Table 3.
Detailed information on the biological function of the 15 ASD and three dopamine related proteins differentially expressed in the MeA.
| Symbol | Comp. | Related | Cat. | Description | References |
|---|---|---|---|---|---|
| BCAS1 | 1,2 | ASD | 3 | Brain Enriched Myelin Associated Protein 1 associates with a variety of aggressive tumors. In the brain, BCAS1 isrequired for myelination and is expressed in oligodendrocytes and Schwann cells, showing decreased expression in demyelination. Mice lacking BCAS1 showed schizophrenia-like behaviors. Exome sequencing confirmed association with autism. | Ishimoto et al. (2017) |
| CD38 | 1 | ASD | 3 | CD38 is an ectoenzyme widely expressed (especially in leukocytes), with functions in calcium transportation and signaling, cell adhesion, signal transduction and regulation of oxytocin and paternal behavior. CD38 expression was significantly reduced in ASD subjects. Genetic association to ASD was found in AGRE, Japanese and Israeli cohorts. | Martucci et al. (2019) |
| CD99L2 | 3 | ASD | 3 | CD99 Molecule Like 2 is a cell-surface protein similar to CD99 and plays a role in leukocyte extravasation, helping immune cell transmigration through the endothelial basement membrane. As in other immune-related genes, SNPs in CD99L2 were significantly associated with ASD. | Ramos et al. (2012) |
| CDKL5 | 2 | ASD | 1 | Cyclin Dependent Kinase Like 5 is a member of Ser/Thr protein kinase family involved in the phosporilation of proteins, especially important in the posttranslational modifications. In mice, CDKL5 deficiency compromised the GABA/Glut balance.Mutations in CDKL5 associates with syndromic autism, Rett syndrome, Angelman and seizures. | Tang et al. (2019) |
| ERMN | 2 | ASD | 3 | Ermin is an oligodendrocyte cytoskeletal protein involved in myelination. Deficient myelination has been reported in ASD subjects. Hypomethylation caused by genetic variants at ERMN significantly associated with ASD. | Galvez-Contreras et al. (2020) |
| FGA | 1 | ASD | 3 | Fibrinogen Alpha Chain, the alpha subunit of the coagulation factor fibrinogen, is a component of the blood clot also involved in the stabilization of the lesion and cell migration guidance. Several SNPs in FGA showed association with ASD. | Yang et al. (2018) |
| GLO1 | 1,3 | ASD | 3 | Glyoxalase I mediates catalysis and formation of S-lactoyl-glutathione from methylglyoxal (MG) and reduced glutathione, decreasing MG levels. MG is a precursor of advanced glycation end products (AGE) and both MG and AGEs can induce oxidative stress, mitochondrial dysfunction and inflammation. High AGE levels were found in the brain of ASD subjects. | Kovač et al. (2015) |
| GSTM1 | 3 | ASD | 3 | Glutathione S-Transferase Mu 1 functions in the detoxification of electrophilic compounds including drugs and environmental toxins, by conjugating with glutathione, an antioxidant acting as a free radical scavenger. Deficits in GSTM1 may increase sensitivity to toxicant exposure early in life, which has been pointed out to trigger ASD. | Yochum et al. (2010) |
| LRRC4C | 2 | ASD | 1-Satt. | Leucine Rich Repeat Containing 4C is a specific binding partner for netrin G1 (NTNG1), a member of the netrin family of axon guidance molecules. LRRC4C plays a central role in early nervous system development and differentiation, and it may promote neurite outgrowth. Genetic variants in LRRC4C have been detected in ASD subjects. | Um et al. (2018) |
| NFIB | 2 | ASD | Synd. | Nuclear Factor I B is a transcription factor essential in embryonic development. NFIB acts as a cofactor of FOXP2 to activate genes involved in neuronal maturation and is a transcriptional activator of GFAP, essential for brain development. Mutations in NFIB led to intellectual disability, speech delay, macrocephaly, behavioral deficits and ASD. | Hickey et al. (2019) |
| NTRK3 | 1,3 | ASD | 3 | Neurotrophic Receptor Tyrosine Kinase 3 is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway that control cell survival and differentiation. Genetic association of NTRK3 has been found with autism and Asperger syndrome. | Chakrabarti et al. (2009) |
| PSD3 | 1,2 | ASD | 3 | Pleckstrin And Sec7 Domain Containing 3 is a guanine nucleotide exchange factor for ARF6 and is involved in phospholipid binding and endocytosis. Rare mutations involving PSD3 have been identified in individuals with ASD. | Pinto et al. (2010) |
| SDC2 | 1,2 | ASD | 3 | Syndecan 2 is a transmembrane heparan sulfate proteoglycan. The syndecans mediate cell binding, cell signaling, cytoskeletal organization, cell proliferation and cell migration. In neurons, SDC2 is highly expressed during development and is involved in spine and synapse formation. A rare mutation in the SDC2 gene has been identified in autism. | Hu et al. (2016) |
| SRPR | 1 | ASD | Satt. | SRP Receptor Subunit Alpha is a component of the SRP (signal recognition particle) receptor of the Endoplasmic Reticulum that ensures the correct targeting of the nascent secretory proteins to the endoplasmic reticulum membrane system. In autism, its expression in the cortex may be regulated by ASD-associated SNPs through DNA methylation. | Sun et al. (2019) |
| GFAP | 1 | ASD /DOPA | 1-Satt. | Fibrous astrocytes Glial Fibrillary Acidic Protein is a major intermediate filament protein of mature astrocytes, common marker of astrocytes and a target of dopamine. It is involved in responses to brain inflammation, injury and disease. Astrocytic abnormalities and increased mRNA levels of GFAP have been observed in post-mortem brains of autistic individuals. | Edmonson et al. (2014) |
| DNM1 | 3 | DOPA | Dynamin 1 is a GTP-binding protein important for synaptic vesicle endocytosis in neurotransmission that exhibits D2 dopamine receptor binding. Genetic variants in DNM1 are one of the most common causes of epileptic encephalopathy. | Bonnycastle (2018) | |
| FLNA | 1 | DOPA | Filamin A promotes branching of actin filaments and anchors transmembrane proteins to the cytoskeleton. In the brain, FLNA plays a role in cell-cell contacts and adherens junctions during the development and intervenes in the internalization of transmembrane receptors such as dopamine receptor type 2 and 3 (DRD2 and DRD3). FLNA is also involved in neuronal migration and it is required for growth cone collapse in axons. | Coelho et al. (2019) |
Column “Comp.” states in which comparison(s) each of these proteins were differentially expressed (i.e., 1: Foxp2+/– female vs. ctr female; 2: Foxp2+/− male vs. ctr male; 3: Foxp2+/– female vs. Foxp2+/– male). ASD-related proteins were classified according to SFARI categories (syndromic; 1: high confidence; 2: strong candidate, and 3: suggestive evidence) and/or present in the largest exome sequencing study of ASD individuals by Satterstrom et al. (2020). From the list, GFAP was the only protein related to both ASD (Cat. 1/Satt.) and dopamine signaling; and NF1B was the only one classified as “syndromic”. Information in the table was summarized from Genecards and SFARI websites, as well as additional references. Expression of CD38, FGA, NTRK3, and GFAP had been previously reported to be sexually dimorphic in the brain (Jin et al., 2007; Berchtold et al., 2008; Arias et al., 2009; Ramsey et al., 2012); and CDKL5 disorders to primarily affect females (Bahi-Buisson and Bienvenu, 2011).