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GeneE
9 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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GRXCR2
glutaredoxin and cysteine rich domain containing 2
Chromosome 5 Β· 5q32
NCBI Gene: 643226Ensembl: ENSG00000204928.3HGNC: HGNC:33862UniProt: A6NFK2
6PubMed Papers
21Diseases
0Drugs
7Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
sensory perception of soundmicrovillusstereocilium shaftstereocilium basehearing loss, autosomal recessivedeafnessbenign chondrogenic neoplasmNon-syndromic genetic deafness
✦AI Summary

GRXCR2 is a glutaredoxin and cysteine-rich domain protein essential for auditory function, localized to the base of stereocilia in cochlear hair cells 1. Its primary function is regulating stereocilia morphology through control of taperin localization; GRXCR2 forms a complex with taperin and restricts it to the stereocilia base, preventing its diffusion along the stereociliary length 1. In GRXCR2-deficient hair cells, taperin mislocalization leads to abnormally elongated and disorganized stereocilia that impair sound-induced mechanotransduction 1. GRXCR2 also interacts with CLIC5 at the stereociliary base; this interaction is crucial for normal hearing, particularly at higher frequencies 2. Mutations in GRXCR2 cause autosomal recessive nonsyndromic hearing loss (DFNB101), presenting as moderate-to-severe progressive deafness 3. Frameshift mutations produce unstable, mislocalized proteins resulting in loss-of-function 3. Significantly, reducing taperin expression levels can rescue stereocilia morphology and restore hearing in GRXCR2-deficient mice, suggesting potential therapeutic strategies 1 4. GRXCR2 mutations have been identified in multiple populations with hearing impairment, including Chinese Han and Cameroonian families 5 6.

Sources cited
1
GRXCR2 localizes to stereocilia base, forms complex with taperin, restricts taperin localization, and mutations cause stereocilia disorganization
PMID: 30380417
2
GRXCR2 is expressed during postnatal development and required for stereocilia bundle orientation and organization in cochlea and vestibular organs
PMID: 30157177
3
GRXCR2 mutations identified in Chinese Han families with nonsyndromic hearing loss
PMID: 32048449
4
Reducing taperin expression restores hearing and corrects stereocilia morphology in GRXCR2 null mice
PMID: 35752427
5
GRXCR2 N-terminus interacts with CLIC5 at stereociliary base, and this interaction is essential for normal hearing
PMID: 34026762
6
Frameshift mutation in GRXCR2 causes DFNB101 hearing loss; mutant protein is unstable and mislocalized
PMID: 24619944
7
GRXCR2 frameshift mutation identified in Cameroonian families with hearing impairment; mutation causes protein truncation and loss of zinc-finger domain
PMID: 33528103
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.60Moderate
deafnessOpen Targets
0.53Moderate
benign chondrogenic neoplasmOpen Targets
0.29Weak
Non-syndromic genetic deafnessOpen Targets
0.21Weak
nonsyndromic genetic hearing lossOpen Targets
0.18Weak
autosomal dominant nonsyndromic hearing lossOpen Targets
0.12Weak
amyotrophic lateral sclerosisOpen Targets
0.10Weak
celiac diseaseOpen Targets
0.10Suggestive
auditory neuropathy, autosomal dominant 3Open Targets
0.10Suggestive
autosomal recessive nonsyndromic hearing loss 86Open Targets
0.09Suggestive
hearing loss, autosomal dominant 88Open Targets
0.09Suggestive
hearing loss, autosomal dominant 89Open Targets
0.09Suggestive
autosomal recessive nonsyndromic hearing loss 1BOpen Targets
0.09Suggestive
autosomal dominant nonsyndromic hearing loss 17Open Targets
0.09Suggestive
autosomal dominant nonsyndromic hearing loss 7Open Targets
0.09Suggestive
autosomal recessive nonsyndromic hearing loss 102Open Targets
0.09Suggestive
deafness, aminoglycoside-inducedOpen Targets
0.09Suggestive
Mitochondrial non-syndromic sensorineural deafness with susceptibility to aminoglycoside exposureOpen Targets
0.09Suggestive
autosomal dominant nonsyndromic hearing loss 65Open Targets
0.09Suggestive
autosomal recessive nonsyndromic hearing loss 9Open Targets
0.08Suggestive
Deafness, autosomal recessive, 101UniProt
Pathogenic Variants7
NM_001080516.2(GRXCR2):c.247C>T (p.Gln83Ter)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 101
β˜…β˜…β˜†β˜†2025β†’ Residue 83
NM_001080516.2(GRXCR2):c.397C>T (p.Arg133Ter)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 101
β˜…β˜†β˜†β˜†2025β†’ Residue 133
NM_001080516.2(GRXCR2):c.88C>T (p.Arg30Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 101
β˜…β˜†β˜†β˜†2023β†’ Residue 30
NM_001080516.2(GRXCR2):c.100C>T (p.Gln34Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 34
NM_001080516.2(GRXCR2):c.463G>T (p.Glu155Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 155
NM_001080516.2(GRXCR2):c.323C>T (p.Ala108Val)Pathogenic
Hearing loss, autosomal recessive
β˜†β˜†β˜†β˜†2021β†’ Residue 108
NM_001080516.2(GRXCR2):c.714dup (p.Gly239fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 101
β˜†β˜†β˜†β˜†2014β†’ Residue 239
View on ClinVar β†—
Related Genes
ZNF354AShared pathway100%LRIG2Shared pathway100%LRIG1Shared pathway100%CLRN3Shared pathway100%LRIG3Shared pathway100%LOXHD1Shared pathway100%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
0%
Ovary
0%
Liver
0%
Brain
0%
Lung
0%
Gene Interaction Network
Click a node to explore
GRXCR2ZNF354ALRIG2LRIG1CLRN3LRIG3LOXHD1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt A6NFK2
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.35LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.94 [0.67–1.35]
RankingsWhere GRXCR2 stands among ~20K protein-coding genes
  • #18,091of 20,598
    Most Researched6
  • #3,277of 5,498
    Most Pathogenic Variants7
  • #14,155of 17,882
    Most Constrained (LOEUF)1.35
Genes detectedGRXCR2
Sources retrieved9 papers
Response timeβ€”
πŸ“„ Sources
9β–Ό
1
GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing.
PMID: 30380417
Cell Rep Β· 2018
1.00
2
Grxcr2 is required for stereocilia morphogenesis in the cochlea.
PMID: 30157177
PLoS One Β· 2018
0.89
3
Clinical and genetic study of 12 Chinese Han families with nonsyndromic deafness.
PMID: 32048449
Mol Genet Genomic Med Β· 2020
0.78
4
Reducing Taperin Expression Restores Hearing in Grxcr2 Mutant Mice.
PMID: 35752427
Neuroscience Β· 2022
0.67
5
N-Terminus of GRXCR2 Interacts With CLIC5 and Is Essential for Auditory Perception.
PMID: 34026762
Front Cell Dev Biol Β· 2021
0.56