DFNB31

WHRN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1UEZ, 1UF1, 1UFX
Identifiers
Aliases	WHRN , CIP98, PDZD7B, USH2D, WI, DFNB31, whirlin, Whirin
External IDs	OMIM: 607928 MGI: 2682003 HomoloGene: 18739 GeneCards: WHRN
Gene location (Human) Chr. Chromosome 9 (human) [1] Band 9q32 Start 114,402,080 bp [1] End 114,505,473 bp [1]
Gene location (Mouse) Chr. Chromosome 4 (mouse) [2] Band 4 B3|4 33.97 cM Start 63,333,147 bp [2] End 63,414,228 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Left adrenal gland pituitary gland right uterine tube anterior pituitary canal of the cervix spleen gastric mucosa oocyte inferior ganglion of vagus nerve substantia nigra Top expressed in interventricular septum visual cortex thymus superior frontal gyrus cerebellar cortex otolith organ utricle lip oocyte secondary oocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding protein homodimerization activity protein heterodimerization activity Cellular component cytoplasm growth cone cell projection stereocilium photoreceptor inner segment stereocilia ankle link stereocilia ankle link complex actin filament cilium photoreceptor connecting cilium stereocilium bundle stereocilium tip ciliary basal body periciliary membrane compartment USH2 complex plasma membrane neuronal cell body cell junction synapse Biological process retina homeostasis sensory perception of light stimulus sensory perception of sound inner ear receptor cell stereocilium organization positive regulation of gene expression cerebellar Purkinje cell layer formation establishment of protein localization auditory receptor cell stereocilium organization paranodal junction maintenance detection of mechanical stimulus involved in sensory perception of sound Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 25861 73750 Ensembl ENSG00000095397 ENSMUSG00000039137 UniProt Q9P202 Q80VW5 RefSeq (mRNA) NM_001083885 NM_001173425 NM_015404 NM_001346890 NM_001008791 NM_001008792 NM_001008793 NM_001008794 NM_001008795 NM_001008796 NM_001008797 NM_001008798 NM_001276371 NM_028640 RefSeq (protein) NP_001077354 NP_001166896 NP_001333819 NP_056219 NP_001008791 NP_001008792 NP_001008793 NP_001263300 NP_082916 Location (UCSC) Chr 9: 114.4 – 114.51 Mb Chr 4: 63.33 – 63.41 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Whirlin is a protein that in humans is encoded by the DFNB31 gene. ^{[5] [6] [7]}

In rat brain, WHRN interacts with a calmodulin-dependent serine kinase, CASK, and may be involved in the formation of scaffolding protein complexes that facilitate synaptic transmission in the central nervous system (CNS). ^[8] Mutations in this gene, also known as WHRN, cause autosomal recessive deafness. ^[7]

Model organisms

Whrn mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Abnormal [9]
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Abnormal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
All tests and analysis from [10] [11]

Model organisms have been used in the study of WHRN function. A conditional knockout mouse line, called Whrn^{tm1a(EUCOMM)Wtsi [12] [13]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. ^{[14] [15] [16]}

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. ^{[10] [17]} Twenty tests were carried out on mutant mice and two significant abnormalities were observed. ^[10] Whrn^{tm1a(EUCOMM)Wtsi} homozygote mice show a moderate to severe hearing loss at 14 weeks. Female homozygous mutant animals also displayed an increased thermal nociceptive threshold in a hot plate test. ^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000095397 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039137 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Mburu P, Mustapha M, Varela A, Weil D, El-Amraoui A, Holme RH, Rump A, Hardisty RE, Blanchard S, Coimbra RS, Perfettini I, Parkinson N, Mallon AM, Glenister P, Rogers MJ, Paige AJ, Moir L, Clay J, Rosenthal A, Liu XZ, Blanco G, Steel KP, Petit C, Brown SD (Aug 2003). "Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31". Nat Genet. 34 (4): 421–8. doi:10.1038/ng1208. PMID   12833159. S2CID   39603776.
6. Ebermann I, Scholl HP, Charbel Issa P, Becirovic E, Lamprecht J, Jurklies B, Millan JM, Aller E, Mitter D, Bolz H (Mar 2007). "A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing loss". Hum Genet. 121 (2): 203–11. doi:10.1007/s00439-006-0304-0. PMID   17171570. S2CID   22632047.
7. "Entrez Gene: DFNB31 deafness, autosomal recessive 31".
8. Yap CC, Liang F, Yamazaki Y, et al. (2003). "CIP98, a novel PDZ domain protein, is expressed in the central nervous system and interacts with calmodulin-dependent serine kinase". J. Neurochem. 85 (1): 123–34. doi: 10.1046/j.1471-4159.2003.01647.x . PMID   12641734. S2CID   46526881.
9. "Hot plate data for Whrn". Wellcome Trust Sanger Institute.
10. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID   85911512.
11. Mouse Resources Portal, Wellcome Trust Sanger Institute.
12. "International Knockout Mouse Consortium".
13. "Mouse Genome Informatics".
14. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC   3572410 . PMID   21677750.
15. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi: 10.1038/474262a . PMID   21677718.
16. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi: 10.1016/j.cell.2006.12.018 . PMID   17218247. S2CID   18872015.
17. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC   3218837 . PMID   21722353.

Further reading

• Holm G, Björkholm M, Mellstedt H, Johansson B (1976). "Cytotoxic activity of lymphocytes from patients with Hodgkin's disease". Clin. Exp. Immunol. 21 (3): 376–83. PMC   1538308 . PMID   1081933.
• Nagase T, Kikuno R, Ishikawa K, et al. (2000). "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (2): 143–50. doi: 10.1093/dnares/7.2.143 . PMID   10819331.
• Mustapha M, Chouery E, Chardenoux S, et al. (2002). "DFNB31, a recessive form of sensorineural hearing loss, maps to chromosome 9q32-34". Eur. J. Hum. Genet. 10 (3): 210–2. doi: 10.1038/sj.ejhg.5200780 . PMID   11973626.
• Nakayama M, Kikuno R, Ohara O (2003). "Protein–Protein Interactions Between Large Proteins: Two-Hybrid Screening Using a Functionally Classified Library Composed of Long cDNAs". Genome Res. 12 (11): 1773–84. doi:10.1101/gr.406902. PMC   187542 . PMID   12421765.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC   1356129 . PMID   16344560.
• van Wijk E, van der Zwaag B, Peters T, et al. (2006). "The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1". Hum. Mol. Genet. 15 (5): 751–65. doi: 10.1093/hmg/ddi490 . PMID   16434480.

External links

• GeneReviews/NCBI/NIH/UW entry on Usher Syndrome Type II