TJP2

tight junction protein 2, the group of PDZ domain containing|Membrane associated guanylate kinases

Basic information

Region (hg38): 9:69121263-69274615

Previous symbols: [ "DFNA51" ]

Links

ENSG00000119139 ∙ NCBI:9414 ∙ OMIM:607709 ∙ HGNC:11828 ∙ Uniprot:Q9UDY2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• familial hypercholanemia (Supportive), mode of inheritance: AR
• cholestasis, progressive familial intrahepatic, 4 (Strong), mode of inheritance: AR
• autosomal dominant nonsyndromic hearing loss (Limited), mode of inheritance: AD
• cholestasis, progressive familial intrahepatic, 4 (Strong), mode of inheritance: AR
• hypercholanemia, familial 1 (Limited), mode of inheritance: Unknown
• nonsyndromic genetic hearing loss (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypercholanemia, familial; Cholestasis, progressive familial intrahepatic 4	AR	Gastrointestinal; Oncologic	In Hypercholanemia, Individuals may present with findings such as fat malabsorption, with consequent failure to thrive, coagulopathy, and rickets, and typically respond to medical treatment (eg, with ursodeoxycholic acid); In Familial intrahepatic cholestasis, medical treatment (eg, with ursodeoxycholine) may be beneficial, though liver transplantation has been described as necessary in some individuals; Medications (eg, OCPs) may lead to adverse reactions; In pregnancy, the condition can cause severe sequelae (including death) in the fetus, as well as adverse maternal health outcomes, and precautions, including early delivery, may be beneficial; Individuals have been reported with hepatocellular carcnioma, and awareness may allow early diagnosis and management	Audiologic/Otolaryngologic; Gastrointestinal; Oncologic	12704386; 20602916; 24614073; 25921221
Deafness, autosomal dominant 51 has been reported as due to genomic duplications, though evidence for causation of other variants appears to be unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TJP2 gene.

• not provided (517 variants)
• not specified (74 variants)
• Inborn genetic diseases (60 variants)
• Cholestasis, progressive familial intrahepatic, 4 (44 variants)
• Hypercholanemia, familial 1 (10 variants)
• Hypercholanemia, familial 1;Cholestasis, progressive familial intrahepatic, 4 (9 variants)
• TJP2-related condition (8 variants)
• Nonsyndromic Hearing Loss, Dominant (6 variants)
• Cholestasis, progressive familial intrahepatic, 4;Hypercholanemia, familial 1 (4 variants)
• Hearing impairment (3 variants)
• Melnick-Fraser syndrome (1 variants)
• Primary biliary cholangitis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TJP2 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	36	11	69
missense	1	5	231	5	10	252
nonsense	14	4				18
start loss						0
frameshift	13	2	1			16
inframe indel			9			9
splice donor/acceptor (+/-2bp)	5	6	2			13
splice region		1	16	9		26
non coding			20	61	59	140
Total	33	17	285	102	80

Highest pathogenic variant AF is 0.000499

Variants in TJP2

This is a list of pathogenic ClinVar variants found in the TJP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-69151771-G-A			Uncertain significance (Aug 17, 2016)
9-69173834-G-A			Likely benign (Dec 23, 2018)
9-69173991-G-A			Benign (Jan 25, 2019)
9-69174015-C-T			Likely benign (Feb 18, 2019)
9-69174033-C-A			Benign (Nov 12, 2018)
9-69174188-G-A			Benign (Dec 06, 2018)
9-69174240-C-T			Benign (Nov 12, 2018)
9-69174347-G-A		not specified	Likely benign (Mar 05, 2018)
9-69174357-G-T		not specified	Benign/Likely benign (Jul 17, 2018)
9-69174368-C-T			Uncertain significance (Jan 12, 2017)
9-69174374-T-TGCCGGTGC			Pathogenic (Nov 19, 2023)
9-69174391-C-T			Uncertain significance (Sep 28, 2021)
9-69174395-G-C			Uncertain significance (Jun 10, 2021)
9-69174409-C-T			Uncertain significance (Apr 05, 2022)
9-69174421-G-C			Uncertain significance (Jan 10, 2022)
9-69174427-C-T		TJP2-related disorder	Likely benign (Mar 31, 2021)
9-69174439-G-C		TJP2-related disorder	Likely benign (Dec 05, 2022)
9-69174470-T-TCGTGAG			Benign (Jun 14, 2018)
9-69204747-G-T			Benign (Nov 12, 2018)
9-69204856-T-C			Benign (Dec 14, 2018)
9-69205092-A-G			Benign (Jun 22, 2018)
9-69205132-G-A			Likely benign (Oct 06, 2018)
9-69205157-A-C			Uncertain significance (Jun 01, 2018)
9-69205189-A-T			Uncertain significance (Aug 15, 2017)
9-69205204-G-C		not specified • TJP2-related disorder	Benign/Likely benign (Mar 22, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TJP2	protein_coding	protein_coding	ENST00000539225	23	133916

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.24e-11	1.00	125666	0	82	125748	0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.567	700	744	0.941	0.0000472	7951
Missense in Polyphen		236	280.64	0.84094		3168
Synonymous	0.759	269	285	0.943	0.0000181	2382
Loss of Function	3.87	28	60.4	0.463	0.00000331	687

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000921	0.000920
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.000218	0.000217
Finnish	0.0000479	0.0000462
European (Non-Finnish)	0.000363	0.000360
Middle Eastern	0.000218	0.000217
South Asian	0.000300	0.000294
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in tight junctions and adherens junctions.
• Disease: DISEASE: Cholestasis, progressive familial intrahepatic, 4 (PFIC4) [MIM:615878]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. {ECO:0000269|PubMed:24614073}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tight junction - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Signal Transduction;Apoptotic cleavage of cell adhesion proteins;Apoptotic cleavage of cellular proteins;Apoptotic execution phase;Apoptosis;Programmed Cell Death;EGFR1;Signaling by Hippo;Validated targets of C-MYC transcriptional repression (Consensus)

Recessive Scores

• pRec: 0.250

Intolerance Scores

• loftool: 0.887
• rvis_EVS: 1.46
• rvis_percentile_EVS: 95.18

Haploinsufficiency Scores

• pHI: 0.303
• hipred: Y
• hipred_score: 0.652
• ghis: 0.438

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.924

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tjp2
• Phenotype: growth/size/body region phenotype; cellular 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); embryo phenotype

Gene ontology

• Biological process: hippo signaling;GMP metabolic process;GDP metabolic process;intestinal absorption;establishment of endothelial intestinal barrier;regulation of membrane permeability
• Cellular component: nucleoplasm;cytosol;plasma membrane;adherens junction;bicellular tight junction;cell junction
• Molecular function: guanylate kinase activity;protein binding;protein domain specific binding;protein binding, bridging;cadherin binding