Associated disorders

The AP4M1 gene is associated with autosomal recessive hereditary spastic paraplegia 50 (SPG50) (MedGen UID: 442869).

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AP4M1 is a rare cause of hereditary spastic paraplegia, and the percentage of HSP attributed to pathogenic variants identified in AP4M1 is unknown.

The AP4M1 gene encodes a subunit of the heterotetrameric AP-4 complex. The encoded protein belongs to the adaptor complexes medium subunits family. This AP-4 complex is involved in the recognition and sorting of cargo proteins with tyrosine-based motifs from the trans-golgi network to the endosomal-lysosomal system.

  1. Tüysüz, B, et al. Autosomal recessive spastic tetraplegia caused by AP4M1 and AP4B1 gene mutation: expansion of the facial and neuroimaging features. Am. J. Med. Genet. A. 2014; 164A(7):1677-85. doi: 10.1002/ajmg.a.36514. PMID: 24700674
  2. Hirst, J, et al. Characterization of a fourth adaptor-related protein complex. Mol. Biol. Cell. 1999; 10(8):2787-802. doi: 10.1091/mbc.10.8.2787. PMID: 10436028
  3. Fink, JK. Hereditary Spastic Paraplegia Overview. 2000 Aug 15. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1509/ PMID: 20301682
  4. Jameel, M, 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. doi: 10.1186/s12881-014-0133-2. PMID: 25496299
  5. Wang, X, Kilimann, MW. Identification of two new mu-adaptin-related proteins, mu-ARP1 and mu-ARP2. FEBS Lett. 1997; 402(1):57-61. doi: 10.1016/s0014-5793(96)01500-1. PMID: 9013859
  6. Verkerk, AJ, et al. Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy. Am. J. Hum. Genet. 2009; 85(1):40-52. doi: 10.1016/j.ajhg.2009.06.004. PMID: 19559397
  7. Najmabadi, H, et al. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011; 478(7367):57-63. doi: 10.1038/nature10423. PMID: 21937992
  8. Nakatsu, F, Ohno, H. Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct. Funct. 2003; 28(5):419-29. doi: 10.1247/csf.28.419. PMID: 14745134

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AP4M1 NM_004722.3