TFCP2

Summary

TFCP2 (transcription factor CP2, HGNC:11748) is a protein-coding gene on chromosome 12q13.12-q13.13, encoding Alpha-globin transcription factor CP2 (Q12800). Binds a variety of cellular and viral promoters including fibrinogen, alpha-globin, SV40 and HIV-1 promoters.

This gene encodes a transcription factor that binds the alpha-globin promoter and activates transcription of the alpha-globin gene. The encoded protein regulates erythroid gene expression, plays a role in the transcriptional switch of globin gene promoters, and it activates many other cellular and viral gene promoters. The gene product interacts with certain inflammatory response factors, and polymorphisms of this gene may be involved in the pathogenesis of Alzheimer’s disease.

Source: NCBI Gene 7024 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total
• Transcription factor: yes — 84 downstream targets (CollecTRI)
• MANE Select transcript: NM_005653

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11748
Approved symbol	TFCP2
Name	transcription factor CP2
Location	12q13.12-q13.13
Locus type	gene with protein product
Status	Approved
Aliases	SEF, CP2, LSF, LBP-1C, TFCP2C
Ensembl gene	ENSG00000135457
Ensembl biotype	protein_coding
OMIM	189889
Entrez	7024

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000257915, ENST00000546822, ENST00000548108, ENST00000548115, ENST00000549867, ENST00000685804, ENST00000903740, ENST00000903741, ENST00000903742, ENST00000903743, ENST00000903744, ENST00000903745, ENST00000903746, ENST00000903747, ENST00000903748, ENST00000903749, ENST00000930487, ENST00000930488

RefSeq mRNA: 3 — MANE Select: NM_005653 NM_001173452, NM_001173453, NM_005653

CCDS: CCDS55827, CCDS8808

Canonical transcript exons

ENST00000257915 — 15 exons

Exon	Start	End
ENSE00000939525	51106525	51106613
ENSE00000939526	51104155	51104203
ENSE00000939527	51103670	51103763
ENSE00001156333	51109121	51109273
ENSE00001617028	51107236	51107346
ENSE00001672283	51116315	51116420
ENSE00001729899	51110877	51110983
ENSE00002328403	51093656	51095278
ENSE00002392134	51172301	51173135
ENSE00003506683	51101935	51102025
ENSE00003515602	51095989	51096040
ENSE00003584003	51098776	51098918
ENSE00003588047	51118621	51118772
ENSE00003624582	51117671	51117747
ENSE00003629313	51099655	51099779

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 93.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6783 / max 152.9024, expressed in 1643 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130934	7.7876	1590
130932	2.2618	1025
130933	0.6289	353

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	93.69	gold quality
superficial temporal artery	UBERON:0001614	92.99	gold quality
ventricular zone	UBERON:0003053	92.45	gold quality
monocyte	CL:0000576	90.85	gold quality
ganglionic eminence	UBERON:0004023	90.78	gold quality
leukocyte	CL:0000738	90.55	gold quality
mononuclear cell	CL:0000842	90.51	gold quality
granulocyte	CL:0000094	89.21	gold quality
cortical plate	UBERON:0005343	89.12	gold quality
rectum	UBERON:0001052	89.03	gold quality
gastrocnemius	UBERON:0001388	88.46	gold quality
muscle of leg	UBERON:0001383	88.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.13	gold quality
islet of Langerhans	UBERON:0000006	87.85	gold quality
stromal cell of endometrium	CL:0002255	87.58	gold quality
endothelial cell	CL:0000115	87.52	silver quality
mucosa of transverse colon	UBERON:0004991	87.21	gold quality
lower lobe of lung	UBERON:0008949	87.14	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.94	gold quality
lymph node	UBERON:0000029	86.78	gold quality
corpus callosum	UBERON:0002336	86.75	gold quality
tonsil	UBERON:0002372	86.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.47	gold quality
right adrenal gland	UBERON:0001233	86.40	gold quality
minor salivary gland	UBERON:0001830	86.36	gold quality
heart left ventricle	UBERON:0002084	86.20	gold quality
spinal cord	UBERON:0002240	86.20	gold quality
prefrontal cortex	UBERON:0000451	86.17	gold quality
body of uterus	UBERON:0009853	86.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.76

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

84 targets.

Target	Regulation
A2M	Unknown
ABCB1
ACTA2
APP
ASCL1
ATM
BDNF
BMP4	Activation
CAT
CCNA1
CD79A
CDKN2A
CEBPD
CES1
CRH
CRYAA	Unknown
CYP2F1	Unknown
DLST
DPEP1
ESR1
FGA	Unknown
FGFR1
FN1
GART	Unknown
GATA1	Activation
GFAP
GHRHR
GNAS
GSK3B	Unknown
H1-2

JASPAR motifs

Motif	Name	Family
MA1968.1	TFCP2	CP2-related factors
MA1968.2	TFCP2	CP2-related factors

JASPAR matrix evidence (PMIDs): PMID:9668115

Upstream regulators (CollecTRI, top): TFCP2

miRNA regulators (miRDB)

60 targeting TFCP2, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391

Literature-anchored findings (GeneRIF, showing 40)

• Positively regulates Serum Amyloid A3 (SAA3). Identified as SAA3 Enhancer Factor (SEF). (PMID:10455131)
• Activates Exon 1 Enhancer of Pax6 along with Sp1 (PMID:11574690)
• The human PcG protein dinG interacts with CP2, a mammalian member of the grainyhead-like family of transcription factors, in vitro and in vivo. The functional consequence of this interaction is repression of CP2-dependent transcription (PMID:11865070)
• Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28 (PMID:12393799)
• Case control study indicates LSF polymorphism may have a moderate protective effect against the risk of Alzheimer’s disease. (PMID:12555245)
• CP2 is a major factor in the regulation of globin expression in human and mouse erythroid cells, and CP2 binding to the globin gene promoter is essential for the enhanced transcription of globin genes in erythroid differentiation. (PMID:12661759)
• LBP-1c/CP2/LSF may have a role in Alzheimer’s disease (PMID:16272261)
• The functional interaction of CP2 with GATA1 in the regulation of erythroid promoters was studied. (PMID:16648487)
• CP2/LBP-1c/LSF as a factor that likely mediates enhanced transcription of GARS-AIRS-GART in Down syndrome-related Alzheimer disease. (PMID:17902044)
• a novel mechanism by which RNF2 and PHB2 modulate the CP2-mediated transcriptional pathway. (PMID:18629613)
• The protein structure prediction of CP2 family in order to elucidate the molecular mechanism of the CP2-directed regulation of gene expression. (PMID:18787404)
• SRY is a hybrid of DGCR8 and SOX3, and is regulated by the transcription factor CP2. (PMID:19902333)
• The expression of osteopontin (OPN), a gene regulating every step in tumor progression and metastasis, was robustly up-regulated by LSF. (PMID:20404171)
• Study show that CRTR-1 is generally an activator of transcription and that it modulates the activity of other family members, CP2, NF2d9 and altNF2d9, in a cell specific manner. (PMID:20661472)
• Secreted OPN, induced by LSF, activates c-Met via a potential interaction between OPN and its cell surface receptor CD44. A significant correlation was observed among LSF, OPN, and activated c-Met levels in HCC. (PMID:21703197)
• Data suggest that LSF is a key mediator of the Notch1 signaling pathway, suggesting that it might be a novel therapeutic target for the treatment of hepatocellular carcinoma. (PMID:21876634)
• Inhibition of MMP-9 significantly abrogated LSF-induced angiogenesis as well as in vivo tumorigenesis, thus reinforcing the role of MMP-9 in facilitating LSF function. (PMID:22167195)
• Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma (PMID:22396589)
• LSF is an important mediator in colorectal carcinoma tumorigenesis and progression, and LSF expression is an important index for and prognostic prediction. (PMID:25337247)
• The results suggest potential roles of LSF (TFCP2 ) as a growth regulator through control of the transcription of p21CIP1 in melanocytes and melanoma cells as well as a biomarker for nevus. (PMID:26506241)
• Complement proteins C7 and CFH control the stemness of liver cancer cells via LSF-1 pathway. (PMID:26723877)
• FQI1 mediates alteration of the tumor epigenome by DNMT1-LSF complex disruption, leading to aberrant DNA methylation and gene expression. (PMID:27845898)
• High expression of CP2c was significantly correlated with patient age, and higher histological grade, stage, and small and large vessel invasion in HCC tissues. (PMID:28412749)
• Metformin disrupts malignant behavior of oral squamous cell carcinoma via a novel signaling involving Late SV40 factor/Aurora-A. Findings showed that a novel Late SV40 Factor and Aurora-A-signaling inhibition supports the rationale of using metformin as potential oral squamous cell carcinoma therapeutics. (PMID:28465536)
• TFCP2 acts as a transcription co-factor that stimulates YAP transcription by facilitating YAP binding with YAP binding motif (YBF)-containing transcription factors. (PMID:29091762)
• Studies reveal that TFCP2, TFCP2L1, UBP1 belong to a transcription factors subfamily and involved in various aspects of cancer types and development as either proto-oncogenes or tumor suppressors. They can directly interact with each other; TFCP2, TFCP2L1 and UBP1 can form heteromeric DNA-binding complexes. In addition, TFCP2L1 can modulate the activity of TFCP2 and UBP1. [review] (PMID:29410248)
• TFCP2 signaling is regulated by circular RNA hsa_circ_0023404 in the cervical cancer. (PMID:29738762)
• MAGE-A11 and transcription factors SP1,TFCP2 and ZEB1 expression were associated with some clinical features in patients, such as pathological differentiation, tumor size, clinical stage, lymph node metastasis and distant metastasis. Patients with ESCC having high MAGE-A11 and transcription factors (SP1,TFCP2 and ZEB1) expression had a worse prognosis compared to the patients with low expression. (PMID:31126819)
• A subset of epithelioid and spindle cell rhabdomyosarcomas is associated with TFCP2 fusions and common ALK upregulation. (PMID:31383960)
• CCT3 acts upstream of YAP and TFCP2 as a potential target and tumour biomarker in liver cancer. (PMID:31501420)
• The microtubule-associated histone methyltransferase SET8, facilitated by transcription factor LSF, methylates alpha-tubulin. (PMID:32111740)
• A Feedback Loop Comprising EGF/TGFalpha Sustains TFCP2-Mediated Breast Cancer Progression. (PMID:32193292)
• Transcription factors CP2 and YY1 as prognostic markers in head and neck squamous cell carcinoma: analysis of The Cancer Genome Atlas and a second independent cohort. (PMID:33315124)
• DNA hypermethylation contributes to colorectal cancer metastasis by regulating the binding of CEBPB and TFCP2 to the CPEB1 promoter. (PMID:33892791)
• circITCH suppresses cell proliferation and metastasis through miR-660/TFCP2 pathway in melanoma. (PMID:35274492)
• Transcription factor cellular promoter 2 is required for upstream binding protein 1 -mediated angiogenesis. (PMID:36889372)
• TFCP2 is a transcriptional regulator of heparan sulfate assembly and melanoma cell growth. (PMID:37061003)
• Human umbilical cord mesenchymal stem cell-derived extracellular vesicles loaded with TFCP2 activate Wnt/beta-catenin signaling to alleviate preeclampsia. (PMID:37724958)
• Multi-omic and functional analysis for classification and treatment of sarcomas with FUS-TFCP2 or EWSR1-TFCP2 fusions. (PMID:38168093)
• Analysis of the Expression of LSF Transcription Factor in the Regulation of Transcription and TSG101 during the Neoplastic Transformation of Endometrial Cells. (PMID:38607019)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tfcp2	ENSDARG00000060306
mus_musculus	Tfcp2	ENSMUSG00000009733
rattus_norvegicus	Tfcp2	ENSRNOG00000032395
drosophila_melanogaster	gem	FBGN0050011
caenorhabditis_elegans	grh-1	WBGENE00001707

Paralogs (5): GRHL2 (ENSG00000083307), TFCP2L1 (ENSG00000115112), GRHL1 (ENSG00000134317), UBP1 (ENSG00000153560), GRHL3 (ENSG00000158055)

Protein

Protein identifiers

Alpha-globin transcription factor CP2 — Q12800 (reviewed: Q12800)

Alternative names: SAA3 enhancer factor, Transcription factor LSF

All UniProt accessions (4): A0A8I5KWR0, Q12800, F8VWL0, F8VX55

UniProt curated annotations — full annotation on UniProt →

Function. Binds a variety of cellular and viral promoters including fibrinogen, alpha-globin, SV40 and HIV-1 promoters. Activation of the alpha-globin promoter in erythroid cells is via synergistic interaction with UBP1. Functions as part of the SSP (stage selector protein) complex. Facilitates the interaction of the gamma-globin genes with enhancer elements contained in the locus control region in fetal erythroid cells. Interacts by binding to the stage selector element (SSE) in the proximal gamma-globin promoter.

Subunit / interactions. Binds to DNA as a dimer, isoform 3 does not bind to DNA or affect the binding of isoform 1 to DNA. Interacts with UBP1 and PIAS1, and is probably part of a complex containing TFCP2, UBP1 and PIAS1. Component of the SSP (stage selector protein) complex, which appears to be a heteromer of TFCP2 and 2 copies of NFE4.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Expressed in brain, ovary, kidney, thymus, spleen, liver, adrenal, heart and lung (at protein level).

Miscellaneous. In PubMed:8114710 authors noted that a 10-fold molar excess of isoform 3 over isoform 1 inhibited DNA-binding.

Similarity. Belongs to the grh/CP2 family. CP2 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q12800-1	1, LBP-1c	yes
Q12800-2	2
Q12800-3	3, LBP-1d
Q12800-4	4

RefSeq proteins (3): NP_001166923, NP_001166924, NP_005644* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007604	CP2	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR037599	TFCP2_SAM	Domain
IPR040167	TF_CP2-like	Family
IPR041418	SAM_3	Domain
IPR057520	GRHL1/CP2_C	Domain

Pfam: PF04516, PF18016, PF25416

UniProt features (16 total): mutagenesis site 4, sequence conflict 3, region of interest 3, splice variant 2, chain 1, domain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12800-F1	77.64	0.53

Functional residue map

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

Post-translational modifications (1): 353

Mutagenesis-validated functional residues (4):

Position	Phenotype
213	does not affect dna-binding activity.
234	significant reduction of dna-binding activity.
236	significant reduction of dna-binding activity.
211	does not affect dna-binding activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 112 (showing top): PID_HDAC_CLASSI_PATHWAY, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_MRNA_TRANSCRIPTION, DODD_NASOPHARYNGEAL_CARCINOMA_UP, LEF1_Q6, NRF2_01, SASAKI_ADULT_T_CELL_LEUKEMIA, GRUETZMANN_PANCREATIC_CANCER_UP, URS_ADIPOCYTE_DIFFERENTIATION_UP, CETS1P54_01, SCGGAAGY_ELK1_02, ZHENG_IL22_SIGNALING_DN, GOMF_TRANSCRIPTION_FACTOR_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, WEST_ADRENOCORTICAL_TUMOR_UP

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of transcription by RNA polymerase II (GO:0045944), DNA biosynthetic process (GO:0071897)

GO Molecular Function (10): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), transcription factor binding (GO:0008134), sequence-specific double-stranded DNA binding (GO:1990837), transcription cis-regulatory region binding (GO:0000976), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), protein-containing complex (GO:0032991), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
mRNA transcription	1
positive regulation of DNA-templated transcription	1
DNA metabolic process	1
nucleic acid biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription regulator activity	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
binding	1
chromosome	1
nuclear lumen	1
cellular_component	1
organelle inner membrane	1
mitochondrial membrane	1

Protein interactions and networks

STRING

982 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TFCP2	APBB1	O00213	904
TFCP2	TYMS	P04818	845
TFCP2	DPYD	Q12882	818
TFCP2	MTDH	Q86UE4	770
TFCP2	NFE2	Q16621	691
TFCP2	NFE4	Q86UQ8	649
TFCP2	NCAPD3	P42695	638
TFCP2	PID1	Q7Z2X4	626
TFCP2	CENPC	Q03188	591
TFCP2	ZNF410	Q86VK4	545
TFCP2	VGLL2	Q8N8G2	498
TFCP2	PHC2	Q8IXK0	496
TFCP2	SIN3A	Q96ST3	463
TFCP2	GATA1	P15976	453
TFCP2	HBE1	P02100	449

IntAct

323 interactions, top by confidence:

A	B	Type	Score
CA1	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
CDC73	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
ZCCHC12	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
YJU2	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
CBX8	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
DNAJC27	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
TFCP2	CDC73	psi-mi:“MI:0915”(physical association)	0.720
TFCP2	ZCCHC12	psi-mi:“MI:0915”(physical association)	0.720
TFCP2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
TFCP2	DNAJC27	psi-mi:“MI:0915”(physical association)	0.720
TFCP2	YJU2	psi-mi:“MI:0915”(physical association)	0.720
PHF1	TFCP2	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (515): TFCP2 (Two-hybrid), TFCP2 (Two-hybrid), TFCP2 (Two-hybrid), TFCP2 (Two-hybrid), TFCP2 (Two-hybrid), TFCP2 (Two-hybrid), TFCP2 (Two-hybrid), TFCP2 (Two-hybrid), TFCP2 (Two-hybrid), SUMO1 (Two-hybrid), BAG6 (Two-hybrid), GPANK1 (Two-hybrid), PPIG (Two-hybrid), PITPNM1 (Two-hybrid), EIF5B (Two-hybrid)

ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, D3Z7P3, E9PV86, G3MWR8, O54865, O60907, O89050, O94925, P13264, P16068, P20595, P58058, Q02153, Q08211, Q12800, Q13042, Q14722, Q28141, Q28D01, Q3MHJ2, Q3ULA2, Q4R8H1, Q4ZHR9, Q5R874, Q5RB35, Q5SP67, Q5SRY7, Q5ZHN3, Q6DN14, Q7RTP6, Q7T2U9, Q7Z6J6, Q8BTG7, Q8C6G8, Q8CJ19, Q8K4Q0, Q8N122, Q8N2K0, Q8R349

Diamond homologs: G5EDF0, P13002, Q12800, Q3UNW5, Q4V860, Q5EY87, Q5FWH3, Q5M7R9, Q5PPL8, Q5RAR8, Q5RB16, Q6GL65, Q6ISB3, Q6NZH6, Q7T2U9, Q811S7, Q8K5C0, Q8TE85, Q921D9, Q9ERA0, Q9NZI5, Q9NZI6, Q9NZI7

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
PPP2CA	up-regulates	TFCP2	dephosphorylation
CDK2	down-regulates	TFCP2	phosphorylation
CDK3	down-regulates	TFCP2	phosphorylation
MAPK1	down-regulates	TFCP2	phosphorylation
MAPK3	down-regulates	TFCP2	phosphorylation
CyclinE/CDK2	down-regulates	TFCP2	phosphorylation
TFCP2	“up-regulates quantity by expression”	TF	“transcriptional regulation”
Gbeta	down-regulates	TFCP2	phosphorylation
ERK1/2	down-regulates	TFCP2	phosphorylation
CyclinC/CDK3	“down-regulates activity”	TFCP2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2399 predictions. Top by Δscore:

Variant	Effect	Δscore
12:51095981:A:AC	donor_gain	1.0000
12:51095982:C:CC	donor_gain	1.0000
12:51095986:TACC:T	donor_loss	1.0000
12:51095987:A:T	donor_loss	1.0000
12:51095988:CC:C	donor_loss	1.0000
12:51096037:TCAT:T	acceptor_gain	1.0000
12:51096038:CAT:C	acceptor_gain	1.0000
12:51096038:CATC:C	acceptor_gain	1.0000
12:51096039:AT:A	acceptor_gain	1.0000
12:51096040:TCTGA:T	acceptor_loss	1.0000
12:51096041:C:CC	acceptor_gain	1.0000
12:51096041:C:CG	acceptor_loss	1.0000
12:51096048:A:AC	acceptor_gain	1.0000
12:51096048:A:C	acceptor_gain	1.0000
12:51098775:CCTCA:C	donor_gain	1.0000
12:51098919:C:CC	acceptor_gain	1.0000
12:51099681:T:TA	donor_gain	1.0000
12:51099775:CCATC:C	acceptor_gain	1.0000
12:51099776:CATCC:C	acceptor_gain	1.0000
12:51104154:CAT:C	donor_gain	1.0000
12:51106523:AC:A	donor_gain	1.0000
12:51106524:CC:C	donor_gain	1.0000
12:51106612:CA:C	acceptor_gain	1.0000
12:51106614:C:CC	acceptor_gain	1.0000
12:51107231:TTTAC:T	donor_loss	1.0000
12:51107232:TTACC:T	donor_loss	1.0000
12:51107233:TAC:T	donor_loss	1.0000
12:51107235:C:G	donor_loss	1.0000
12:51107235:CCT:C	donor_gain	1.0000
12:51107237:T:TA	donor_gain	1.0000

AlphaMissense

3339 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:51095248:A:G	L501P	1.000
12:51101956:A:G	L377P	1.000
12:51101958:T:A	R376S	1.000
12:51101958:T:G	R376S	1.000
12:51101959:C:G	R376T	1.000
12:51101965:C:A	G374V	1.000
12:51101965:C:T	G374E	1.000
12:51101966:C:G	G374R	1.000
12:51101966:C:T	G374R	1.000
12:51103720:A:G	L337S	1.000
12:51107243:A:G	L274P	1.000
12:51107315:T:C	D250G	1.000
12:51107316:C:A	D250Y	1.000
12:51107316:C:G	D250H	1.000
12:51107322:T:C	K248E	1.000
12:51107326:C:A	K246N	1.000
12:51107326:C:G	K246N	1.000
12:51107327:T:A	K246M	1.000
12:51107327:T:G	K246T	1.000
12:51107328:T:C	K246E	1.000
12:51107328:T:G	K246Q	1.000
12:51107329:T:A	R245S	1.000
12:51107329:T:G	R245S	1.000
12:51107330:C:A	R245I	1.000
12:51107330:C:G	R245T	1.000
12:51107331:T:C	R245G	1.000
12:51107334:C:G	D244H	1.000
12:51107336:G:A	A243V	1.000
12:51107336:G:T	A243E	1.000
12:51107337:C:G	A243P	1.000

dbSNP variants (sampled 300 via entrez): RS1000005599 (12:51151843 T>C), RS1000031856 (12:51159190 A>G), RS1000094972 (12:51165518 ATATGATCC>A), RS1000104445 (12:51098499 G>A), RS1000119318 (12:51150761 G>C), RS1000190914 (12:51093718 G>T), RS1000209470 (12:51153043 C>A), RS1000210157 (12:51100296 T>C), RS1000282615 (12:51106284 T>C), RS1000288185 (12:51138634 T>C), RS1000312094 (12:51164925 T>C), RS1000341506 (12:51113628 T>A), RS1000377550 (12:51127252 C>CA), RS1000400221 (12:51146921 T>C), RS1000403930 (12:51152259 C>G,T)

Disease associations

OMIM: gene MIM:189889 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	2
triphenyl phosphate	affects expression	1
geraniol	decreases expression	1
terbufos	increases methylation	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, increases expression	1
Irinotecan	decreases expression	1
Cadmium	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Isoflavones	affects expression	1
Ivermectin	decreases expression	1
Parathion	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1

Clinical trials (associated diseases)

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