CLDN1

claudin 1, the group of Claudins

Basic information

Region (hg38): 3:190305706-190322446

Links

ENSG00000163347 ∙ NCBI:9076 ∙ OMIM:603718 ∙ HGNC:2032 ∙ Uniprot:O95832 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neonatal ichthyosis-sclerosing cholangitis syndrome (Strong), mode of inheritance: AR
• neonatal ichthyosis-sclerosing cholangitis syndrome (Strong), mode of inheritance: AR
• neonatal ichthyosis-sclerosing cholangitis syndrome (Strong), mode of inheritance: AR
• neonatal ichthyosis-sclerosing cholangitis syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis	AR	Gastrointestinal	Individuals can have manifest with hepatic disease, and liver transplantation has been described as beneficial; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic; Gastrointestinal	12164927; 15521008; 16619213; 20645982; 21865982

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLDN1 gene.

• not provided (53 variants)
• not specified (7 variants)
• Inborn genetic diseases (6 variants)
• Neonatal ichthyosis-sclerosing cholangitis syndrome (2 variants)
• CLDN1-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLDN1 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			3	4	5	12
missense			22	3		25
nonsense	2	1	1			4
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	2		5
non coding			1	1	11	13
Total	2	1	27	8	16

Variants in CLDN1

This is a list of pathogenic ClinVar variants found in the CLDN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-190308016-G-T			Benign (Nov 10, 2018)
3-190308175-C-T			Benign (Nov 10, 2018)
3-190308270-C-T		CLDN1-related disorder	Likely benign (Mar 17, 2021)
3-190308282-C-T			Uncertain significance (Aug 19, 2023)
3-190308295-G-A			Uncertain significance (Jun 01, 2018)
3-190308303-G-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
3-190308322-C-A		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
3-190308350-C-T		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
3-190308372-G-A			Likely benign (Mar 04, 2022)
3-190308388-G-T			Uncertain significance (Jun 23, 2022)
3-190308401-G-C		CLDN1-related disorder	Likely benign (Jan 18, 2023)
3-190308403-A-C			Likely benign (Jul 23, 2023)
3-190308413-G-A			Uncertain significance (Mar 06, 2018)
3-190308420-G-C			Uncertain significance (Jul 28, 2017)
3-190308429-C-A		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
3-190308594-C-T			Benign (Nov 10, 2018)
3-190308707-A-G			Benign (Jun 19, 2021)
3-190310155-C-T			Likely benign (Dec 11, 2023)
3-190310163-C-T		not specified	Likely benign (Oct 14, 2023)
3-190310164-G-A			Uncertain significance (May 15, 2022)
3-190310178-A-G		Inborn genetic diseases	Uncertain significance (Jun 06, 2022)
3-190310209-C-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
3-190310210-G-A			Uncertain significance (Jul 27, 2017)
3-190310234-G-A		CLDN1-related disorder	Likely benign (Nov 22, 2021)
3-190310483-A-T			Benign (Nov 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLDN1	protein_coding	protein_coding	ENST00000295522	4	16775

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00101	0.832	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0323	121	122	0.992	0.00000621	1362
Missense in Polyphen		54	46.777	1.1544		552
Synonymous	-0.134	50	48.8	1.02	0.00000282	434
Loss of Function	1.19	6	10.1	0.597	5.18e-7	100

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000214	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000440	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermeable barriers, others mediate the permeability to ions and small molecules. Often, several claudin family members are coexpressed and interact with each other, and this determines the overall permeability. CLDN1 is required to prevent the paracellular diffusion of small molecules through tight junctions in the epidermis and is required for the normal barrier function of the skin. Required for normal water homeostasis and to prevent excessive water loss through the skin, probably via an indirect effect on the expression levels of other proteins, since CLDN1 itself seems to be dispensable for water barrier formation in keratinocyte tight junctions (PubMed:23407391). {ECO:0000269|PubMed:23407391}.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Tight junction - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Pathogenic Escherichia coli infection;Primary Focal Segmental Glomerulosclerosis FSGS;EMT transition in Colorectal Cancer;Tight junction interactions;Cell-cell junction organization;Cell junction organization;Cell-Cell communication;Nectin adhesion pathway (Consensus)

Recessive Scores

• pRec: 0.235

Intolerance Scores

• loftool: 0.210
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.89

Haploinsufficiency Scores

• pHI: 0.229
• hipred: Y
• hipred_score: 0.706
• ghis: 0.567

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.938

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cldn1
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; 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)

Gene ontology

• Biological process: aging;establishment of blood-nerve barrier;calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules;response to lipopolysaccharide;hyperosmotic salinity response;cell-cell junction organization;response to ethanol;viral entry into host cell;protein homooligomerization;protein heterooligomerization;establishment of skin barrier;drug transport across blood-nerve barrier;response to interleukin-18;bicellular tight junction assembly;cellular response to lead ion;cellular response to interferon-gamma;cellular response to tumor necrosis factor;response to dexamethasone;cellular response to transforming growth factor beta stimulus;establishment of endothelial intestinal barrier;liver regeneration;positive regulation of bicellular tight junction assembly;cellular response to butyrate
• Cellular component: cytoplasm;integral component of plasma membrane;bicellular tight junction;integral component of membrane;basolateral plasma membrane;apical plasma membrane;lateral plasma membrane
• Molecular function: virus receptor activity;structural molecule activity;protein binding;identical protein binding