protein
Probable phospholipid-transporting ATPase IIA
Gene
ATP9A
Organism
Homo sapiens(9606)
Length
1047 aa
Mass
118,583 Da
ATP9A encodes a probable phospholipid-transporting ATPase that regulates membrane trafficking through multiple pathways. The protein plays key roles in endosome-to-plasma membrane recycling and endosome-to-trans-Golgi network retrograde transport, likely via RAB5 and RAB11 activation (UniProt: O75110). It forms a complex with MON2 and DOP1B to coordinate SNX3 retromer-mediated sorting of the Wnt transporter WLS, preventing its lysosomal degradation. ATP9A also appears to negatively regulate exosome release and is required for neurite morphology and synaptic transmission maintenance.
ATP9A is associated with Neurodevelopmental Disorder with Poor Growth and Behavioral Abnormalities (NEDGBA; MIM 620242) as an autosomal recessive disease, highlighting its importance in neural development and function (UniProt: O75110).
In Alzheimer's disease, ATP9A is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2FC −0.31; Chaparral AD proteomics). This reduction in a protein critical for membrane trafficking and synaptic function may contribute to the trafficking deficits and neurodegeneration characteristic of AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.308
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.3076 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Plays a role in regulating membrane trafficking of cargo proteins, namely endosome to plasma membrane recycling, probably acting through RAB5 and RAB11 activation (PubMed:27733620, PubMed:30213940, PubMed:36604604). Also involved in endosome to trans-Golgi network retrograde transport (PubMed:27733620, PubMed:30213940). In complex with MON2 and DOP1B, regulates SNX3 retromer-mediated endosomal sorting of WLS, a transporter of Wnt morphogens in developing tissues. Participates in the formation of endosomal carriers that direct WLS trafficking back to Golgi, away from lysosomal degradation (PubMed:30213940). Appears to be implicated in intercellular communication by negatively regulating the release of exosomes (PubMed:30947313). The flippase activity towards membrane lipids and its role in membrane asymmetry remains to be proved (PubMed:30947313). Required for the maintenance of neurite morphology and synaptic transmission (By similarity)
Disease associations
Neurodevelopmental disorder with poor growth and behavioral abnormalitiesNEDGBA
An autosomal recessive disorder characterized by global developmental delay, impaired intellectual development, absent speech, and behavioral abnormalities, including hyperactivity and attention deficit disorder. Affected individuals show failure to thrive with poor overall growth, and some have microcephaly. Additional features may include non-specific facial dysmorphism, hypotonia, and feeding difficulties.
Sources
Last updated 5/8/2026, 6:26:23 AM