• 30
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
WHRN (HGNC:16361) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
whirlin
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
DFNB31
Alias symbols
CIP98, USH2D, PDZD7B
%HI
38.98(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0(Read more about gnomAD pLI score)
LOEUF
0.67(Read more about gnomAD LOEUF score)
Cytoband
9q32
Genomic Coordinates
GRCh37/hg19: chr9:117164360-117267753 NCBI Ensembl UCSC
GRCh38/hg38: chr9:114402080-114505473 NCBI Ensembl UCSC
MANE Select Transcript
NM_015404.4 ENST00000362057.4 (Read more about MANE Select)
Function
Involved in hearing and vision as member of the USH2 complex. Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear. Involved in the maintenance of the hair bundle ankle region, which connects stereocilia in cochlear hair cells of the inner ear. In retina photoreceptors, required for the maintenance of periciliary membrane complex that seems to play a role in regulating intracellular protein transport. {ECO:0000250|UniProtKB:Q80V... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-26477
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Gene Associated with Autosomal Recessive Phenotype (30)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
08/22/2016

Haploinsufficiency (HI) Score Details

HI Score:
30
HI Evidence Strength:
Gene Associated with Autosomal Recessive Phenotype (Disclaimer)
HI Disease:
  • Deafness, autosomal recessive 31 Monarch
HI Evidence:
  • PUBMED: 12833159
    Mburu et al. 2003 identified a consanguineous family from Jordan with 5 autosomal recessive segregations with profound prelingual deafness (6 affected, 11 unaffected). The variant was NM_015404.3:c.2332C>T (p.Arg778Ter) which causes a stop codon in exon 10/12 and therefore leads to absent or truncated protein.
  • PUBMED: 15841483
    Tilili et al. 2005 identified a consanguineous family with profound prelingual deafness. The NM_015404.3:c.2423delG (p.Gly808fsX12) variant segregated with disease 3 times. Of note, this variant occurs in the second to last exon (11/12) though the stop codon that it produces does occur more than 50 bp from the final intron. It is unclear as to whether the product of this transcript will undergo nonsense mediated decay. However, this variant still provides support for this gene being associated with autosomal recessive prelingual profound deafness.
HI Evidence Comments:
There have been 2 families with autosomal recessive nonsyndromic profound prelingual deafness associated with loss of function variants segregating in WHRN. There have also been experimental studies conducted by Ebrahim et al. 2016 and Zou et al. 2014. Ebrahim 2016 generated a mouse model, Whrn which have a spontaneous deletion including exons 6-10 of the gene. The mice are profoundly deaf and exhibit headbobbing and circling characteristics of vestibular dysfunction. These mice also have abnormally short inner hair cells and outer hair cells (OHC) have irregular spacing. Whrn (tm1b/tm1b) mice have an exon 4 deletion and cassette including lacZ inserted into intron 3, and do not exhibit vestibular dysfunction. The (tm1b/tm1b) mice have OHC phenotype but not the shortened stereocilia. Zou 2014 found that WHRN colocalizes with PDZD7 at the base of hair bundles and that knockout of PDZD7 seemed to prevent WHRN localization. PDZD7 is associated with autosomal recessive hearing loss as well. In summary, WHRN is associated with autosomal recessive nonsyndromic profound prelingual sensorineural deafness. Variation in WHRN has been reported in individuals with Usher Syndrome 2 (USH2) and ARNSHL. Furthermore, the association between WHRN and USH2 has been expert reviewed by the ClinGen Hearing Loss Working Group and classified as DEFINITIVE. However, the overall evidence that WHRN, when altered, causes ARNSHL was classified as MODERATE after primary curation.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
There has not been a distinct phenotype associated with triplosensitivity of WHRN.

Genomic View

Select assembly: (NC_000009.11) (NC_000009.12)