TNN

Summary

TNN (tenascin N, HGNC:22942) is a protein-coding gene on chromosome 1q25.1, encoding Tenascin-N (Q9UQP3). Extracellular matrix protein that seems to be a ligand for ITGA8:ITGB1, ITGAV:ITGB1 and ITGA4:ITGB1.

Predicted to enable integrin binding activity. Involved in positive regulation of sprouting angiogenesis; regulation of cell adhesion; and regulation of cell migration. Located in collagen-containing extracellular matrix. Part of tenascin complex.

Source: NCBI Gene 63923 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 239 total
• MANE Select transcript: NM_022093

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22942
Approved symbol	TNN
Name	tenascin N
Location	1q25.1
Locus type	gene with protein product
Status	Approved
Aliases	TNW
Ensembl gene	ENSG00000120332
Ensembl biotype	protein_coding
OMIM	617472
Entrez	63923

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000239462, ENST00000621086, ENST00000860454, ENST00000860455, ENST00000946425

RefSeq mRNA: 1 — MANE Select: NM_022093 NM_022093

CCDS: CCDS30943

Canonical transcript exons

ENST00000239462 — 19 exons

Exon	Start	End
ENSE00000789953	175079333	175079707
ENSE00000789954	175080163	175080426
ENSE00000789955	175083750	175083935
ENSE00000789956	175085405	175085494
ENSE00000789957	175093990	175094253
ENSE00000789963	175126955	175127085
ENSE00000789964	175128032	175128164
ENSE00001162161	175116939	175117205
ENSE00001166156	175128595	175128746
ENSE00001365153	175067833	175067935
ENSE00001366070	175135845	175135941
ENSE00001370745	175146931	175148075
ENSE00001382811	175136821	175136988
ENSE00001382883	175144387	175144550
ENSE00001420349	175097417	175097683
ENSE00001696151	175077384	175077827
ENSE00002413035	175098332	175098595
ENSE00002419005	175123400	175123663
ENSE00002423667	175118561	175118824

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 99.24.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1307 / max 44.5223, expressed in 26 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6820	0.1307	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	99.24	gold quality
hair follicle	UBERON:0002073	94.70	gold quality
cartilage tissue	UBERON:0002418	81.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.02	gold quality
thoracic mammary gland	UBERON:0005200	75.21	gold quality
mammary gland	UBERON:0001911	75.13	gold quality
epithelium of mammary gland	UBERON:0003244	75.00	gold quality
mammary duct	UBERON:0001765	74.01	gold quality
tibia	UBERON:0000979	72.63	gold quality
adipose tissue	UBERON:0001013	67.97	gold quality
connective tissue	UBERON:0002384	67.20	gold quality
subcutaneous adipose tissue	UBERON:0002190	67.03	gold quality
endothelial cell	CL:0000115	66.74	gold quality
skin of hip	UBERON:0001554	64.84	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	64.44	gold quality
parietal pleura	UBERON:0002400	64.28	gold quality
gall bladder	UBERON:0002110	63.51	gold quality
pleura	UBERON:0000977	63.47	gold quality
adipose tissue of abdominal region	UBERON:0007808	62.81	gold quality
adenohypophysis	UBERON:0002196	62.45	gold quality
frontal pole	UBERON:0002795	62.25	gold quality
middle frontal gyrus	UBERON:0002702	62.19	gold quality
pancreatic ductal cell	CL:0002079	61.94	silver quality
omental fat pad	UBERON:0010414	61.93	gold quality
peritoneum	UBERON:0002358	61.87	gold quality
paraflocculus	UBERON:0005351	61.82	gold quality
endometrium epithelium	UBERON:0004811	61.21	gold quality
skin of abdomen	UBERON:0001416	59.81	gold quality
colonic epithelium	UBERON:0000397	59.42	gold quality
minor salivary gland	UBERON:0001830	58.86	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting TNN, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312

Literature-anchored findings (GeneRIF, showing 10)

• The expression of tenascin-W is dependent on p38MAPK and JNK signaling pathways in mammary tumors. (tenascin-W) (PMID:15592496)
• data imply that tenascin-W expression in the activated tumor stroma facilitates tumorigenesis by supporting the migratory behavior of breast cancer cells (PMID:17909022)
• results reveal a clear association between elevated levels of tenascin-W and the presence of colorectal cancer and breast cancer (PMID:18306355)
• Results show that tenascin-W acts as a niche component for breast cancer metastasis to bone by supporting cell migration and cell proliferation of the cancer cells. (PMID:25868708)
• This study demonstrated that the genetic defect was totally or partly clarified in 21 patients with nine of them having potential disease-causing mutations in TTN. (PMID:26627873)
• specific association of NR1I3, C6 and TNN with low hip BMD risk (PMID:28629900)
• Tenascin-W: Discovery, Evolution, and Future Prospects. (PMID:33603752)
• Tenascin-W Is a Novel Stromal Marker in Biliary Tract Cancers. (PMID:33692777)
• Tenascin-C can Serve as an Indicator for the Immunosuppressive Microenvironment of Diffuse Low-Grade Gliomas. (PMID:35371015)
• TNN is first linked to auditory neuropathy. (PMID:36206596)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tnn	ENSMUSG00000026725
rattus_norvegicus	Tnn	ENSRNOG00000002548

Paralogs (25): TNC (ENSG00000041982), FCN1 (ENSG00000085265), ANGPT2 (ENSG00000091879), ANGPT4 (ENSG00000101280), FGL1 (ENSG00000104760), FN1 (ENSG00000115414), TNR (ENSG00000116147), ANGPTL1 (ENSG00000116194), FGL2 (ENSG00000127951), FIBCD1 (ENSG00000130720), ANGPTL6 (ENSG00000130812), ANGPTL3 (ENSG00000132855), ANGPTL2 (ENSG00000136859), FCN3 (ENSG00000142748), FNDC7 (ENSG00000143107), ANGPT1 (ENSG00000154188), FCN2 (ENSG00000160339), MFAP4 (ENSG00000166482), ANGPTL4 (ENSG00000167772), TNXB (ENSG00000168477), FGG (ENSG00000171557), FGA (ENSG00000171560), FGB (ENSG00000171564), ANGPTL7 (ENSG00000171819), ANGPTL5 (ENSG00000187151)

Protein

Protein identifiers

Tenascin-N — Q9UQP3 (reviewed: Q9UQP3)

Alternative names: Tenascin-W

All UniProt accessions (2): Q9UQP3, A0A087WXC4

UniProt curated annotations — full annotation on UniProt →

Function. Extracellular matrix protein that seems to be a ligand for ITGA8:ITGB1, ITGAV:ITGB1 and ITGA4:ITGB1. Involved in neurite outgrowth and cell migration in hippocampal explants. During endochondral bone formation, inhibits proliferation and differentiation of proteoblasts mediated by canonical WNT signaling. In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells. Expressed in most mammary tumors, may facilitate tumorigenesis by supporting the migratory behavior of breast cancer cells.

Subunit / interactions. Homohexamer.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Not detected in normal adult mammary tissues or brain but expressed in most breast tumors and brain tumors, such as glioblastomas, astrocytomas and oligodendrogliomas, tested. In brain tumors, detected around the endothelial cell layer of the clood vessels.

Similarity. Belongs to the tenascin family.

RefSeq proteins (1): NP_071376* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002181	Fibrinogen_a/b/g_C_dom	Domain
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014716	Fibrinogen_a/b/g_C_1	Homologous_superfamily
IPR020837	Fibrinogen_CS	Conserved_site
IPR036056	Fibrinogen-like_C	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR050991	ECM_Regulatory_Proteins	Family

Pfam: PF00041, PF00147, PF23106

UniProt features (38 total): domain 13, sequence variant 10, disulfide bond 9, region of interest 2, signal peptide 1, chain 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UQP3-F1	81.83	0.29

Functional residue map

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

Disulfide bonds (9): 171–181, 175–186, 188–197, 202–212, 206–217, 219–228, 233–243, 237–248, 250–259

Glycosylation sites (1): 1149

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3000178	ECM proteoglycans
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 134 (showing top): GOBP_NEURON_RECOGNITION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_GROWTH, GOCC_CELL_SURFACE, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_BONE_DEVELOPMENT, GOBP_BONE_DEVELOPMENT, GOBP_SMOOTH_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_SPROUTING_ANGIOGENESIS, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (12): cell-matrix adhesion (GO:0007160), axonogenesis (GO:0007409), positive regulation of neuron projection development (GO:0010976), regulation of cell adhesion (GO:0030155), regulation of cell migration (GO:0030334), dendrite self-avoidance (GO:0070593), regulation of bone development (GO:1903010), positive regulation of sprouting angiogenesis (GO:1903672), regulation of smooth muscle tissue development (GO:1905899), neuron projection extension (GO:1990138), negative regulation of neuron migration (GO:2001223), regulation of multicellular organismal development (GO:2000026)

GO Molecular Function (3): integrin binding (GO:0005178), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (9): obsolete extracellular space (GO:0005615), cell surface (GO:0009986), extracellular matrix (GO:0031012), neuronal cell body (GO:0043025), tenascin complex (GO:0090733), CA3 pyramidal cell dendrite (GO:0097442), hippocampal mossy fiber expansion (GO:1990026), extracellular region (GO:0005576), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron projection morphogenesis	2
cellular anatomical structure	2
cell-substrate adhesion	1
cell morphogenesis involved in neuron differentiation	1
axon development	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
cell adhesion	1
regulation of cellular process	1
cell migration	1
regulation of cell motility	1
neuron recognition	1
bone development	1
regulation of multicellular organismal development	1
sprouting angiogenesis	1
positive regulation of angiogenesis	1
regulation of sprouting angiogenesis	1
smooth muscle tissue development	1
regulation of muscle tissue development	1
developmental cell growth	1
developmental growth involved in morphogenesis	1
neuron migration	1
negative regulation of cell migration	1
regulation of neuron migration	1
multicellular organism development	1
regulation of developmental process	1
regulation of multicellular organismal process	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
protein binding	1
binding	1
external encapsulating structure	1
somatodendritic compartment	1
cell body	1
protein complex involved in cell-matrix adhesion	1
non-collagenous component of interstitial matrix	1
extracellular protein-containing complex	1
dendrite	1

Protein interactions and networks

STRING

1200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNN	DENR	O43583	495
TNN	NOMO2	Q5JPE7	476
TNN	NOMO3	P69849	474
TNN	NOMO1	P78421	447
TNN	FCF1	Q9Y324	418
TNN	TAPBP	O15533	383
TNN	TXN2	Q99757	336
TNN	THBS4	P35443	290
TNN	KCNV1	Q6PIU1	284
TNN	RIMS2	Q9UQ26	275
TNN	MEPE	Q9NQ76	268
TNN	PACC1	Q9H813	246
TNN	THBS3	P49746	245
TNN	CILP	O75339	241
TNN	THBS2	P35442	239

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TNN	TLR4	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (28): TNN (Co-fractionation), TNN (Affinity Capture-MS), TNN (Reconstituted Complex), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS)), TNN (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A072TK64, A0A072ULZ1, A0A6P8HC43, A2PYL6, A2PYL7, A2PYL8, A2XE45, A2XEA0, A2Y6J9, A5A3E0, B5DUH6, E9Q0N2, F4HWL4, F4JCB2, O04309, O08528, O24521, O95744, P0CG38, P0CG39, P25071, P27881, P28316, P29127, P35753, P37842, P52789, Q1W674, Q29428, Q6S8J3, Q70SU7, Q70SU8, Q75II4, Q84JE8, Q8L727, Q8LRK8, Q8RXK2, Q8VC49, Q90WJ7, Q93Y92

Diamond homologs: A0A8J8, A2AV25, D8VNS7, D8VNS8, D8VNS9, D8VNT0, E2IYB3, E9PV24, O00602, O08538, O15123, O18920, O35460, O35462, O35608, O43827, O70165, O70497, O75636, O77802, O93526, O95841, P02671, P02675, P02676, P02678, P02679, P02680, P04115, P06399, P10039, P12799, P12804, P14448, P14480, P17634, P19477, P21520, P22105, P24821

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	206
Likely benign	14
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3581 predictions. Top by Δscore:

Variant	Effect	Δscore
1:175067933:CAGG:C	donor_loss	1.0000
1:175067934:AGG:A	donor_loss	1.0000
1:175067936:G:GG	donor_gain	1.0000
1:175077818:G:GT	donor_gain	1.0000
1:175079706:GG:G	donor_gain	1.0000
1:175079707:GG:G	donor_gain	1.0000
1:175080159:GCA:G	acceptor_loss	1.0000
1:175080161:A:AG	acceptor_gain	1.0000
1:175080161:AGT:A	acceptor_gain	1.0000
1:175080161:AGTG:A	acceptor_gain	1.0000
1:175080162:G:A	acceptor_loss	1.0000
1:175080162:G:GG	acceptor_gain	1.0000
1:175080162:GT:G	acceptor_gain	1.0000
1:175080162:GTG:G	acceptor_gain	1.0000
1:175080162:GTGG:G	acceptor_gain	1.0000
1:175080162:GTGGT:G	acceptor_gain	1.0000
1:175080387:G:GT	donor_gain	1.0000
1:175080424:CAGGT:C	donor_loss	1.0000
1:175080425:AGG:A	donor_loss	1.0000
1:175080426:GGTG:G	donor_loss	1.0000
1:175080427:G:T	donor_loss	1.0000
1:175080428:T:G	donor_loss	1.0000
1:175083144:G:GT	donor_gain	1.0000
1:175083748:A:AG	acceptor_gain	1.0000
1:175083749:G:GG	acceptor_gain	1.0000
1:175083875:G:GT	donor_gain	1.0000
1:175085399:TTCCA:T	acceptor_loss	1.0000
1:175085400:TCCA:T	acceptor_loss	1.0000
1:175085401:CCAGG:C	acceptor_loss	1.0000
1:175085402:CAG:C	acceptor_loss	1.0000

AlphaMissense

8550 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:175144461:T:A	C1224S	1.000
1:175144462:G:C	C1224S	1.000
1:175144500:T:A	C1237S	1.000
1:175144501:G:C	C1237S	1.000
1:175135892:G:C	W1126C	0.999
1:175135892:G:T	W1126C	0.999
1:175144461:T:C	C1224R	0.999
1:175144462:G:A	C1224Y	0.999
1:175144463:T:G	C1224W	0.999
1:175144485:T:A	W1232R	0.999
1:175144485:T:C	W1232R	0.999
1:175144490:G:C	W1233C	0.999
1:175144490:G:T	W1233C	0.999
1:175144500:T:C	C1237R	0.999
1:175144501:G:A	C1237Y	0.999
1:175144501:G:T	C1237F	0.999
1:175144502:C:G	C1237W	0.999
1:175146942:G:C	W1257C	0.999
1:175146942:G:T	W1257C	0.999
1:175146951:G:C	W1260C	0.999
1:175146951:G:T	W1260C	0.999
1:175135858:G:C	R1115P	0.998
1:175144420:T:G	F1210C	0.998
1:175144462:G:T	C1224F	0.998
1:175144487:G:C	W1232C	0.998
1:175144487:G:T	W1232C	0.998
1:175144488:T:A	W1233R	0.998
1:175144488:T:C	W1233R	0.998
1:175144500:T:G	C1237G	0.998
1:175144503:C:G	H1238D	0.998

dbSNP variants (sampled 300 via entrez): RS1000099064 (1:175132974 C>T), RS1000108505 (1:175095837 G>A,T), RS1000136101 (1:175116346 C>G), RS1000186204 (1:175146714 T>C), RS1000200585 (1:175110898 G>A), RS1000201649 (1:175116066 T>C), RS1000210190 (1:175074609 C>T), RS1000241951 (1:175101587 C>G,T), RS1000250611 (1:175117332 C>T), RS1000253329 (1:175086596 C>A,T), RS1000286842 (1:175106131 C>T), RS1000335628 (1:175109896 G>A), RS1000338165 (1:175145760 T>C), RS1000376518 (1:175067147 T>G), RS1000532084 (1:175072476 C>T)

Disease associations

OMIM: gene MIM:617472 | 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
GCST007094_229	Diastolic blood pressure	4.000000e-08
GCST009391_1362	Metabolite levels	4.000000e-06
GCST009391_2110	Metabolite levels	9.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0010366	lysophosphatidylethanolamine 16:0 measurement
EFO:0010381	phosphatidylcholine 36:3 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation, increases mutagenesis	2
Nickel	decreases expression	2
Valproic Acid	increases expression	2
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
belinostat	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Calcitriol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Thiram	increases expression	1
Isotretinoin	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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