TNR

tenascin R, the group of Tenascins

Basic information

Region (hg38): 1:175315194-175743595

Links

ENSG00000116147 ∙ NCBI:7143 ∙ OMIM:601995 ∙ HGNC:11953 ∙ Uniprot:Q92752 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus (Strong), mode of inheritance: AR

ClinVar

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

• Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus (7 variants)
• Non-progressive neurodevelopmental disorder with spasticity and transient opisthotonus (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNR 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				11	12	23
missense	2	2	99	6	3	112
nonsense	2		1			3
start loss						0
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				3		3
non coding			1		2	3
Total	7	3	101	17	17

Highest pathogenic variant AF is 0.00000658

Variants in TNR

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

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

Position	Type	Phenotype	Significance	ClinVar
1-175323397-C-T		Inborn genetic diseases	Uncertain significance (Mar 31, 2024)
1-175323401-G-C		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
1-175323475-C-T		Inborn genetic diseases	Uncertain significance (Jun 21, 2021)
1-175324376-C-T		Inborn genetic diseases	Uncertain significance (Feb 26, 2024)
1-175324397-T-G		Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus	Pathogenic (May 04, 2022)
1-175324400-G-A		Inborn genetic diseases	Uncertain significance (Mar 19, 2024)
1-175324400-G-T			Likely benign (Dec 20, 2017)
1-175324434-C-T			Benign (Dec 31, 2019)
1-175324435-G-A		Inborn genetic diseases	Uncertain significance (Jan 20, 2023)
1-175324493-G-A		Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus • Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
1-175330075-C-T		TNR-related disorder	Likely benign (Dec 29, 2022)
1-175330098-T-G		Inborn genetic diseases	Likely benign (Mar 17, 2023)
1-175330113-G-A			Benign (Feb 01, 2024)
1-175330153-G-A			Likely benign (Dec 31, 2019)
1-175330170-C-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
1-175330175-C-T		Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
1-175335732-C-T		Inborn genetic diseases	Uncertain significance (Aug 16, 2022)
1-175335734-T-C		Inborn genetic diseases	Uncertain significance (Dec 05, 2022)
1-175335768-G-A		Non-progressive neurodevelopmental disorder with spasticity and transient opisthotonus • Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus	Pathogenic (Jul 25, 2019)
1-175335782-T-A		Inborn genetic diseases	Uncertain significance (Sep 12, 2023)
1-175335805-T-C			Likely benign (May 01, 2024)
1-175337548-T-C		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
1-175337622-G-A			Benign (Dec 31, 2019)
1-175354403-C-T		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
1-175354415-T-C		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNR	protein_coding	protein_coding	ENST00000367674	21	428577

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.524	0.476	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.60	685	813	0.843	0.0000480	8851
Missense in Polyphen		253	353.43	0.71585		3767
Synonymous	-0.508	341	329	1.04	0.0000214	2717
Loss of Function	6.14	16	72.4	0.221	0.00000436	700

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000221	0.000217
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000221	0.000217
South Asian	0.0000327	0.0000327
Other	0.000653	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components. These interactions can influence cellular behavior by either evoking a stable adhesion and differentiation, or repulsion and inhibition of neurite growth. Binding to cell surface gangliosides inhibits RGD-dependent integrin-mediated cell adhesion and results in an inhibition of PTK2/FAK1 (FAK) phosphorylation and cell detachment. Binding to membrane surface sulfatides results in a oligodendrocyte adhesion and differentiation. Interaction with CNTN1 induces a repulsion of neurons and an inhibition of neurite outgrowth. Interacts with SCN2B may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier. TNR-linked chondroitin sulfate glycosaminoglycans are involved in the interaction with FN1 and mediate inhibition of cell adhesion and neurite outgrowth. The highly regulated addition of sulfated carbohydrate structure may modulate the adhesive properties of TNR over the course of development and during synapse maintenance (By similarity). {ECO:0000250}.
• 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;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Extracellular matrix organization;ECM proteoglycans (Consensus)

Recessive Scores

• pRec: 0.373

Intolerance Scores

• loftool: 0.502
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.04

Haploinsufficiency Scores

• pHI: 0.140
• hipred: Y
• hipred_score: 0.663
• ghis: 0.554

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.832

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tnr
• 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)

Zebrafish Information Network

• Gene name: tnr
• Affected structure: optic tract
• Phenotype tag: abnormal
• Phenotype quality: branchiness

Gene ontology

• Biological process: cell adhesion;neuron cell-cell adhesion;axon guidance;associative learning;telencephalon cell migration;negative regulation of cell-cell adhesion;extracellular matrix organization;locomotory exploration behavior;negative regulation of axon extension involved in regeneration;negative regulation of synaptic transmission;synapse organization;neuromuscular process controlling balance;positive regulation of synaptic transmission, glutamatergic;positive regulation of transmission of nerve impulse;long-term synaptic potentiation
• Cellular component: extracellular region;cell surface;membrane raft;perineuronal net;Schaffer collateral - CA1 synapse;glutamatergic synapse