CLDN5

claudin 5, the group of Claudins

Basic information

Region (hg38): 22:19523024-19527545

Previous symbols: [ "AWAL", "TMVCF" ]

Links

ENSG00000184113 ∙ NCBI:7122 ∙ OMIM:602101 ∙ HGNC:2047 ∙ Uniprot:O00501 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLDN5 gene.

• not provided (1 variants)
• CLDN5-related neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLDN5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense	2	1	7	1		11
nonsense			2			2
start loss						0
frameshift						0
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			3		1	4
Total	2	2	13	1	2

Variants in CLDN5

This is a list of pathogenic ClinVar variants found in the CLDN5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-19523532-C-A			Benign (Apr 19, 2021)
22-19523613-TC-AA			Uncertain significance (Feb 23, 2024)
22-19523663-A-C		Inborn genetic diseases	Uncertain significance (Dec 19, 2023)
22-19523730-C-A		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
22-19523788-C-A			Uncertain significance (Dec 18, 2023)
22-19523831-ATGT-A		Syndromic disease	Uncertain significance (Sep 20, 2024)
22-19523847-A-G		Inborn genetic diseases	Uncertain significance (May 10, 2024)
22-19523903-G-T			Uncertain significance (Dec 18, 2023)
22-19523921-G-C		Inborn genetic diseases	Likely benign (Nov 25, 2024)
22-19523953-G-A			Benign (Apr 09, 2021)
22-19524003-C-T		Inborn genetic diseases	Uncertain significance (May 29, 2024)
22-19524014-C-T		Inborn genetic diseases	Uncertain significance (Sep 10, 2024)
22-19524069-G-T		CLDN5-related neurodevelopmental disorder	Likely pathogenic (-)
22-19524078-C-T		CLDN5-related neurodevelopmental disorder	Pathogenic (Oct 10, 2023)
22-19524078-C-CGGT		CLDN5-related neurodevelopmental disorder	Likely pathogenic (Feb 29, 2024)
22-19524080-G-A		CLDN5 deficiency	Pathogenic (Sep 19, 2024)
22-19524092-A-G		Neurodevelopmental abnormality	Uncertain significance (Apr 03, 2020)
22-19524135-C-T		Neurodevelopmental disorder	Pathogenic (Oct 11, 2023)
22-19524153-A-G		CLDN5-associated neurodevelopmental disorder	Uncertain significance (Mar 04, 2025)
22-19524202-C-T			Uncertain significance (Apr 12, 2024)
22-19524284-C-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2021)
22-19524348-C-G		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
22-19524386-G-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2023)
22-19524397-CTC-TT			Uncertain significance (Oct 10, 2024)
22-19524420-C-T			Uncertain significance (Dec 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLDN5	protein_coding	protein_coding	ENST00000406028	1	4522

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.895	0.104	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.44	108	159	0.679	0.00000720	1835
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a major role in tight junction-specific obliteration of the intercellular space. {ECO:0000250}.
• Pathway: 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;Transcriptional regulation by RUNX1;EMT transition in Colorectal Cancer;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Tight junction interactions;Cell-cell junction organization;Cell junction organization;Cell-Cell communication;RUNX1 regulates expression of components of tight junctions;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.286

Haploinsufficiency Scores

• pHI: 0.205
• hipred: N
• hipred_score: 0.493
• ghis: 0.543

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.694

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cldn5
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: cldn5a
• Affected structure: neuroepithelial cell
• Phenotype tag: abnormal
• Phenotype quality: increased permeability

Gene ontology

• 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;roof of mouth development;face morphogenesis;positive regulation of establishment of endothelial barrier;regulation of bicellular tight junction assembly
• Cellular component: plasma membrane;cell-cell junction;bicellular tight junction;integral component of membrane;apicolateral plasma membrane;cell junction;cortical actin cytoskeleton
• Molecular function: structural molecule activity;identical protein binding