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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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MSRB3
methionine sulfoxide reductase B3
Chromosome 12 Β· 12q14.3
NCBI Gene: 253827Ensembl: ENSG00000174099.13HGNC: HGNC:27375UniProt: Q8IXL7
50PubMed Papers
21Diseases
0Drugs
10Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingzinc ion bindingpeptide-methionine (R)-S-oxide reductase activityprotein repairhearing loss, autosomal recessivedeafnessatrial fibrillationSnoring
✦AI Summary

MSRB3 is a methionine sulfoxide reductase that catalyzes the stereospecific reduction of methionine sulfoxide to methionine, functioning as a critical antioxidant enzyme in multiple cellular compartments 1. The protein localizes to the endoplasmic reticulum via an N-terminal signal sequence and contains redox-active cysteines that shuttle oxidizing equivalents during catalysis, coupling MSRB3 activity to dithiol-disulfide exchange reactions in the secretory pathway 1. MSRB3 protects cells from oxidative damage by reducing intracellular reactive oxygen species and maintaining actin redox dynamics 23. Loss of MSRB3 function causes autosomal recessive prelingual deafness (DFNB74), involving profound hearing loss accompanied by stereocilia bundle abnormalities, cuticular plate degeneration, and hair cell apoptosis 24. The disease-causing mechanism involves compromised actin repolymerization capability, as pathogenic variants like p.Cys89Gly cannot repolymerize oxidized actin, leading to altered actin redox ratios in inner ear sensory cells 2. Beyond auditory function, MSRB3 modulates mitochondrial oxidative phosphorylation and protects cardiomyocytes from hypoxia-induced ferroptosis 3, while also regulating endoplasmic reticulum stress-dependent apoptosis in cancer cells 5. These findings establish MSRB3 as essential for maintaining redox homeostasis in specialized sensory and metabolically active tissues.

Sources cited
1
MSRB3 structure, ER localization, active site mechanism, and redox-active cysteines
PMID: 32517586
2
MSRB3 antioxidant function in actin redox dynamics, stereocilia structure, hair cell integrity, and DFNB74 pathogenesis
PMID: 40827380
3
MSRB3 role in mitochondrial oxidative phosphorylation and cardiomyocyte ferroptosis protection
PMID: 40743621
4
MSRB3 involvement in auditory system development, otolith formation, hair cell apoptosis, and DFNB74
PMID: 26505252
5
MSRB3 function in endoplasmic reticulum stress-induced apoptosis and calcium homeostasis
PMID: 28389299
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.65Moderate
deafnessOpen Targets
0.50Moderate
atrial fibrillationOpen Targets
0.42Moderate
SnoringOpen Targets
0.41Moderate
sleep apneaOpen Targets
0.41Moderate
obstructive sleep apneaOpen Targets
0.38Weak
odontogenesisOpen Targets
0.38Weak
hearing lossOpen Targets
0.37Weak
Non-syndromic genetic deafnessOpen Targets
0.37Weak
nonsyndromic genetic hearing lossOpen Targets
0.37Weak
diverticular diseaseOpen Targets
0.36Weak
risk-taking behaviourOpen Targets
0.32Weak
alcohol drinkingOpen Targets
0.31Weak
upper respiratory tract disorderOpen Targets
0.31Weak
tooth eruptionOpen Targets
0.30Weak
portal hypertensionOpen Targets
0.30Weak
tonsillitisOpen Targets
0.30Weak
Abnormality of the skeletal systemOpen Targets
0.29Weak
facial morphologyOpen Targets
0.28Weak
Rare genetic deafnessOpen Targets
0.27Weak
Deafness, autosomal recessive, 74UniProt
Pathogenic Variants10
NM_001031679.3(MSRB3):c.-147T>GLikely pathogenic
Autosomal recessive nonsyndromic hearing loss 74
β˜…β˜…β˜†β˜†2024
NM_001031679.3(MSRB3):c.292G>T (p.Gly98Cys)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 74
β˜…β˜†β˜†β˜†2025β†’ Residue 98
NM_001031679.3(MSRB3):c.449dup (p.Tyr150Ter)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 74
β˜…β˜†β˜†β˜†2025β†’ Residue 150
NM_001031679.3(MSRB3):c.293-2A>GLikely pathogenic
Autosomal recessive nonsyndromic hearing loss 74
β˜…β˜†β˜†β˜†2023
NM_001031679.3(MSRB3):c.185+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2021
NM_001031679.3(MSRB3):c.264-1G>ALikely pathogenic
Rare genetic deafness|Hearing loss
β˜…β˜†β˜†β˜†2015
NM_001031679.3(MSRB3):c.244T>G (p.Cys82Gly)Pathogenic
Autosomal recessive nonsyndromic hearing loss 74|Hearing loss, autosomal recessive
β˜…β˜†β˜†β˜†β†’ Residue 82
NM_001031679.3(MSRB3):c.391-1G>APathogenic
Autosomal recessive nonsyndromic hearing loss 74
β˜…β˜†β˜†β˜†
NM_001031679.3(MSRB3):c.55C>T (p.Arg19Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 74
β˜†β˜†β˜†β˜†2011β†’ Residue 19
NM_001031679.3(MSRB3):c.406G>A (p.Gly136Arg)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 74
β˜†β˜†β˜†β˜†β†’ Residue 136
View on ClinVar β†—
Related Genes
MSRAProtein interaction77%MSRB2Shared pathway67%PCMT1Shared pathway50%TLDC2Shared pathway50%NCOA7Shared pathway50%OXR1Shared pathway50%
Tissue Expression6 tissues
Heart
100%
Lung
26%
Bone Marrow
16%
Ovary
10%
Brain
5%
Liver
2%
Gene Interaction Network
Click a node to explore
MSRB3MSRAMSRB2PCMT1TLDC2NCOA7OXR1
PROTEIN STRUCTURE
Preparing viewer…
PDB6QA0 Β· 1.71 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.96LoF Tolerant
pLIβ“˜
0.08Tolerant
Observed/Expected LoF0.51 [0.29–0.96]
RankingsWhere MSRB3 stands among ~20K protein-coding genes
  • #8,845of 20,598
    Most Researched50
  • #2,874of 5,498
    Most Pathogenic Variants10
  • #9,059of 17,882
    Most Constrained (LOEUF)0.96
Genes detectedMSRB3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain.
PMID: 30448975
J Anesth Β· 2019
1.00
2
Structure and Electron-Transfer Pathway of the Human Methionine Sulfoxide Reductase MsrB3.
PMID: 32517586
Antioxid Redox Signal Β· 2020
0.90
3
MSRB3 antioxidant activity is necessary for inner ear cuticular plate structure and hair bundle integrity.
PMID: 40827380
Dis Model Mech Β· 2025
0.80
4
The Lipid Droplet Knowledge Portal: A resource for systematic analyses of lipid droplet biology.
PMID: 35134345
Dev Cell Β· 2022
0.70
5
MsrB3 deficiency induces cancer cell apoptosis through p53-independent and ER stress-dependent pathways.
PMID: 28389299
Arch Biochem Biophys Β· 2017
0.60