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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
ESPN
espin
Chromosome 1 Β· 1p36.31
NCBI Gene: 83715Ensembl: ENSG00000187017.18HGNC: HGNC:13281UniProt: B1AK53
29PubMed Papers
22Diseases
0Drugs
26Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
microvillusmicrovillar actin bundle assemblystereociliumfilamentous actinhearing loss, autosomal recessiveUsher syndrome type 1Usher syndrome, type 1Mneurodegenerative disease
✦AI Summary

ESPN encodes espin, a multifunctional actin-bundling protein essential for inner ear mechanotransduction. ESPN regulates the organization, dynamics, and signaling of actin filament-rich microvilli in sensory cells 1. The protein is required for assembly and stabilization of stereociliary parallel actin bundles, playing a crucial role in formation and maintenance of hair cell stereocilia 1. In extrastriolar hair cells, ESPN is necessary for targeting MYO3B to stereocilia tips and regulating stereocilia diameter and staircase formation. ESPN promotes actin elongation within stereocilia, directly supporting mechanotransduction function 1. Pathogenic ESPN variants cause autosomal recessive deafness (DFNB36) with or without vestibular involvement, and have been associated with Usher syndrome type 1M, a syndromic form combining progressive hearing loss with retinitis pigmentosa. The protein's role in actin bundle organization makes it critical for the structural and functional integrity of sensory organelles. Mutations disrupting ESPN function impair stereocilia morphogenesis and mechanotransduction, leading to sensorineural hearing loss across the spectrum from early-onset profound deafness to progressive hearing impairment.

Sources cited
1
ESPN regulates organization, dimension, dynamics and signaling of actin filament-rich microvilli; involved in actin elongation in stereocilia
PMID: 29572253
⚠Limited data available β€” This gene has 1 indexed publication. Summary and analysis may be incomplete.
Disease Associationsβ“˜22
hearing loss, autosomal recessiveOpen Targets
0.70Strong
Usher syndrome type 1Open Targets
0.46Moderate
Usher syndrome, type 1MOpen Targets
0.40Weak
neurodegenerative diseaseOpen Targets
0.37Weak
Non-syndromic genetic deafnessOpen Targets
0.37Weak
nonsyndromic genetic hearing lossOpen Targets
0.37Weak
Rare genetic deafnessOpen Targets
0.33Weak
Retinal dystrophyOpen Targets
0.32Weak
deafnessOpen Targets
0.28Weak
Sensorineural hearing impairmentOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
multiple sclerosisOpen Targets
0.19Weak
sensorineural hearing lossOpen Targets
0.15Weak
optic atrophyOpen Targets
0.14Weak
cellulitisOpen Targets
0.13Weak
poisoningOpen Targets
0.10Weak
response to antibioticOpen Targets
0.10Weak
melanomaOpen Targets
0.08Suggestive
autosomal recessive nonsyndromic hearing loss 9Open Targets
0.07Suggestive
autosomal dominant nonsyndromic hearing lossOpen Targets
0.07Suggestive
Deafness, autosomal recessive, 36, with or without vestibular involvementUniProt
Usher syndrome 1MUniProt
Pathogenic Variants26
NM_031475.3(ESPN):c.1464+1G>ALikely pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜…β˜†β˜†2025
NM_031475.3(ESPN):c.489-2A>GPathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2025
NM_031475.3(ESPN):c.487_488+2delLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_031475.3(ESPN):c.1995_2056del (p.Lys666fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2025β†’ Residue 666
NM_031475.3(ESPN):c.1916-1G>APathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2025
NM_031475.3(ESPN):c.2398del (p.Glu800fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 800
NM_031475.3(ESPN):c.2539AAG[1] (p.Lys848del)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 36|DEAFNESS, AUTOSOMAL DOMINANT 91
β˜…β˜†β˜†β˜†2023β†’ Residue 848
NM_031475.3(ESPN):c.1649_1665del (p.Arg550fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2023β†’ Residue 550
NM_031475.3(ESPN):c.1972G>A (p.Glu658Lys)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2023β†’ Residue 658
NM_031475.3(ESPN):c.2496C>G (p.Tyr832Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2023β†’ Residue 832
NM_031475.3(ESPN):c.244dup (p.His82fs)Likely pathogenic
Rare genetic deafness
β˜…β˜†β˜†β˜†2022β†’ Residue 82
NM_031475.3(ESPN):c.677del (p.Val226fs)Likely pathogenic
Rare genetic deafness
β˜…β˜†β˜†β˜†2022β†’ Residue 226
NM_031475.3(ESPN):c.2524C>T (p.Arg842Ter)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2022β†’ Residue 842
NM_031475.3(ESPN):c.2081_2082del (p.Ser694fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2020β†’ Residue 694
NM_031475.3(ESPN):c.1916-1G>CPathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2020
NM_031475.3(ESPN):c.2446G>T (p.Glu816Ter)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 36
β˜…β˜†β˜†β˜†2018β†’ Residue 816
NM_031475.3(ESPN):c.292C>T (p.Gln98Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 98
NM_031475.3(ESPN):c.264G>A (p.Trp88Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 88
NM_031475.3(ESPN):c.2369_2386del (p.Arg790_Arg795del)Pathogenic
Usher syndrome type 1|Usher syndrome, type 1M
β˜…β˜†β˜†β˜†2017β†’ Residue 790
NM_031475.3(ESPN):c.1464+2T>GLikely pathogenic
Retinal dystrophy
β˜†β˜†β˜†β˜†2022
View on ClinVar β†—
Related Genes
LIMD2Shared pathway100%MSNProtein interaction94%EPS8Protein interaction93%GSNProtein interaction93%MPP1Protein interaction93%CASKProtein interaction93%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
50%
Brain
3%
Lung
1%
Heart
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
ESPNLIMD2MSNEPS8GSNMPP1CASK
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt B1AK53
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.31LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.06 [0.87–1.31]
RankingsWhere ESPN stands among ~20K protein-coding genes
  • #12,138of 20,598
    Most Researched29
  • #1,954of 5,498
    Most Pathogenic Variants26
  • #13,753of 17,882
    Most Constrained (LOEUF)1.31
Genes detectedESPN
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.
PMID: 29377879
Nat Rev Endocrinol Β· 2018
1.00
2
Dent disease: clinical practice recommendations.
PMID: 39794284
Nephrol Dial Transplant Β· 2025
0.90
3
Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group.
PMID: 33514942
Nat Rev Nephrol Β· 2021
0.80
4
Diagnosis, management and treatment of the Alport syndrome - 2024 guideline on behalf of ERKNet, ERA and ESPN.
PMID: 39673454
Nephrol Dial Transplant Β· 2025
0.70
5
Effect of Early vs Late Supplemental Parenteral Nutrition in Patients Undergoing Abdominal Surgery: A Randomized Clinical Trial.
PMID: 35293973
JAMA Surg Β· 2022
0.60