WDR45

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; OMA:WDR45 - orthologs
Gene location (Human)
Chr.	X chromosome (human)
End	49,101,170 bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	7,728,206 bp
RNA expression pattern
	Top expressed in
	apex of heart; ; gastric mucosa; ; granulocyte; ; right adrenal gland; ; right adrenal cortex; ; left adrenal cortex; ; canal of the cervix; ; right lobe of thyroid gland; ; left lobe of thyroid gland; ; body of stomach;
	Top expressed in
	morula; ; morula; ; left lung lobe; ; granulocyte; ; neural layer of retina; ; right lung lobe; ; right kidney; ; muscle of thigh; ; superior frontal gyrus; ; saccule;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	phosphatidylinositol-3-phosphate binding; phosphatidylinositol-3,5-bisphosphate binding; protein binding; protein kinase binding; phosphatidylinositol phosphate binding; lipid binding;
Cellular component	cytosol; phagophore assembly site membrane; extrinsic component of membrane; phagophore assembly site; cytoplasm;
Biological process	autophagy; autophagy of mitochondrion; protein lipidation; protein localization to phagophore assembly site; autophagy of nucleus; autophagosome assembly; cellular response to starvation;
	Sources:Amigo / QuickGO
Orthologs
	11152
	54636
	ENSG00000196998
	ENSMUSG00000039382
	Q9Y484
	Q91VM3
	NM_007075; NM_001029896
	NM_001290792; NM_001290794; NM_001290795; NM_172372
	NP_001025067; NP_009006; NP_001025067.1
	NP_001277721; NP_001277723; NP_001277724; NP_758960
	Wikidata
View/Edit Human	View/Edit Mouse

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) called Beta-propeller protein-associated neurodegeneration (BPAN).^[7]

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 progressive neurodegeneration and evidence of iron on brain MRI scans.^[7] The mutations cause an X-linked dominant form of brain iron accumulation disorder now called Beta-propeller protein-associated neurodegeneration (BPAN).^[7] 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.

BPAN typically causes developmental delay and epilepsy from early childhood. An unusual feature experienced by many is a tendency to overeat without feeling full. Diagnosis might be suggested by the combination of developmental delay, epilepsy, and no satiety response.^[8] A pattern of abnormality on MRI brain scans shows early swelling of the basal ganglia (globus pallidus and substantia nigra) and dentate nucleus, with later accumulation of iron in the globus pallidus and substantia nigra.^[9] Diagnosis is usually established by genetic testing.

There are no current treatments for BPAN, though medications and therapies can be used to treat symptoms.^[8]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000196998 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000039382 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
^ ^a ^b "Entrez Gene: WDR45 WD repeat domain 45".
^ ^a ^b ^c Haack TB, Hogarth P, Kruer MC, Gregory A, Wieland T, Schwarzmayr T, et al. (December 2012). "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. 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.
^ ^a ^b Spaull RV, Soo AK, Hogarth P, Hayflick SJ, Kurian MA (24 November 2021). "Towards Precision Therapies for Inherited Disorders of Neurodegeneration with Brain Iron Accumulation". Tremor and Other Hyperkinetic Movements. 11 (1): 51. doi:10.5334/tohm.661. PMC 8641530. PMID 34909266.
^ Papandreou, A.; Soo, A. K. S.; Spaull, R.; Mankad, K.; Kurian, M. A.; Sudhakar, S. (December 2022). "Expanding the Spectrum of Early Neuroradiologic Findings in β Propeller Protein-Associated Neurodegeneration". AJNR. American Journal of Neuroradiology. 43 (12): 1810–1814. doi:10.3174/ajnr.A7693. ISSN 1936-959X. PMID 36328404.

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