TJP3

protein-coding

tight junction protein 3, the group of PDZ domain containing|Membrane associated guanylate kinases

Gene summary

The protein encoded by this gene is a member of the membrane-associated guanylate kinase-like (MAGUK) protein family which is characterized by members having multiple PDZ domains, a single SH3 domain, and a single guanylate kinase-like (GUK)-domain. In addition, members of the zonula occludens protein subfamily have an acidic domain, a basic arginine-rich region, and a proline-rich domain. The protein encoded by this gene plays a role in the linkage between the actin cytoskeleton and tight-junctions and also sequesters cyclin D1 at tight junctions during mitosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. This gene has a partial pseudogene on chromosome 1. [provided by RefSeq, May 2012]

MANE transcript

NM_001267560.2

Inheritance

—

ClinVar variants

U:23B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr19:3,708,362-3,750,813

External References & Databases

Ensembl (ENSG00000105289)

Transcript & Mutation Effects

hg38 • Region Span ~42.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TJP3 variants in ClinVar

1 Conditions Cataloged

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001267560.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	5 clinvar	1 clinvar	9
missense			10 clinvar	1 clinvar		11
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	23	6	1	30

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001267560.2	RefSeq	NP_001254489.1	20	MANE Select
ENST00000541714.7	Ensembl	ENSP00000439278.1	20	MANE Select
NM_001267561.2	RefSeq	NP_001254490.1	21	Standard
ENST00000539908.6	Ensembl	ENSP00000439991.1	19	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tjp3	Danio rerio	Structure: post-vent region Quality: increased curvature abnormal

Gene / Model

Organism

Observed Phenotype

tjp3

Danio rerio

Structure: post-vent region

Quality: increased curvature

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)

Molecular Function

protein binding

Cellular Component

nucleus
plasma membrane
bicellular tight junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000589378
Coding exons: 21
Length: 42705
Individuals with no LoFs: 125543
Homozygous LoFs: 0
Heterozygous LoFs: 205
Defined: 125748
p: 0.000815

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.670	686	638	1.07	0.0000465	5930
Missense (PolyPhen)		258	255.31	1.0105		2417
Synonymous	0.0487	269	270	0.996	0.0000204	1929
Loss of Function	1.12	39	47.3	0.825	0.00000276	474

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00096	0.00092	rare
Latino/Admixed American	0.00047	0.00046	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.0037	0.0036	notable
Finnish	0.0013	0.0012	notable
European (Non-Finnish)	0.00045	0.00043	rare
South Asian	0.00059	0.00059	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

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:16129888). 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. Binds and recruits PATJ to tight junctions where it connects and stabilizes apical and lateral components of tight junctions (PubMed:16129888). Promotes cell-cycle progression through the sequestration of cyclin D1 (CCND1) at tight junctions during mitosis which prevents CCND1 degradation during M-phase and enables S-phase transition (PubMed:21411630). With TJP1 and TJP2, participates to the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for individual viability, embryonic development, epithelial differentiation, and the establishment of TJs, at least in the laboratory environment (By similarity). {ECO:0000250|UniProtKB:O62683, ECO:0000250|UniProtKB:Q9QXY1, ECO:0000269|PubMed:16129888, ECO:0000269|PubMed:21411630}.;

Intolerance Scores

RVIS EVS: 0.13
RVIS percentile EVS: 63.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.671

Gene Damage Prediction

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