CLDN5

protein-coding

claudin 5, 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. Mutations in this gene have been found in patients with velocardiofacial syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2018]

Previous symbols:

AWAL
TMVCF

MANE transcript

NM_001363066.2

Inheritance

ClinVar variants

P:4U:24B:8

Top phenotype

Inborn genetic diseases

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr22:19,523,024-19,527,545

External References & Databases

Ensembl (ENSG00000184113)

Transcript & Mutation Effects

hg38 • Region Span ~4.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLDN5 variants in ClinVar

9 Conditions Cataloged

Inborn genetic diseasesTotal: 19

not providedTotal: 13

Syndromic diseaseTotal: 3

CLDN5-related neurodevelopmental disorderTotal: 2

Neurodevelopmental disorderTotal: 1

CLDN5-associated neurodevelopmental disorderTotal: 1

CLDN5-related conditionTotal: 1

Neurodevelopmental abnormalityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001363066.2. 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				1 clinvar	1 clinvar	2
missense	3 clinvar	1 clinvar	21 clinvar	6 clinvar		31
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	3	1	24	7	1	36

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001363066.2	RefSeq	NP_001349995.1	1	MANE Select
ENST00000618236.2	Ensembl	ENSP00000480623.1	1	MANE Select
NM_001130861.1	RefSeq	NP_001124333.1	1	Standard
NM_001363067.2	RefSeq	NP_001349996.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cldn5a	Danio rerio	Structure: neuroepithelial cell Quality: increased permeability abnormal

Gene / Model

Organism

Observed Phenotype

cldn5a

Danio rerio

Structure: neuroepithelial cell

Quality: increased permeability

abnormal

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)
Exercise-induced Circadian Regulation

Biological Process

outflow tract morphogenesis
cell-cell junction assembly
transforming growth factor beta receptor signaling pathway
learning
calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules

Molecular Function

structural molecule activity
identical protein binding

Cellular Component

plasma membrane
cell-cell junction
bicellular tight junction
integral component of membrane
apicolateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000406028
Coding exons: 1
Length: 4522
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	1.44	108	159	0.679	0.00000720	1835
Missense (PolyPhen)		19	55.492	0.34239		595
Synonymous	0.384	74	78.3	0.945	0.00000376	696
Loss of Function	2.50	0	7.31	0.00	3.18e-7	68

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. {ECO:0000250}.;

Recessive Scores

pRec: 0.286

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.694

Gene Damage Prediction

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