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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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MARVELD2
MARVEL domain containing 2
Chromosome 5 Β· 5q13.2
NCBI Gene: 153562Ensembl: ENSG00000152939.18HGNC: HGNC:26401UniProt: Q8N4S9
66PubMed Papers
21Diseases
0Drugs
39Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingestablishment of endothelial barriertricellular tight junctiontight junctionhearing loss, autosomal recessivedeafnessRare genetic deafnessNon-syndromic genetic deafness
✦AI Summary

MARVELD2 encodes tricellulin, a tricellular tight junction protein essential for epithelial barrier function. 1 The protein localizes to tricellular junctions where three epithelial cells meet, playing a critical role in sealing intercellular spaces. 2 In the inner ear, MARVELD2 is required for normal hearing by maintaining separation of endolymphatic and perilymphatic compartments and ensuring hair cell survival in the organ of Corti. 1 Loss of MARVELD2 function causes DFNB49, autosomal recessive non-syndromic hearing loss, representing approximately 1.5% of prelingual deafness in Pakistani populations and the second most common cause in Czech Roma. 1 Pathogenic variants include frameshift mutations and splice site alterations that impair protein stability and localization. 3 4 Beyond hearing, MARVELD2 mutations affect tissues with specialized barrier functions; mouse models exhibit additional defects in salivary glands, thyroid, and olfactory epithelium, though human syndromic manifestations remain unreported. 1 Recent evidence reveals MARVELD2's role in salivary gland barrier dysfunction in SjΓΆgren's syndrome, where tricellulin downregulation occurs via JAK/STAT1/miR-145 signaling. 5 MARVELD2 represents a promising candidate for vestibular disorder research given its cochlear and vestibular tissue expression. 6

Sources cited
1
MARVELD2 encodes tricellulin, a tricellular tight junction protein; causes DFNB49 hearing loss; ~1.5% of non-syndromic hearing loss in Pakistani families; mouse models show additional phenotypic effects in heart, salivary gland, thyroid, and olfactory epithelium
PMID: 25666562
2
Tricellulin localizes to tricellular tight junctions; tight junction expression is heterogenous across intestinal tract
PMID: 38925921
3
Frameshift MARVELD2 variant c.1058dup causes non-syndromic hearing loss; leads to early stop codon and loss of C-terminal domain; impairs barrier function and ion homeostasis in inner ear
PMID: 40244166
4
Novel compound heterozygous MARVELD2 variants (c.1331+1G>A, c.1325A>G, c.782G>A) cause autosomal recessive sensorineural hearing loss in Chinese families
PMID: 39078259
5
Tricellulin maintains salivary gland acinar epithelial barrier; MARVELD2 expression is reduced in SjΓΆgren's syndrome; JAK/STAT1/miR-145 axis mediates IFN-Ξ³-induced tricellulin downregulation
PMID: 40108118
6
MARVELD2 is prioritized candidate for vestibular disorder research; expressed in both cochlear and vestibular tissues
PMID: 41430327
7
MARVELD2 (tricellulin) expression is decreased in middle ear cholesteatoma epithelium; contributes to increased epithelial permeability
PMID: 25319490
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.73Strong
deafnessOpen Targets
0.62Moderate
Rare genetic deafnessOpen Targets
0.45Moderate
Non-syndromic genetic deafnessOpen Targets
0.38Weak
hearing lossOpen Targets
0.37Weak
nonsyndromic genetic hearing lossOpen Targets
0.37Weak
Abnormality of the earOpen Targets
0.34Weak
ear malformationOpen Targets
0.34Weak
Hearing impairmentOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
Ehlers-Danlos syndrome, progeroid typeOpen Targets
0.12Weak
Ehlers-Danlos syndrome, spondylodysplastic type, 2Open Targets
0.12Weak
multiple sclerosisOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.08Suggestive
colorectal cancerOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
synovial sarcomaOpen Targets
0.06Suggestive
autosomal dominant nonsyndromic hearing lossOpen Targets
0.06Suggestive
Down syndromeOpen Targets
0.06Suggestive
Deafness, autosomal recessive, 49UniProt
Pathogenic Variants39
NM_001038603.3(MARVELD2):c.1331+2T>CPathogenic
not provided|Hearing impairment|Autosomal recessive nonsyndromic hearing loss 49|Monogenic hearing loss
β˜…β˜…β˜†β˜†2025
NM_001038603.3(MARVELD2):c.1498C>T (p.Arg500Ter)Pathogenic
Rare genetic deafness|not provided|Autosomal recessive nonsyndromic hearing loss 49|Ear malformation
β˜…β˜…β˜†β˜†2025β†’ Residue 500
NM_001038603.3(MARVELD2):c.490C>T (p.Arg164Ter)Likely pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜…β˜†β˜†2023β†’ Residue 164
NM_001038603.3(MARVELD2):c.1183-1G>APathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜…β˜†β˜†2023
NM_001038603.3(MARVELD2):c.188C>A (p.Ser63Ter)Likely pathogenic
Rare genetic deafness|Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜…β˜†β˜†2022β†’ Residue 63
NM_001038603.3(MARVELD2):c.1331+1G>APathogenic
Autosomal recessive nonsyndromic hearing loss 49|Rare genetic deafness
β˜…β˜…β˜†β˜†2022
NM_001038603.3(MARVELD2):c.880_890del (p.Phe294fs)Likely pathogenic
not provided|Hearing impairment
β˜…β˜…β˜†β˜†2021β†’ Residue 294
NM_001038603.3(MARVELD2):c.111_114del (p.Glu38fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 38
NM_001038603.3(MARVELD2):c.1138C>T (p.Gln380Ter)Pathogenic
Hearing loss, autosomal recessive|Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 380
NM_001038603.3(MARVELD2):c.1363C>T (p.Arg455Ter)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 455
NM_001038603.3(MARVELD2):c.1512_1515del (p.Arg505fs)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 505
NM_001038603.3(MARVELD2):c.1578del (p.Glu527fs)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 527
NM_001038603.3(MARVELD2):c.719del (p.Gly240fs)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 240
NM_001038603.3(MARVELD2):c.802ATT[2] (p.Ile270del)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 270
NM_001038603.3(MARVELD2):c.1123dup (p.Arg375fs)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 375
NM_001038603.3(MARVELD2):c.1295del (p.His432fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 432
NM_001038603.3(MARVELD2):c.1332-1delPathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025
NM_001038603.3(MARVELD2):c.1374T>A (p.Tyr458Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 458
NM_001038603.3(MARVELD2):c.1399del (p.Ser467fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 467
NM_001038603.3(MARVELD2):c.1467del (p.Val489_Met490insTer)Pathogenic
Autosomal recessive nonsyndromic hearing loss 49
β˜…β˜†β˜†β˜†2025β†’ Residue 489
View on ClinVar β†—
Related Genes
AFDNProtein interaction99%TJP1Protein interaction99%MPDZProtein interaction99%CLDN1Protein interaction99%TJP2Protein interaction99%TJP3Protein interaction99%
Tissue Expression6 tissues
Liver
100%
Lung
28%
Brain
23%
Bone Marrow
10%
Heart
5%
Ovary
3%
Gene Interaction Network
Click a node to explore
MARVELD2AFDNTJP1MPDZCLDN1TJP2TJP3
PROTEIN STRUCTURE
Preparing viewer…
PDB5N7H Β· 2.20 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.99LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.75 [0.58–0.99]
RankingsWhere MARVELD2 stands among ~20K protein-coding genes
  • #7,084of 20,598
    Most Researched66
  • #1,569of 5,498
    Most Pathogenic Variants39
  • #9,553of 17,882
    Most Constrained (LOEUF)0.99
Genes detectedMARVELD2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A defective lysophosphatidic acid-autophagy axis increases miscarriage risk by restricting decidual macrophage residence.
PMID: 35220880
Autophagy Β· 2022
1.00
2
Molecular genetics of MARVELD2 and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss.
PMID: 25666562
Hum Genet Β· 2015
0.90
3
In focus in HCB.
PMID: 31897604
Histochem Cell Biol Β· 2020
0.80
4
Heterogenous Gene Expression of Bicellular and Tricellular Tight Junction-Sealing Components in the Human Intestinal Tract.
PMID: 38925921
Biol Pharm Bull Β· 2024
0.70
5
Bi-Allelic
PMID: 40244166
Int J Mol Sci Β· 2025
0.60