BPAN 101: WDR45


Source: https://ghr.nlm.nih.gov/gene/WDR45

The WDR45 gene provides instructions for making a protein called WD40 repeat protein interacting with phosphoinositides 4 (WIPI4). WIPI4 is a member of a group of proteins each with a characteristic structure resembling a seven-bladed propeller. The WIPI4 protein is involved in the early stages of a process called autophagy, which helps clear unneeded materials from cells, including excess amounts of an iron storage protein called ferritin. In autophagy, worn-out cell parts (such as organelles, which are specialized structures that perform certain tasks within the cell) and other materials that are no longer needed are isolated in tiny compartments called autophagosomes. The WIPI4 protein helps control (regulate) the production and elongation of autophagosomes to contain the materials. The autophagosomes are then transported to organelles called lysosomes, which act as recycling centers within cells. Lysosomes use digestive enzymes to break down waste substances and recycle worn-out cell components.


More than 50 WDR45 gene mutations have been identified in people with beta-propeller protein-associated neurodegeneration (BPAN), a disorder that damages the nervous system. Most of the WDR45 gene mutations identified in people with BPAN are thought to result in the production of an unstable WIPI-4 protein that is quickly broken down, leading to loss of WIPI-4 protein function. Without functional WIPI4 protein, the process of autophagy is impaired, making cells less efficient at removing damaged organelles and waste materials. Researchers suggest that nerve cells (neurons) may be particularly vulnerable to impaired autophagy because they have long extensions (axons and dendrites), making it even more difficult to transport the waste materials from these structures to the lysosomes in the cell body for recycling. The waste materials can build up in these areas and damage them. Damage to neurons results in the neurological problems that occur in BPAN.

Cytogenetic Location: Xp11.23, which is the short (p) arm of the X chromosome at position 11.23

Molecular Location: base pairs 49,074,433 to 49,101,121 on the X chromosome (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)



Credit: Genome Decoration Page/NCBI


Other Names for This Gene:

  • JM5

  • NBIA4

  • NBIA5

  • WD repeat-containing protein 45

  • WD repeat domain phosphoinositide-interacting protein 4 isoform 1

  • WD repeat domain phosphoinositide-interacting protein 4 isoform 2

  • WD repeat domain, X-linked 1

  • WD45 repeat protein interacting with phosphoinositides 4

  • WDRX1

  • WIPI-4

  • WIPI4

  • BPAN

  • NBIA5

  • neurodegeneration with brain iron accumulation 5


  • static encephalopathy of childhood with neurodegeneration in adulthood


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