DSCAM

Summary

DSCAM (DS cell adhesion molecule, HGNC:3039) is a protein-coding gene on chromosome 21q22.2, encoding Cell adhesion molecule DSCAM (O60469). Cell adhesion molecule that plays a role in neuronal self-avoidance.

This gene is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs), and is involved in human central and peripheral nervous system development. This gene is a candidate for Down syndrome and congenital heart disease (DSCHD). A gene encoding a similar Ig-CAM protein is located on chromosome 11. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 1826 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autism (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 24
• Clinical variants (ClinVar): 355 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 3
• Dosage sensitivity (ClinGen): haploinsufficiency emerging evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001389

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3039
Approved symbol	DSCAM
Name	DS cell adhesion molecule
Location	21q22.2
Locus type	gene with protein product
Status	Approved
Aliases	CHD2-42, CHD2-52
Ensembl gene	ENSG00000171587
Ensembl biotype	protein_coding
OMIM	602523
Entrez	1826

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000400454, ENST00000404019, ENST00000617870

RefSeq mRNA: 2 — MANE Select: NM_001389 NM_001271534, NM_001389

CCDS: CCDS42929

Canonical transcript exons

ENST00000400454 — 33 exons

Exon	Start	End
ENSE00001138378	40369099	40369245
ENSE00001174802	40338101	40338376
ENSE00001174805	40339119	40339415
ENSE00001174811	40347670	40347945
ENSE00001174815	40353465	40353743
ENSE00001175237	40080152	40080340
ENSE00001175244	40083908	40084006
ENSE00001175248	40085602	40085765
ENSE00001175254	40087170	40087287
ENSE00001175262	40093721	40093874
ENSE00001203412	40078687	40078977
ENSE00001203423	40124195	40124328
ENSE00001290276	40051958	40052107
ENSE00001290929	40075037	40075213
ENSE00001296378	40187131	40187259
ENSE00001297675	40296055	40296174
ENSE00001299928	40276097	40276270
ENSE00001300225	40692810	40692956
ENSE00001301674	40055725	40055840
ENSE00001301906	40187891	40187987
ENSE00001303370	40312081	40312359
ENSE00001305503	40144491	40144731
ENSE00001306377	40133854	40134009
ENSE00001317868	40044078	40044275
ENSE00001318915	40178927	40179094
ENSE00001322604	40042371	40042673
ENSE00001325865	40167218	40167288
ENSE00001327150	40142558	40142704
ENSE00001330905	40189042	40189238
ENSE00001542956	40010999	40013386
ENSE00001543045	40708454	40708771
ENSE00001543050	40846619	40847158
ENSE00002519798	40062869	40062899

Expression profiles

Bgee: expression breadth broad, 83 present calls, max score 91.32.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1311 / max 127.0483, expressed in 192 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190520	0.7204	131
190523	0.4409	116
190522	0.3803	120
190519	0.2261	99
190524	0.1083	64
190517	0.0905	47
190518	0.0807	58
190525	0.0528	26
190521	0.0311	18

Top tissues by expression

266 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	91.32	gold quality
cortical plate	UBERON:0005343	87.11	gold quality
lateral nuclear group of thalamus	UBERON:0002736	83.65	gold quality
buccal mucosa cell	CL:0002336	81.07	silver quality
entorhinal cortex	UBERON:0002728	79.57	gold quality
lateral globus pallidus	UBERON:0002476	78.98	gold quality
postcentral gyrus	UBERON:0002581	78.97	gold quality
Brodmann (1909) area 46	UBERON:0006483	78.59	silver quality
superior frontal gyrus	UBERON:0002661	78.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	78.22	gold quality
substantia nigra pars reticulata	UBERON:0001966	78.15	silver quality
temporal lobe	UBERON:0001871	77.93	gold quality
medial globus pallidus	UBERON:0002477	77.86	gold quality
parietal lobe	UBERON:0001872	77.85	gold quality
globus pallidus	UBERON:0001875	77.61	gold quality
substantia nigra pars compacta	UBERON:0001965	77.51	silver quality
primary visual cortex	UBERON:0002436	77.46	gold quality
amygdala	UBERON:0001876	77.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.22	gold quality
prefrontal cortex	UBERON:0000451	77.18	gold quality
middle temporal gyrus	UBERON:0002771	76.92	gold quality
paraflocculus	UBERON:0005351	76.70	gold quality
middle frontal gyrus	UBERON:0002702	76.47	silver quality
cingulate cortex	UBERON:0003027	76.21	gold quality
anterior cingulate cortex	UBERON:0009835	76.09	gold quality
Ammon’s horn	UBERON:0001954	75.97	gold quality
cerebral cortex	UBERON:0000956	75.90	gold quality
neocortex	UBERON:0001950	75.84	gold quality
occipital lobe	UBERON:0002021	75.76	gold quality
frontal cortex	UBERON:0001870	75.73	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	7906.26
E-HCAD-35	yes	7055.45
E-HCAD-30	yes	6837.65
E-HCAD-25	yes	5778.33
E-GEOD-84465	yes	25.59
E-ANND-3	yes	7.00
E-GEOD-93593	yes	4.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting DSCAM, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209

Functional genomics

ClinGen dosage: haploinsufficiency 2 (emerging evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 24)

• A specific promoter region directs expression of DSCAM in the developing choroid plexus and roof of the fourth ventricle, the floor plate of the fourth ventricle, pons and medulla oblongata, and the eye, limb buds, and dorsal root ganglion (PMID:12435380)
• The specificity of Drosophila Dscam is due to complementarity of variable residues in epitope I. (PMID:17721508)
• These results suggest the possible contribution of DSCAM gene in bipolar disorder. (PMID:18197079)
• findings demonstrate an essential role of vertebrate DSCAM in axon guidance, indicating that DSCAM functions as a receptor of netrin-1 (PMID:19196994)
• Dscam transgene with or without exon 19 in its endodomain is used to govern different stage-specific neuronal morphogenetic processes, possibly due to differences in protein targeting. (PMID:19211897)
• In all transgenic retinal cell types examined, both DSCAM and DSCAM-LIKE1 genes are functioning similarly in self-avoidance, whereas the stratification of neurites and synaptic specificity are intact in their absence. (PMID:19945391)
• Dscam may be involved in the generation and development of intractable epilepsy. (PMID:21360594)
• functionally conserved with Drosophila Dscam[TM1] isoforms (PMID:21645617)
• knockdown of DSCAM inhibits netrin-induced tyrosine phosphorylation of UNC5C and Fyn as well as the interaction of UNC5C with Fyn. The double knockdown of both receptors abolishes the induction of Fyn tyrosine phosphorylation by netrin-1 (PMID:22685302)
• Overall, our study found a significant association of IL-17RC gene polymorphisms with AIS in a Chinese Han population, indicating IL-17RC gene may be as a susceptibility gene for AIS. (PMID:22744455)
• Down syndrome cell adhesion molecule interacts with PRKAG1 subunit and plays an important role in netrin-1 induced neurite outgrowth. (PMID:23479427)
• DSCAM as a Hirschsprung disease (HSCR) susceptibility locus, both in Down syndrome and HSCR isolated cases. (PMID:23671607)
• Our study did not repeatedly confirm the association of the rs2222973 or the rs11770843 SNP with adolescent idiopathic scoliosis in a Chinese Han population. (PMID:25408124)
• DSCAM physically interacts with tubulin folding cofactor D. (PMID:25653356)
• The most significant was DSCAM, a neurological gene expressed widely in the developing brain and in the amygdala and hippocampus of the adult brain. (PMID:25867994)
• There is an association between DSCAM polymorphisms and non-syndromic HSCR in South Chinese population. (PMID:30005639)
• Genome wide analysis identified DSCAM as a new imprinted gene in the human placenta. (PMID:30206355)
• We further show that introns drive selection of both proximal and distal variable exons. Since exon 4 cluster introns lack conserved sequences that could mediate robust long-range base-pairing to bring exons into proximity for splicing, our data argue for a central role of introns in mutually exclusive alternative splicing of Dscam exon 4 cluster (PMID:30541104)
• Long non-coding RNA DSCAM-AS1 contributes to the tumorigenesis of cervical cancer by targeting miR-877-5p/ATXN7L3 axis. (PMID:31737900)
• DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome. (PMID:33945512)
• Dysfunction of NMDA receptors in neuronal models of an autism spectrum disorder patient with a DSCAM mutation and in Dscam-knockout mice. (PMID:34253863)
• Long non-coding RNA Down syndrome cell adhesion molecule-anti-sense 1 promotes gastric carcinoma cell proliferation and migration by regulating the miR-204/TPT1 axis. (PMID:34372727)
• Role of DSCAM in the Development of Neural Control of Movement and Locomotion. (PMID:34445216)
• Increased endothelial sclerostin caused by elevated DSCAM mediates multiple trisomy 21 phenotypes. (PMID:38828726)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dscama	ENSDARG00000024865
danio_rerio	dscamb	ENSDARG00000028118
mus_musculus	Dscam	ENSMUSG00000050272
rattus_norvegicus	Dscam	ENSRNOG00000027992

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), IGSF9 (ENSG00000085552), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), IGDCC4 (ENSG00000103742), CNTN3 (ENSG00000113805), IGSF21 (ENSG00000117154), CNTN6 (ENSG00000134115), CHL1 (ENSG00000134121), PTPRQ (ENSG00000139304), CNTN4 (ENSG00000144619), BOC (ENSG00000144857), SDK1 (ENSG00000146555), HMCN2 (ENSG00000148357), NCAM1 (ENSG00000149294), CNTN5 (ENSG00000149972), IGSF10 (ENSG00000152580), ROBO4 (ENSG00000154133), ROBO3 (ENSG00000154134), NCAM2 (ENSG00000154654), VCAM1 (ENSG00000162692), NFASC (ENSG00000163531), PRTG (ENSG00000166450), ROBO1 (ENSG00000169855), IGDCC3 (ENSG00000174498), VSIG10 (ENSG00000176834), DSCAML1 (ENSG00000177103), CNTN2 (ENSG00000184144), ROBO2 (ENSG00000185008), VSIG10L (ENSG00000186806), DCC (ENSG00000187323), L1CAM (ENSG00000198910)

Protein

Protein identifiers

Cell adhesion molecule DSCAM — O60469 (reviewed: O60469)

Alternative names: CHD2, Down syndrome cell adhesion molecule

All UniProt accessions (3): A0A087WUI7, O60469, Q8WY19

UniProt curated annotations — full annotation on UniProt →

Function. Cell adhesion molecule that plays a role in neuronal self-avoidance. Promotes repulsion between specific neuronal processes of either the same cell or the same subtype of cells. Mediates within retinal amacrine and ganglion cell subtypes both isoneuronal self-avoidance for creating an orderly dendritic arborization and heteroneuronal self-avoidance to maintain the mosaic spacing between amacrine and ganglion cell bodies. Receptor for netrin required for axon guidance independently of and in collaboration with the receptor DCC. Might also collaborate with UNC5C in NTN1-mediated axon repulsion independently of DCC. In spinal cord development plays a role in guiding commissural axons projection and pathfinding across the ventral midline to reach the floor plate upon ligand binding. Mediates intracellular signaling by stimulating the activation of MAPK8 and MAP kinase p38. Adhesion molecule that promotes lamina-specific synaptic connections in the retina: expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promotes synaptic connectivity via homophilic interactions.

Subunit / interactions. Homodimer; mediates homophilic interactions to promote cell adhesion. Interacts with DCC; the interaction is abolished in response to NTN1. Interacts (via extracellular domain) with NTN1. Interacts (via extracellular domain) with UNC5C (via Ig-like C2-type domain). Interacts with PTK2. Interacts with FYN.

Subcellular location. Secreted Cell membrane. Cell projection. Axon. Dendrite. Growth cone. Synapse.

Tissue specificity. Primarily expressed in brain.

Post-translational modifications. Phosphorylated at tyrosine residues. Phosphorylation is enhanced by NTN1.

Domain organisation. Ig-like C2-type domains 7 to 9 are sufficient for interaction with NTN1 and commissural axon outgrowth. The transmembrane domain is necessary for interaction with DCC.

Isoforms (2)

UniProt ID	Names	Canonical?
O60469-1	Long, CHD2-42	yes
O60469-2	Short, CHD2-52

RefSeq proteins (2): NP_001258463, NP_001380* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR056754	DSCAM/DSCAML_C	Domain

Pfam: PF00041, PF07679, PF13927, PF25059

UniProt features (59 total): glycosylation site 18, domain 16, disulfide bond 10, region of interest 4, topological domain 2, compositionally biased region 2, splice variant 2, signal peptide 1, chain 1, transmembrane region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6ZR7	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60469-F1	69.98	0.06

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (10): 46–102, 145–197, 246–293, 335–385, 428–484, 525–575, 617–669, 711–766, 809–865, 1307–1359

Glycosylation sites (18): 28, 78, 470, 487, 512, 556, 658, 666, 710, 748, 795, 924, 1142, 1160, 1250, 1271, 1341, 1488

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-376172	DSCAM interactions

MSigDB gene sets: 289 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_NEURON_RECOGNITION, GOBP_BEHAVIOR, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, AAGTCCA_MIR422B_MIR422A, GOBP_NEURON_PROJECTION_EXTENSION_INVOLVED_IN_NEURON_PROJECTION_GUIDANCE, AREB6_03, GOZGIT_ESR1_TARGETS_DN, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_GROWTH, KYNG_DNA_DAMAGE_DN, GOBP_NEUROGENESIS

GO Biological Process (19): cell adhesion (GO:0007155), homophilic cell-cell adhesion (GO:0007156), negative regulation of cell adhesion (GO:0007162), nervous system development (GO:0007399), axon guidance (GO:0007411), synapse assembly (GO:0007416), central nervous system development (GO:0007417), locomotory behavior (GO:0007626), retina layer formation (GO:0010842), social behavior (GO:0035176), synaptic transmission, glutamatergic (GO:0035249), positive regulation of phosphorylation (GO:0042327), dendrite morphogenesis (GO:0048813), positive regulation of axon extension involved in axon guidance (GO:0048842), post-embryonic retina morphogenesis in camera-type eye (GO:0060060), camera-type eye photoreceptor cell differentiation (GO:0060219), dendritic spine development (GO:0060996), dendrite self-avoidance (GO:0070593), netrin-activated signaling pathway (GO:0038007)

GO Molecular Function (4): cell-cell adhesion mediator activity (GO:0098632), protein tyrosine kinase binding (GO:1990782), netrin receptor binding (GO:1990890), protein binding (GO:0005515)

GO Cellular Component (9): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), axon (GO:0030424), dendrite (GO:0030425), growth cone (GO:0030426), neuronal cell body (GO:0043025), synapse (GO:0045202), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Netrin-1 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retina morphogenesis in camera-type eye	3
cellular anatomical structure	3
cell-cell adhesion	2
system development	2
nervous system development	2
behavior	2
neural retina development	2
dendrite development	2
neuron projection	2
cellular process	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
axonogenesis	1
neuron projection guidance	1
cell junction assembly	1
synapse organization	1
anatomical structure formation involved in morphogenesis	1
biological process involved in intraspecies interaction between organisms	1
chemical synaptic transmission	1
phosphorylation	1
regulation of phosphorylation	1
positive regulation of phosphate metabolic process	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
positive regulation of axon extension	1
regulation of axon extension involved in axon guidance	1
axon extension involved in axon guidance	1
positive regulation of chemotaxis	1
post-embryonic animal morphogenesis	1
eye photoreceptor cell differentiation	1
anatomical structure development	1
neuron recognition	1
cell surface receptor signaling pathway	1
cell adhesion mediator activity	1
protein kinase binding	1
signaling receptor binding	1
netrin-activated signaling pathway	1
binding	1
membrane	1

Protein interactions and networks

STRING

2500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DSCAM	NTN1	O95631	995
DSCAM	UNC5B	Q8IZJ1	797
DSCAM	NTN4	Q9HB63	794
DSCAM	DRAXIN	Q8NBI3	729
DSCAM	NRXN1	Q9ULB1	686
DSCAM	DCC	P43146	663
DSCAM	UNC5A	Q6ZN44	635
DSCAM	TBCD	Q9BTW9	621
DSCAM	PFKL	P17858	590
DSCAM	COL6A2	P12110	563
DSCAM	DLG4	P78352	553
DSCAM	ALOX12	P18054	547
DSCAM	PCDH11X	Q9BZA7	542
DSCAM	MAGI2	Q86UL8	531
DSCAM	UNC5C	O95185	528

IntAct

180 interactions, top by confidence:

A	B	Type	Score
DSCAM	PIH1D2	psi-mi:“MI:0915”(physical association)	0.560
DSCAM	PSG7	psi-mi:“MI:0915”(physical association)	0.540
DSCAM	PSG9	psi-mi:“MI:0915”(physical association)	0.540
DSCAM	PTPRM	psi-mi:“MI:0915”(physical association)	0.540
DSCAM	PTPRT	psi-mi:“MI:0915”(physical association)	0.540
PSG7	DSCAM	psi-mi:“MI:0915”(physical association)	0.540
PTPRM	DSCAM	psi-mi:“MI:0407”(direct interaction)	0.540
PTPRT	DSCAM	psi-mi:“MI:0407”(direct interaction)	0.540
PSG7	DSCAM	psi-mi:“MI:0407”(direct interaction)	0.540
PSG9	DSCAM	psi-mi:“MI:0407”(direct interaction)	0.540
DSCAM	DLG2	psi-mi:“MI:0915”(physical association)	0.490
DSCAM	NOTCH3	psi-mi:“MI:0915”(physical association)	0.400
DSCAM	PSG4	psi-mi:“MI:0915”(physical association)	0.400
DSCAM	PSG6	psi-mi:“MI:0915”(physical association)	0.400
DSCAM	PTPRK	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF8	DSCAM	psi-mi:“MI:0915”(physical association)	0.400
DSCAM	DLG1	psi-mi:“MI:0915”(physical association)	0.370
PIH1D2	DSCAM	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	atp6v1b_human	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	PPP1R16B	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	PAX6	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	CIT	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	COG4	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	GFPT1	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	ZBTB47	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	FLNB	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	RUFY3	psi-mi:“MI:0915”(physical association)	0.000
DSCAM	DNAJA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (168): DSCAM (Two-hybrid), DSCAM (Affinity Capture-RNA), DSCAM (Proximity Label-MS), DLG1 (Two-hybrid), DLG2 (Two-hybrid), DLG4 (Two-hybrid), ZNF202 (Two-hybrid), TRIP11 (Two-hybrid), BICD1 (Two-hybrid), TARSL2 (Two-hybrid), CAMK2A (Two-hybrid), RUFY3 (Two-hybrid), RCBTB1 (Two-hybrid), TFIP11 (Two-hybrid), MORF4L2 (Two-hybrid)

ESM2 similar proteins: A0A6I8TCE0, B0X4T2, F1NY98, O00533, O35158, O55005, O60469, O89026, O97394, P12960, P14781, P16092, P17790, P18460, P18461, P21802, P21803, P28685, P29074, P35331, P35832, P57097, P70232, P97686, Q12860, Q12866, Q28106, Q32MD9, Q3UH53, Q4KMG0, Q60805, Q61851, Q63198, Q7Z5N4, Q7ZXX1, Q810U4, Q8AV58, Q8AXZ4, Q8JG38, Q8VHZ8

Diamond homologs: A0A0R4IGV4, A3KPA0, F1NY98, O15146, O60469, P29534, P57087, Q24372, Q26474, Q2WGK2, Q61006, Q62838, Q68FQ2, Q8N475, Q8VHZ8, Q967D7, Q9BX67, Q9D8B7, Q9ERC8, Q9JI59, Q9XT56, Q9Y624, A0N0X6, A1KZ92, A2A8L5, A3KNN3, A4IFW2, A4IGL7, A4IIW9, A6H793, A7MBJ4, A8WGA3, B0BNK7, B0V2N1, B3MH43, B3NS99, B4GBH0, B4HNW4, B4KPU0, B4MR28

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
gamma-secretase	“down-regulates quantity”	DSCAM	cleavage
IPO5	“up-regulates activity”	DSCAM	relocalization
DSCAM	down-regulates	Neurite_outgrowth
DSCAM	“up-regulates activity”	STAT3	binding
DSCAM	“up-regulates activity”	SH2D2A	binding
DSCAM	down-regulates	Synaptic_plasticity
Netrin	“up-regulates activity”	DSCAM	binding
NTN1	“up-regulates activity”	DSCAM	binding
DSCAM	up-regulates	Axonal_growth_cone_formation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Nephrin family interactions	6	22.8×	1e-04
Ras activation upon Ca2+ influx through NMDA receptor	5	22.8×	4e-04
Unblocking of NMDA receptors, glutamate binding and activation	5	21.8×	4e-04
Negative regulation of NMDA receptor-mediated neuronal transmission	5	21.8×	4e-04
Long-term potentiation	5	19.0×	6e-04
RHOV GTPase cycle	6	13.7×	6e-04
RHOU GTPase cycle	5	11.1×	5e-03
Intra-Golgi traffic	5	10.4×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of axon extension	5	15.9×	8e-03
nervous system development	17	4.8×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

355 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	229
Likely benign	82
Benign	17

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
4244940	NM_001389.5(DSCAM):c.1848_1849del (p.Val618fs)	Pathogenic
4840129	NM_001389.5(DSCAM):c.3617_3618del (p.Phe1206fs)	Pathogenic
521597	NM_001389.5(DSCAM):c.5260C>T (p.Arg1754Ter)	Pathogenic
986263	NM_001389.5(DSCAM):c.3276del (p.Glu1093fs)	Pathogenic
1098395	NM_001389.5(DSCAM):c.4216G>A (p.Gly1406Ser)	Likely pathogenic
3061432	NM_001389.5(DSCAM):c.750del (p.His251fs)	Likely pathogenic
599423	NM_001389.5(DSCAM):c.2363C>T (p.Ala788Val)	Likely pathogenic

SpliceAI

8590 predictions. Top by Δscore:

Variant	Effect	Δscore
21:40042368:TAC:T	donor_loss	1.0000
21:40042369:A:C	donor_loss	1.0000
21:40042370:C:A	donor_loss	1.0000
21:40045485:G:C	donor_gain	1.0000
21:40055718:AGCTT:A	donor_loss	1.0000
21:40055719:GCTTA:G	donor_loss	1.0000
21:40055720:CTTAC:C	donor_loss	1.0000
21:40055721:TTAC:T	donor_loss	1.0000
21:40055722:TAC:T	donor_loss	1.0000
21:40055723:A:AC	donor_gain	1.0000
21:40055723:ACC:A	donor_loss	1.0000
21:40055724:C:CA	donor_loss	1.0000
21:40055724:C:CC	donor_gain	1.0000
21:40055837:CTTA:C	acceptor_gain	1.0000
21:40055838:TTA:T	acceptor_gain	1.0000
21:40055839:TA:T	acceptor_gain	1.0000
21:40055840:ACTG:A	acceptor_loss	1.0000
21:40055841:C:CC	acceptor_gain	1.0000
21:40055841:C:CG	acceptor_loss	1.0000
21:40055842:T:A	acceptor_loss	1.0000
21:40055847:A:AC	acceptor_gain	1.0000
21:40078685:A:AC	donor_gain	1.0000
21:40078685:ACTG:A	donor_gain	1.0000
21:40078685:ACTGC:A	donor_gain	1.0000
21:40078686:C:CC	donor_gain	1.0000
21:40078686:CTG:C	donor_gain	1.0000
21:40078686:CTGC:C	donor_gain	1.0000
21:40078686:CTGCC:C	donor_gain	1.0000
21:40080337:TATC:T	acceptor_gain	1.0000
21:40080338:ATCCT:A	acceptor_loss	1.0000

AlphaMissense

13155 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:40087181:C:A	W1319C	1.000
21:40087181:C:G	W1319C	1.000
21:40187934:A:C	N869K	1.000
21:40187934:A:T	N869K	1.000
21:40189132:C:A	W821C	1.000
21:40189132:C:G	W821C	1.000
21:40189134:A:G	W821R	1.000
21:40189134:A:T	W821R	1.000
21:40296068:C:A	W723C	1.000
21:40296068:C:G	W723C	1.000
21:40296070:A:G	W723R	1.000
21:40296070:A:T	W723R	1.000
21:40312253:C:A	W630C	1.000
21:40312253:C:G	W630C	1.000
21:40312255:A:G	W630R	1.000
21:40312255:A:T	W630R	1.000
21:40338275:A:G	W537R	1.000
21:40338275:A:T	W537R	1.000
21:40339306:C:A	W440C	1.000
21:40339306:C:G	W440C	1.000
21:40339308:A:G	W440R	1.000
21:40339308:A:T	W440R	1.000
21:40347839:C:A	W347C	1.000
21:40347839:C:G	W347C	1.000
21:40347841:A:G	W347R	1.000
21:40347841:A:T	W347R	1.000
21:40692838:C:A	W160C	1.000
21:40692838:C:G	W160C	1.000
21:40692840:A:G	W160R	1.000
21:40692840:A:T	W160R	1.000

dbSNP variants (sampled 300 via entrez): RS1000006023 (21:40558431 G>A), RS1000006389 (21:40786801 T>C), RS1000006602 (21:40493325 C>T), RS1000008192 (21:40083112 G>A), RS1000008489 (21:40307152 C>A,T), RS1000009565 (21:40347260 T>A,C), RS1000010517 (21:40159878 C>T), RS1000013280 (21:40524974 C>T), RS1000013717 (21:40568181 A>G), RS1000019661 (21:40679167 T>C), RS1000021563 (21:40718779 C>A), RS1000024084 (21:40668510 G>A), RS1000027425 (21:40807757 A>T), RS1000032896 (21:40236196 T>C), RS1000033919 (21:40838047 C>G,T)

Disease associations

OMIM: gene MIM:602523 | disease phenotypes: MIM:209850, MIM:142623

GenCC curated gene-disease

Disease	Classification	Inheritance
autism	Strong	Autosomal dominant
autism spectrum disorder	Moderate	Autosomal dominant

Mondo (6): autism (MONDO:0005260), intellectual disability (MONDO:0001071), Hirschsprung disease (MONDO:0018309), esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561), autism spectrum disorder (MONDO:0005258)

Orphanet (2): Hirschsprung disease (Orphanet:388), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000717	Autism
HP:0002032	Esophageal atresia
HP:0002021	Pyloric stenosis

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000871_2	Non-small cell lung cancer (survival)	4.000000e-06
GCST001059_16	Neutrophil count	1.000000e-06
GCST001762_67	Obesity-related traits	3.000000e-06
GCST001762_719	Obesity-related traits	9.000000e-07
GCST002198_23	Tuberculosis	2.000000e-06
GCST002202_8	Anxiety in major depressive disorder	3.000000e-07
GCST006585_635	Blood protein levels	5.000000e-06
GCST006948_27	Feeling nervous	1.000000e-08
GCST007354_27	Intracranial aneurysm	4.000000e-14
GCST007708_14	Worry/vulnerability (special factor of neuroticism)	2.000000e-08
GCST008144_7	Fasting plasma glucose	3.000000e-09
GCST008181_17	Spontaneous preterm birth without premature rupture of membranes	2.000000e-06
GCST008394_11	Mild to moderate chronic kidney disease	3.000000e-07
GCST008889_4	Systemising	2.000000e-07
GCST009846_13	Hallux valgus	3.000000e-06
GCST010002_76	Refractive error	5.000000e-08
GCST010396_151	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06
GCST010988_334	Adult body size	5.000000e-09
GCST012309_11	Schizophrenia	6.000000e-06
GCST012310_18	Schizophrenia x sex interaction	7.000000e-06
GCST012490_197	Femur bone mineral density x serum urate levels interaction	9.000000e-10
GCST90006990_8	Gut microbiota relative abundance (Prevotella)	7.000000e-06
GCST90007528_1	Low hand grip strength (60 years and older) (EWGSOP)	1.000000e-08
GCST90013407_20	Liver enzyme levels (gamma-glutamyl transferase)	6.000000e-18

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0005108	arm span
EFO:0009597	feeling nervous measurement
EFO:0009589	worry measurement
EFO:0006917	spontaneous preterm birth
EFO:0010221	systemising measurement
EFO:0007874	gut microbiome measurement
EFO:0008343	sex interaction measurement
EFO:0004531	urate measurement
EFO:0006941	grip strength measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D011707	Pyloric Stenosis	C06.405.748.340.690

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9981861	Efficacy	3	carboplatin;paclitaxel	Neoplasms;Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9981861	DSCAM	3	0.00	1	carboplatin;paclitaxel

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Aflatoxin B1	decreases methylation	2
Cadmium Chloride	increases expression	2
bisphenol A	decreases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
MRK 003	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Phthalic Acids	increases methylation	1
Asbestos, Serpentine	decreases methylation	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B5NA	PGPC1_73	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

394 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder