Supplemenary information: Functions of prioritised genes Family #1

1. SETDB1: Encodes histone methyl transferase and involved in the regulation of a large neuron specific topological chromatin domain(Jiang et al., 2017)and known to regulate mood related behaviours and NMDA receptor subunit NR2B expression (Jiang et al., 2017) 2. LRP2: is a member of the LDL receptor family, the gene is involved in various neurodevelopmental processes and signalling (Auderset et al., 2016; Fisher and Howie, 2006; Gomes et al., 2016; Spoelgen, 2005; Spuch et al., 2012) 3. TTC21B: Involved in various neurodevelopmental processes (Driver et al., 2017; Stottmann et al., 2009). 4. ADAMTS3: Encodes a member of the ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs) protein family. Recently the protein is reported to inactivate Reelin (RELN), which is involved in cell positioning and neuronal migration during brain development and modulate NMDA receptor function (Campo et al., 2009; Chen, 2005). A segregating rare variant in RELN is reported in a family with SZ and in an animal model showing behavioral abnormalities related to neuropsychiatric disorders (Sakai et al., 2016; Z. Zhou et al., 2016). 5. LRRTM2: Through the interaction with PSD-95 LRRTM2 regulates surface expression of AMPA receptors and through the LRRTM2 interaction with Neurexin1 the gene also has an important role in excitatory synapse development(de Wit et al., 2009) and maintenance of long-term potentiation (Soler-Llavina et al., 2013). The knockout micealso showed behavioural abnormalities (Voikar et al., 2013). 6. TIAM2: encodes guanine nucleotide exchange factor and is involved in neurite outgrowth, neuronal migration and synapse formation in the cerebral cortex (Goto et al., 2011; Kawauchi et al., 2003). 7. GRIN3A: encodes a subunit of the N-methyl-D-aspartate (NMDA) receptors. Knockout mice showed abnormal behavioural and cognitive functions (Mohamad et al., 2013) 8. UNC13B: is a presynaptic protein and is involved in vesicle priming for exocytosis and thus involved in neuro transmission and plasticity (Breustedt et al., 2010; Chen et al., 2013; Jahn and Fasshauer, 2012). Rare missense variants are reported in a multiply affected SZ family from Japan. 9. SHANK2: encodes protein is a member of the Shank family of synaptic proteins, in the postsynaptic density of excitatory synapses, which functions as a molecular scaffold. Because of NMDAR hypofunction and concomitant impairment of NMDAR signalling, Shank2–/– mice showed impaired long-term potentiation (LTP) and long-term depression (LTD). The mutant mice were hyperactive and recapitulated many of the behavioural phenotypes associated with autism spectrum disorder (Schmeisser et al., 2012; Won et al., 2012). Rare variants in this gene are also reported in SZ (Peykov et al., 2015) 10. AKAP5: This gene is involved in AMPA Receptor Phosphorylation and Cell-Surface Targeting (Diering et al., 2014). Knockout mice showed defect in synaptic plasticity, learning and memory related abnormalities (Weisenhaus et al., 2010) 11. PRODH: is located in 22q11, the strongest known risk factor of SZ (Levinson et al., 2011). This catalyses the first step in proline catabolism and activates NMDA and AMPA receptors and may act as a neuromodulator (Cohen and Nadler, 1997; Nadler et al., 1992). The proline is also a precursor for the neurotransmitter glutamate. The same variant rs2904551 is already reported in patients with SZ(Bender et al., 2005; Jacquet et al., 2002; Ota et al., 2014). Deletion of this gene in mice showed various psychiatry relevant phenotypes (Crabtree et al., 2016; Gogos et al., 1999; Paterlini et al., 2005; Williams, 2011) 12. FLNA: involved in neural progenitor proliferation (Lian et al., 2016)and neuronal migration (Lian et al., 2016). The protein is known to interact with glutamate receptor type 7 (Enz, 2002), dopamine D2 and D3 receptors(Lin et al., 2001) and Kv4.2 potassium channels(Lin et al., 2001).

Family #2

1. GABRR3: This gene encodes a subunit of the GABA(C) receptor. Gamma amino butyric acid (GABA) is one of the neurotransmitters in the central nervous system and it regulates synaptic neurotransmission in the neurons. Alteration in the GABA neurotransmitter system is observed in SZ (Wassef et al., 2003) 2. CASR: involved in synaptic plasticity, neurotransmission, neuronal growth (Ruat and Traiffort, 2013) and promotes resting spontaneous glutamate release(Ruat and Traiffort, 2013). 3. DOCK3: regulates BDNF-TrkB signalling and, neurite and axonal outgrowth (Namekata et al., 2012, 2010). It interacts with NMDA receptors containing NR2D subunit and reduces the surface expression of NR2D (Bai et al., 2013) 4. PDE8B: encodes cyclic nucleotide phosphodiesterase (PDE). It is involved in the hydrolysis of the second messenger cAMP and is involved in various cognitive functions (Tsai et al., 2012) 5. MAGI2: involved in the recruitment of AMPA and NMDA-type glutamate receptors (Deng et al., 2006). Structural variations reported in patients with SZ and bipolar disorder (Karlsson et al., 2012; Walsh et al., 2008). Common variants in this gene reportedly increased risk of cognitive impairment in patients with SZ (Koide et al., 2012). 6. GLI3: involved in development of the cerebral cortex, hypothalamus, corpus callosum (Amaniti et al., 2013; Haddad-TÃ3volli et al., 2015; Wilson et al., 2012), and maintenance and fate specification of cortical progenitors (Wang et al., 2011) 7. VPS13B: Has an important role in the development of the central nervous system 8. CALHM1: involved in the regulation of Ca²⁺-dependent MEK, ERK, RSK and MSK signalling in cerebral neurons (Dreses-Werringloer et al., 2013). Involved in memory, long-term potentiation and NMDA and AMPA receptors phosphorylation and knockout mice showed a severe impairment in memory flexibility(Vingtdeux et al., 2016) 9. INA: is involved in intracellular transport to axons and dendrites and morphogenesis of neurons. 10. CACNG7: encodes a type II transmembrane AMPA receptor regulatory protein (TARP), involved in synaptic expression of cerebellar AMPA receptors and function (Kato et al., 2007; Studniarczyk et al., 2013; Yamazaki et al., 2010) 11. PLAUR: encodes the receptor for urokinase plasminogen activator and the gene is involved in the development of GABAergic interneurons and knockout mice have shown various behavioural abnormalities (Eagleson et al., 2011, 2010)

Family #3

1. KIRREL: is a member of the nephrin-like protein family and the protein has an important role in synaptogenesis (Gerke et al., 2006). 2. GBX2: Involved in various neurodevelopmental processes, including neuronal differentiation, migration, growth etc. (Hagan et al., 2017; Sunmonu et al., 2011). 3. CELSR3: conditional knock out of Celsr3, in the mouse hippocampus has shown ∼50% reduction? of glutamatergic synapses and deficits in fear conditioning, spatial learning and memory(Thakar et al., 2017).Their roles in brain development, interneuron migration, glutamatergic synapse formation etc. are previously reported (Feng et al., 2012; Jia et al., 2014; Thakar et al., 2017; Ying et al., 2009). The gene is also known to regulate the expression of NRG1 and its receptor ErbB4 (Ying et al., 2009). 4. SCN11A: encodes a member of the sodium channel alpha subunit gene family and it is required for BDNF evoked depolarization (Blum et al., 2002) 5. UBA6: Involved in development of hippocampus and amygdala. Knockout mice showed various behavioural abnormalities relevant to autism like increased anxiety, impaired communication and decreased social interaction (Hagan et al., 2017; Sunmonu et al., 2011) 6. CDCA7L: involved in negative regulation of monoamine oxidase A (MAOA) gene expression and implicated in depressive disorder (Johnson et al., 2011; Ou et al., 2006) 7. MINK1: is a postsynaptically enriched protein and required for dendritic arborization and surface expression of AMPA receptors and has a role in maintaining the morphological integrity of dendrites and synaptic transmission (Hussain et al., 2010).

8. NTN1: is a member of laminin-related secreted proteins. Netrin-1 is implicated in the organization, plasticity and function of mesocorticolimbic DA neurons in rodents(Flores, 2011).

Family #4

1. LRRC7: It is known to influence the function of mGluRs and CaMKII at synapses and involved in the localisation of mGluR5 and DISC1 in the PSD fraction. Knockout mice showed various relevant endophenotypes of schizophrenia and autism spectrum disorders(Carlisle et al., 2011). 2. KIF1A: is a member of the kinesin family. It is an anterograde motor protein and involved in the transport of membranous organelles along axonal microtubules. In the brain, interacts with AMPA receptors and therefore could potentially act as a neuronal AMPAR transport in neurons (Shin et al., 2003). It is involved in synapse maturation, postsynaptic density maturation and perisynaptic scaffold organization (Zhang et al., 2017, 2016). 3. SCN10A: encodes a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit, and is involved in action potential initiation and propagation in excitable cells. Hypermorphic mutation of this gene in mice is reported to have a phenotype resembling catatonia in schizophrenic humans (Blasius et al., 2011). 4. FZD9: is a receptor for WNT2 and is involved in Wnt-5a-mediated increase in dendritic spine density in hippocampal neurons (Ramírez et al., 2016) and the gene is involved in various cognitive functions (Ramírez et al., 2016).The knockout mice showed defects in visuospatial learning and memory (Zhao, 2005) 5. SYT12: involved in modulation of spontaneous neurotransmitter release and long-term potentiation (Kaeser-Woo et al., 2013; Maximov et al., 2007) 6. CCKAR: involved in the regulation of central dopamine transmission in brain and absorption rate. Not having CCKAR has been shown to result in significantly elevated levels of extracellular dopamine in the central nervous system (Feifel et al., 2003). The gene has been previously associated with SZ (Koefoed et al., 2009; Sanjuan et al., 2004; Zheng et al., 2012). 7. SMARCC2: is a member of the SWI/SNF family of proteins, involved in cerebral development, neural stem cell proliferation and differentiation. Conditional deletion of the gene in mice shown learning/memory dysfunction (Tuoc et al., 2017, 2013). 8. GNB1L: is located on chromosome 22q11, a well know SZ candidate gene. SZ like behaviour is reported in mice with hemizygous deletion (Basson et al., 1999). The gene has been previously associated with SZ (Williams et al., 2008) 9. PQBP1: is a well known mental retardation causative gene (Jensen et al., 2011; Rejeb et al., 2011). It is involved in neural development and cognitive functions (Ito et al., 2015, 2009; Tamura et al., 2010; Yoshimura et al., 2006)

Family #5

1. KDM4A: is involved in BDNF expression, neuronal differentiation and survival (Milstein et al., 2007). 2. NOTCH2: is a member of the Notch family and is involved in various developmental processes. In hippocampal neurons, NOTCH2 is involved in the regulation of Vesicular glutamate transporter 1 (VGLUT1) protein levels (Wojcik et al., 2004) 3. DLG1: is a multi-domain scaffolding protein involved in various developmental processes. In the brain the protein is involved in trafficking and localisation of AMPA and NMDA-type glutamate receptor, Kv1.4, Kv4.2, and Kir2.2 potassium channels and astrocytic glutamate transporter EAAT2b (Cai et al., 2006; Fourie et al., 2014; Hong et al., 2015; Underhill et al., 2015; Walch, 2013). Knockout mice showed reduced sociability (Coba et al., 2018). 4. ABHD6: negatively regulates surface expression of AMPA receptors and synaptic function(Wei et al., 2017, 2016) 5. WASF1: is involved in BDNF-NTRK2 endocytic trafficking and in the regulation of cellular and behavioural actions of cocaine (Ceglia et al., 2017; Xu et al., 2016). Disruption of this gene in mice causes sensorimotor and cognitive deficits (Raber et al., 2002)

6. TRPA1: It is involved in GABA transport in hippocampal astrocytes and the activation of TRPA1 reducing GABA transport by GAT-3,that leads to activation increases the extracellular GABA concentration, which in turn decrease interneuron inhibitory synapse efficacy (Shigetomi et al., 2012). The gene is also involved in the modulation of glutamate release (Sun et al., 2009; Yokoyama et al., 2011) 7. HTR3A: encodes subunit A of the type 3 receptor for 5-hydroxytryptamine (serotonin). This gene is reported to associated with schizophrenic and bipolar disorder (Ji et al., 2008; Niesler et al., 2001b, 2001a). 8. PLCB3: encodes a protein that catalyses the production of diacylglycerol and inositol 1,4,5-triphosphate from phosphatidylinositol. Through the interaction with SHANK2, PLCB3 is involved in the mGluR-mediated calcium signal (Hwang et al., 2005). 9. RIC8A: In the brain, it is involved in the regulation of synapse number and neurotransmitter release (Mansilla et al., 2017; Romero-Pozuelo et al., 2014). Haploisuficiency of the gene in mice causes various behavioural abnormalities such as decreased (increased)? anxiety-like behaviour and impaired spatial memory (Ruisu et al., 2013; Tõnissoo et al., 2006) 10. ARPC3: encodes one of seven subunits of the Arp2/3 protein complex, which is involved in formation of dendritic filopodia and the recruitment of AMPA receptors (Spence et al., 2016).Deletion of this gene in mice showed various abnormalities relevant to SZ related disorders such as cognitive deficits, reduced prepulse inhibition, hyperactivity, and social isolation (Kim et al., 2013). 11. ACTN1: a postsynaptic scaffold protein, in the brain, that knows to interact with SHANK3, TSC1 and HOMER3(Kaeser-Woo et al., 2013). 12. TSC2: is involved in the regulation of the mammalian target of the rapamycin (mTOR) pathway and has an important role in activity dependent protein synthesis in neurons. Activation of NMDAR mediated signalling pathway induces mTOR signaling and negatively regulates TSC2 (Ru et al., 2012). Loss of Tsc2 in the mouse brain showed various phenotypes relevant to autism (Reith et al., 2013; Sato, 2016; Sato et al., 2012) 13. CACNG4: involved in trafficking and gating properties of AMPA glutamate receptors(Korber et al., 2007; Milstein et al., 2007)

Family #6 1. INPP4A: encodes an enzyme, which catalyses dephosphorylation of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4- bisphosphate. It is found in postsynaptic density and involved in the regulation of NMDAR-mediated excitatory postsynaptic current and localization of NMDAR in the synapse (Sasaki et al., 2010) 2. KIF5C: encodes a kinesin heavy chain subunit and involved in cargo transport in the central nervous system. It is also involved in axonal localization of GABA receptors (Smith et al., 2006; Wang and Xu, 2015) 3. IQSEC1: IQSEC1 directly interacts with AMPAR subunit GluA2, which is known to control the activity of IQSEC1. Subsequent IQSEC1 mediated activation of Arf6 promotes AMPAR endocytosis and is essential for mGluR- and NMDAR-dependent LTD(Scholz et al., 2010). It also has an important role in the development of mature glutamatergic synapses(Scholz et al., 2010). 4. NSUN2: encodes RNA methyltransferase that methylates RNAs. With the deletion of NSUN2 Drosophila melanogaster, severe short-term-memory deficits were observed (Abbasi-Moheb et al., 2012) 5. SFRP1: is a member of Wnt inhibitors, which are antagonists of Wnt signalling. Through the regulation of NMDAR currents and synaptic NMDAR subunit composition, the gene is involved in the induction of synaptic plasticity (Panaccione et al., 2013). Its role in dopamine neuron development is also reported (Kele et al., 2012).

6. TNC: This gene has an important role in neurodevelopment and modulation of synaptic functions (Andjus et al., 2005; Dityatev et al., 2007; Evers et al., 2002; Šekeljić and Andjus, 2012).Knockout mice showed abnormal behaviour such as hyperlocomotion, poor sensorimotor coordination and swimming ability. In addition decreased serotonin and dopamine transmission in different parts of the brain such as hippocampus, striatum, cerebral cortex etc. were also observed (Fukamauchi et al., 1996; Stamenkovic et al., 2017).

7. ABL1: encodes a protein tyrosine kinase and involved in receptor endocytosis, cell motility, adhesion, cell growth, DNA damage response and apoptosis. Through the phosphorylation of PSD-95 on tyrosine 533 residue ABL1 regulates PSD-95 clustering and synapse formation. PSD-95 is involved in NMDA and AMPA receptor clustering and localisation (de Arce et al., 2010) 8. LIN7C: enriched in brain synapses.Interacts with PSD-95 and NMDA receptor subunit and is involved in the localisation of NMDA receptor and synaptic vesicle exocytosis(Butz et al., 1998; Jo et al., 1999; Setou et al., 2000) 9. PAX6: encodes a homeobox and paired domain-containing protein, and acts as a regulator of transcription. In the thalamus, it regulates the balance between GABAergic and glutamatergic neurogenesis (Robertshaw et al., 2013) and it is involved in the regulation of balance between neural stem cell self-renewal and neurogenesis (Sansom et al., 2009). It is known to regulate the expression of Na(+) -dependent glutamate transporter GLT-1 (EAAT2) in astrocytes (Ghosh et al., 2016). Pax6 heterozygous rats showed impaired prepulse inhibition (PPI), abnormality in social interaction, impairment in rearing activity as well as in fear-conditioned memory and significantly reduced levels of serotonin levels in the plasma and brain (Tuoc et al., 2009). 10. CHRM4: muscarinic acetylcholine receptor M4, is a member of the G protein-coupled receptors family. It is involved in the regulation of cholinergic and dopaminergic neurotransmission and knockout mice showed elevated dopamine (DA) basal values and enhanced DA response to psychostimulants, dopaminergic hyperexcitability and increased basal acetylcholine efflux in the midbrain (Tzavara et al., 2004). The knockout mice showed increased sensitivity to the psychomimetic phencyclidine (noncompetitive NMDA receptor antagonist) mediated deficits in prepulse inhibition (Tuoc et al., 2009), amphetamine-induced hyperactivity in rats (Brady et al., 2008). 11. LRP4: is a regulator of Wnt signalling and involved in synapse formation (Scholz et al., 2010).Lrp4−/− mice showed defects in postsynaptic integration, synaptic transmission, long-term plasticity, learning and memory (Gomez et al., 2014; Karakatsani et al., 2017; Mosca et al., 2017; Pohlkamp et al., 2015). 12. ASCL1: involved in brain development, neural differentiation(Kim et al., 2011; Krolewski et al., 2012; Liu et al., 2017; Pattyn et al., 2006)and development of serotonergic neurons(Pattyn et al., 2006). 13. PRRT2: Involved in the cell surface expression of glutamate receptor and glutamate signalling (Li et al., 2015), spinogenesis, neuronal migration, synchronous neurotransmitter release and synapse formation and maintenance (Valtorta et al., 2016). Knockout mice showed paroxysmal movements, abnormal motor behaviours and altered synaptic transmission in the cerebellar cortex (Bai et al., 2013). 14. RAI1: Involved in various neurodevelopmental processes. Rai1+/−mice showed abnormal submissive tendencies, increased repetitive behaviours and reduced interest in social odours (Rao et al., 2017), whereas knockout mice showed learning impairment and motor dysfunction (Rao et al., 2017)

Family #7

1. DISC1: DISC1 is proposed to be involved in the release of glutamate (Maher and LoTurco, 2012) and known to impact the NMDAR expression and function (Yan et al., 2014). DISC1 knockout mouse models showed various phenotypes relevant to schizophrenia and other psychiatric disorders (Jaaro-Peled, 2009; Johnstone et al., 2011) 2. AGRN: plays an important role in neuronal responses to excitatory neurotransmitters both in vitro and in vivo (Hilgenberg et al., 2002). Agrin also has an important role in synaptic development, synaptic activity and plasticity (Daniels, 2012) 3. PTPRN: member of the protein tyrosine phosphatase (PTP) family, required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. Knockout mice showed various behavioural and cognitive abnormalities (Cai and Notkins, 2016; Carmona et al., 2014; Nishimura et al., 2010, 2009) 4. SLC25A12: encodes a calcium binding mitochondrial protein and it is involved in exchange of aspartate for glutamate across the inner mitochondrial membrane. The gene has been previously implicated in both SZ and autism (Aoki and Cortese, 2016; Hong et al., 2007). Knockout mice showed altered dopamine levels in the brain, hyper-reactivity and anxiety-like behaviour (Llorente-Folch et al., 2013) 5. WNT2: involved in the development of dopaminergic progenitors and dopaminergic neurons. Knockdown of the gene in mouse brains cause depression-like behaviours, impaired Wnt/β-catenin signalling and neurogenesis (Sousa et al., 2010; W. J. Zhou et al., 2016) 6. PTPRD: is a member of the protein tyrosine phosphatase (PTP) family and the gene is involved in hippocampal long-term potentiation and learning processes (Uetani, 2000). Recent GWAS showed that PTPRD is associated with Antipsychotic-induced weight gain (Yu et al., 2016). PTPRD deficient mice showed impairment in cognition and enhanced long-term potentiation (LTP) (Bruining et al., 2015). Structural variation is reported in autism spectrum disorder, dipolar disorder and ADHD (Bruining et al., 2015) 7. PLCB3: encodes a member of the phosphoinositide phospholipase C beta enzyme family. Through the interaction with SHANK2, PLCB3 regulates mGluR-mediated calcium signalling in the brain (Hwang et al., 2005) 8. PCDH9: is a member of the protocadherin family and the gene is involved in various neurodevelopmental processes (Asahina et al., 2012). Knockout mice showed specific long-term social and object recognition deficits (Bruining et al., 2015) 9. DYNC1H1: is a microtubule activated ATPase and acts as a molecular motor. This gene is involved in the modulation of dopamine signalling in striatum (Braunstein et al., 2010) and various neuro developmental processes (Ori-McKenney and Vallee, 2011). 10. TRPV3: is a member of nonselective cation channels and involved in temperature sensation and vasoregulation. Recently its role in modulation of mesolimbic-dopamine signalling has been reported (Singh et al., 2016). 11. PNPO: encodes pyridoxamine 5'-phosphate oxidase, a rate-limiting enzyme in pyridoxal 5'-phosphate (vitamin B(6)) synthesis. Vitamin B6 acts as a co-factor in the synthesis of neurotransmitters such as catecholamine and in homocysteine metabolism. 12. BSG: is a plasma membrane protein. It is an obligatory subunit of native plasma membrane Ca2+-ATPases,is involved in the extrusion Ca2+ ions from the cytosol and is a regulator of Ca2+ signalling. So it is involved in the regulation of intracellular Ca2+ concentration(Kina et al., 2007).Knockout mice showed abnormalities in sensory and memory functions (Naruhashi et al., 1997) Family #8

1. EIF2AK3: Through phosphorylation, it inactivates the alpha subunit of eukaryotic translation-initiation factor 2 and thus causes repression of translational initiation and global protein synthesis. Brain-specific disruption of the gene in mice leads to various behavioural abnormalities including cognitive and information processing deficits, and reduced prepulse inhibition (Trinh et al., 2012) 2. INPP4A: encodes an enzyme which catalyses dephosphorylation of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4- bisphosphate. It is found in postsynaptic density and involved in the regulation of NMDAR-mediated excitatory postsynaptic current and localization of NMDAR in the synapse (Sasaki et al., 2010). 3. PTPN4: is a member of the protein tyrosine phosphatase (PTP) family and in the brain it interacts with glutamate receptor delta 2 and epsilon subunits(Hironaka et al., 2000). The gene is also involved in phosphorylation and dephosphorylation of glutamate receptors (GluD2, GluA2) and thus long-term depression (Kohda et al., 2013). It is also involved in learning and cerebellar synaptic plasticity (Kina et al., 2007).Knockout mice had shown impaired motor learning and cerebellar long- term depression (Kina et al., 2007). 4. TRAK1: The gene is involved in trafficking of EGF-EGFR complexes and the γ- Aminobutyric acid type A (GABAA) receptor (Brickley et al., 2005; Kina et al., 2007; Webber et al., 2008) 5. EGF: is a member of member of the epidermal growth factor superfamily and it has an important role in dopaminergic precursor cell proliferation, dopaminergic neuron survival and development (O’Keeffe et al., 2009). Transgenic mice overexpressing the gene showed decreases in prepulse inhibition and context-dependent fear learning and higher behavioural sensitivity to the repeated cocaine injections (Eda et al., 2013) 6. MPDZ: The protein is known to interact with serotonin (5-HT2A, HTR2C), gamma aminobutyric acid B receptor 2 (GABA; GABBR2), dopamine (DRD2, DRD3 and DRD4) and NMDA receptors (Parker et al., 2003). The protein has an important role in NMDA-dependent AMPA receptor trafficking cascade (Funk et al., 2009; Karpyak et al., 2012; Krapivinsky et al., 2004; Parker et al., 2003) 7. KIF20B: required for cortical pyramidal neuron morphogenesis and is involved in branching and outgrowth of axon and dendrite, and neuron polarization (Janisch et al., 2013; McNeely et al., 2017). 8. ANK3:is involved in glutamatergic AMPA receptor mediated synaptic transmission, maintenance of spine morphology and MDA receptor-dependent plasticity (Smith et al., 2014). Knockout/heterozygous mice recapitulate a number of features of various human psychiatric disorders including bipolar disorder and schizophrenia(Cordner et al., 2017; van der Werf et al., 2017; Zhu et al., 2017) 9. PRRT2: is involved in neurotransmitter release, synapse formation and brain development (Liu et al., 2016; Valente et al., 2016). PRRT2 interacts with AMPA receptor GRIA1 and has an important role in glutamate signalling, membrane distribution of GRIA1 and glutamate receptor activity (Li et al., 2015). Knockout mice showed paroxysmal movements, abnormal motor behaviours and altered synaptic transmission in the cerebellar cortex (Bai et al., 2013). 10. GRIN3B: is a subunit of a glutamate N-methyl-D-aspartate (NMDA) receptor. Knockout mice showed impairment in motor learning or coordination, changes in home cage activity, social interaction, and increased anxiety-like behaviour (Kina et al., 2007) 11. TBX1: encodes a transcription factor.The gene lies within the 22q11.2 region and is a SZ and DiGeorge syndrome linked locus. Tbx1 haploinsufficiency in mice caused reduced prepulse inhibition (PPI) (Paylor et al., 2006) and another study showed that the congenic Tbx1 heterozygous mice displayed various Autism related phenotypes (Hiramoto et al., 2011). This gene is known to be involved in various neurodevelopmental processes and functions of neuronal circuits (Cioffi et al., 2014; Flore et al., 2016) Family #9 1. SCN2A: is a voltage-gated sodium channel involved in the generation and propagation of action potentials in excitable cells. This gene is already implicated in various neuropsychiatric disorders including SZ (Carroll et al., 2016). Scn2aKO/+ mice showed a range of behavioural and neurological phenotype observed in various rodent models of schizophrenia and autism spectrum disorder (Trinh et al., 2012). 2. KALRN: has an important role in synaptic structure and function as well as cognitive functions (Ma et al., 2008). KALRN is known to interact with the NR2B subunit of the NMDA receptor and the interactions are essential for normal synaptic plasticity (Kiraly et al., 2011). It has an important role in AMPA receptor uptake regulation during LTP (Herring and Nicoll, 2016). Knockout mice showed various behavioural abnormalities (Cahill et al., 2009; LaRese et al., 2017; Mandela and Ma, 2012; Xie et al., 2011) 3. CLSTN2: is a neuronal cell surface synaptic protein involved in learning and memory. The knockout mice showed high exploration and hyperactivity, stereotyped behaviour, reduced social behaviour and deficits in spatial learning and memory. The knockout mice showed a deficit of GABAergic interneurons and aberrant inhibitory transmission (Lipina et al., 2016; Ranneva et al., 2017). 4. DRD3: is a D3 subtype of the five dopamine receptors and is a well known SZ candidate gene (Nunokawa et al., 2010; Utsunomiya et al., 2008).

5. PDGFRB: is a cell surface tyrosine kinase receptor. This gene is involved in inhibition of excitatory transmission and NMDA receptor function (Lei et al., 1999; Valenzuela et al., 1996). PDGFRβ is known to be transactivated by dopamine receptor D4 and this transactivation is independent of PDGF ligand, PDGFRβ cross-phosphorylation and dimerization (Chi et al., 2010).Knockout mice showed behavioral and neuroanatomical features associated with various psychiatric disorders especially negative symptoms of schizophrenia, socio-emotional disturbances of autism and reduced number of parvalbumin-positive interneurons(Bai et al., 2013).

6. GPR151: is a member of a rhodopsin-like family of G-protein-coupled receptors (GPCRs) and is mainly expressed in habenular axonal projections. It is considered a novel drug target for various neuropsychiatric disorders (Broms et al., 2015).

7. GTF2IRD1: knockout mice have shown enhanced prefrontal serotonin 5-HT1A mediated responses and various behavioural abnormalities (Proulx et al., 2010).

8. KCNT1: is a voltage-gated ion channel, activated by elevations in intracellular sodium. It is known to interact and localise with PSD-95 (DLG4) (Uchino et al., 2003). It negatively regulates AMPA receptor mediated current, and the amplitude of synaptic potential (Nanou et al., 2008). 9. LAMA1: encodes one of the alpha 1 subunits of laminin and is involved in cell adhesion, migration, neurite outgrowth and angiogenesis. It has an important role in cerebellum development. Knockout mice showed behavioural abnormalities and impaired formation of the cerebellum (Heng et al., 2011; Ichikawa-Tomikawa et al., 2012) 10. LMTK3: is a member of the LMTK family of protein kinases and it is involved in endocytic trafficking of N-methyl-d-aspartate receptors. Lmtk3−/− mice showed reduced anxiety and depression-like behaviour, and pronounced locomotor hyperactivity. In the striatum of the knock out mice, dopamine metabolite levels and dopamine turnover rates increased (Inoue et al., 2014). 11. L3MBTL1: is a polycomb group gene, and the gene product is involved in chromatin modification. Knock out mice showed significant reduction in depression and and anxiety like behaviours (Shen et al., 2015). . Family #10 1. PLXNA2: is a member of the plexin-A family of semaphorin co-receptors and has a role in axon guidance, invasive growth and cell migration. Plxna2−/− mice showed malformed dentate gyrus and SZ like behaviours (Zhao et al., 2018).

2. GRM7: is a member of the metabotropic class of glutamate receptors.

3. GRM2:is a member of the metabotropic class of glutamate receptors. Through positive allosteric modulation of mGluR2 in translational models of cognitive symptoms associated with schizophrenia, showed improvement in memory and attention deficits (Yu et al., 2013) 4. PLD1: encodes phosphatidylcholine-specific phospholipase and catalyses the hydrolysis of phosphatidylcholine to phosphatidic acid and choline. In the brain, it is involved in BDNF induced signalling (Ammar et al., 2015), which in turn is involved in glutamatergic and GABAergic synapse formation, maturation and plasticity (Gottmann et al., 2009). Knockout mice displayed impaired brain development and reduced cognitive function (Zoubovsky et al., 2015). 5. PCM1: is a DISC1 interacting protein, implicated in centrosome assembly and function, implicated in SZ (Moens et al., 2010). Haploinsufficient for PCM1 (Pcm1+/−) mice showed reduced whole brain volume and impairment in social interaction (Zoubovsky et al., 2015). 6. NRP1: is a semaphorin receptor, involved in neuronal migration and patterning (Fantin et al., 2009). During the construction of GABAergic circuitry, NRP1 is involved in axon guidance and subcellular target recognition (Telley et al., 2016). 7. NEURL1: Through the modulation of CPEB3 levels and CPEB3-dependent synthesis of GluR1 and GluR2, NEURL1 is involved in hippocampal plasticity and hippocampal- dependent memory (Yu et al., 2013). In addition, it also affects the growth of new dendritic spines and increases the expression of GluA1 and GluA2 subunits of AMPA receptors. Inhibition of the gene impairs hippocampal-dependent memory and synaptic plasticity, and reduces GluA1 and GluA2 levels (Pavlopoulos et al., 2011). 8. TH: is a rate limiting enzyme in the biosynthesis of catecholamine, like dopamine and noradrenaline. 9. IQSEC3: is a member of the brefeldin A-resistant Arf-GEF/IQSEC family. Through interaction with gephyrin IQSEC3, promotes the formation of inhibitory synapses (Fukaya et al., 2011; Um et al., 2016). 10. THBS1: is a glycoprotein and is involved in cell-to-matrix and cell-to-cell interactions and in the regulation of excitatory synaptogenesis through the gabapentin receptor α2δ- 1(Crawford et al., 2012; Eroglu et al., 2009) and neuroligin 1 (NRG1)(Xu et al., 2010). 11. LAMA1: encodes one of the alpha 1 subunits of laminin and is involved in cell adhesion, migration, neurite outgrowth and angiogenesis. It has an important role in cerebellum development. Knockout mice showed behavioural abnormalities and impaired formation of the cerebellum (Heng et al., 2011; Ichikawa-Tomikawa et al., 2012) 12. EFNA2: in the developing neocortex, it is involved in interneuron migration and excitatory neuron differentiation (Homman-Ludiye et al., 2017). It is also involved in the modulation of experience-dependent, NMDA receptor-mediated, synaptic pruning during maturation of the mouse cortex (Yu et al., 2013). 13. PTPRT: is a member of the protein tyrosine phosphatase (PTP) family. Through interaction with cell adhesion molecules and Fyn protein tyrosine kinase, PTPRT regulates synapse formation in CNS (Lim et al., 2009). (Please rewrite the next two sentences. They don’t make sense as is.)Through interactions between the Syntaxin- binding protein, the Syntaxin protein known to regulate neurotransmitter release and the protein also known to be involved in various neurodevelopmental process by dephosphorylating synaptic molecules and its interaction with neuronal adhesion molecules (Lee, 2015). 14. SHANK3: is a multidomain scaffold postsynaptic density protein of excitatory synapses. It is involved in NMDA receptor signalling (Duffney et al., 2013), regulation of Metabotropic Glutamate Receptor 5 expression (Duffney et al., 2013) and AMPA Receptor Recycling and Synaptic LTP (Raynaud et al., 2013). SHANK3 knockout mice showed autistic-like behaviours, striatal dysfunction, spatial memory deficit and abnormal social interaction (Jaramillo et al., 2016; Lee et al., 2015; Peça et al., 2011) 15. PLXNA3: is a class 3 semaphorin receptor involved in the development of hippocampal axonal projections (Pavlopoulos et al., 2011)

Family #11 1. ANK2: is a member of the Ankyrin protein family and connects integral membrane proteins to underlying spectrin-actin cytoskeleton. The gene has an important role in synaptic stability (Koch et al., 2008). 2. KMT2E: involved in promoter related histone acetylation and H3K4 tri- and di- methylation 3. FGF23: is a member of the fibroblast growth factor family of proteins. In the hippocampal neurons, it induces phospholipase Cγ activity, inhibits neuronal ramification and enhances the synaptic density. It may also be involved in memory formation (Hensel et al., 2016). 4. GRIN3B: is a subunit of a glutamate N-methyl-D-aspartate (NMDA) receptor. Knockout mice showed impairment in motor learning or coordination, changes in home cage activity, social interaction, and increased anxiety-like behaviour (Kina et al., 2007) 5. ARR3: encodes a non-visual arrestin, which binds to agonist-activated, phosphorylated G protein-coupled receptors. This dissociates receptors from the heterotrimeric G protein and thus terminates the signalling process. ARR3 is involved in D2 dopamine receptor internalisation (Skinbjerg et al., 2009).

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