WDR45

WD repeat domain phosphoinositide-interacting protein 4 (WIPI-4) is a protein that in humans is encoded by the WDR45 gene.[5][6] Mutations in this gene cause a distinct form of Neurodegeneration with brain iron accumulation (NBIA).[7]

WDR45
Identifiers
Aliases	WDR45, NBIA4, NBIA5, WDRX1, WIPI-4, WIPI4, JM5, WD repeat domain 45
External IDs	OMIM: 300526 MGI: 1859606 HomoloGene: 48498 GeneCards: WDR45
Gene location (Human) Chr. X chromosome (human)[1] Band Xp11.23 Start 49,074,433 bp[1] End 49,101,170 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X A1.1|X 3.48 cM Start 7,714,333 bp[2] End 7,728,206 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • phosphatidylinositol-3-phosphate binding • phosphatidylinositol-3,5-bisphosphate binding • GO:0001948 protein binding • protein kinase binding • phosphatidylinositol phosphate binding • lipid binding Cellular component • cytosol • pre-autophagosomal structure membrane • extrinsic component of membrane • pre-autophagosomal structure • cytoplasm Biological process • autophagy • mitophagy • protein lipidation • protein localization to pre-autophagosomal structure • autophagy of nucleus • autophagosome assembly • cellular response to starvation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	11152	54636
Ensembl	ENSG00000196998	ENSMUSG00000039382
UniProt	Q9Y484	Q91VM3
RefSeq (mRNA)	NM_007075 NM_001029896	NM_001290792 NM_001290794 NM_001290795 NM_172372
RefSeq (protein)	NP_001025067 NP_009006 NP_001025067.1	NP_001277721 NP_001277723 NP_001277724 NP_758960
Location (UCSC)	Chr X: 49.07 – 49.1 Mb	Chr X: 7.71 – 7.73 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

Role in Disease

De novo loss of function mutations in WDR45 were identified by exome sequencing in 20 patients with NBIA.[7] The mutations cause an X-linked dominant form of NBIA now called Beta-propeller protein-associated neurodegeneration (BPAN).[7]

See also

• WIPI protein family

References

1. GRCh38: Ensembl release 89: ENSG00000196998 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000039382 - 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. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA (Dec 2002). "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.
6. "Entrez Gene: WDR45 WD repeat domain 45".
7. Haack TB, Hogarth P, Kruer MC, Gregory A, Wieland T, Schwarzmayr T, Graf E, Sanford L, Meyer E, Kara E, Cuno SM, Harik SI, Dandu VH, Nardocci N, Zorzi G, Dunaway T, Tarnopolsky M, Skinner S, Frucht S, Hanspal E, Schrander-Stumpel C, Héron D, Mignot C, Garavaglia B, Bhatia K, Hardy J, Strom TM, Boddaert N, Houlden HH, Kurian MA, Meitinger T, Prokisch H, Hayflick SJ (Dec 2012). "Exome Sequencing Reveals De Novo WDR45 Mutations Causing a Phenotypically Distinct, X-Linked Dominant Form of NBIA". Am J Hum Genet. 91 (6): 1144–9. doi:10.1016/j.ajhg.2012.10.019. PMC 3516593. 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.

Further reading

• Proikas-Cezanne T, Waddell S, Gaugel A, et al. (2005). "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): 9314–25. doi:10.1038/sj.onc.1208331. PMID 15602573.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Jeffries TR, Dove SK, Michell RH, Parker PJ (2004). "PtdIns-specific MPR Pathway Association of a Novel WD40 Repeat Protein, WIPI49". Mol. Biol. Cell. 15 (6): 2652–63. doi:10.1091/mbc.E03-10-0732. PMC 420090. PMID 15020712.
• 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.
• Clark AG, Glanowski S, Nielsen R, et al. (2003). "Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios". Science. 302 (5652): 1960–3. doi:10.1126/science.1088821. PMID 14671302.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.