Biology:WDR45
 Generic protein structure example |
WD repeat domain phosphoinositide-interacting protein 4 (WIPI-4) is a protein that in humans is encoded by the WDR45 gene.[1][2] Mutations in this gene cause a distinct form of Neurodegeneration with brain iron accumulation (NBIA) called Beta-propeller protein-associated neurodegeneration (BPAN).[3]
Function
WIPI-4 is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation.
This gene WDR45 has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined.[2]
Role in disease
De novo loss of function mutations in WDR45 were identified by exome sequencing in 20 patients with progressive neurodegeneration and evidence of iron on brain MRI scans.[3] The mutations cause an X-linked dominant form of NBIA now called Beta-propeller protein-associated neurodegeneration (BPAN).[3] A name for the disease before the gene was identified was called static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), though this term is no longer used. There are no current treatments for BPAN, though medications and therapies can be used to treat symptoms.[4]
See also
References
- ↑ "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America 99 (26): 16899–16903. December 2002. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- ↑ 2.0 2.1 "Entrez Gene: WDR45 WD repeat domain 45". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11152.
- ↑ 3.0 3.1 3.2 "Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA". American Journal of Human Genetics 91 (6): 1144–1149. December 2012. doi:10.1016/j.ajhg.2012.10.019. PMID 23176820. "This clinically recognizable disorder is among the more common forms of NBIA, and we suggest that it be named accordingly as beta-propeller protein-associated neurodegeneration.".
- ↑ "Towards Precision Therapies for Inherited Disorders of Neurodegeneration with Brain Iron Accumulation". Tremor and Other Hyperkinetic Movements 11 (1): 51. 24 November 2021. doi:10.5334/tohm.661. PMID 34909266.
Further reading
- "WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy". Oncogene 23 (58): 9314–9325. December 2004. doi:10.1038/sj.onc.1208331. PMID 15602573.
- "PtdIns-specific MPR pathway association of a novel WD40 repeat protein, WIPI49". Molecular Biology of the Cell 15 (6): 2652–2663. June 2004. doi:10.1091/mbc.E03-10-0732. PMID 15020712.
- "Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios". Science 302 (5652): 1960–1963. December 2003. doi:10.1126/science.1088821. PMID 14671302. Bibcode: 2003Sci...302.1960C.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
 |
