CLDN10

protein-coding

claudin 10, the group of Claudins

Gene summary

This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. The expression level of this gene is associated with recurrence of primary hepatocellular carcinoma. Six alternatively spliced transcript variants encoding different isoforms have been reported, but the transcript sequences of some variants are not determined.[provided by RefSeq, Jun 2010]

MANE transcript

NM_006984.5

Inheritance

ClinVar variants

P:8U:35B:2

Top phenotype

Hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, icthyosis, and xerostomia (HELIX syndrome)

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr13:95,433,604-95,579,759

External References & Databases

Ensembl (ENSG00000134873)

Transcript & Mutation Effects

hg38 • Region Span ~146.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

HELIX syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0060564

Submitter: Orphanet

HELIX syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0060564

Submitter: Labcorp Genetics (formerly Invitae)

HELIX syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0060564

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, icthyosis, and xerostomia (HELIX syndrome)AR

Manifestation: Dental; Dermatologic; Renal

Intervention: Renal

Rationale: Among other findings, patients may have electrolyte abnormalities, and identification may allow early management

Refs: 28686597; 28771254

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CLDN10 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 24

HELIX syndromeTotal: 10

CLDN10-related disorderTotal: 5

not providedTotal: 4

not specifiedTotal: 2

HypokalemiaTotal: 1

HypomagnesemiaTotal: 1

Lower limb muscle weaknessTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006984.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense	2 clinvar	2 clinvar	33 clinvar			37
nonsense	2 clinvar					2
start loss	1 clinvar					1
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	5	3	35	0	2	45

Highest pathogenic variant AF is 0.000001858842

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006984.5	RefSeq	NP_008915.1	5	MANE Select
ENST00000299339.3	Ensembl	ENSP00000299339.2	5	MANE Select
NM_001160100.2	RefSeq	NP_001153572.1	5	Standard
NM_182848.4	RefSeq	NP_878268.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

ion transport
cell adhesion
calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules
regulation of ion transport

Molecular Function

structural molecule activity
identical protein binding

Cellular Component

cytoplasm
plasma membrane
bicellular tight junction
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299339
Coding exons: 5
Length: 146156
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.536	114	131	0.868	0.00000640	1468
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00040	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.153

Intolerance Scores

LoFtool: 0.300
RVIS EVS: -0.52
RVIS percentile EVS: 21.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.354

Gene Damage Prediction

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