Gene Symbol: AP4M1
Description: adaptor related protein complex 4 subunit mu 1
Alias: CPSQ3, MU-4, MU-ARP2, SPG50, AP-4 complex subunit mu-1, AP-4 adaptor complex mu subunit, adapter-related protein complex 4 mu-1 subunit, adapter-related protein complex 4 subunit mu-1, adaptor related protein complex 4 mu 1 subunit, adaptor-related protein complex AP-4 mu4 subunit, mu subunit of AP-4, mu-adaptin-related protein-2, mu4, mu4-adaptin
Species: human
Products:     AP4M1

Top Publications

  1. Abou Jamra R, Philippe O, Raas Rothschild A, Eck S, Graf E, Buchert R, et al. Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. Am J Hum Genet. 2011;88:788-795 pubmed publisher
    ..Interestingly, two mutations affecting AP4M1 and AP4E1 have recently been found to cause cerebral palsy associated with severe intellectual disability...
  2. Verkerk A, Schot R, Dumee B, Schellekens K, Swagemakers S, Bertoli Avella A, et al. Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy. Am J Hum Genet. 2009;85:40-52 pubmed publisher
    ..In all five patients, a donor splice site pathogenic mutation in intron 14 of the AP4M1 gene (c.1137+1G-->T), was identified...
  3. Hebbar M, Shukla A, Nampoothiri S, Bielas S, Girisha K. Locus and allelic heterogeneity in five families with hereditary spastic paraplegia. J Hum Genet. 2018;: pubmed publisher
    ..paraplegia type 47 (AP4B1) with a common mutation in two families, a family with spastic paraplegia type 50 (AP4M1), and two male siblings with X-linked spastic paraplegia 2 (PLP1)...
  4. Duerinckx S, Verhelst H, Perazzolo C, David P, Desmyter L, Pirson I, et al. Severe congenital microcephaly with AP4M1 mutation, a case report. BMC Med Genet. 2017;18:48 pubmed publisher
    ..Exome sequencing showed a homozygous mutation in AP4M1, causing the replacement of an arginine by a stop codon at position 338 of the protein (p.Arg338X)...
  5. Matsuda S, Miura E, Matsuda K, Kakegawa W, Kohda K, Watanabe M, et al. Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking adaptor protein AP-4. Neuron. 2008;57:730-45 pubmed publisher
    ..These results indicate that AP-4 may regulate proper somatodendritic-specific distribution of its cargo proteins, including AMPA receptor-TARP complexes and the autophagic pathway in neurons. ..
  6. Bettencourt C, Salpietro V, Efthymiou S, Chelban V, Hughes D, Pittman A, et al. Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia. Orphanet J Rare Dis. 2017;12:172 pubmed publisher
    Autosomal recessive hereditary spastic paraplegia (HSP) due to AP4M1 mutations is a very rare neurodevelopmental disorder reported for only a few patients. We investigated a Greek HSP family using whole exome sequencing (WES)...
  7. Wang X, Kilimann M. Identification of two new mu-adaptin-related proteins, mu-ARP1 and mu-ARP2. FEBS Lett. 1997;402:57-61 pubmed
  8. Boehm M, Aguilar R, Bonifacino J. Functional and physical interactions of the adaptor protein complex AP-4 with ADP-ribosylation factors (ARFs). EMBO J. 2001;20:6265-76 pubmed
    ..This complex consists of four subunits (epsilon, beta4, mu4 and sigma4) and localizes to the cytoplasmic face of the trans-Golgi network (TGN)...
  9. Yap C, Murate M, Kishigami S, Muto Y, Kishida H, Hashikawa T, et al. Adaptor protein complex-4 (AP-4) is expressed in the central nervous system neurons and interacts with glutamate receptor delta2. Mol Cell Neurosci. 2003;24:283-95 pubmed
    ..The interaction between mu4 subunit of AP-4 and the delta2 C-terminal involved multiple amino acid sequence motifs other than the classical ..

More Information


  1. Lavezzari G, McCallum J, Dewey C, Roche K. Subunit-specific regulation of NMDA receptor endocytosis. J Neurosci. 2004;24:6383-91 pubmed
    ..Our findings demonstrate fundamental differences between NR2A and NR2B that help clarify developmental changes in NMDA receptor trafficking and surface expression. ..
  2. Simmen T, Honing S, Icking A, Tikkanen R, Hunziker W. AP-4 binds basolateral signals and participates in basolateral sorting in epithelial MDCK cells. Nat Cell Biol. 2002;4:154-9 pubmed
    ..1B, sigma 1), AP-2 (beta 2, alpha, mu 2, sigma 2), AP-3 (beta 3 , delta, mu 3, sigma 3) or AP-4 (beta 4, epsilon, mu 4, sigma 4), have been characterized...
  3. Burgos P, Mardones G, Rojas A, daSilva L, Prabhu Y, Hurley J, et al. Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex. Dev Cell. 2010;18:425-36 pubmed publisher
    ..of an YKFFE sequence from the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) with the mu4 subunit of AP-4...
  4. Aguilar R, Boehm M, Gorshkova I, Crouch R, Tomita K, Saito T, et al. Signal-binding specificity of the mu4 subunit of the adaptor protein complex AP-4. J Biol Chem. 2001;276:13145-52 pubmed
    ..Here, we describe the signal-binding specificity and affinity of the medium subunit mu4 of the recently described adaptor protein complex AP-4...
  5. Jameel M, Klar J, Tariq M, Moawia A, Altaf Malik N, Seema Waseem S, et al. A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency. BMC Med Genet. 2014;15:133 pubmed publisher
    ..We performed whole-exome sequencing (WES) in two brothers with CP and intellectual disability. Analysis of AP4M1 mRNA was performed using quantitative real-time PCR on total RNA from cultured fibroblasts...
  6. Dell Angelica E, Mullins C, Bonifacino J. AP-4, a novel protein complex related to clathrin adaptors. J Biol Chem. 1999;274:7278-85 pubmed
    ..complex (AP-4) that also contains the sigma4 polypeptide and two additional adaptor subunit homologs named mu4 (mu-ARP2) and epsilon...
  7. Raza M, Mattera R, Morell R, Sainz E, Rahn R, Gutierrez J, et al. Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering. Am J Hum Genet. 2015;97:715-25 pubmed publisher
    ..These findings implicate deficits in intracellular trafficking in persistent stuttering. ..
  8. Stephens D, Banting G. Specificity of interaction between adaptor-complex medium chains and the tyrosine-based sorting motifs of TGN38 and lgp120. Biochem J. 1998;335 ( Pt 3):567-72 pubmed
    ..We also show that the newly identified mu-adaptin-related protein 2 (mu4) only interacts weakly with tyrosine-based sorting motifs.
  9. Hirst J, Bright N, Rous B, Robinson M. Characterization of a fourth adaptor-related protein complex. Mol Biol Cell. 1999;10:2787-802 pubmed
    ..by a combination of coimmunoprecipitation and yeast two-hybrid analysis that these four proteins (epsilon, beta4, mu4, and sigma4) are components of a novel adaptor-like heterotetrameric complex, which we are calling AP-4...