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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.
GRXCR1
glutaredoxin and cysteine rich domain containing 1
Chromosome 4 Β· 4p13
NCBI Gene: 389207Ensembl: ENSG00000215203.3HGNC: HGNC:31673UniProt: A8MXD5
12PubMed Papers
21Diseases
0Drugs
17Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingsensory perception of soundvestibular receptor cell developmentinner ear receptor cell developmenthearing loss, autosomal recessivedeafnessRare genetic deafnessNon-syndromic genetic deafness
✦AI Summary

GRXCR1 encodes a 290 amino acid protein containing a glutaredoxin-like domain and a cysteine-rich C-terminal region that plays a critical role in stereocilia morphogenesis in inner ear hair cells 1. The protein localizes along the length of stereocilia, the actin-filament-rich mechanosensory structures essential for hearing and balance 1. GRXCR1 functions to regulate actin cytoskeletal architecture during stereocilia development, with loss of function resulting in abnormally thin and shortened stereocilia 1. Unlike its paralog GRXCR2, GRXCR1 is diffusely distributed throughout stereocilia and has distinct functions in stereocilia morphogenesis, affecting F-actin content and interacting with GRXCR2 2. The gene shows preferential expression in fetal cochlea 3. Mutations in GRXCR1 cause autosomal recessive nonsyndromic hearing loss (DFNB25), characterized by congenital moderate to profound hearing loss that can be progressive 34. Clinical presentations include sensorineural hearing loss with variable vestibular dysfunction, including dizziness and canal paralysis in some patients 4. Various mutation types have been identified, including splice-site, missense, nonsense, and deletion mutations across different populations 345.

Sources cited
1
GRXCR1 encodes a 290 amino acid protein with glutaredoxin-like and cysteine-rich domains, localizes to stereocilia, and regulates actin cytoskeletal architecture
PMID: 20137774
2
GRXCR1 has distinct functions from GRXCR2, is diffusely distributed in stereocilia, affects F-actin content, and interacts with GRXCR2
PMID: 34366792
3
GRXCR1 mutations cause DFNB25 autosomal recessive nonsyndromic hearing loss with preferential expression in fetal cochlea
PMID: 20137778
4
GRXCR1 mutations can cause progressive hearing loss and vestibular dysfunction including dizziness and canal paralysis
PMID: 25802247
5
Novel deletion mutations in GRXCR1 have been identified in congenital hearing loss cases
PMID: 37009772
Disease Associationsβ“˜21
hearing loss, autosomal recessiveOpen Targets
0.71Strong
deafnessOpen Targets
0.57Moderate
Rare genetic deafnessOpen Targets
0.41Moderate
Non-syndromic genetic deafnessOpen Targets
0.39Weak
hearing lossOpen Targets
0.37Weak
nonsyndromic genetic hearing lossOpen Targets
0.37Weak
malignant renal pelvis neoplasmOpen Targets
0.32Weak
alopecia areataOpen Targets
0.32Weak
cardiomyopathyOpen Targets
0.28Weak
glomerulonephritisOpen Targets
0.28Weak
Hearing impairmentOpen Targets
0.27Weak
alcohol drinkingOpen Targets
0.23Weak
connective tissue diseaseOpen Targets
0.23Weak
bone fractureOpen Targets
0.19Weak
gastric cancerOpen Targets
0.19Weak
genetic disorderOpen Targets
0.19Weak
HypocalcemiaOpen Targets
0.17Weak
ovarian neoplasmOpen Targets
0.17Weak
placenta praeviaOpen Targets
0.17Weak
trauma complicationOpen Targets
0.17Weak
Deafness, autosomal recessive, 25UniProt
Pathogenic Variants17
NM_001080476.3(GRXCR1):c.784C>T (p.Arg262Ter)Likely pathogenic
Rare genetic deafness|not provided|Monogenic hearing loss
β˜…β˜…β˜†β˜†2025β†’ Residue 262
NM_001080476.3(GRXCR1):c.628-9C>APathogenic
Autosomal recessive nonsyndromic hearing loss 25|not provided
β˜…β˜…β˜†β˜†2025
NM_001080476.3(GRXCR1):c.469G>T (p.Glu157Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 25|not provided|GRXCR1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 157
NM_001080476.3(GRXCR1):c.594_597dup (p.Val200fs)Pathogenic
Rare genetic deafness|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 200
NM_001080476.3(GRXCR1):c.79C>T (p.Arg27Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 25
β˜…β˜…β˜†β˜†2021β†’ Residue 27
NM_001080476.3(GRXCR1):c.568C>T (p.Arg190Ter)Pathogenic
GRXCR1-related disorder|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 190
NM_001080476.3(GRXCR1):c.672del (p.Asp225fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 25
β˜…β˜†β˜†β˜†2025β†’ Residue 225
NM_001080476.3(GRXCR1):c.181C>T (p.Gln61Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 25
β˜…β˜†β˜†β˜†2025β†’ Residue 61
NM_001080476.3(GRXCR1):c.385-2A>GPathogenic
Autosomal recessive nonsyndromic hearing loss 25
β˜…β˜†β˜†β˜†2024
NM_001080476.3(GRXCR1):c.550G>T (p.Glu184Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 25
β˜…β˜†β˜†β˜†2023β†’ Residue 184
NM_001080476.3(GRXCR1):c.668T>A (p.Leu223Gln)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 25
β˜…β˜†β˜†β˜†2023β†’ Residue 223
NC_000004.12:g.43030359AG[2]Pathogenic
not provided
β˜…β˜†β˜†β˜†2022
NM_001080476.3(GRXCR1):c.717T>A (p.Cys239Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 239
NM_001080476.3(GRXCR1):c.169del (p.Asp57fs)Likely pathogenic
GRXCR1-related disorder
β˜†β˜†β˜†β˜†2024β†’ Residue 57
NM_001080476.3(GRXCR1):c.457T>G (p.Phe153Val)Pathogenic
Autosomal recessive nonsyndromic hearing loss 25
β˜†β˜†β˜†β˜†2023β†’ Residue 153
NM_001080476.3(GRXCR1):c.655G>A (p.Glu219Lys)Pathogenic
Deafness|Hearing loss, autosomal recessive
β˜†β˜†β˜†β˜†2018β†’ Residue 219
NM_001080476.3(GRXCR1):c.229C>T (p.Gln77Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 25|Hearing loss, autosomal recessive
β˜†β˜†β˜†β˜†2018β†’ Residue 77
View on ClinVar β†—
Related Genes
EZRProtein interaction97%SERINC3Protein interaction89%GLRXProtein interaction84%CAP2Protein interaction83%CAP1Protein interaction83%TRIOBPProtein interaction83%
Tissue Expression6 tissues
Brain
100%
Heart
0%
Bone Marrow
0%
Ovary
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
GRXCR1EZRSERINC3GLRXCAP2CAP1TRIOBP
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt A8MXD5
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.38LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.98 [0.71–1.38]
RankingsWhere GRXCR1 stands among ~20K protein-coding genes
  • #16,469of 20,598
    Most Researched12
  • #2,375of 5,498
    Most Pathogenic Variants17
  • #14,354of 17,882
    Most Constrained (LOEUF)1.38
Genes detectedGRXCR1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A Novel Exon 2 Deletion Mutation in the
PMID: 37009772
Ann Otol Rhinol Laryngol Β· 2023
1.00
2
Grxcr2 is required for stereocilia morphogenesis in the cochlea.
PMID: 30157177
PLoS One Β· 2018
0.90
3
Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia.
PMID: 34366792
Front Cell Neurosci Β· 2021
0.80
4
Mutations in Grxcr1 are the basis for inner ear dysfunction in the pirouette mouse.
PMID: 20137774
Am J Hum Genet Β· 2010
0.70
5
Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal-recessive nonsyndromic hearing impairment.
PMID: 20137778
Am J Hum Genet Β· 2010
0.60