CLDN25

protein-coding

claudin 25, the group of Claudins

Gene summary

This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. [provided by RefSeq, Jun 2010]

MANE transcript

NM_001101389.1

Inheritance

—

ClinVar variants

U:43B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.52

Max pathogenic AF

—

Genomic locus

chr11:113,779,796-113,780,485

External References & Databases

Ensembl (ENSG00000228607)

Transcript & Mutation Effects

hg38 • Region Span ~0.7 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 CLDN25 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 44

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001101389.1. 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 clinvar		1
missense			43 clinvar	1 clinvar		44
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	43	2	0	45

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001101389.1	RefSeq	NP_001094859.1	1	MANE Select
ENST00000453129.3	Ensembl	ENSP00000396304.2	1	MANE Select

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)

Molecular Function

structural molecule activity

Cellular Component

plasma membrane
bicellular tight junction
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000453129
Coding exons: 1
Length: 754
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.739	151	128	1.18	0.00000673	1473
Missense (PolyPhen)		45	32.715	1.3755		393
Synonymous	0.523	47	51.8	0.907	0.00000264	501
Loss of Function	-1.24	10	6.56	1.52	3.51e-7	58

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium- independent cell-adhesion activity. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.575
RVIS EVS: -0.1
RVIS percentile EVS: 46.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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