TJP1

Chr 15

tight junction protein 1

Also known as: ZO-1

NCBI Gene: 7082ENSG00000104067UniProt: Q07157

This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family of proteins, and acts as a tight junction adaptor protein that also regulates adherens junctions. Tight junctions regulate the movement of ions and macromolecules between endothelial and epithelial cells. The multidomain structure of this scaffold protein, including a postsynaptic density 95/disc-large/zona occludens (PDZ) domain, a Src homology (SH3) domain, a guanylate kinase (GuK) domain and unique (U) motifs all help to co-ordinate binding of transmembrane proteins, cytosolic proteins, and F-actin, which are required for tight junction function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]

469
ClinVar variants
96
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TJP1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
96 Pathogenic / Likely Pathogenic· 301 VUS of 469 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.07LOEUF
pLI 1.000
Z-score 8.52
OE 0.02 (0.01–0.07)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.54Z-score
OE missense 0.86 (0.81–0.91)
829 obs / 963.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.02 (0.01–0.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.81–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 2 / 88.4Missense obs/exp: 829 / 963.7Syn Z: -0.30

ClinVar Variant Classifications

469 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic91
Likely Pathogenic5
VUS301
Likely Benign27
Benign16
Conflicting3
91
Pathogenic
5
Likely Pathogenic
301
VUS
27
Likely Benign
16
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
91
0
91
Likely Pathogenic
0
0
5
0
5
VUS
0
257
44
0
301
Likely Benign
0
7
7
13
27
Benign
0
4
4
8
16
Conflicting
—3
Total026815121443

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TJP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TJP1-related arrhythmogenic right ventricular cardiomyopathy

limited
ADUndeterminedUncertain
Cardiac
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mitophagy initiates retrograde mitochondrial-nuclear signaling to guide retinal pigment cell heterogeneity.
Datta S et al.·Autophagy
2023
Whole-Exome Sequencing Identifies Pathogenic Variants in TJP1 Gene Associated With Arrhythmogenic Cardiomyopathy.
De Bortoli M et al.·Circ Genom Precis Med
2018
Loss of TJP1 disrupts gastrulation patterning and increases differentiation toward the germ cell lineage in human pluripotent stem cells.
Vasic I et al.·Dev Cell
2023
A Comprehensive Analysis of Non-Desmosomal Rare Genetic Variants in Arrhythmogenic Cardiomyopathy: Integrating in Padua Cohort Literature-Derived Data.
Bueno Marinas M et al.·Int J Mol Sci
2024Cohort
IL-27Ra promotes the progression of neonatal necrotizing enterocolitis.
Yang Y et al.·Sci Rep
2025
The Scribble-SGEF-Dlg1 complex regulates E-cadherin and ZO-1 stability, turnover and transcription in epithelial cells.
Rabino A et al.·J Cell Sci
2024
Tight junction protein 1 promotes vasculature remodeling via regulating USP2/TWIST1 in bladder cancer.
Liu XQ et al.·Oncogene
2022Functional
Integrated Bioinformatics and Clinical Correlation Analysis of Key Genes, Pathways, and Potential Therapeutic Agents Related to Diabetic Nephropathy.
Chen S et al.·Dis Markers
2022
Dysfunctional Epithelial Barrier Is Characterized by Reduced E-Cadherin in Idiopathic Subglottic Stenosis.
Berges AJ et al.·Laryngoscope
2024Functional
Characterization of genome-wide TFCP2 targets in hepatocellular carcinoma: implication of targets FN1 and TJP1 in metastasis.
Xu X et al.·J Exp Clin Cancer Res
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools