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FB2026_03
,
released September 17, 2026
In a patient with intellectual disability and behavioral anomalies, duplication of the human GPM6A gene has been implicated in development of the observed pathologies (FBrf0226833). The GPM6A protein is a neuronal transmembrane glycoprotein; there is a single orthologous gene in Drosophila, M6, for which RNAi-targeting constructs, alleles caused by insertional mutagenesis have been generated, and hypomorphic alleles caused by imprecise excision of a TE insertion have been generated. Dmel\M6 is also orthologous to GPM6B and PLP1 in human; it is most closely related to GPM6A.
The human GPM6A gene has not been introduced into flies.
Animals homozygous for hypomorphic mutations of Dmel\M6 do not exhibit defects in neuromuscular junctions or locomotion, but do exhibit defects in long-term memory; homozygous females exhibit reduced fertility. Ubiquitous knockdown of Dmel\M6 effected by RNAi results in pupal lethality. Neuron-specific knockdown allows survival to adulthood without conspicuous neural defects; however, long-term memory defects are observed (assayed using a courtship behavior). Pan-neuronal overexpression also results in impairment of courtship-based long-term memory, indicating that correct levels of Dmel\M6 are required for this aspect of normal cognitive function.
[updated Jul. 2018 by FlyBase; FBrf0222196]
This disease is represented by a single patient with intellectual disability and behavioral anomalies(FBrf0226833).
Duplication of the human GPM6A gene has been implicated in development of the observed pathologies. No obviously pathogenic truncating mutations in GPM6A have been described (FBrf0226833).
Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol-rich lipid rafts within the plasma membrane and promotes filopodia formation (FBrf0226833 and references cited therein).
Involved in neuronal differentiation, including differentiation and migration of neuronal stem cells. [Gene Cards, GPM6A; 2018.07.23]
Many to one: 3 human to 1 Drosophila; the other human genes are GPM6B and PLP1.
High-scoring ortholog of GPM6A, moderate-scoring ortholog of GPM6B and PLP1 (1 Drosophila to 3 human). Dmel\M6 shares 24-29% identity and 39-49% similarity with the human genes.