CLDN10

claudin 10, the group of Claudins

Basic information

Region (hg38): 13:95433603-95579759

Links

ENSG00000134873 ∙ NCBI:9071 ∙ OMIM:617579 ∙ HGNC:2033 ∙ Uniprot:P78369 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• HELIX syndrome (Moderate), mode of inheritance: AR
• HELIX syndrome (Strong), mode of inheritance: AR
• HELIX syndrome (Strong), mode of inheritance: AR
• HELIX syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, icthyosis, and xerostomia (HELIX syndrome)	AR	Renal	Among other findings, patients may have electrolyte abnormalities, and identification may allow early management	Dental; Dermatologic; Renal	28686597; 28771254

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLDN10 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLDN10 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					2	2
missense		1	14			15
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					3	3
Total	0	2	14	0	5

Variants in CLDN10

This is a list of pathogenic ClinVar variants found in the CLDN10 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-95433626-C-A			Benign (May 20, 2021)
13-95433756-A-G			Benign (May 10, 2021)
13-95433934-C-T		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
13-95434226-C-T			Benign (May 10, 2021)
13-95552516-CG-C			Benign (May 26, 2021)
13-95552554-G-A			Benign (May 11, 2021)
13-95552755-T-C		HELIX syndrome	Pathogenic (Nov 20, 2018)
13-95552788-T-C		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
13-95552815-T-C		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
13-95552880-G-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2024)
13-95552895-A-C		HELIX syndrome	Likely pathogenic (Sep 23, 2021)
13-95552897-C-G		HELIX syndrome	Pathogenic (Sep 15, 2017)
13-95552951-C-A		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
13-95553079-C-T			Benign (May 11, 2021)
13-95553105-A-C			Benign (May 10, 2021)
13-95560139-A-C		CLDN10-related disorder	Benign (Mar 07, 2019)
13-95560153-G-A		Inborn genetic diseases	Uncertain significance (Oct 05, 2022)
13-95560167-G-T		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
13-95560182-T-C		Inborn genetic diseases	Uncertain significance (Jul 09, 2021)
13-95560229-C-T			Uncertain significance (-)
13-95560269-G-T		Inborn genetic diseases	Uncertain significance (Jun 21, 2022)
13-95560282-T-C		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
13-95560391-C-T		HELIX syndrome	Pathogenic (Feb 26, 2018)
13-95560401-A-C		CLDN10-related disorder	Benign (Mar 07, 2019)
13-95560419-C-A			Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLDN10	protein_coding	protein_coding	ENST00000299339	5	146156

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000839	0.800	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.536	114	131	0.868	0.00000640	1468
Missense in Polyphen		22	39.731	0.55372		451
Synonymous	0.709	47	53.6	0.877	0.00000294	463
Loss of Function	1.09	6	9.66	0.621	4.06e-7	126

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000398	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000441	0.0000439
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium- independent cell-adhesion activity. Involved in the regulation of paracellular epithelia permeability to ions in multiple organs. It acts as a paracellular ion channel probably forming permselective pores; isoform 1 appears to create pores preferentially permeable to cations and isoform 2 for anions. In sweat glands and in the thick ascending limb (TAL) of Henle's loop in kidney, it controls paracellular sodium permeability which is essential for proper sweat production and renal function (PubMed:19383724, PubMed:28771254, PubMed:28686597). {ECO:0000269|PubMed:19383724, ECO:0000269|PubMed:28686597, ECO:0000269|PubMed:28771254}.
• Disease: DISEASE: HELIX syndrome (HELIX) [MIM:617671]: An autosomal recessive disease characterized by congenital heat intolerance, generalized anhidrosis, inability to produce tears, dry mouth, electrolyte imbalance, and ichthyosis. {ECO:0000269|PubMed:28686597, ECO:0000269|PubMed:28771254}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cell adhesion molecules (CAMs) - Homo sapiens (human);Tight junction - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);EMT transition in Colorectal Cancer;Tight junction interactions;Cell-cell junction organization;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.153

Intolerance Scores

• loftool: 0.300
• rvis_EVS: -0.52
• rvis_percentile_EVS: 21.2

Haploinsufficiency Scores

• pHI: 0.444
• hipred: N
• hipred_score: 0.474
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.354

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cldn10
• Phenotype: renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

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