TNC

tenascin C, the group of Tenascins

Basic information

Region (hg38): 9:115019575-115118207

Previous symbols: [ "HXB", "DFNA56" ]

Links

ENSG00000041982 ∙ NCBI:3371 ∙ OMIM:187380 ∙ HGNC:5318 ∙ Uniprot:P24821 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 56 (Moderate), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 56 (Limited), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 56	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	23936043
Deafness has been described as postlingual

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TNC gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNC gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	39	23	63
missense		1	146	45	22	214
nonsense			3			3
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				4	1	5
non coding			1	25	78	104
Total	0	1	151	109	123

Variants in TNC

This is a list of pathogenic ClinVar variants found in the TNC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-115021162-C-A		not specified	Uncertain significance (Sep 27, 2021)
9-115021170-C-T		TNC-related disorder	Likely benign (May 23, 2019)
9-115021171-G-A		not specified	Uncertain significance (Jan 07, 2021)
9-115021236-T-C		Autosomal dominant nonsyndromic hearing loss 56 • TNC-related disorder	Uncertain significance (Apr 08, 2022)
9-115021264-C-T		Autosomal dominant nonsyndromic hearing loss 56	Benign/Likely benign (Mar 15, 2022)
9-115021272-TA-T			Benign (Dec 06, 2018)
9-115021283-AAG-A			Likely benign (Aug 13, 2019)
9-115021284-AG-A		Autosomal dominant nonsyndromic hearing loss 56	Uncertain significance (Mar 23, 2020)
9-115023974-T-C		Autosomal dominant nonsyndromic hearing loss 56 • not specified	Uncertain significance (Oct 16, 2023)
9-115023986-T-C		Autosomal dominant nonsyndromic hearing loss 56	Benign (Mar 15, 2022)
9-115024229-G-A			Benign (Dec 10, 2018)
9-115026578-T-G		not specified	Uncertain significance (Jun 05, 2024)
9-115026592-G-A		TNC-related disorder	Likely benign (May 05, 2021)
9-115026630-G-T		not specified	Uncertain significance (Jan 29, 2024)
9-115026635-C-T		not specified • TNC-related disorder	Likely benign (Sep 17, 2021)
9-115026636-G-A		not specified	Uncertain significance (Apr 15, 2024)
9-115026648-G-A		not specified	Uncertain significance (Jun 27, 2022)
9-115026654-C-T		Hearing impairment	Uncertain significance (Apr 12, 2021)
9-115026678-T-C			Uncertain significance (Oct 01, 2022)
9-115026686-T-A		not specified	Uncertain significance (Feb 27, 2024)
9-115026688-G-T		not specified	Uncertain significance (Sep 23, 2023)
9-115026723-G-A			Benign (Dec 23, 2018)
9-115029105-C-T			Likely benign (Dec 23, 2018)
9-115029127-T-A			Likely benign (Jan 25, 2019)
9-115029233-G-C			Likely benign (Jan 06, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNC	protein_coding	protein_coding	ENST00000350763	27	97731

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.26e-7	1.00	125676	0	72	125748	0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0821	1296	1.29e+3	1.01	0.0000778	14375
Missense in Polyphen		488	535.97	0.9105		6125
Synonymous	-0.333	528	518	1.02	0.0000337	4427
Loss of Function	5.95	30	91.4	0.328	0.00000471	1055

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000602	0.000601
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000257	0.000255
Middle Eastern	0.000109	0.000109
South Asian	0.000794	0.000784
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Extracellular matrix protein implicated in guidance of migrating neurons as well as axons during development, synaptic plasticity as well as neuronal regeneration. Promotes neurite outgrowth from cortical neurons grown on a monolayer of astrocytes. Ligand for integrins alpha-8/beta-1, alpha-9/beta-1, alpha-V/beta-3 and alpha-V/beta-6. In tumors, stimulates angiogenesis by elongation, migration and sprouting of endothelial cells (PubMed:19884327). {ECO:0000269|PubMed:19884327}.
• Disease: DISEASE: Deafness, autosomal dominant, 56 (DFNA56) [MIM:615629]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA56 is characterized by progressive hearing impairment with post-lingual onset. {ECO:0000269|PubMed:23936043}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Focal Adhesion;TGF-beta Signaling Pathway;Amplification and Expansion of Oncogenic Pathways as Metastatic Traits;TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Post-translational protein phosphorylation;Integrin cell surface interactions;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Beta3 integrin cell surface interactions;Integrin;Syndecan interactions;Non-integrin membrane-ECM interactions;ECM proteoglycans;Alpha9 beta1 integrin signaling events;Beta1 integrin cell surface interactions;Syndecan-4-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.692

Intolerance Scores

• loftool: 0.625
• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.99

Haploinsufficiency Scores

• pHI: 0.634
• hipred: Y
• hipred_score: 0.706
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.662

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Tnc
• Phenotype: homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: tnc
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: increased branchiness

Gene ontology

• Biological process: osteoblast differentiation;cell adhesion;negative regulation of cell adhesion;neuromuscular junction development;positive regulation of cell population proliferation;response to wounding;response to mechanical stimulus;positive regulation of gene expression;peripheral nervous system axon regeneration;extracellular matrix organization;wound healing;odontogenesis of dentin-containing tooth;post-translational protein modification;cellular protein metabolic process;response to ethanol;bud outgrowth involved in lung branching;mesenchymal-epithelial cell signaling involved in prostate gland development;prostate gland epithelium morphogenesis;cellular response to retinoic acid;cellular response to vitamin D;response to fibroblast growth factor;cellular response to prostaglandin D stimulus
• Cellular component: extracellular region;basement membrane;interstitial matrix;extracellular space;endoplasmic reticulum lumen;focal adhesion;membrane;collagen-containing extracellular matrix;perisynaptic extracellular matrix
• Molecular function: extracellular matrix structural constituent;protein binding;syndecan binding