CLDN14

claudin 14, the group of Claudins

Basic information

Region (hg38): 21:36460621-36576569

Previous symbols: [ "DFNB29" ]

Links

ENSG00000159261 ∙ NCBI:23562 ∙ OMIM:605608 ∙ HGNC:2035 ∙ Uniprot:O95500 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 29 (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 29 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 29 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 29	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	11163249; 22246673

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLDN14 gene.

• not_provided (93 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_29 (46 variants)
• Inborn_genetic_diseases (31 variants)
• not_specified (18 variants)
• Hearing_impairment (5 variants)
• CLDN14-related_disorder (5 variants)
• Vein_of_Galen_aneurysmal_malformation (4 variants)
• Hearing_loss,_autosomal_recessive (2 variants)
• Nonsyndromic_genetic_hearing_loss (1 variants)
• Sensorineural_hearing_loss_disorder (1 variants)
• Alport_syndrome (1 variants)
• Monogenic_hearing_loss (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLDN14 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001146079.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	33	3	39
missense	1	7	72	4		84
nonsense	4	2				6
start loss			1			1
frameshift	6	1	3			10
splice donor/acceptor (+/-2bp)						0
Total	11	10	79	37	3

Highest pathogenic variant AF is 0.000711841

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLDN14	protein_coding	protein_coding	ENST00000399137	1	115949

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000111	0.385	125691	0	22	125713	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.197	148	155	0.956	0.0000107	1512
Missense in Polyphen		55	64.454	0.85332		643
Synonymous	-0.354	81	77.0	1.05	0.00000637	538
Loss of Function	0.0745	6	6.20	0.968	2.74e-7	59

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000496	0.000492
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.000140	0.000139
European (Non-Finnish)	0.0000546	0.0000528
Middle Eastern	0.000164	0.000163
South Asian	0.0000653	0.0000653
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);EMT transition in Colorectal Cancer;Tight junction interactions;Cell-cell junction organization;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.0819
• rvis_EVS: -0.6
• rvis_percentile_EVS: 17.91

Haploinsufficiency Scores

• pHI: 0.138
• hipred: N
• hipred_score: 0.408
• ghis: 0.428

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.618

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cldn14
• Phenotype: hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

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