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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.
WHRN
whirlin
Chromosome 9 Β· 9q32
NCBI Gene: 25861Ensembl: ENSG00000095397.18HGNC: HGNC:16361UniProt: A0A669KBJ1
45PubMed Papers
22Diseases
0Drugs
55Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
retina homeostasissensory perception of soundcytoplasmprotein bindingUsher syndrome type 2Dautosomal recessive nonsyndromic hearing loss 31Usher syndromedeafness
✦AI Summary

WHRN (whirlin) is a cytoskeletal scaffold protein essential for hearing and vision, functioning as a core component of the ankle link complex (ALC) in the inner ear and periciliary membrane complex in the retina 1. In cochlear hair cells, WHRN is necessary for elongation and maintenance of stereocilia and organization of the hair bundle ankle region, which mechanically connects stereocilia 2. WHRN orchestrates ALC assembly with USH2A, ADGRV1, and PDZD7 through liquid-liquid phase separation, a process disrupted by deafness-associated mutations 2. The protein's phosphorylation state, regulated by ADGRV1-mediated cAMP-PKA signaling, controls USH2A stability through WDSUB1-dependent ubiquitination 3. In photoreceptors, WHRN maintains the periciliary membrane complex regulating intracellular protein transport 4. Pathogenic WHRN variants cause both non-syndromic deafness and Usher syndrome type 2 (USH2), the most common cause of deaf-blindness 1, affecting approximately 1 in 10,000 individuals worldwide 1. Gene therapy and cell-based therapeutic approaches for USH2 are under investigation 4. WHRN mutations impair stereocilia architecture and mechanoelectrical transduction, ultimately resulting in hearing loss and progressive retinal degeneration 3.

Sources cited
1
WHRN is a USH2 gene; Usher syndrome is the most common cause of deaf-blindness affecting ~400,000 people worldwide with 1/10,000 prevalence
PMID: 35353227
2
WHRN orchestrates ankle link complex assembly through liquid-liquid phase separation with ADGRV1, USH2A, and PDZD7; deafness mutations weaken this interaction
PMID: 36964137
3
ADGRV1 inhibits WHRN phosphorylation through cAMP-PKA signaling, regulating USH2A stability via WDSUB1-dependent ubiquitination
PMID: 37066759
4
WHRN mutations cause USH2; USH2A is the most frequently mutated gene explaining 50% of cases; therapeutic approaches are under development
PMID: 34331125
5
WHRN variants cause non-syndromic hearing loss and Usher syndrome type II
PMID: 37924449
Disease Associationsβ“˜22
Usher syndrome type 2DOpen Targets
0.71Strong
autosomal recessive nonsyndromic hearing loss 31Open Targets
0.67Moderate
Usher syndromeOpen Targets
0.57Moderate
deafnessOpen Targets
0.51Moderate
hearing loss, autosomal recessiveOpen Targets
0.50Moderate
Rare genetic deafnessOpen Targets
0.43Moderate
Usher syndrome type 2Open Targets
0.37Weak
hearing lossOpen Targets
0.37Weak
eye diseaseOpen Targets
0.37Weak
skull disorderOpen Targets
0.28Weak
type 2 diabetes mellitusOpen Targets
0.27Weak
ocular hypotensionOpen Targets
0.27Weak
Aland island eye diseaseOpen Targets
0.26Weak
skin diseaseOpen Targets
0.25Weak
Abnormality of the liverOpen Targets
0.25Weak
metabolic syndromeOpen Targets
0.25Weak
Abnormality of the skeletal systemOpen Targets
0.24Weak
diabetes mellitusOpen Targets
0.22Weak
diabetic ketoacidosisOpen Targets
0.22Weak
nervous system diseaseOpen Targets
0.22Weak
Deafness, autosomal recessive, 31UniProt
Usher syndrome 2DUniProt
Pathogenic Variants55
NM_015404.4(WHRN):c.1203+2T>CLikely pathogenic
not provided
β˜…β˜…β˜†β˜†2026
NM_015404.4(WHRN):c.1417-1G>APathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 31;Usher syndrome type 2D
β˜…β˜…β˜†β˜†2026
NM_015404.4(WHRN):c.737del (p.Pro246fs)Pathogenic
Usher syndrome type 2D|not provided|Usher syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 246
NM_015404.4(WHRN):c.856dup (p.Asp286fs)Pathogenic
not provided|Usher syndrome type 2D;Autosomal recessive nonsyndromic hearing loss 31
β˜…β˜…β˜†β˜†2025β†’ Residue 286
NM_015404.4(WHRN):c.2332C>T (p.Arg778Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 31|not provided|Usher syndrome|Autosomal recessive nonsyndromic hearing loss 31;Usher syndrome type 2D
β˜…β˜…β˜†β˜†2025β†’ Residue 778
NM_015404.4(WHRN):c.1122G>A (p.Trp374Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 374
NM_015404.4(WHRN):c.559C>T (p.Gln187Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 187
NM_015404.4(WHRN):c.23_26dup (p.Ser11fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 11
NM_015404.4(WHRN):c.915C>A (p.Tyr305Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 305
NM_015404.4(WHRN):c.331_334dup (p.Glu112fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 112
NM_015404.4(WHRN):c.1563del (p.Tyr522fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 522
NM_015404.4(WHRN):c.838-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_015404.4(WHRN):c.1285C>T (p.Gln429Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 429
NM_015404.4(WHRN):c.1626+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_015404.4(WHRN):c.327C>A (p.Tyr109Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 109
NM_015404.4(WHRN):c.2430_2445del (p.Glu811fs)Pathogenic
Autosomal recessive nonsyndromic hearing loss 31
β˜…β˜†β˜†β˜†2025β†’ Residue 811
NM_015404.4(WHRN):c.2426T>C (p.Leu809Pro)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 31
β˜…β˜†β˜†β˜†2025β†’ Residue 809
NM_015404.4(WHRN):c.26C>A (p.Ser9Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 31
β˜…β˜†β˜†β˜†2025β†’ Residue 9
NM_015404.4(WHRN):c.1584dup (p.Thr529fs)Pathogenic
Usher syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 529
NM_015404.4(WHRN):c.366C>A (p.Tyr122Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 122
View on ClinVar β†—
Related Genes
RPGRProtein interaction100%PCDH15Protein interaction99%EPS8L2Protein interaction95%CIB2Protein interaction95%GPSM2Protein interaction95%MSNProtein interaction94%
Tissue Expression6 tissues
Ovary
100%
Brain
40%
Bone Marrow
29%
Liver
26%
Lung
12%
Heart
5%
Gene Interaction Network
Click a node to explore
WHRNRPGRPCDH15EPS8L2CIB2GPSM2MSN
PROTEIN STRUCTURE
Preparing viewer…
PDB6KZ1 Β· 1.69 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.81LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.62 [0.48–0.81]
RankingsWhere WHRN stands among ~20K protein-coding genes
  • #9,548of 20,598
    Most Researched45
  • #1,249of 5,498
    Most Pathogenic Variants55 Β· top quartile
  • #6,773of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedWHRN
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.
PMID: 22135276
J Med Genet Β· 2012
1.00
2
The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification.
PMID: 35353227
Hum Genet Β· 2022
0.90
3
Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.
PMID: 37066759
Adv Sci (Weinh) Β· 2023
0.80
4
Temporal and spatial assembly of inner ear hair cell ankle link condensate through phase separation.
PMID: 36964137
Nat Commun Β· 2023
0.70
5
Genetics, pathogenesis and therapeutic developments for Usher syndrome type 2.
PMID: 34331125
Hum Genet Β· 2022
0.60