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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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CLDN14
claudin 14
Chromosome 21 Β· 21q22.13
NCBI Gene: 23562Ensembl: ENSG00000159261.13HGNC: HGNC:2035UniProt: O95500
48PubMed Papers
21Diseases
0Drugs
19Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
endoplasmic reticulumplasma membraneprotein bindingcalcium-independent cell-cell adhesionhearing loss, autosomal recessivedeafnessnephrolithiasisgout
✦AI Summary

CLDN14 encodes claudin 14, a tight junction protein that plays a critical role in regulating paracellular permeability in epithelial cells, particularly in the kidney and inner ear 1. The protein functions as a key component of tight junctions, facilitating calcium-independent cell-cell adhesion and controlling the differential handling of divalent cations like magnesium and calcium 2. In the kidney, claudin 14 is expressed in distal nephron segments and its expression is regulated by dietary magnesium content, influencing the paracellular transport of Mg2+ and Ca2+ 2. CLDN14 mutations are associated with autosomal recessive non-syndromic hearing loss (DFNB29), with various pathogenic variants identified in affected families 34. Additionally, common variants in CLDN14 are strongly associated with kidney stone formation, with approximately 62% of the population carrying risk alleles that confer 1.64 times greater disease risk 1. These same variants also associate with reduced bone mineral density, suggesting broader effects on calcium homeostasis 1. The gene's role in Meniere's disease has also been reported, further highlighting its importance in inner ear function 5. CLDN14 represents a clinically significant gene linking tight junction function to both renal stone disease and hereditary deafness.

Sources cited
1
CLDN14 encodes claudin 14, a tight junction protein that plays a critical role in regulating paracellular permeability in epithelial cells, particularly in the kidney and inner ear .
PMID: 19561606
2
The protein functions as a key component of tight junctions, facilitating calcium-independent cell-cell adhesion and controlling the differential handling of divalent cations like magnesium and calcium .
PMID: 27915449
3
CLDN14 mutations are associated with autosomal recessive non-syndromic hearing loss (DFNB29), with various pathogenic variants identified in affected families .
PMID: 24339547
4
CLDN14 mutations are associated with autosomal recessive non-syndromic hearing loss (DFNB29), with various pathogenic variants identified in affected families .
PMID: 38790217
5
The gene's role in Meniere's disease has also been reported, further highlighting its importance in inner ear function .
PMID: 31874721
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.71Strong
deafnessOpen Targets
0.61Moderate
nephrolithiasisOpen Targets
0.53Moderate
goutOpen Targets
0.50Moderate
urolithiasisOpen Targets
0.48Moderate
ureterolithiasisOpen Targets
0.47Moderate
vein of Galen aneurysmOpen Targets
0.45Moderate
Hearing impairmentOpen Targets
0.44Moderate
bladder calculusOpen Targets
0.44Moderate
nonsyndromic genetic hearing lossOpen Targets
0.40Weak
hearing lossOpen Targets
0.37Weak
Non-syndromic genetic deafnessOpen Targets
0.37Weak
sensorineural hearing lossOpen Targets
0.34Weak
Sensorineural hearing impairmentOpen Targets
0.34Weak
lower urinary tract calculusOpen Targets
0.32Weak
retinopathy of prematurityOpen Targets
0.31Weak
liver and intrahepatic bile duct neoplasmOpen Targets
0.27Weak
hypertensionOpen Targets
0.25Weak
ventricular fibrillationOpen Targets
0.24Weak
genetic disorderOpen Targets
0.19Weak
Deafness, autosomal recessive, 29UniProt
Pathogenic Variants19
NM_001146079.2(CLDN14):c.89G>A (p.Trp30Ter)Pathogenic
Hearing impairment|not provided|Autosomal recessive nonsyndromic hearing loss 29
β˜…β˜…β˜†β˜†2025β†’ Residue 30
NM_001146079.2(CLDN14):c.291C>A (p.Cys97Ter)Pathogenic
Hearing loss, autosomal recessive|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 97
NM_001146079.2(CLDN14):c.401del (p.Val134fs)Likely pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 134
NM_001146079.2(CLDN14):c.242G>A (p.Arg81His)Pathogenic
Autosomal recessive nonsyndromic hearing loss 29|Hearing impairment|not provided|CLDN14-related disorder
β˜…β˜…β˜†β˜†2022β†’ Residue 81
NM_001146079.2(CLDN14):c.611del (p.Thr204fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 204
NM_001146079.2(CLDN14):c.554_556del (p.Cys185_Gln186delinsTer)Pathogenic
Autosomal recessive nonsyndromic hearing loss 29
β˜…β˜†β˜†β˜†2025β†’ Residue 185
NM_001146079.2(CLDN14):c.355_361del (p.Ile119fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 29
β˜…β˜†β˜†β˜†2025β†’ Residue 119
NM_001146079.2(CLDN14):c.285C>A (p.Cys95Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 29
β˜…β˜†β˜†β˜†2025β†’ Residue 95
NM_001146079.2(CLDN14):c.167_168del (p.Trp56fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 29
β˜…β˜†β˜†β˜†2025β†’ Residue 56
NM_001146079.2(CLDN14):c.548_588dup (p.Pro197fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 197
NM_001146079.2(CLDN14):c.414G>A (p.Trp138Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 138
NM_001146079.2(CLDN14):c.203del (p.Arg68fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 68
NM_001146079.2(CLDN14):c.242_243delinsAT (p.Arg81His)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 81
NM_001146079.2(CLDN14):c.167G>A (p.Trp56Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 29|CLDN14-related disorder
β˜…β˜†β˜†β˜†2022β†’ Residue 56
NM_001146079.2(CLDN14):c.254T>A (p.Val85Asp)Pathogenic
Autosomal recessive nonsyndromic hearing loss 29|Hearing impairment|Hearing loss, autosomal recessive
β˜…β˜†β˜†β˜†2022β†’ Residue 85
NM_001146079.2(CLDN14):c.40_41insTGGTGCACGGCCGTGCA (p.Ser14fs)Pathogenic
Sensorineural hearing loss disorder
β˜…β˜†β˜†β˜†2020β†’ Residue 14
NM_001146079.2(CLDN14):c.694G>A (p.Gly232Arg)Pathogenic
Autosomal recessive nonsyndromic hearing loss 29
β˜†β˜†β˜†β˜†2019β†’ Residue 232
NM_001146079.2(CLDN14):c.191G>A (p.Cys64Tyr)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 29
β˜†β˜†β˜†β˜†2018β†’ Residue 64
NM_001146079.2(CLDN14):c.398del (p.Met133fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 29
β˜†β˜†β˜†β˜†2001β†’ Residue 133
View on ClinVar β†—
Related Genes
CLDN19Protein interaction100%TJP1Protein interaction98%OCLNProtein interaction96%TJP3Protein interaction87%TJP2Protein interaction76%CLDN3Protein interaction72%
Tissue Expression6 tissues
Liver
100%
Lung
0%
Ovary
0%
Brain
0%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CLDN14CLDN19TJP1OCLNTJP3TJP2CLDN3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O95500
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.75LoF Tolerant
pLIβ“˜
0.03Tolerant
Observed/Expected LoF0.86 [0.42–1.75]
RankingsWhere CLDN14 stands among ~20K protein-coding genes
  • #9,055of 20,598
    Most Researched48
  • #2,247of 5,498
    Most Pathogenic Variants19
  • #16,315of 17,882
    Most Constrained (LOEUF)1.75
Genes detectedCLDN14
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Claudins and hepatocellular carcinoma.
PMID: 38185042
Biomed Pharmacother Β· 2024
1.00
2
Genetic and molecular analysis of the CLDN14 gene in Moroccan family with non-syndromic hearing loss.
PMID: 24339547
Indian J Hum Genet Β· 2013
0.90
3
Common variants in CLDN14 are associated with differential excretion of magnesium over calcium in urine.
PMID: 27915449
Pflugers Arch Β· 2017
0.80
4
Genetics and calcium nephrolithiasis.
PMID: 20962745
Kidney Int Β· 2011
0.70
5
Pathophysiology-based treatment of urolithiasis.
PMID: 27539983
Int J Urol Β· 2017
0.60