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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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POU4F3
POU class 4 homeobox 3
Chromosome 5 Β· 5q32
NCBI Gene: 5459Ensembl: ENSG00000091010.7HGNC: HGNC:9220UniProt: Q15319
46PubMed Papers
21Diseases
0Drugs
50Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of transcription by RNA polymerase IIRNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription activator activity, RNA polymerase II-specificcytoplasmautosomal dominant nonsyndromic hearing lossdeafnessneurodegenerative diseaseNon-syndromic genetic deafness
✦AI Summary

POU4F3 is a transcription factor essential for auditory hair cell development and survival. It functions as a transcriptional activator by binding to octamer motif sequences (5'-ATGCAAAT-3') in target gene regulatory regions 1. POU4F3 is required for terminal differentiation of hair cells in the inner ear and plays a crucial role in hair cell survival, as evidenced by its ability to directly regulate genes like Caprin-1 involved in cellular stress responses 1. The protein works synergistically with other transcription factors including Atoh1, Gfi1, and Six1 to promote hair cell regeneration and differentiation 23. Mutations in POU4F3 cause autosomal dominant non-syndromic deafness 15 (DFNA15), accounting for approximately 6.5% of dominant hearing loss cases in European populations 4. Recent therapeutic approaches have successfully used base editing to restore hearing function in DFNA15 mouse models, demonstrating near-complete hearing recovery 5. The gene's critical role in cochlear development and hair cell maintenance makes it a key target for understanding auditory system function and developing treatments for hereditary hearing loss.

Sources cited
1
POU4F3 acts as transcriptional activator binding octamer motifs and directly regulates Caprin-1
PMID: 21402877
2
POU4F3 works synergistically with Atoh1, Gfi1, and Six1 for hair cell regeneration
PMID: 38103445
3
POU4F3 can reprogram nonsensory cochlear cells to generate hair cell-like cells
PMID: 38266052
4
POU4F3 mutations account for 6.5% of dominant hearing loss cases in Europe
PMID: 35044523
5
Base editing of POU4F3 mutations restores hearing function in DFNA15 mouse models
PMID: 40968144
Disease Associationsβ“˜21
autosomal dominant nonsyndromic hearing lossOpen Targets
0.72Strong
deafnessOpen Targets
0.54Moderate
neurodegenerative diseaseOpen Targets
0.53Moderate
Non-syndromic genetic deafnessOpen Targets
0.39Weak
nonsyndromic genetic hearing lossOpen Targets
0.37Weak
Hearing impairmentOpen Targets
0.32Weak
hearing loss, autosomal recessiveOpen Targets
0.28Weak
Rare genetic deafnessOpen Targets
0.27Weak
injuryOpen Targets
0.24Weak
genetic disorderOpen Targets
0.19Weak
Congenital sensorineural hearing impairmentOpen Targets
0.11Weak
migraine disorderOpen Targets
0.10Weak
hearing loss, autosomal dominant 87Open Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.07Suggestive
hearing loss, autosomal dominant 80Open Targets
0.07Suggestive
hearing loss, autosomal dominant 85Open Targets
0.07Suggestive
X-linked nonsyndromic hearing lossOpen Targets
0.07Suggestive
hearing loss, autosomal dominant 75Open Targets
0.07Suggestive
hearing loss, autosomal dominant 86Open Targets
0.07Suggestive
peroxisome biogenesis disorder 4BOpen Targets
0.06Suggestive
Deafness, autosomal dominant, 15UniProt
Pathogenic Variants50
NM_002700.3(POU4F3):c.502del (p.Ala168fs)Pathogenic
not provided|Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜…β˜†β˜†2020β†’ Residue 168
NM_002700.3(POU4F3):c.282del (p.Val95fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 95
NM_002700.3(POU4F3):c.842T>A (p.Ile281Asn)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 281
NM_002700.3(POU4F3):c.97C>T (p.Arg33Ter)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 33
NM_002700.3(POU4F3):c.976A>G (p.Arg326Gly)Pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 326
NM_002700.3(POU4F3):c.592C>A (p.Arg198Ser)Pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 198
NM_002700.3(POU4F3):c.130_136del (p.Asn44fs)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 44
NM_002700.3(POU4F3):c.296_297dup (p.Pro100fs)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 100
NM_002700.3(POU4F3):c.371C>A (p.Ser124Ter)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 124
NM_002700.3(POU4F3):c.413C>A (p.Ser138Ter)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 138
NM_002700.3(POU4F3):c.592C>G (p.Arg198Gly)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 198
NM_002700.3(POU4F3):c.608_610dup (p.Val203_Thr204insMet)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 203
NM_002700.3(POU4F3):c.631G>C (p.Ala211Pro)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 211
NM_002700.3(POU4F3):c.671G>A (p.Ser224Asn)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2025β†’ Residue 224
NM_002700.3(POU4F3):c.488del (p.His163fs)Likely pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2024β†’ Residue 163
NM_002700.3(POU4F3):c.823_842del (p.Lys275fs)Pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2024β†’ Residue 275
NM_002700.3(POU4F3):c.218del (p.Pro73fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 73
NM_002700.3(POU4F3):c.904G>T (p.Glu302Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 302
NM_002700.3(POU4F3):c.414_418del (p.Val139fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 139
NM_002700.3(POU4F3):c.564dup (p.Ala189fs)Pathogenic
Autosomal dominant nonsyndromic hearing loss 15
β˜…β˜†β˜†β˜†2023β†’ Residue 189
View on ClinVar β†—
Related Genes
ATOH1Protein interaction91%GFI1Protein interaction91%MYO7AProtein interaction82%CABP4Shared pathway67%CABP2Shared pathway67%GRXCR2Shared pathway50%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
23%
Ovary
15%
Lung
8%
Heart
0%
Liver
0%
Gene Interaction Network
Click a node to explore
POU4F3ATOH1GFI1MYO7ACABP4CABP2GRXCR2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q15319
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.56Moderately Constrained
pLIβ“˜
0.91Intolerant
Observed/Expected LoF0.30 [0.17–0.56]
RankingsWhere POU4F3 stands among ~20K protein-coding genes
  • #9,365of 20,598
    Most Researched46
  • #1,341of 5,498
    Most Pathogenic Variants50 Β· top quartile
  • #3,699of 17,882
    Most Constrained (LOEUF)0.56 Β· top quartile
Genes detectedPOU4F3
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Combinatorial Atoh1, Gfi1, Pou4f3, and Six1 gene transfer induces hair cell regeneration in the flat epithelium of mature guinea pigs.
PMID: 38103445
Hear Res Β· 2024
1.00
2
Genetic etiology of non-syndromic hearing loss in Europe.
PMID: 35044523
Hum Genet Β· 2022
0.90
3
Non-syndromic autosomal-dominant deafness.
PMID: 12123480
Clin Genet Β· 2002
0.80
4
Recent advances in molecular studies on cochlear development and regeneration.
PMID: 37356371
Curr Opin Neurobiol Β· 2023
0.70
5
Caprin-1 is a target of the deafness gene Pou4f3 and is recruited to stress granules in cochlear hair cells in response to ototoxic damage.
PMID: 21402877
J Cell Sci Β· 2011
0.60