CLDN2

claudin 2, the group of Claudins

Basic information

Region (hg38): X:106900164-106930861

Links

ENSG00000165376 ∙ NCBI:9075 ∙ OMIM:300520 ∙ HGNC:2041 ∙ Uniprot:P57739 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary chronic pancreatitis (Limited), mode of inheritance: AD
• azoospermia, obstructive, with nephrolithiasis (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Azoospermia, obstructive, with nephrolithiasis	XL	General	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	Genitourinary; Renal	31320686

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLDN2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLDN2 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						0
missense			1	1		2
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)					1	1
splice region						0
non coding			10	3	5	18
Total	0	0	11	4	6

Variants in CLDN2

This is a list of pathogenic ClinVar variants found in the CLDN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-106900765-T-A		not specified	Uncertain significance (Dec 03, 2021)
X-106900793-C-T		not specified	Uncertain significance (Dec 17, 2023)
X-106900812-G-A			Benign (Jun 10, 2018)
X-106900843-T-C		RIPPLY1-related disorder • not specified	Conflicting classifications of pathogenicity (Sep 15, 2021)
X-106900874-G-A		RIPPLY1-related disorder	Likely benign (Mar 21, 2022)
X-106900889-G-A		not specified	Uncertain significance (Aug 04, 2023)
X-106900897-G-A		not specified	Uncertain significance (Sep 19, 2022)
X-106901485-A-T		not specified	Uncertain significance (May 18, 2023)
X-106901501-G-A			Benign (Dec 20, 2017)
X-106901502-C-T		not specified	Uncertain significance (May 30, 2023)
X-106901507-G-T		not specified	Uncertain significance (Dec 27, 2023)
X-106901514-C-T			Uncertain significance (Mar 03, 2020)
X-106901521-C-T			Benign (Dec 20, 2017)
X-106902183-G-T		RIPPLY1-related disorder	Likely benign (Apr 11, 2023)
X-106903178-G-T		not specified	Uncertain significance (Dec 07, 2023)
X-106903194-G-T		not specified	Uncertain significance (Jun 01, 2023)
X-106903280-G-A		not specified	Uncertain significance (Apr 22, 2024)
X-106903281-A-G		not specified	Likely benign (Aug 17, 2021)
X-106927928-G-GT			Benign (Jun 14, 2019)
X-106927946-CAT-C			Benign (Jun 14, 2019)
X-106928040-A-AT			Benign (Aug 07, 2019)
X-106928421-G-C			Uncertain significance (-)
X-106928690-C-G		not specified	Uncertain significance (Mar 30, 2024)
X-106928701-T-A			Likely benign (Aug 16, 2018)
X-106928709-G-C		Male infertility • Azoospermia, obstructive, with nephrolithiasis	Pathogenic (Mar 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLDN2	protein_coding	protein_coding	ENST00000541806	1	30698

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.703	0.282	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.61	44	86.2	0.511	0.00000609	1472
Missense in Polyphen		8	30.285	0.26416		528
Synonymous	0.831	29	35.3	0.822	0.00000254	509
Loss of Function	1.85	0	3.99	0.00	3.27e-7	60

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, through calcium- independent cell-adhesion activity. {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);Vitamin D Receptor Pathway;EMT transition in Colorectal Cancer;Tight junction interactions;Cell-cell junction organization;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.11

Haploinsufficiency Scores

• pHI: 0.312
• hipred: Y
• hipred_score: 0.623
• ghis: 0.405

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cldn2
• Phenotype: renal/urinary system phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules
• Cellular component: plasma membrane;bicellular tight junction;integral component of membrane
• Molecular function: structural molecule activity;protein binding;identical protein binding