DFNB31

Deafness, autosomal recessive 31
PDB rendering based on 1uez.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1UEZ​, 1UF1​, 1UFX​
Identifiers
Symbols	DFNB31 ; CIP98; PDZD7B; USH2D; WHRN; WI
External IDs	OMIM: 607928 MGI: 2682003 HomoloGene: 18739 GeneCards: DFNB31 Gene
Gene ontology Molecular function • protein binding Cellular component • cytoplasm • growth cone • stereocilium Biological process • retina homeostasis • sensory perception of sound • sensory perception of light stimulus • inner ear receptor stereocilium organization Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	25861	73750
Ensembl	ENSG00000095397	ENSMUSG00000039137
UniProt	Q9P202	Q80VW5
RefSeq (mRNA)	NM_001083885	NM_001008791
RefSeq (protein)	NP_001077354	NP_001008791
Location (UCSC)	Chr 9: 114.4 – 114.51 Mb	Chr 4: 63.41 – 63.5 Mb
PubMed search

Whirlin is a protein that in humans is encoded by the DFNB31 gene.^[1][2][3]

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).^[4] Mutations in this gene, also known as WHRN, cause autosomal recessive deafness.^[3]

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[5]
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[6][7]

Model organisms have been used in the study of WHRN function. A conditional knockout mouse line, called Whrn^{tm1a(EUCOMM)Wtsi[8][9]} 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.^[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[6][13] Twenty tests were carried out on mutant mice and two significant abnormalities were observed.^[6] 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.^[6]

References

1. 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.
2. 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.
3. "Entrez Gene: DFNB31 deafness, autosomal recessive 31".
4. 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.
5. "Hot plate data for Whrn". Wellcome Trust Sanger Institute.
6. 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.
7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
8. "International Knockout Mouse Consortium".
9. "Mouse Genome Informatics".
10. 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.
11. Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. 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.
13. 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. 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