Table 2 QMI targets, autism linkage, and antibody information

GRM5

mGluR5

Metabotropic glutamate receptor. G-protein coupled receptor activates Erk and PI3K cascades in response to glutamate.

NS

Rare variants identified in ASD patients [61, 75]. Plays a key role in Fragile X [41] and possibly other ASD models.

Millipore 5675 Cat#AB5675

Neuromab N75/3

Cat# 75-115

GRIN1

NMDAR1

NMDA-type glutamate receptor subunits. NMDARs are heterotetramers with high Ca2+ permeability, essential for learning and memory. Subunits confer different functional properties to the receptor.

3

Rare variant in ASD siblings [76]

Thermo 54.1 Cat# 02-0500

Santa Cruz polyclonal C20 Cat# sc-1467

GRIN2A

NMDAR2A

4

Genetic association [77]

Neuromab N327/95 Cat#75-288

Biolegend N327A/38 Cat# 832401

GRIN2B

NMDAR2B

1

Multiple rare variants identified in ASD patients. [4, 78, 79]

Biolegend N59/20 Cat# 832501

Biolegend N59/36 Cat# 818701

GRIA1

GluR1

AMPA-type glutamate receptor subunits. AMPARs are also tetramers. Subunits confer different functional properties to the receptor.

2

Recurrent missence mutations [4, 80]

Biolegend N355/1 Cat# 819801

Millipore polyclonal 1504 Cat# AB1504

GRIA2

GluR2

–

Contained in an ASD-linked deletion [81]

Biolegend L21/32 Cat# 810501

Santa Cruz polyclonal C20 Cat# sc-7610

NLGN3

NL3

Postsynaptic Neuroligin 3 binds presynaptic neurexins to create trans-synaptic adhesion bridges. Cleavage following activity may be involved in cell signaling.

2

Rare mutations; TADA study [82, 83]

Thermo 566209 Cat# MA5-24253

Santa Cruz G2 Cat # sc-271880

HOMER1

Homer1

Postsynaptic scaffold linking Shanks, mGluRs, and many other postsynaptic components. Forms homo-tetramer via N-terminal coiled-coil domain.

4

Rare variants [61]

Lifespan Biosciences AT1F3 Cat# LS-C103482

Santa Cruz D3

Cat # SC-17842

Homer1A

Activity-dependent isoform of Homer1 that lacks coiled-coil domain and acts as a dominant negative, preventing scaffolding by long Homers.

–

Santa Cruz polyclonal M13 Cat# sc-8922

DLG4

PSD95

Major component of postsynaptic density, scaffolds NMDARs and other components of the PSD via multiple binding domains.

NS

Rare variants and network gene analyses [84,85,86]

Biolegend K28/74 Cat# 810301

Biolegend K28/43 Cat# 810401

DLG1

SAP97

Scaffold with similar function to PSD95, but differentspecific binding affinities.

NS

Exome sequencing revealed rare variants [85]

Enzo RPI197.4 Cat# ADI-VAM-PS00

SantaCruz polyclonal H60 Cat# sc-25661

SHANK3

SHANK3

Scaffolding protein that forms a polymeric structure with Homer, and links multiple receptor types to downstream signaling pathways

1S

Recurrent rare de novo mutations and copy number variations (deletions) [87]

NeuroMab N367/62 Cat# 75-344

Enzo Life Sciences RPI197.4 Cat# ADI-VAM-PS00

UBE3A

Ube3A

E3 ubiquitin ligase, phospho-regulated by synaptic activity, that ubiquitinates Arc as well as other neuronal targets; also acts as a transcriptional regulator.

3S

Rare variants and copy number variations (duplications) [88, 89]

Santa Cruz H182 Cat# sc-25509

Santa Cruz E-4 Cat # sc-166689

SYNGAP1

SynGAP1

A RAS GTPase that is heavily expressed at the PSD. Negatively regulates RAS. PSD95 binding may be important in regulating synaptic binding “slots.”

1S

Multiple rare variants [90]

Cell Signaling D20C7 Cat# 5539

SantaCruz polyclonal R19 Cat# sc8572

FYN

Fyn Kinase

Associates with PSD95 and NMDARs, phosphorylates the latter. Also binds and is activated by mGluRs.

–

None reported

Santa Cruz Fyn15 Cat# sc-434

BioLegend FYN59 Cat# B149751

PIK3R1

PI3K

PI3K is a lipid kinase that phosphorylates membrane phospholipids and initiates PI3K/AKT/mTOR signaling. The enzyme consists of a p85 regulatory and p110 catalytic subunit. Our antibodies target p85alpha.

–

PI3K subunits PIK3CG and PIK3R2 (Simons score 4 and S, respectively) have been linked to autism [91, 92]

Thermo-Fisher U5 Cat# MA1-74183

Millipore AB6 Cat# 05-212