CLDN6
protein-codingclaudin 6, the group of Claudins
Gene summary
Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. This gene encodes a component of tight junction strands, which is a member of the claudin family. The protein is an integral membrane protein and is one of the entry cofactors for hepatitis C virus. The gene methylation may be involved in esophageal tumorigenesis. This gene is adjacent to another family member CLDN9 on chromosome 16.[provided by RefSeq, Aug 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.4 kbGenCC 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 CLDN6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021195.5. 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 | 1 | 1 | 2 | |||
| missense | 39 | 4 | 43 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 40 | 4 | 1 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_067018.2 | 1 | MANE Select | |
| Ensembl | ENSP00000328674.4 | 1 | MANE Select | |
| Ensembl | ENSP00000380131.1 | 1 | Standard | |
| Ensembl | ENSP00000458783.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell adhesion molecules (CAMs) - Homo sapiens (human)
- Tight junction - Homo sapiens (human)
- Hepatitis C - Homo sapiens (human)
- Leukocyte transendothelial migration - Homo sapiens (human)
- EMT transition in Colorectal Cancer
Biological Process
- calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules
- cell-cell junction organization
- viral entry into host cell
Molecular Function
- virus receptor activity
- structural molecule activity
- protein binding
- identical protein binding
Cellular Component
- plasma membrane
- bicellular tight junction
- integral component of membrane
- apicolateral plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396925
- Coding exons
- 1
- Length
- 5360
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125708
- p
- 0.0000438
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.428 | 148 | 134 | 1.10 | 0.00000844 | 1365 |
| Missense (PolyPhen) | 59 | 54.636 | 1.0799 | 614 | ||
| Synonymous | -2.18 | 85 | 63.0 | 1.35 | 0.00000416 | 509 |
| Loss of Function | 0.602 | 4 | 5.53 | 0.724 | 2.40e-7 | 60 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000062 | 0.000062 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a major role in tight junction-specific obliteration of the intercellular space. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.147
Intolerance Scores
- LoFtool
- 0.204
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.51
Essentials
- Essential (CRISPR)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.910
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |