protein
Rho GTPase-activating protein 26
Gene
ARHGAP26
Organism
Homo sapiens(9606)
Length
814 aa
Mass
92,235 Da
ARHGAP26 (Rho GTPase-activating protein 26) is a GAP protein that negatively regulates RhoA and Cdc42, thereby modulating Rho family GTPase signaling (UniProt: Q9UNA1). The protein facilitates mitochondrial quality control by promoting Parkin-mediated autophagy of damaged mitochondria and participates in endosomal trafficking by associating with MICAL1 and recruiting WDR44 to coordinate ER-endosomal contacts (UniProt: Q9UNA1). Beyond these canonical roles, ARHGAP26 negatively regulates parainfluenza virus infection through RHOA inhibition.
ARHGAP26 is primarily implicated in juvenile myelomonocytic leukemia (JMML, MIM 607785) according to UniProt records, though its broader cellular contexts span mitochondrial homeostasis, membrane trafficking, and antiviral immunity.
In Alzheimer's disease, ARHGAP26 is significantly downregulated in post-mortem AD brain tissue relative to age-matched controls, with a mean log2 fold-change of −1.40 across subcellular fractions measured by quantitative proteomics (Chaparral AD proteomics). This reduction may reflect diminished capacity for Rho GTPase regulation and mitochondrial quality control in the AD brain, although the functional consequences remain to be determined.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
not detected
P2
not detected
S2
-1.396
S3
not detected
Mean log₂FC across detected fractions: -1.3959 (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
GTPase-activating protein for RHOA and CDC42. Facilitates mitochondrial quality control by promoting Parkin-mediated recruitment of autophagosomes to damaged mitochondria (PubMed:38081847). Negatively regulates the growth of human parainfluenza virus type 2 by inhibiting hPIV-2-mediated RHOA activation via interaction with two of its viral proteins P and V (PubMed:27512058)
Associates with MICAL1 on the endosomal membrane to promote Rab8-Rab10-dependent tubule extension. After dissociation of MICAL1, recruits WDR44 which connects the endoplasmic reticulum (ER) with the endosomal tubule, thereby participating in the export of a subset of neosynthesized proteins
Disease associations
Leukemia, juvenile myelomonocyticJMML
An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages.
Sources
Last updated 5/8/2026, 6:30:38 AM