TJP1

tight junction protein 1, the group of PDZ domain containing|Membrane associated guanylate kinases

Basic information

Region (hg38): 15:29699366-29968915

Links

ENSG00000104067 ∙ NCBI:7082 ∙ OMIM:601009 ∙ HGNC:11827 ∙ Uniprot:Q07157 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• arrhythmogenic right ventricular cardiomyopathy (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TJP1 gene.

• Inborn genetic diseases (63 variants)
• not provided (7 variants)
• Cerebral edema (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TJP1 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				2		2
missense			60	3	3	66
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	60	5	3

Variants in TJP1

This is a list of pathogenic ClinVar variants found in the TJP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-29701636-C-A		not specified	Uncertain significance (Aug 02, 2022)
15-29701654-C-T		not specified	Uncertain significance (Jan 23, 2024)
15-29701664-C-A		not specified	Uncertain significance (Dec 08, 2021)
15-29701684-G-A		not specified	Uncertain significance (Apr 13, 2023)
15-29704217-C-T		TJP1-related disorder	Likely benign (Jul 28, 2020)
15-29704268-G-A		TJP1-related disorder	Likely benign (Feb 20, 2019)
15-29704280-C-T		TJP1-related disorder	Likely benign (Mar 23, 2020)
15-29705554-A-G		not specified	Uncertain significance (Aug 02, 2023)
15-29705580-A-G		TJP1-related disorder	Likely benign (May 27, 2019)
15-29705668-T-C		not specified	Uncertain significance (Aug 19, 2023)
15-29708628-G-C		not specified	Uncertain significance (Sep 16, 2021)
15-29708630-G-C		not specified	Uncertain significance (Aug 03, 2022)
15-29708646-C-T		not specified	Uncertain significance (Aug 10, 2023)
15-29708719-A-G		not specified	Uncertain significance (Jan 26, 2022)
15-29708887-C-T		not specified	Uncertain significance (Nov 21, 2023)
15-29708911-G-A		not specified	Uncertain significance (Nov 09, 2021)
15-29708945-T-C		TJP1-related disorder	Likely benign (Jul 25, 2019)
15-29708973-T-C		not specified	Uncertain significance (Dec 23, 2023)
15-29710839-T-C		not specified	Uncertain significance (Mar 28, 2023)
15-29710858-T-C		not specified	Uncertain significance (Dec 15, 2022)
15-29710891-G-A		not specified	Uncertain significance (Feb 28, 2024)
15-29710902-T-C		not specified	Uncertain significance (Dec 19, 2023)
15-29710917-G-A		not specified	Uncertain significance (Nov 20, 2023)
15-29710924-G-A		not specified	Uncertain significance (Dec 01, 2022)
15-29710947-T-C		not specified	Uncertain significance (Nov 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TJP1	protein_coding	protein_coding	ENST00000346128	28	269498

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.12e-13	124782	0	14	124796	0.0000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.54	829	964	0.860	0.0000534	11372
Missense in Polyphen		213	334.06	0.63762		3935
Synonymous	-0.298	358	351	1.02	0.0000200	3466
Loss of Function	8.52	2	88.4	0.0226	0.00000526	1020

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000219	0.000212
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.0000644	0.0000556
Finnish	0.00	0.00
European (Non-Finnish)	0.0000748	0.0000618
Middle Eastern	0.0000644	0.0000556
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:7798316, PubMed:9792688). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Necessary for lumenogenesis, and particularly efficient epithelial polarization and barrier formation (By similarity). Plays a role in the regulation of cell migration by targeting CDC42BPB to the leading edge of migrating cells (PubMed:21240187). Plays an important role in podosome formation and associated function, thus regulating cell adhesion and matrix remodeling (PubMed:20930113). With TJP2 and TJP3, participates to the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). {ECO:0000250|UniProtKB:O97758, ECO:0000269|PubMed:20930113, ECO:0000269|PubMed:21240187}.
• Pathway: Salmonella infection - Homo sapiens (human);Adherens junction - Homo sapiens (human);Tight junction - Homo sapiens (human);Gap junction - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Transcriptional regulation by RUNX1;EMT transition in Colorectal Cancer;Signal Transduction;Gene expression (Transcription);Vesicle-mediated transport;Membrane Trafficking;Generic Transcription Pathway;RNA Polymerase II Transcription;Apoptotic cleavage of cell adhesion proteins;Apoptotic cleavage of cellular proteins;Apoptotic execution phase;Apoptosis;Programmed Cell Death;c-src mediated regulation of Cx43 function and closure of gap junctions;Signaling by Hippo;Regulation of gap junction activity;Gap junction trafficking and regulation;RUNX1 regulates expression of components of tight junctions;Transcriptional regulation by RUNX1;Nephrin/Neph1 signaling in the kidney podocyte;E-cadherin signaling in the nascent adherens junction (Consensus)

Recessive Scores

• pRec: 0.738

Intolerance Scores

• loftool: 0.382
• rvis_EVS: -1.78
• rvis_percentile_EVS: 2.26

Haploinsufficiency Scores

• pHI: 0.254
• hipred: Y
• hipred_score: 0.824
• ghis: 0.563

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.798

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tjp1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; embryo phenotype; renal/urinary system 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); 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); normal 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)

Zebrafish Information Network

• Gene name: tjp1b
• Affected structure: Mauthner neuron
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: cell-cell junction assembly;hippo signaling;establishment of endothelial intestinal barrier;cell-cell signaling involved in cell-cell junction organization;regulation of bicellular tight junction assembly
• Cellular component: podosome;cytoplasm;cytosol;plasma membrane;cell-cell adherens junction;gap junction;bicellular tight junction;basolateral plasma membrane;cell junction;cell projection;apical junction complex;apical part of cell
• Molecular function: protein binding;calmodulin binding;cadherin binding