TJP1

Chr 15

tight junction protein 1

Also known as: ZO-1

NCBI Gene: 7082 ENSG00000104067 UniProt: Q07157 OMIM: 601009

TJP1 encodes a tight junction scaffolding protein that links transmembrane proteins to the actin cytoskeleton, regulating the movement of substances between epithelial and endothelial cells and maintaining cell polarity. Mutations cause autosomal dominant progressive familial intrahepatic cholestasis type 4, which presents in infancy with cholestasis, pruritus, and progressive liver disease. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 0.071), indicating that haploinsufficiency is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

arrhythmogenic right ventricular cardiomyopathy · ADLimitednot for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

132

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.07

LOEUF· LoF intol.

LOF

Mechanism· predicted