TC2N

Summary

TC2N (tandem C2 domains, nuclear, HGNC:19859) is a protein-coding gene on chromosome 14q32.12, encoding Tandem C2 domains nuclear protein (Q8N9U0).

Predicted to be active in nucleus.

Source: NCBI Gene 123036 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 80 total
• MANE Select transcript: NM_001128596

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19859
Approved symbol	TC2N
Name	tandem C2 domains, nuclear
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36557, Tac2-N, C2CD1
Ensembl gene	ENSG00000165929
Ensembl biotype	protein_coding
OMIM	619305
Entrez	123036

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 25 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000340892, ENST00000360594, ENST00000435962, ENST00000554424, ENST00000555302, ENST00000556018, ENST00000556590, ENST00000891182, ENST00000891183, ENST00000891184, ENST00000891185, ENST00000891186, ENST00000891187, ENST00000891188, ENST00000891189, ENST00000891190, ENST00000891191, ENST00000937661, ENST00000971252, ENST00000971253, ENST00000971254, ENST00000971255, ENST00000971256, ENST00000971257, ENST00000971258, ENST00000971259, ENST00000971260

RefSeq mRNA: 4 — MANE Select: NM_001128596 NM_001128595, NM_001128596, NM_001289134, NM_152332

CCDS: CCDS73679, CCDS9897

Canonical transcript exons

ENST00000435962 — 12 exons

Exon	Start	End
ENSE00001098179	91798299	91798399
ENSE00001098181	91797785	91797901
ENSE00001098185	91785162	91785361
ENSE00001098186	91787513	91787627
ENSE00001098187	91792367	91792558
ENSE00001128862	91812312	91812545
ENSE00001195798	91798989	91799064
ENSE00001195804	91800281	91800372
ENSE00001268916	91779746	91783210
ENSE00001384911	91813703	91813825
ENSE00001668162	91867262	91867536
ENSE00001723970	91802254	91802421

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.28.

FANTOM5 (CAGE): breadth broad, TPM avg 11.7594 / max 587.9364, expressed in 693 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144538	7.1304	178
144530	1.1732	348
144537	1.0709	87
207333	1.0549	478
144531	0.6622	279
144529	0.4344	206
144532	0.1962	122
144528	0.0373	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.28	gold quality
pancreas	UBERON:0001264	96.91	gold quality
tonsil	UBERON:0002372	96.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.98	gold quality
gall bladder	UBERON:0002110	95.74	gold quality
descending thoracic aorta	UBERON:0002345	95.26	gold quality
thoracic aorta	UBERON:0001515	94.66	gold quality
ascending aorta	UBERON:0001496	94.56	gold quality
islet of Langerhans	UBERON:0000006	94.35	gold quality
colonic epithelium	UBERON:0000397	93.81	gold quality
saliva-secreting gland	UBERON:0001044	93.77	gold quality
minor salivary gland	UBERON:0001830	93.62	gold quality
lymph node	UBERON:0000029	92.94	gold quality
rectum	UBERON:0001052	92.68	gold quality
endometrium	UBERON:0001295	92.42	gold quality
vermiform appendix	UBERON:0001154	91.37	gold quality
duodenum	UBERON:0002114	89.41	gold quality
granulocyte	CL:0000094	88.97	gold quality
esophagus mucosa	UBERON:0002469	88.87	gold quality
stomach	UBERON:0000945	88.42	gold quality
body of stomach	UBERON:0001161	88.21	gold quality
thoracic mammary gland	UBERON:0005200	88.20	gold quality
left coronary artery	UBERON:0001626	88.15	gold quality
tibial artery	UBERON:0007610	88.04	gold quality
popliteal artery	UBERON:0002250	88.03	gold quality
right uterine tube	UBERON:0001302	87.80	gold quality
prostate gland	UBERON:0002367	87.31	gold quality
lung	UBERON:0002048	86.87	gold quality
right lung	UBERON:0002167	86.78	gold quality
fallopian tube	UBERON:0003889	86.74	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-70580	yes	412.60
E-GEOD-81547	yes	22.63
E-MTAB-5061	yes	20.13
E-CURD-122	yes	19.74
E-ANND-3	yes	10.66
E-MTAB-7606	no	246.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

142 targeting TC2N, 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-4668-3P	100.00	68.74	2635
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 5)

• The TC2N attenuates p53 signaling pathway through inhibiting Cdk5-induced phosphorylation of p53 via inducing Cdk5 degradation or disrupting the interaction between Cdk5 and p53. (PMID:30254375)
• Study provided proof of principle to show that Tac2-N serves as a novel oncogene gene and plays an important role in the progression and metastasis of lung cancer. (PMID:31466523)
• TC2N: A Novel Vital Oncogene or Tumor Suppressor Gene In Cancers. (PMID:34925334)
• TC2N Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Targeting the Wnt/beta-Catenin Signaling Pathway. (PMID:37839635)
• TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis. (PMID:38167440)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	TC2N	ENSDARG00000095067
mus_musculus	Tc2n	ENSMUSG00000021187
rattus_norvegicus	Tc2n	ENSRNOG00000004754

Paralogs (31): SYT7 (ENSG00000011347), SYT13 (ENSG00000019505), SYT1 (ENSG00000067715), RPH3A (ENSG00000089169), SYTL4 (ENSG00000102362), SYT17 (ENSG00000103528), SYT10 (ENSG00000110975), SYT5 (ENSG00000129990), SYT11 (ENSG00000132718), SYT4 (ENSG00000132872), SYT6 (ENSG00000134207), SYTL2 (ENSG00000137501), SYT16 (ENSG00000139973), SYTL1 (ENSG00000142765), SYT14 (ENSG00000143469), SYT2 (ENSG00000143858), SYTL5 (ENSG00000147041), SYT8 (ENSG00000149043), DOC2A (ENSG00000149927), SYTL3 (ENSG00000164674), SYT9 (ENSG00000170743), SYT12 (ENSG00000173227), RPH3AL (ENSG00000181031), C2CD4C (ENSG00000183186), C2CD4A (ENSG00000198535), SYT15 (ENSG00000204176), C2CD4B (ENSG00000205502), SYT3 (ENSG00000213023), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

Tandem C2 domains nuclear protein — Q8N9U0 (reviewed: Q8N9U0)

Alternative names: Membrane targeting tandem C2 domain-containing protein 1, Tandem C2 protein in nucleus

All UniProt accessions (2): Q8N9U0, H0YJ73

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N9U0-1	1	yes
Q8N9U0-2	2

RefSeq proteins (4): NP_001122067, NP_001122068, NP_001276063, NP_689545 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR030542	Tac2-N	Family
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037786	C2A_Tac2-N	Domain
IPR037788	C2B_Tac2-N	Domain

Pfam: PF00168

UniProt features (18 total): modified residue 8, domain 2, sequence variant 2, chain 1, splice variant 1, sequence conflict 1, region of interest 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N9U0-F1	68.26	0.33

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 (8): 211, 214, 216, 218, 83, 156, 168, 174

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): GOZGIT_ESR1_TARGETS_DN, MENSE_HYPOXIA_UP, TAL1ALPHAE47_01, MARTINEZ_RB1_TARGETS_DN, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, SANSOM_APC_TARGETS_UP, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, HAND1E47_01, chr14q32, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, SANSOM_APC_TARGETS, BOCHKIS_FOXA2_TARGETS, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TC2N	STXBP5	Q5T5C0	628
TC2N	CATSPERB	Q9H7T0	626
TC2N	SCARA5	Q6ZMJ2	581
TC2N	STAB2	Q8WWQ8	571
TC2N	CLEC4M	Q9H2X3	544
TC2N	MYO5A	Q9Y4I1	531
TC2N	WDR48	Q8TAF3	461
TC2N	NPIPA7	E9PJI5	448
TC2N	TMEM200A	Q86VY9	441
TC2N	DOC2B	Q14184	431
TC2N	FJX1	Q86VR8	423
TC2N	OTUD3	Q5T2D3	419
TC2N	FAM76A	Q8TAV0	374
TC2N	PPP4R3A	Q6IN85	359
TC2N	MYOF	Q9NZM1	356

IntAct

10 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
GPBP1L1	CNOT1	psi-mi:“MI:0914”(association)	0.530
GPBP1L1	CNOT1	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
CADPS	ACOT7	psi-mi:“MI:0914”(association)	0.350
MADD	NR2F2	psi-mi:“MI:0914”(association)	0.350

BioGRID (31): TC2N (Two-hybrid), TC2N (Affinity Capture-MS), TC2N (Affinity Capture-MS), TC2N (Biochemical Activity), TC2N (Synthetic Lethality), TC2N (Proximity Label-MS), TC2N (Affinity Capture-MS), TC2N (Proximity Label-MS), TC2N (Proximity Label-MS), TC2N (Proximity Label-MS), TC2N (Proximity Label-MS), TC2N (Affinity Capture-MS), TC2N (Affinity Capture-MS), TC2N (Affinity Capture-MS), TC2N (Affinity Capture-MS)

ESM2 similar proteins: A0JM23, A2VDM0, A5WW08, A6NFN9, B5DE70, E9Q173, F6U5F9, H0UZ81, O13034, P0C6R2, P25022, P34089, P50851, P97573, Q0VCL9, Q0VGW0, Q14B46, Q2I0E5, Q2MHQ9, Q32L18, Q32M84, Q3TTL0, Q4QR86, Q5F479, Q5FWP4, Q5JPI3, Q5XGX5, Q5XIB9, Q5ZLG9, Q60760, Q66H33, Q6AXU1, Q6AZT6, Q6AZT7, Q6P256, Q6PJI9, Q793I8, Q7Z494, Q8C0M0, Q8C0W1

Diamond homologs: Q8N9U0, Q91XT6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2599 predictions. Top by Δscore:

Variant	Effect	Δscore
14:91785158:TAA:T	donor_loss	1.0000
14:91785159:AAC:A	donor_loss	1.0000
14:91785161:C:CT	donor_loss	1.0000
14:91785360:ACC:A	acceptor_loss	1.0000
14:91785362:CTA:C	acceptor_loss	1.0000
14:91786096:C:CA	donor_gain	1.0000
14:91787507:ACTT:A	donor_loss	1.0000
14:91787508:CT:C	donor_loss	1.0000
14:91787509:TTA:T	donor_loss	1.0000
14:91787510:TA:T	donor_loss	1.0000
14:91787511:A:AC	donor_gain	1.0000
14:91787511:AC:A	donor_loss	1.0000
14:91787511:ACT:A	donor_gain	1.0000
14:91787512:C:CA	donor_gain	1.0000
14:91787512:CT:C	donor_gain	1.0000
14:91787512:CTC:C	donor_gain	1.0000
14:91787512:CTCA:C	donor_gain	1.0000
14:91787512:CTCAA:C	donor_gain	1.0000
14:91787626:ACC:A	acceptor_loss	1.0000
14:91787627:CCT:C	acceptor_loss	1.0000
14:91792365:A:AC	donor_gain	1.0000
14:91792366:C:CC	donor_gain	1.0000
14:91797897:CTGCA:C	acceptor_gain	1.0000
14:91797900:CA:C	acceptor_gain	1.0000
14:91797902:C:CC	acceptor_gain	1.0000
14:91799063:CT:C	acceptor_gain	1.0000
14:91800369:CAAA:C	acceptor_gain	1.0000
14:91800370:AAA:A	acceptor_gain	1.0000
14:91800373:C:CC	acceptor_gain	1.0000
14:91812307:TTTA:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000111591 (14:91866138 G>A), RS1000170674 (14:91830519 C>T), RS1000209520 (14:91812260 A>T), RS1000259271 (14:91784006 G>C,T), RS1000304434 (14:91812518 G>A), RS1000359113 (14:91836876 G>C), RS1000387993 (14:91799017 T>C), RS1000455540 (14:91844918 T>C), RS1000490515 (14:91785862 T>C), RS1000503743 (14:91832186 C>T), RS1000545508 (14:91813947 TGAGG>T), RS1000552683 (14:91819513 T>C), RS1000584306 (14:91831871 T>C), RS1000605042 (14:91784243 G>A,C), RS1000640649 (14:91838740 C>T)

Disease associations

OMIM: gene MIM:619305 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007445_13	Factor VIII levels	7.000000e-09
GCST007445_34	Factor VIII levels	6.000000e-09
GCST007445_49	Factor VIII levels	2.000000e-08
GCST007445_5	Factor VIII levels	3.000000e-08
GCST008839_586	Height	3.000000e-19

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004630	factor VIII measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	7
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
daidzein	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
trichostatin A	increases expression	1
daidzin	increases expression, affects cotreatment	1
arsenite	affects expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
genistin	affects cotreatment, increases expression	1
mercuric bromide	affects cotreatment, increases expression	1
pentanal	decreases expression	1
glycitein	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
glycitin	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
(+)-JQ1 compound	decreases expression	1
Panobinostat	affects cotreatment, increases expression	1
Air Pollutants	decreases expression	1
Aldehydes	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Coumestrol	decreases expression	1

Clinical trials (associated diseases)

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