TINCR

Summary

TINCR (TINCR ubiquitin domain containing, HGNC:14607) is a protein-coding gene on chromosome 19p13.3, encoding Ubiquitin domain-containing protein TINCR (A0A2R8Y7D0). Promotes epithelial differentiation by enhancing the sumoylation and activation of CDC42.

This gene produces a spliced long non-coding RNA that binds RNAs. This transcript interacts with staufen-1 protein to regulate the stability of mRNAs for genes involved in the differentiation of epidermal tissue. Variation in this gene may be associated with cancer progression.

Source: NCBI Gene 257000 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001396408

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14607
Approved symbol	TINCR
Name	TINCR ubiquitin domain containing
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90734, NCRNA00036, LINC00036, onco-lncRNA-16, TUBL
Ensembl gene	ENSG00000223573
Ensembl biotype	protein_coding
OMIM	615241
Entrez	257000

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000448587, ENST00000587632, ENST00000590789, ENST00000646160, ENST00000646675

RefSeq mRNA: 2 — MANE Select: NM_001396408 NM_001396408, NM_001396409

CCDS: CCDS92495, CCDS92496

Canonical transcript exons

ENST00000448587 — 3 exons

Exon	Start	End
ENSE00001663551	5558167	5561399
ENSE00001664989	5567665	5567953
ENSE00001665747	5562082	5562211

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 97.96.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2831 / max 63.9641, expressed in 287 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178543	1.0081	243
178544	0.2750	162

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	97.96	gold quality
skin of leg	UBERON:0001511	96.37	gold quality
skin of abdomen	UBERON:0001416	96.35	gold quality
upper leg skin	UBERON:0004262	95.91	gold quality
zone of skin	UBERON:0000014	95.53	gold quality
skin of hip	UBERON:0001554	93.78	gold quality
lower esophagus mucosa	UBERON:0035834	93.67	gold quality
amniotic fluid	UBERON:0000173	93.20	gold quality
placenta	UBERON:0001987	91.36	gold quality
esophagus mucosa	UBERON:0002469	89.63	gold quality
mammalian vulva	UBERON:0000997	88.49	gold quality
nipple	UBERON:0002030	87.39	gold quality
esophagus squamous epithelium	UBERON:0006920	86.18	gold quality
buccal mucosa cell	CL:0002336	85.85	gold quality
vagina	UBERON:0000996	82.72	gold quality
pancreatic ductal cell	CL:0002079	81.10	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.81	gold quality
gingiva	UBERON:0001828	79.71	gold quality
gingival epithelium	UBERON:0001949	79.70	gold quality
lateral nuclear group of thalamus	UBERON:0002736	78.65	gold quality
tibialis anterior	UBERON:0001385	77.92	silver quality
mucosa of transverse colon	UBERON:0004991	77.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.63	gold quality
ileal mucosa	UBERON:0000331	74.93	gold quality
esophagus	UBERON:0001043	74.78	gold quality
anterior cingulate cortex	UBERON:0009835	74.41	gold quality
mouth mucosa	UBERON:0003729	73.67	gold quality
oral cavity	UBERON:0000167	73.64	gold quality
minor salivary gland	UBERON:0001830	72.53	gold quality
penis	UBERON:0000989	72.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	74.37
E-ANND-3	yes	12.94

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• a 3.7-kilobase lncRNA, terminal differentiation-induced ncRNA (TINCR), controls human epidermal differentiation by a post-transcriptional mechanism (PMID:23201690)
• TINCR, together with Staufen1, seems to stabilize a subset of mRNAs required for epidermal differentiation. (PMID:24019000)
• It is a functional molecule which plays essential roles by forming complexes with each other to maintain life. Long ncRNA and small ncRNA play a role as a ligand with sequence information. (PMID:24291846)
• findings suggest that TINCR contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease. (PMID:25728677)
• Study suggests that TINCR promotes proliferation, migration and invasion of esophageal squamous cell carcinoma (ESCC) cells, acting as a potential oncogene of ESCC. (PMID:26833746)
• These findings elucidate that loss of TINCR expression promotes proliferation and metastasis in colorectal cancer and it could be considered as a potential cancer suppressor gene. (PMID:27009809)
• long non-coding RNA TINCR polymorphisms may be implicated in GC development. (PMID:27893425)
• Our results firstly indicate that SNP rs2288947 and rs8105637 may act as independent biomarkers associated with occurrence and progression of CRC. (PMID:28418933)
• These results provide the first evidence that the expression of TINCR in HCC may play an oncogenic role in HCC differentiation, invasion, and metastasis. miR-137/miR-133a-TINCR pathway may serve as a promising target for tumor recurrence and prognosis of patients with HCC. (PMID:28546230)
• our findings demonstrated that TINCR could attenuate myocardial hypertrophy by epigenetically silencing of CaMKII, which may provide a novel therapeutic strategy for cardiac hypertrophy. (PMID:28548932)
• E2F1 induces TINCR transcriptional activity and accelerates gastric cancer progression via activation of TINCR/STAU1/CDKN2B signaling axis. (PMID:28569791)
• Low TINCR expression is associated with pituitary null cell adenomas. (PMID:28656268)
• TINCR suppressed proliferation and invasion through regulating miR-544a/FBXW7 axis in lung cancer. (PMID:29324317)
• TINCR upregulation may signal through the MAPK pathway to promote NSCLC tumorigenesis (PMID:29427662)
• in this study we characterized TINCR overexpression regulated by SP1 transcription factor. High level of TINCR consequently contributed to the oncogenic activity of TINCR. (PMID:29614984)
• lncRNA TINCR is downregulated in diabetic cardiomyopathy and it can inhibit cardiomyocyte apoptosis. (PMID:30453794)
• a regulatory function of the lncRNA TINCR/miR-107/CD36 axis in colorectal cancer was revealed; lncRNA TINCR overexpression exerted suppressive influence on CRC progression through modulating the PPAR signaling pathway via the miR-107/CD36 axis (PMID:30521471)
• significantly upregulated in burn-injured skin tissues in vivo and heat-stimulated dermal fibroblasts in vitro, accompanied by an increase in TGF-beta1 expression. Direct binding to SND! was verified. Silencing TINCR reduced expression of TGF-beta1, cell proliferation, colony formation and inflammation in heat-stressed fibroblasts. (PMID:30642630)
• lncRNA TINCR participates in ALA-PDT-induced apoptosis and autophagy in cutaneous squamous cell carcinoma. (PMID:30993776)
• The rs2288947 A > G polymorphism of the lncRNA TINCR may not be associated with recurrent miscarriage in a Southern Chinese population. (PMID:31124188)
• TINCR sponges miR-302 to upregulate cyclin D1 in CSCC, thereby promoting cell proliferation. (PMID:31388923)
• lncRNA PLAC2 down-regulated miR-21 in non-small cell lung cancer and inhibited cancer cell migration and invasion. (PMID:31500623)
• these findings suggest that TINCR knockdown inhibits TCF4 by regulating miR-137 expression in colorectal cancer cells (PMID:31540772)
• Knockdown of terminal differentiation induced ncRNA (TINCR) suppresses proliferation and invasion in hepatocellular carcinoma by targeting the miR-218-5p/DEAD-box helicase 5 (DDX5) axis. (PMID:31994189)
• TINCR is not a non-coding RNA but encodes a protein component of cornified epidermal keratinocytes. (PMID:32012357)
• Deregulation of long noncoding RNAs ANCR, TINCR, HOTTIP and SPRY4-IT1 in plasma of systemic sclerosis patients: SPRY4-IT1 as a novel biomarker of scleroderma and its subtypes. (PMID:32442909)
• Overexpression of lncRNA TINCR is associated with high-grade, invasive, and recurring tumors, and facilitates proliferation in vitro and in vivo of urothelial carcinoma of the bladder. (PMID:32622721)
• miR5893p sponged by the lncRNA TINCR inhibits the proliferation, migration and invasion and promotes the apoptosis of breast cancer cells by suppressing the Akt pathway via IGF1R. (PMID:32705168)
• Circ_0000376 enhances the proliferation, metastasis, and chemoresistance of NSCLC cells via repressing miR-384. (PMID:32716343)
• lncRNA TINCR facilities bladder cancer progression via regulating miR7 and mTOR. (PMID:33000269)
• Long Noncoding RNA TINCR-Mediated Regulation of Acetyl-CoA Metabolism Promotes Nasopharyngeal Carcinoma Progression and Chemoresistance. (PMID:33067266)
• Serum lncRNA TINCR Serve as a Novel Biomarker for Predicting the Prognosis in Triple-Negative Breast Cancer. (PMID:33084530)
• Long non-coding RNA PLAC2 suppresses the survival of gastric cancer cells through down-regulating C-Myc. (PMID:33336736)
• lncRNA TINCR SNPs and Expression Levels Are Associated with Bladder Cancer Susceptibility. (PMID:33372851)
• LncRNA TINCR favors tumorigenesis via STAT3-TINCR-EGFR-feedback loop by recruiting DNMT1 and acting as a competing endogenous RNA in human breast cancer. (PMID:33446634)
• Long noncoding RNA TINCR is a novel regulator of human bronchial epithelial cell differentiation state. (PMID:33527707)
• Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs. (PMID:33762305)
• Long non-coding RNA TINCR promotes hepatocellular carcinoma proliferation and invasion via STAT3 signaling by direct interacting with T-cell protein tyrosine phosphatase (TCPTP). (PMID:34057016)
• Expression of lncRNA TINCR in the placenta of patients with pre-eclampsia and its effect on the biological behaviours of trophoblasts. (PMID:34176530)
• Hypermethylation of Genes in New Long Noncoding RNA in Ovarian Tumors and Metastases: A Dual Effect. (PMID:34292442)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tincr	ENSMUSG00000110218
rattus_norvegicus	Tincr	ENSRNOG00000087313

Protein

Protein identifiers

Ubiquitin domain-containing protein TINCR — A0A2R8Y7D0 (reviewed: A0A2R8Y7D0)

Alternative names: Placenta-specific protein 2, Terminal differentiation-induced cornification regulator, pTINCR microprotein

All UniProt accessions (2): A0A1B0GTR7, A0A2R8Y7D0

UniProt curated annotations — full annotation on UniProt →

Function. Promotes epithelial differentiation by enhancing the sumoylation and activation of CDC42. Promotes keratinocyte proliferation. This contributes to the maintenance of skin homeostasis by enhancing wound healing after skin injury. Acts as a tumor suppressor in epithelial tumors.

Subunit / interactions. Interacts (via SUMO-interacting motif) with SUMO1 and SUMO2; the interactions increase TINCR protein stability. Interacts with CDC42; the interaction promotes CDC42 sumoylation and activation.

Subcellular location. Nucleus. Cell junction. Cytoplasm.

Tissue specificity. Detected in the stratum corneum, the outermost layer of the epidermis (at protein level). Detected in skin, sweat and sebaceous glands (at protein level). Expressed in cutaneous basal keratinocytes with a prominent up-regulation in more differentiated spinocellular and granular skin layers.

Induction. Up-regulated upon cellular stress such as exposure to UV radiation in a TP53/p53-dependent manner.

RefSeq proteins (2): NP_001383337, NP_001383338 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000626	Ubiquitin-like_dom	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily

Pfam: PF00240

UniProt features (19 total): sequence variant 6, strand 4, turn 3, helix 2, chain 1, domain 1, short sequence motif 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7MRJ	X-RAY DIFFRACTION	2.12

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A2R8Y7D0-F1	77.23	0.12

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
79–82	abolishes interaction with sumo1, sumo2 and cdc42. reduces protein stability.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): FUJII_YBX1_TARGETS_UP, MODULE_397, MODULE_48, MODULE_95, MODULE_332, chr19p13, FORTSCHEGGER_PHF8_TARGETS_DN, MODULE_163, GSE10463_CD40L_AND_VA347_VS_CD40L_IN_DC_DN, BLANCO_MELO_MERS_COV_INFECTION_MCR5_CELLS_UP, MODULE_9, GSE15659_RESTING_TREG_VS_NONSUPPRESSIVE_TCELL_DN, DESCARTES_MAIN_FETAL_TROPHOBLAST_GIANT_CELLS, DESCARTES_FETAL_EYE_CORNEAL_AND_CONJUNCTIVAL_EPITHELIAL_CELLS, DESCARTES_FETAL_LUNG_SQUAMOUS_EPITHELIAL_CELLS

GO Biological Process (2): positive regulation of keratinocyte proliferation (GO:0010838), positive regulation of wound healing (GO:0090303)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
positive regulation of epithelial cell proliferation	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

86 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TINCR	STAU1	O95793	763
TINCR	KRT80	Q6KB66	639
TINCR	ALOX12B	O75342	604
TINCR	ALOXE3	Q9BYJ1	591
TINCR	EZH2	Q15910	585
TINCR	ABCA12	Q86UK0	560
TINCR	CASP14	P31944	549
TINCR	ELOVL3	Q9HB03	534
TINCR	UPF1	Q92900	505
TINCR	ZNRF4	Q8WWF5	418
TINCR	ZNF750	Q32MQ0	371
TINCR	SAFB2	Q14151	367
TINCR	PGLYRP3	Q96LB9	336
TINCR	UBE2L5	A0A1B0GUS4	323
TINCR	KLF2	Q9Y5W3	277

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A2R8Y7D0, A3KMV1, A6NDN8, B9EHT4, D3YWQ0, F1MAB7, O23702, O54788, O75426, O76075, P04413, P0C5J9, P49897, P55073, Q1LZC5, Q28969, Q2T9Z2, Q2VPJ9, Q39491, Q3MHJ7, Q3TGW2, Q4R327, Q57VU6, Q58CZ0, Q5BIR3, Q5I3B1, Q5R4R7, Q5R686, Q5SPX3, Q5XI74, Q6DN07, Q6NXT1, Q6P7W2, Q6QN11, Q6X4W1, Q7L9B9, Q7TPD7, Q80TL4, Q8K485, Q8TBC3

Diamond homologs: A0A2R8Y7D0, Q96CB5, Q9P1C3, Q7Z5D8, Q9NRJ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

540 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:5567878:A:T	I16N	0.993
19:5567758:A:G	F56S	0.991
19:5567878:A:G	I16T	0.991
19:5567878:A:C	I16S	0.990
19:5567686:A:T	L80Q	0.980
19:5567804:G:T	R41S	0.980
19:5567794:A:G	L44P	0.979
19:5567693:A:G	S78P	0.978
19:5567757:G:C	F56L	0.978
19:5567757:G:T	F56L	0.978
19:5567759:A:G	F56L	0.978
19:5567833:A:T	V31E	0.977
19:5567749:T:A	N59I	0.975
19:5567806:A:G	L40P	0.971
19:5567680:A:T	L82H	0.970
19:5567686:A:G	L80P	0.970
19:5567794:A:T	L44Q	0.967
19:5567695:C:A	G77V	0.965
19:5567758:A:C	F56C	0.965
19:5567839:A:G	L29P	0.963
19:5567806:A:T	L40Q	0.962
19:5567821:T:A	D35V	0.962
19:5567889:C:A	K12N	0.962
19:5567889:C:G	K12N	0.962
19:5567686:A:C	L80R	0.961
19:5567719:A:T	V69E	0.961
19:5567683:A:G	L81P	0.958
19:5567680:A:G	L82P	0.956
19:5567769:C:A	W52C	0.956
19:5567769:C:G	W52C	0.956

dbSNP variants (sampled 300 via entrez): RS1000107404 (19:5562748 C>T), RS1000139312 (19:5569181 A>AG), RS1000178061 (19:5564049 C>A), RS1000546238 (19:5562481 G>A), RS1000696305 (19:5567925 G>A,C), RS1001726627 (19:5565617 A>G), RS1001818926 (19:5560851 G>A), RS1001834253 (19:5565627 C>G), RS1002123451 (19:5560082 C>T), RS1002345286 (19:5559611 A>G,T), RS1002481216 (19:5559856 C>T), RS1002559336 (19:5559755 C>A,T), RS1003491159 (19:5560857 G>A,T), RS1003623186 (19:5564133 A>C), RS1003630409 (19:5564317 A>C)

Disease associations

OMIM: gene MIM:615241 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST011878_6	Mitochondrial heteroplasmy measurement	2.000000e-13
GCST012116_6	Rheumatic heart disease	6.000000e-06
GCST90000255_19	Severe COVID-19 infection with respiratory failure (analysis I)	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0600008	mitochondrial heteroplasmy measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	4
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
propionaldehyde	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	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
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
monomethyl phthalate	affects expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
Arsenic Trioxide	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Camptothecin	increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Copper	affects binding, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Propofol	increases expression	1
Aflatoxin B1	increases expression	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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