TNXB

tenascin XB, the group of Tenascins

Basic information

Region (hg38): 6:32041152-32115334

Previous symbols: [ "TNXB1", "TNXB2" ]

Links

ENSG00000168477 ∙ NCBI:7148 ∙ OMIM:600985 ∙ HGNC:11976 ∙ Uniprot:P22105 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ehlers-Danlos syndrome due to tenascin-X deficiency (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome due to tenascin-X deficiency (Strong), mode of inheritance: AR
• Ehlers-Danlos syndrome due to tenascin-X deficiency (Definitive), mode of inheritance: AR
• Ehlers-Danlos syndrome due to tenascin-X deficiency (Supportive), mode of inheritance: AR
• familial vesicoureteral reflux (Supportive), mode of inheritance: AD
• Ehlers-Danlos syndrome due to tenascin-X deficiency (Strong), mode of inheritance: AR
• vesicoureteral reflux 8 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vesicoureteral reflux 8; Ehlers-Danlos syndrome, classic-like	AD/AR	Cardiovascular; Gastrointestinal; Renal	In Vesicoureteral reflux, monitoring and intervention related to renal sequelae may be beneficial in terms of helping to preserve renal function; In Ehlers-Danlos syndrome, reported features include aortic dilatation (which may not have a high risk of progression), severe diverticular intestinal disease with ruptured diverticula, pancolonic diverticulitis, and rectal prolapse, mitral valve prolapse requiring valve replacement, and obstructive airway disease, though it is not clear if these are all related to TNXB or to other genetic anomalies; Surveillance related to cardiovascular anomalies may be beneficial	Cardiovascular; Dermatologic; Gastrointestinal; Musculoskeletal; Renal	9288108; 11642233; 12180144; 12865992; 15793839; 15733269; 19921645; 19557868; 20301456; 21959861; 23284009; 23620400; 23768946
Variants may also be involved in vesicoureteral reflux

ClinVar

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

• Cardiovascular phenotype (1510 variants)
• not provided (827 variants)
• Ehlers-Danlos syndrome (210 variants)
• Inborn genetic diseases (132 variants)
• not specified (109 variants)
• Ehlers-Danlos syndrome due to tenascin-X deficiency (70 variants)
• Vesicoureteral reflux 8 (54 variants)
• Ehlers-Danlos syndrome due to tenascin-X deficiency;Vesicoureteral reflux 8 (49 variants)
• Vesicoureteral reflux 8;Ehlers-Danlos syndrome due to tenascin-X deficiency (20 variants)
• TNXB-related condition (17 variants)
• See cases (6 variants)
• 7 conditions (2 variants)
• Ehlers-Danlos syndrome, type 3 (2 variants)
• Ehlers-Danlos syndrome due to tenascin-X deficiency;Vesicoureteral reflux (1 variants)
• TNXB-related hypermobile Ehlers-Danlos syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNXB 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			22	591	25	638
missense		2	1064	72	41	1179
nonsense	4	7	1			12
start loss						0
frameshift	10	17	3			30
inframe indel			12			12
splice donor/acceptor (+/-2bp)		3	3			6
splice region			11	15	2	28
non coding			7	60	44	111
Total	14	29	1112	723	110

Highest pathogenic variant AF is 0.0000197

Variants in TNXB

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

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

Position	Type	Phenotype	Significance	ClinVar
6-32041186-C-T		Ehlers-Danlos syndrome due to tenascin-X deficiency;Vesicoureteral reflux 8	Benign (Aug 09, 2021)
6-32041190-C-G			Likely benign (Aug 06, 2019)
6-32041310-C-T		not specified	Likely benign (Jul 10, 2018)
6-32041353-C-A			Uncertain significance (Mar 01, 2023)
6-32041356-C-A		Cardiovascular phenotype	Uncertain significance (Jul 09, 2021)
6-32041359-C-G		Cardiovascular phenotype	Uncertain significance (Aug 02, 2021)
6-32041369-A-G		Cardiovascular phenotype	Likely benign (Dec 20, 2023)
6-32041372-G-A			Uncertain significance (Jul 01, 2023)
6-32041502-T-C			Benign (Jul 09, 2018)
6-32041507-G-A			Benign (Jul 09, 2018)
6-32041524-A-G			Benign (Jul 09, 2018)
6-32041550-C-T			Likely benign (Jun 09, 2019)
6-32041574-C-T			Likely benign (Aug 06, 2019)
6-32041577-T-C			Likely benign (Aug 06, 2019)
6-32041679-A-G			Benign (Jul 09, 2018)
6-32041765-C-CCTCACCTGATG			Uncertain significance (Dec 02, 2019)
6-32041792-G-A		not specified	Likely benign (Feb 29, 2024)
6-32041793-T-C		Cardiovascular phenotype	Uncertain significance (Jan 31, 2024)
6-32041800-C-T		Cardiovascular phenotype	Uncertain significance (Jan 08, 2024)
6-32041801-G-A			Likely benign (Aug 01, 2022)
6-32041812-C-T		Vesicoureteral reflux 8;Ehlers-Danlos syndrome due to tenascin-X deficiency	Likely benign (Apr 01, 2024)
6-32041860-A-T			Uncertain significance (May 06, 2022)
6-32041864-G-A			Likely benign (Apr 01, 2024)
6-32041874-C-T		Ehlers-Danlos syndrome due to tenascin-X deficiency • not specified	Conflicting classifications of pathogenicity (Jun 25, 2015)
6-32041876-G-A			Likely benign (Oct 23, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TNXB	protein_coding	protein_coding	ENST00000451343	13	74181

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0185	0.981	125689	0	5	125694	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0433	245	247	0.992	0.0000160	4182
Missense in Polyphen		158	166.01	0.95173		2892
Synonymous	0.804	95	106	0.900	0.00000774	1359
Loss of Function	2.94	7	21.8	0.321	0.00000110	324

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000547	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000547	0.0000544
South Asian	0.0000691	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Appears to mediate interactions between cells and the extracellular matrix. Substrate-adhesion molecule that appears to inhibit cell migration. Accelerates collagen fibril formation. May play a role in supporting the growth of epithelial tumors. {ECO:0000269|PubMed:17033827}.
• Disease: DISEASE: Ehlers-Danlos syndrome, classic-like (EDSCLL) [MIM:606408]: A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. EDSCLL patients lack atrophic scars, a major diagnostic criteria for classic Ehlers-Danlos syndrome. Delayed wound healing is only present in a subset of patients. EDSCLL inheritance is autosomal recessive. {ECO:0000269|PubMed:11642233, ECO:0000269|PubMed:15733269, ECO:0000269|PubMed:23768946}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Vesicoureteral reflux 8 (VUR8) [MIM:615963]: A disease belonging to the group of congenital anomalies of the kidney and urinary tract. It is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys, and is a risk factor for urinary tract infections. Primary disease results from a developmental defect of the ureterovesical junction. In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy. Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, renal insufficiency and end-stage renal disease. {ECO:0000269|PubMed:23620400}. 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);miRNA targets in ECM and membrane receptors;Focal Adhesion;VEGFA-VEGFR2 Signaling Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Extracellular matrix organization;Integrin;ECM proteoglycans (Consensus)

Haploinsufficiency Scores

• pHI: 0.198
• hipred: Y
• hipred_score: 0.618
• ghis: 0.509

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.161

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tnxb
• Phenotype: homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: cell adhesion;actin cytoskeleton organization;collagen fibril organization;collagen metabolic process;elastic fiber assembly
• Cellular component: extracellular region;extracellular space;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: integrin binding;extracellular matrix structural constituent;protein binding;heparin binding;collagen fibril binding