH51	HAP1 CCNT2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists