protein
WD repeat domain phosphoinositide-interacting protein 4
aka WIPI-4
Gene
WDR45
Organism
Homo sapiens(9606)
Length
360 aa
Mass
39,868 Da
WDR45, also known as WIPI-4, is a 360-amino acid phosphoinositide-binding protein that functions as a core component of the autophagy machinery (UniProt: Q9Y484). It binds phosphatidylinositol 3-phosphate and regulates autophagosome assembly downstream of WIPI2, controlling the size of forming autophagosomes. Together with WIPI1, it promotes ATG2-mediated lipid transfer to phosphatidylinositol 3-monophosphate-containing membranes, facilitating the major intracellular degradation pathway by which cytoplasmic materials are delivered to lysosomes.
WDR45 is activated by the STK11/AMPK signaling pathway during starvation conditions and plays an essential role in cellular homeostasis through autophagy regulation (UniProt: Q9Y484). Mutations in WDR45 are associated with Neurodegeneration with Brain Iron Accumulation 5 (NBIA5), a neurodegenerative disorder characterized by iron accumulation in the basal ganglia, developmental delay in early childhood, and progressive dystonia, parkinsonism, and dementia in adulthood.
WDR45 is classified as a syndromic autism-associated gene (SFARI Cat 2), indicating evidence for a role in autism spectrum disorder within a broader neurological syndrome context. The connection to early developmental delay in NBIA5 and the protein's critical role in neuronal autophagy suggest potential relevance to neurodevelopmental pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
Strong candidate — functional studies support ASD association
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:23435086, PubMed:28561066). Binds phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:28561066). Activated by the STK11/AMPK signaling pathway upon starvation, WDR45 is involved in autophagosome assembly downstream of WIPI2, regulating the size of forming autophagosomes (PubMed:28561066). Together with WIPI1, promotes ATG2 (ATG2A or ATG2B)-mediated lipid transfer by enhancing ATG2-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes (PubMed:31271352). Probably recruited to membranes through its PtdIns3P activity (PubMed:28561066)
Disease associations
Neurodegeneration with brain iron accumulation 5NBIA5
A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. NBIA5 is characterized by global developmental delay in early childhood that is essentially static, with slow motor and cognitive gains until adolescence or early adulthood. In young adulthood, affected individuals develop progressive dystonia, parkinsonism, extrapyramidal signs, and dementia resulting in severe disability.
Sources
Last updated 5/6/2026, 5:23:40 AM