Beta-propeller Protein-Associated Neurodegeneration, or BPAN, is a rare genetic condition caused by mutations in the WDR45 gene. It is characterized by seizures, complex epileptic encephalopathies, developmental delays, and neurodegenerative symptoms similar to those found in Parkinson’s disease and currently has no cure.

Sarah Chisholm launched the BPAN warriors organization 10 months after her own daughter’s diagnosis with BPAN, and came across Mastermind in her efforts to gather and organize all of the existing medical literature for BPAN. Her goal was simple – to find a cure for her daughter. Soon after, Genomenon reached out to see if we could assist in her cause, and we have now officially partnered with the BPAN Warriors.

See the December edition of The Journal of Precision Medicine for more information on Sarah’s story and what inspired our partnership.

This partnership has culminated in the development of a variant database for the WDR45 gene, which is now freely available to all researchers and pharmaceutical companies interested in exploring the data. The comprehensive dataset contains 107 unique variants*, all of which are interpreted according to the standards set by the American College of Medical Genetics (ACMG). These clinical criteria require information from three main sources: the medical literature (both clinical and functional studies), population databases, and computational predictions of effects on protein function. All of the evidence supporting these conclusions are organized for review in the Mastermind Reporter software.

Because of the rarity of BPAN as well as its high phenotypic variability and the resulting propensity for misdiagnosis, we included all variants within the WDR45 gene that were found in patients with BPAN or a disorder with similar clinical symptoms. Additionally, we took careful note of these symptoms, such that the phenotype of patients with WDR45 mutations can be characterized in further detail.

Overall, this dataset provides a comprehensive view of the genetic landscape of BPAN and related disorders harboring WDR45 mutations. It may be useful in the following ways:

  • To aid diagnosis: Developing a more detailed understanding of the genetic causes of BPAN will assist in ensuring higher overall diagnostic rates and earlier individual diagnosis
  • To aid therapeutic decisions: Investigating therapies that have been tested in BPAN patients and their success at managing symptoms in patients with specific clinical presentations can assist in deciding the best course of treatment for newly diagnosed patients
  • To aid new therapy development: Functional studies involving variants in the WDR45 gene can provide a deeper understanding of the genetic mechanism for BPAN, which can aid in the development of targeted therapies
Below is the list of variants in the WDR45 gene:
GeneVariantMastermind LinkVariant TypeArticlesProvisional ACMG Call  
WDR45p.R134Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R134XNonsense11Pathogenic
WDR45c.830+1G>Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.830+1G>ASplice Donor8Pathogenic
WDR45p.R7Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R7XNonsense8Pathogenic
WDR45p.R234Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R234XNonsense7Pathogenic
WDR45p.Y336fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y336fsFrameshift7Pathogenic
WDR45p.Q290Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q290XNonsense6Pathogenic
WDR45p.W83Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.W83XNonsense6Pathogenic
WDR45c.235+1G>Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.235+1G>ASplice Donor5Pathogenic
WDR45c.342-2A>Chttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.342-2A>CSplice Acceptor5Pathogenic
WDR45p.E76fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.E76fsFrameshift5Pathogenic
WDR45p.G342fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.G342fsFrameshift5Pathogenic
WDR45p.I196fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.I196fsFrameshift5Pathogenic
WDR45p.L232fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L232fsFrameshift5Pathogenic
WDR45p.L98Phttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L98PSubstitution5Pathogenic
WDR45p.R7fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R7fsFrameshift5Pathogenic
WDR45c.131-1G>Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.131-1G>ASplice Acceptor4Pathogenic
WDR45c.55+1G>Chttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.55+1G>CSplice Donor4Pathogenic
WDR45c.56-1G>Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.56-1G>ASplice Acceptor4Pathogenic
WDR45c.831-1G>Chttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.831-1G>CSplice Acceptor4Pathogenic
WDR45p.D174fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D174fsFrameshift4Pathogenic
WDR45p.G205Dhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.G205DSubstitution4Pathogenic
WDR45p.K121fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.K121fsFrameshift4Pathogenic
WDR45p.K135fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.K135fsFrameshift4Pathogenic
WDR45p.L148fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L148fsFrameshift4Pathogenic
WDR45p.L159fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L159fsFrameshift4Pathogenic
WDR45p.M1delhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.M1delDeletion4Pathogenic
WDR45p.N345fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.N345fsFrameshift4Pathogenic
WDR45p.Q213Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q213XNonsense4Pathogenic
WDR45p.Q295fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q295fsFrameshift4Pathogenic
WDR45p.V324fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.V324fsFrameshift4Pathogenic
WDR45p.Y352Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y352XNonsense4Pathogenic
WDR45c.345-1G>Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.345-1G>ASplice Acceptor3Pathogenic
WDR45c.439+1G>Thttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.439+1G>TSplice Donor3Pathogenic
WDR45c.440-2A>Ghttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.440-2A>GSplice Acceptor3Pathogenic
WDR45c.830+2T>Chttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.830+2T>CSplice Donor3Pathogenic
WDR45p.C149Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C149XNonsense3Pathogenic
WDR45p.C22fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C22fsFrameshift3Pathogenic
WDR45p.C344fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C344fsFrameshift3Pathogenic
WDR45p.F221Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.F221XNonsense3Pathogenic
WDR45p.L201fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L201fsFrameshift3Pathogenic
WDR45p.L63fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L63fsFrameshift3Pathogenic
WDR45p.P163fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.P163fsFrameshift3Pathogenic
WDR45p.S108fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S108fsFrameshift3Pathogenic
WDR45c.235+1G>Thttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.235+1G>TSplice Donor2Pathogenic
WDR45p.C152fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C152fsFrameshift2Pathogenic
WDR45p.F221fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.F221fsFrameshift2Pathogenic
WDR45p.L107fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L107fsFrameshift2Pathogenic
WDR45p.S184fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S184fsFrameshift2Pathogenic
WDR45p.Y242Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y242XNonsense2Pathogenic
WDR45c.344+1G>Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.344+1G>ASplice Donor1Pathogenic
WDR45c.830+1G>Chttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.830+1G>CSplice Donor1Pathogenic
WDR45p.A255fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A255fsFrameshift1Pathogenic
WDR45p.A305fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A305fsFrameshift1Pathogenic
WDR45p.A308fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A308fsFrameshift1Pathogenic
WDR45p.C254Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.C254XNonsense1Pathogenic
WDR45p.D114Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D114XNonsense1Pathogenic
WDR45p.D84fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D84fsFrameshift1Pathogenic
WDR45p.E347fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.E347fsFrameshift1Pathogenic
WDR45p.S210fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S210fsFrameshift1Pathogenic
WDR45p.Y291Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y291XNonsense1Pathogenic
WDR45p.V54delhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.V54delDeletion6Likely Pathogenic
WDR45p.S251delhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S251delDeletion5Likely Pathogenic
WDR45p.A209Dhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A209DSubstitution4Likely Pathogenic
WDR45p.M1Vhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.M1VSubstitution4Likely Pathogenic
WDR45p.N61Khttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.N61KSubstitution4Likely Pathogenic
WDR45p.R13Phttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R13PSubstitution4Likely Pathogenic
WDR45p.E138delhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.E138delDeletion3Likely Pathogenic
WDR45p.F265fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.F265fsFrameshift2Likely Pathogenic
WDR45p.L266fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L266fsFrameshift2Likely Pathogenic
WDR45p.Q16Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q16XNonsense2Likely Pathogenic
WDR45c.345-2A>Chttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.345-2A>CSplice Acceptor1Likely Pathogenic
WDR45c.827+2T>Ghttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.827+2T>GSplice Donor1Likely Pathogenic
WDR45p.D113Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D113ASubstitution1Likely Pathogenic
WDR45p.E155Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.E155XNonsense1Likely Pathogenic
WDR45p.F100Shttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.F100SSubstitution1Likely Pathogenic
WDR45p.G168Ehttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.G168ESubstitution1Likely Pathogenic
WDR45p.K115Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.K115XNonsense1Likely Pathogenic
WDR45p.L160Rhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L160RSubstitution1Likely Pathogenic
WDR45p.N202Khttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.N202KSubstitution1Likely Pathogenic
WDR45p.Q171Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q171XNonsense1Likely Pathogenic
WDR45p.R134Phttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R134PSubstitution1Likely Pathogenic
WDR45p.R219fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R219fsFrameshift1Likely Pathogenic
WDR45p.T260fshttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.T260fsFrameshift1Likely Pathogenic
WDR45p.V34Mhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.V34MSubstitution1Likely Pathogenic
WDR45p.D84Ghttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D84GSubstitution5Variant of Uncertain Signifigance
WDR45p.G147Vhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.G147VSubstitution3Variant of Uncertain Signifigance
WDR45p.R13Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R13XNonsense3Variant of Uncertain Signifigance
WDR45p.R7Qhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R7QSubstitution3Variant of Uncertain Signifigance
WDR45p.S210Phttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.S210PSubstitution3Variant of Uncertain Signifigance
WDR45c.236-18A>Ghttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.236-18A>GIntronic2Variant of Uncertain Signifigance
WDR45p.L278Xhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L278XNonsense2Variant of Uncertain Signifigance
WDR45p.Y336Chttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y336CSubstitution2Variant of Uncertain Signifigance
WDR45c.344+4A>Chttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.344+4A>CIntronic1Variant of Uncertain Signifigance
WDR45c.519+1_519+3delhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:c.519+1_519+3delSplice Donor1Variant of Uncertain Signifigance
WDR45p.A255Shttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.A255SSubstitution1Variant of Uncertain Signifigance
WDR45p.D17Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.D17ASubstitution1Variant of Uncertain Signifigance
WDR45p.L63Whttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.L63WSubstitution1Variant of Uncertain Signifigance
WDR45p.N15Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.N15ASubstitution1Variant of Uncertain Signifigance
WDR45p.Q16Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q16ASubstitution1Variant of Uncertain Signifigance
WDR45p.Q223delhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q223delDeletion1Variant of Uncertain Signifigance
WDR45p.R112Chttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R112CSubstitution1Variant of Uncertain Signifigance
WDR45p.R112Hhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R112HSubstitution1Variant of Uncertain Signifigance
WDR45p.R233Ahttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R233ASubstitution1Variant of Uncertain Signifigance
WDR45p.R274Hhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.R274HSubstitution1Variant of Uncertain Signifigance
WDR45p.V230Lhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.V230LSubstitution1Variant of Uncertain Signifigance
WDR45p.Y291Yhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Y291YSynonymous1Variant of Uncertain Signifigance
WDR45p.Q212delhttps://mastermind.genomenon.com/detail?gene=wdr45&mutation=wdr45:p.Q212delDeletion1Variant of Uncertain Signifigance

We have been so inspired by Sarah’s story and the potential to make a difference in these parents’ quest that we have made the comprehensive genomic landscape of BPAN freely available to any pharmaceutical company or researcher interested in exploring the data. The availability of this data will not only help researchers better understand this rare disease, but will provide a solid foundation for pharmaceutical companies to begin the search for a cure with a resource that would otherwise take years to assemble.

* At the time the article in The Journal for Precision Medicine was written, there were 94 variants related to WDR45, but since the time of original publication, Mastermind has identified 13 new variants, taking the total to 107, all of which are in the current dataset.

To request access to the BPAN variant dataset, sign up below: