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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MPZL2
myelin protein zero like 2
Chromosome 11 Β· 11q23.3
NCBI Gene: 10205Ensembl: ENSG00000149573.10HGNC: HGNC:3496UniProt: O60487
24PubMed Papers
21Diseases
0Drugs
16Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingplasma membranecell-cell adhesionhomophilic cell-cell adhesionhearing loss, autosomal recessivenonsyndromic genetic hearing lossNon-syndromic genetic deafnessdeafness
✦AI Summary

MPZL2 (myelin protein zero like 2) is a cell adhesion molecule that mediates homophilic cell-cell interactions 1. Located on chromosome 11, MPZL2 is widely expressed across multiple cell types within the inner ear, including outer hair cells and supporting cells like Deiters cells 12. Mutations in MPZL2 cause autosomal recessive deafness (DFNB111), the second leading genetic cause of mild-to-moderate hereditary hearing loss 1. The disease characteristically presents with progressive sensorineural hearing loss, with onset varying from congenital to young adulthood 3. A founder mutation c.220C>T (p.Gln74*) is prevalent in East Asian populations 43, while c.72delA is common in European populations 3. Clinically, MPZL2-related deafness is moderately progressive and symmetrical, affecting multiple cochlear cell types 13. Gene replacement therapy via AAV vectors successfully restores hearing function and structural integrity in mouse models, maintaining therapeutic effects for extended periods 12. Base editing approaches can correct specific MPZL2 mutations without inducing DNA double-strand breaks, showing promise for treatment 4. Beyond hearing, MPZL2 expression appears relevant to cancer biology as Eva1, a protein transcribed from MPZL2, shows broad tumor expression 5.

Sources cited
1
MPZL2 is the second leading cause of mild-to-moderate hereditary deafness, widely expressed in different inner ear cells including hair cells and Deiters cells; gene replacement therapy restores hearing function
PMID: 39241775
2
MPZL2 c.220C>T is an East Asian founder mutation causing DFNB111; adenine base editing can correct this mutation and restore hearing in humanized mouse models
PMID: 40764318
3
MPZL2 mutations cause autosomal recessive DFNB111 with moderate, progressive sensorineural hearing loss; c.220C>T is a hotspot variant in Chinese/East Asian populations
PMID: 38254107
4
MPZL2 p.Q74* is a founder allele in East Asians; gene supplementation with AAV-DJ-EF1Ξ±-hMPZL2 restores hearing and Deiter's cell survival for 24 weeks in knockout mice
PMID: 41058175
5
Eva1, transcribed from MPZL2, is a small surface protein highly expressed on various tumor cells, selected as a novel solid tumor-target antigen for CAR-T cell therapy
PMID: 40341026
6
MPZL2 variants cause mild-to-moderate progressive hearing loss; c.220C>T;p.Gln74Ter should be included in common deafness variant prescreening
PMID: 37390746
7
MPZL2 expression is associated with overall survival in AML patients with FLT3-ITD mutations
PMID: 35249471
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.70Strong
Non-syndromic genetic deafnessOpen Targets
0.37Weak
nonsyndromic genetic hearing lossOpen Targets
0.37Weak
deafnessOpen Targets
0.34Weak
SplenomegalyOpen Targets
0.34Weak
genetic disorderOpen Targets
0.34Weak
lung adenocarcinomaOpen Targets
0.33Weak
lung cancerOpen Targets
0.30Weak
hemolytic anemiaOpen Targets
0.27Weak
non-small cell lung carcinomaOpen Targets
0.22Weak
lung carcinomaOpen Targets
0.14Weak
Abruptio PlacentaeOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.06Suggestive
Blackfan-Diamond anemiaOpen Targets
0.05Suggestive
hearing lossOpen Targets
0.05Suggestive
Piebald trait - neurologic defectsOpen Targets
0.05Suggestive
piebald trait-neurologic defects syndromeOpen Targets
0.05Suggestive
Griscelli diseaseOpen Targets
0.05Suggestive
Deafness, autosomal recessive, 111UniProt
Pathogenic Variants16
NM_005797.4(MPZL2):c.72del (p.Ile24fs)Pathogenic
Hearing loss, autosomal recessive 111|not provided|MPZL2-related disorder|Hearing loss, autosomal recessive|Monogenic hearing loss
β˜…β˜…β˜†β˜†2026β†’ Residue 24
NM_005797.4(MPZL2):c.220C>T (p.Gln74Ter)Pathogenic
Hearing loss, autosomal recessive 111|not provided|Monogenic hearing loss
β˜…β˜…β˜†β˜†2026β†’ Residue 74
NM_005797.4(MPZL2):c.226-2A>TPathogenic
not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025
NM_005797.4(MPZL2):c.68del (p.Pro23fs)Pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜…β˜†β˜†2022β†’ Residue 23
NM_005797.4(MPZL2):c.463del (p.Ala155fs)Pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜…β˜†β˜†2022β†’ Residue 155
NM_005797.4(MPZL2):c.544C>T (p.Arg182Ter)Likely pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜…β˜†β˜†2022β†’ Residue 182
NM_005797.4(MPZL2):c.340C>T (p.Gln114Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 114
NM_005797.4(MPZL2):c.500dup (p.Ile168fs)Pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜†β˜†β˜†2025β†’ Residue 168
NM_005797.4(MPZL2):c.417del (p.Leu140fs)Likely pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜†β˜†β˜†2024β†’ Residue 140
NM_005797.4(MPZL2):c.280C>T (p.Arg94Trp)Likely pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜†β˜†β˜†2023β†’ Residue 94
NM_005797.4(MPZL2):c.161del (p.Pro54fs)Pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜†β˜†β˜†2023β†’ Residue 54
NM_005797.4(MPZL2):c.3G>T (p.Met1Ile)Likely pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜†β˜†β˜†2022β†’ Residue 1
NM_005797.4(MPZL2):c.319_320dup (p.Ile108fs)Likely pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜†β˜†β˜†2020β†’ Residue 108
NM_005797.4(MPZL2):c.58+1G>ALikely pathogenic
Hearing loss, autosomal recessive 111
β˜…β˜†β˜†β˜†
NM_005797.4(MPZL2):c.290G>A (p.Trp97Ter)Likely pathogenic
MPZL2-related disorder
β˜†β˜†β˜†β˜†2024β†’ Residue 97
NM_005797.4(MPZL2):c.226-1G>ALikely pathogenic
Hearing loss, autosomal recessive 111
β˜†β˜†β˜†β˜†2020
View on ClinVar β†—
Related Genes
DSC3Shared pathway50%CDH16Shared pathway50%DSG4Shared pathway40%IGSF11Shared pathway33%VSIG10L2Shared pathway33%CADM2Shared pathway33%
Tissue Expression6 tissues
Lung
100%
Liver
53%
Heart
27%
Brain
15%
Ovary
8%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
MPZL2DSC3CDH16DSG4IGSF11VSIG10L2CADM2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O60487
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.70LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.26 [0.94–1.70]
RankingsWhere MPZL2 stands among ~20K protein-coding genes
  • #13,243of 20,598
    Most Researched24
  • #2,424of 5,498
    Most Pathogenic Variants16
  • #16,117of 17,882
    Most Constrained (LOEUF)1.70
Genes detectedMPZL2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Hearing restoration by gene replacement therapy for a multisite-expressed gene in a mouse model of human DFNB111 deafness.
PMID: 39241775
Am J Hum Genet Β· 2024
1.00
2
Development and optimization of Eva1 (
PMID: 40341026
J Immunother Cancer Β· 2025
0.90
3
Establishment and evaluation cuproptosis-related gene signature for predicting the prognosis and immunotherapy response of hepatocellular carcinoma.
PMID: 40296031
Cancer Cell Int Β· 2025
0.80
4
PAM-flexible adenine base editing rescues hearing loss in a humanized MPZL2 mouse model harboring an East Asian founder mutation.
PMID: 40764318
Nat Commun Β· 2025
0.70
5
MPZL2-a common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population.
PMID: 38254107
BMC Med Genomics Β· 2024
0.60