TABLE 1.

Summary of key risk factors and potentially affected cells and disrupted neurodevelopmental processes

ASD classification		Risk factor	Potentially affected cells in the cortex29	Potentially disrupted neurodevelopmental processes
Syndromic ASD	RS	MECP2	Ubiquitous	Proliferation, neurogenesis, migration, morphogenesis, synaptogenesis, gliogenesis, BBB formation
	FXS	FMR1
	TSCS	TSC1, TSC2
	PTENS	PTEN
	TS	CACNA1C	Neurons, mural and endothelial cells	Migration, morphogenesis, synaptogenesis, BBB formation
	PMS	SHANK3
Idiopathic ASD	Common variants13,28	APOPT1, BAG4, BAG5, CUEDC2, DDHD2, FGFR1, FOXP1, KLC1, KMT2E, LSM1, MARK3, POU3F2, PPDPF, PTBP2, SEC13, SLC30A9, SRM, SRPK2, TMEM33, WHSC1L1, XRN2, ZNF318, ZNF441	Ubiquitous	Proliferation, neurogenesis, migration, morphogenesis, synaptogenesis, gliogenesis, BBB formation
		BEND4, CKB, MMS22L, NUDT1, XRCC3	Progenitors	Proliferation, neurogenesis, migration
		CADPS, EEF1A2, MACROD2, NEGRI	Neurons	Migration, morphogenesis, synaptogenesis,
		GHRLOS, KIZ, FHIT, NKX2–2	Glia	Gliogenesis, synaptogenesis
		PRKG1, SOX7	Mural and endothelial cells	BBB formation
		ABCC10, ATP2B2, ATDN2, C8orp4, CRIP3, DCAF4L1, GHRL, LETM2, TLINC00852, LOC102723661, MIR1284, MIR378B, MIR6780B, MIR885, MROH5, NKX2–4, PINX1, PLPP5, PTK6, SLC22A7, TRMT61A, TTBK1, ZNF440, ZNF491, ZNF823	Very few or undetected
	Rare variants30,31	ADNP, AKAP9, ANK2, ANKRD11, AP2S1, ARID IB, ASH1L, BCL11A, CHD2, CREBBP, CTNNB1, CTTNBP2, CUL3, DIP2A, DNMT3A, DPYSL2, DYNC1H1, DYRK1A, ERBB2IP, ETFB, FOXP1, GIGYF1, GNAI1, GRIA2, HDLBP, HECTD4, ILF2, INTS6, IRF2BPL, KDM5B, KDM6B, KIAA0232, KMT2C, KMT2E, LDB1, MAPI A, MBD5, MED13L, MIB1, NAA15, NCKAP1, NCOA1, NINL, NLGN3, NRXN1, NSD1, NUP155, PHF12, PHF21A, POGZ, PPP2R5D, PTEN, RANBP17, RFX3, RORB, SATB1, SETD5, SIN3A, SKI, SLC6A1, SMARCC2, SPAST, STXBP1, SUV420H, TAOK1, TBL1XR1, TCF20, TCF4, TLK2, TM9SF4, TNRC6B, TRIM23, TRIO, TRIP 12, UBR1, VEZF1, WAC, WDFY3, ZMYND8, ZNF559	Ubiquitous	Proliferation, neurogenesis, migration, morphogenesis, synaptogenesis, gliogenesis, BBB formation
		ASXL3, CACNA1E, CACNA2D3, CELF4, CDH8, DEAF1, DSCAM, ELAVL3, FOXP2, GABRB2, GABRB3, GRIN2B, KCNMA1, KCNQ3, MYT1L, NR3C2, SCN1A, SCN2A, SHANK2, SHANK3, TBR1,	Neurons	Migration, morphogenesis, synaptogenesis,
		COROIA, GFAP, KAT2B, LRRC4C, SCN1A, SRPR, TCF7L2	Glia	Gliogenesis, synaptogenesis
		MKX, PHF2, SHANK3, TEK	Mural and endothelial cells	BBB formation
		ACHE, APH1A, CAPN12, KATNAL2, KMT5B, MFRP, NACC1, OR52M1, P2RX5, PAX5, PPP1R9B, PPP5C, PRR12, PTK7, SYNGAP1, TRAF7, USP45	Very few or undetected
	Medications	Valproic Acid, nAchRα antagonists	Progenitors, neurons	Proliferation, neurogenesis, migration, synaptogenesis
	Maternal infection	Cytomegalovirus, Herpes Simplex Virus, Rubella, Measles, Mumps, Varicella	Progenitors, neurons	Proliferation, neurogenesis, migration, synaptogenesis

Note: ASDs are broadly classified into syndromic and idiopathic. Syndromic ASD have been detected in patients with neurodevelopmental disorders, including Rett Syndrome (RS), Fragile X Syndrome (FXS), Tuberous Sclerosis Complex Syndrome (TSCS), PTEN Syndrome (PTENS), Timothy Syndrome (TS), and Phelan-McDermid Syndrome (PMS). For most of these syndromes, we know potentially affected cells and neurodevelopmental processes, based on the gene expression profiles and results of studies in rodent and human iPSC-based models. Idiopathic ASD has been associated with both common and rare genetic abnormalities, as well as certain medications and maternal infections. We extracted genes that have been found to carry common and rare genetic variants detected in the most recent studies and analyzed the expression pattern of these genes in different cells in the developing human cortex using publicly available database (http://cortex-dev.cells.ucsc.edu/). Using this analysis, all genes were subjectively classified into six groups: ubiquitously expressed in most cells; Primarily expressed in neural progenitors; neurons, including both excitatory and inhibitory neurons; glial cells, including astrocytes, oligodendrocyte progenitors, and choroid plexus cells; mural cells and/or endothelial cells; and those expressed in only few cells and/or at very low to undetectable levels.