TJP2

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

Basic information

Region (hg38): 9:69121264-69274615

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 (24 variants)
Cholestasis, progressive familial intrahepatic, 4 (18 variants)
Hypercholanemia, familial 1 (2 variants)
Autosomal dominant nonsyndromic hearing loss 51 (1 variants)
TJP2-related disorder (1 variants)
Inborn genetic diseases (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. These statistics are base on transcript: . Only rare variants are included in the table.

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			17 clinvar	52 clinvar	11 clinvar	80
missense	1 clinvar	7 clinvar	278 clinvar	5 clinvar	10 clinvar	301
nonsense	14 clinvar	5 clinvar				19
start loss						0
frameshift	15 clinvar	3 clinvar	1 clinvar			19
splice donor/acceptor (+/-2bp)	5 clinvar	9 clinvar	3 clinvar			17
Total	35	24	299	57	21

Highest pathogenic variant AF is 0.0000239758

Loading clinvar variants...

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