Relevance to Autism

Kim et al., 2026 reported two individuals with ASD carrying compound heterozygous missense mutations in the MDGA1 gene [(p.Val116Met/p.Ala688Val) and (p.Tyr635Cys/p.Glu756Gln)]; murine in utero overexpression of MDGA1 p.Val116Met/p.Ala688Val altered cortical neuron migration, while MDGA1 p.Tyr635Cys/p.Glu756Gln disrupted the triangular extracellular structure of MDGA1 and rendered it unable to impact GABAergic synapses in hippocampal CA1 neurons. Furthermore, Kim et al., 2026 found that male Mdga1 knock-in mice harboring the p.Tyr653Cys/p.Glu756Gln mutation exhibited impaired ultrasonic vocalizations and sensorimotor gating, similar to male Mdga1 conditional knockout mice, while no behavioral deficits were seen in female counterparts. Additional de novo and inherited heterozygous variants in the MDGA1 gene were previously identified in ASD probands from the Simons Simplex Collection, the Autism Sequencing Consortium, the SPARK cohort, the MSSNG cohort, and the mAGRE cohort (Lim et al., 2017; Zhou et al., 2022; Fu et al., 2022; Trost et al., 2022; Cirnigliaro et al., 2023). Pettem et al., 2013 demonstrated that MDGA1 inhibited the synapse-promoting activity of neuroligin-2, without altering neuroligin-2 surface trafficking, by inhibiting interaction of neuroligin-2 with neurexin.

Molecular Function

This gene encodes a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that is expressed predominantly in the developing nervous system. In addition to possessing several cell adhesion molecule-like domains, the mature protein has six Ig-like domains, a single fibronectin type III domain, a MAM domain and a C-terminal GPI-anchoring site. Studies in other mammals suggest this protein plays a role in cell adhesion, migration, and axon guidance and, in the developing brain, neuronal migration. In humans, this gene is associated with bipolar disorder and schizophrenia.

External Links

References