CLDN10

claudin 10, the group of Claudins

Basic information

Region (hg38): 13:95433604-95579759

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

Inborn_genetic_diseases (22 variants)
HELIX_syndrome (8 variants)
not_provided (4 variants)
CLDN10-related_disorder (2 variants)
Hypokalemia (1 variants)
Hypomagnesemia (1 variants)
Lower_limb_muscle_weakness (1 variants)

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. These statistics are base on transcript: NM_000006984.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense	2 clinvar	1 clinvar	25 clinvar			28
nonsense	2 clinvar					2
start loss	1					1
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)						0
Total	5	2	26	0	2

Highest pathogenic variant AF is 0.000001858842

Loading clinvar variants...

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