CADM1

Summary

CADM1 (cell adhesion molecule 1, HGNC:5951) is a protein-coding gene on chromosome 11q23.3, encoding Cell adhesion molecule 1 (Q9BY67). Mediates homophilic cell-cell adhesion in a Ca(2+)-independent manner.

Enables signaling receptor binding activity. Involved in several processes, including cell recognition; positive regulation of cytokine production; and susceptibility to natural killer cell mediated cytotoxicity. Located in plasma membrane. Implicated in breast carcinoma and prostate cancer. Biomarker of cervix uteri carcinoma in situ.

Source: NCBI Gene 23705 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autism spectrum disorder (Limited, GenCC)
• GWAS associations: 41
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_001301043

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5951
Approved symbol	CADM1
Name	cell adhesion molecule 1
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	NECL2, ST17, BL2, SYNCAM, IGSF4A, Necl-2, SYNCAM1, RA175
Ensembl gene	ENSG00000182985
Ensembl biotype	protein_coding
OMIM	605686
Entrez	23705

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 15 protein_coding, 5 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000331581, ENST00000441886, ENST00000452722, ENST00000536727, ENST00000536781, ENST00000537058, ENST00000537140, ENST00000540373, ENST00000540852, ENST00000540951, ENST00000541434, ENST00000542447, ENST00000542450, ENST00000543249, ENST00000543375, ENST00000543540, ENST00000545094, ENST00000545380, ENST00000545960, ENST00000546000, ENST00000612235, ENST00000878172, ENST00000878173, ENST00000878174, ENST00000930502

RefSeq mRNA: 5 — MANE Select: NM_001301043 NM_001098517, NM_001301043, NM_001301044, NM_001301045, NM_014333

CCDS: CCDS53711, CCDS73397, CCDS73398, CCDS73399, CCDS8373

Canonical transcript exons

ENST00000331581 — 12 exons

Exon	Start	End
ENSE00003483862	115178644	115178775
ENSE00003518411	115231353	115231490
ENSE00003523875	115209574	115209657
ENSE00003545011	115169236	115176592
ENSE00003557321	115229113	115229271
ENSE00003562190	115214608	115214780
ENSE00003577454	115217892	115217991
ENSE00003581901	115240274	115240420
ENSE00003617700	115190888	115190941
ENSE00003622227	115238500	115238652
ENSE00003671869	115504271	115504415
ENSE00003673261	115198406	115198438

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.8867 / max 1299.3141, expressed in 1269 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122408	36.1316	1257
122383	0.2103	99
122391	0.1103	27
122385	0.0983	39
122386	0.0969	32
122390	0.0821	20
122393	0.0706	32
122384	0.0545	32
122394	0.0321	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	98.73	gold quality
pons	UBERON:0000988	98.58	gold quality
adrenal tissue	UBERON:0018303	98.47	gold quality
periodontal ligament	UBERON:0008266	98.29	gold quality
calcaneal tendon	UBERON:0003701	98.27	gold quality
caput epididymis	UBERON:0004358	98.22	gold quality
corpus callosum	UBERON:0002336	98.02	gold quality
visceral pleura	UBERON:0002401	97.84	gold quality
islet of Langerhans	UBERON:0000006	97.72	gold quality
dorsal root ganglion	UBERON:0000044	97.70	gold quality
type B pancreatic cell	CL:0000169	97.61	gold quality
CA1 field of hippocampus	UBERON:0003881	97.60	gold quality
entorhinal cortex	UBERON:0002728	97.56	gold quality
frontal pole	UBERON:0002795	97.53	gold quality
trigeminal ganglion	UBERON:0001675	97.50	gold quality
superior vestibular nucleus	UBERON:0007227	97.45	gold quality
cortical plate	UBERON:0005343	97.44	gold quality
corpus epididymis	UBERON:0004359	97.43	gold quality
renal medulla	UBERON:0000362	97.08	gold quality
cranial nerve II	UBERON:0000941	97.06	gold quality
cerebellum	UBERON:0002037	97.06	gold quality
ventral tegmental area	UBERON:0002691	96.88	gold quality
cerebellar hemisphere	UBERON:0002245	96.81	gold quality
cerebellar cortex	UBERON:0002129	96.80	gold quality
lower lobe of lung	UBERON:0008949	96.74	gold quality
orbitofrontal cortex	UBERON:0004167	96.67	gold quality
lateral globus pallidus	UBERON:0002476	96.65	gold quality
globus pallidus	UBERON:0001875	96.46	gold quality
parietal lobe	UBERON:0001872	96.41	gold quality
medial globus pallidus	UBERON:0002477	96.40	gold quality

Single-cell (SCXA)

Detected in 33 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	2175.39
E-GEOD-83139	yes	1080.64
E-GEOD-81608	yes	1024.48
E-GEOD-114530	yes	800.04
E-MTAB-10662	yes	663.82
E-MTAB-9388	yes	589.64
E-MTAB-7407	yes	588.44
E-HCAD-10	yes	380.28
E-MTAB-10018	yes	237.85
E-HCAD-35	yes	80.10
E-CURD-119	yes	59.86
E-MTAB-10287	yes	53.49
E-HCAD-31	yes	30.63
E-HCAD-11	yes	21.75
E-MTAB-5061	yes	19.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT1, FOXA2, MITF, NFKB, RARA, SP1, SP3, TP73, ZNF135

miRNA regulators (miRDB)

210 targeting CADM1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281

Literature-anchored findings (GeneRIF, showing 40)

• TSLC1 mediates intracellular adhesion through homophilic interactions in a Ca(2+)/Mg(2+)-independent manner (PMID:12050160)
• alteration of TSLC1 is involved in prostate cancer (PMID:12079507)
• The TSLC1 promoter region has many methylated cytosines in the CpG islands in chromosome 11q LOH in breast cancer. (PMID:12112527)
• SynCAM1 is expressed in brain and localized to pre- and postsynaptic sites of neurons. SynCAM1 is a homophilic cell adhesion molecule that induces formation of presynaptic terminals by neurons. (PMID:12202822)
• methylation and subsequent inactivation of TSLC1 expression is associated with pancreatic adenocarcinoma (PMID:12432281)
• bi-allelic hypermethylation of the TSLC1 promoter and resulting gene silencing occur in a subset of primary gastric cancers (PMID:12716461)
• The results support the hypothesis that TSLC1 is a tumor suppressor of NSCLC and also suggest that preserved integrity of TSLC1 may contribute to less invasive phenotypes of lepidic growth tumor cells. (PMID:12920246)
• alteration of TSLC1 expression by romoter methylation is involved in advanced nonsmall cell lung cancer (PMID:12925956)
• TSLC1 represents central effector gene for controlling biological aggressiveness of pulmonary adenocarcinoma and is essential biomarker for predicting prognosis (PMID:12942568)
• IGSF4 was found to have roles in adhesion of spermatogenic cells to Sertoli cells and mast cells to fibroblasts and synaptic formation of neural cells–REVIEW (PMID:12973698)
• Lung tumor suppressor gene,TSLC1, associates with MPP3, a human homologue of Drosophila tumor suppressor Dlg. (PMID:13679854)
• The loss of TSLC1 expression has an important role in tumor growth, cell motility, and invasion and is associated with aggressive tumor behavior in esophageal squamous cell carcinoma. (PMID:14559819)
• A549 lung cancer cells expressing wild-type TSLC1 showed suppression of anchorage-independent colony formation in soft agar and markedly increased cell-cell adhesion activity. (PMID:14633730)
• Epigenetic inactivation of TSLC1 gene is associated with nasopharyngeal carcinoma (PMID:14639656)
• TSLC1 gene silencing via promoter hypermethylation is a frequent event in the progression from high-risk HPV-containing, high-grade CIN lesions to invasive cervical cancer (PMID:14970278)
• Our results demonstrate the pro-apoptotic and oncosuppressive activity of TSLC1 protein. (PMID:15184878)
• Ectopic expression of TSLC1 could provide a novel marker for acute-type adi;t acite t-cell leukemia and may participate in tissue invasion, a characteristic feature of the malignant ATL cells. (PMID:15471956)
• TSLC1 plays an important role in meningioma pathogenesis. (PMID:15535129)
• Necl2/CRTAM molecular pair could regulate a large panel of cell/cell interactions both within and outside of the immune system (PMID:15781451)
• NK cells and T8 cells recognize Necl-2 through CRTAM, expressed only on activated cells. CRTAM-Necl-2 interactions promote cytotoxicity of NK cells and IFN-gamma secretion of T8 cells as well as NK cell-mediated rejection of tumors expressing Necl-2 (PMID:15811952)
• SgIGSF/SynCAM expressed on transgenic mouse mast cells and superior cervical ganglion neurons appears to predominantly mediate attachment and promote communication with nerves. (PMID:15905536)
• Gene expression and cell cycle differences provide insights into potential downstream pathways of TSLC1 that mediate the suppression of tumor properties in A549 cells (PMID:16083501)
• Loss of TSLC1 is associated with lower patient survival, supporting its role as a tumor suppressor in lung adenocarcinoma. (PMID:16108829)
• methylation of TSLC1 leading to loss of the expression, is an important event in the pathogenesis of non-small-cell lung cancer (PMID:16205641)
• SynCAM proteins are encoded by a family of four conserved IGSF4 genes found solely in vertebrates; transcripts can be alternatively spliced and encode proteins with three immunoglobulin-like domains. (PMID:16311015)
• lung mast cells adhere avidly to airway smooth muscle in part via TSLC-1 and in part via an as-yet-undefined Ca2+-dependent pathway (PMID:16394014)
• TSLC1 inhibits nasopharyngeal carcinoma cell growth by arresting cells in G(0)-G(1) phase in normal culture conditions. Without serum, TSLC1 induced apoptosis. TSLC1 is a tumor suppressor gene in NPC; its loss is seen in lymphatic metastasis. (PMID:17018592)
• TSLC1 protein and RNA expression is lost in 60% to 65% of high-grade gliomas, and TSLC1 reintroduction into glioma cells results in growth suppression. (PMID:17130425)
• TSLC1 and DAL-1 are involved in the pathogenesis of breast cancer and are frequently inactivated by methylation (PMID:17260099)
• These results indicate that TSLC1 is a novel interameloblast adhesion molecule that may be downregulated during ameloblastic tumorigenesis. (PMID:17300670)
• We propose that SgIGSF is a novel and functional biliary epithelial cell adhesion molecule that is expressed for a limited time during active bile duct/ductule formation [SgIGSF]. (PMID:17326163)
• Downregulation of CADM1 tumour suppressor gene expression is a critical event in neuroblastoma pathogenesis resulting in tumour progression and unfavourable patient outcome. (PMID:18084322)
• Appears to mediate efficient adhesion and growth of malignant pleural mesothelioma cells specifically on mesothelial cells, probably via trans-heterophilic binding. (PMID:18332875)
• The strong correlation between CADM1 expression and hormonally functional phenotypes suggests that CADM1 is involved in hormone secretion from ICTs. (PMID:18471525)
• Density of promoter methylation was associated with the degree of anchorage-independent growth and CADM1 gene silencing in vitro. In cervical squamous lesions, methylation frequency and density increased with severity of disease (PMID:18498117)
• study puts CADM1 forward as a strong candidate neuroblastoma suppressor gene (PMID:18559103)
• Airway smooth muscle cells maintain human lung mast cell survival in vitro by a direct interaction between the two cell types that leads to rapid cell proliferation through a cooperative CADM1-, stem cell factor, and interleukin 6-dependent mechanism. (PMID:18684968)
• TSLC1 acts as a candidate tumor suppressor gene for neuroblastoma. (PMID:18726896)
• TSLC1 expression in Adult T-cell leukemia (ATL) cells plays an important role in the growth and organ infiltration of ATL cells. (PMID:18922876)
• Two missense mutations, C739A(H246N) and A755C(Y251S), in the CADM1 gene of male Caucasian autism spectrum disorder patients and their family members were found. (PMID:18957284)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cadm1a	ENSDARG00000031075
danio_rerio	cadm1b	ENSDARG00000042677
mus_musculus	Cadm1	ENSMUSG00000032076
rattus_norvegicus	Cadm1	ENSRNOG00000018778
drosophila_melanogaster	Fas3	FBGN0000636

Paralogs (14): PVR (ENSG00000073008), CD200 (ENSG00000091972), CADM4 (ENSG00000105767), CRTAM (ENSG00000109943), NECTIN1 (ENSG00000110400), NECTIN2 (ENSG00000130202), NECTIN4 (ENSG00000143217), CD226 (ENSG00000150637), CADM3 (ENSG00000162706), SMAGP (ENSG00000170545), CADM2 (ENSG00000175161), NECTIN3 (ENSG00000177707), TIGIT (ENSG00000181847), NCR3 (ENSG00000204475)

Protein

Protein identifiers

Cell adhesion molecule 1 — Q9BY67 (reviewed: Q9BY67)

Alternative names: Immunoglobulin superfamily member 4, Nectin-like protein 2, Spermatogenic immunoglobulin superfamily, Synaptic cell adhesion molecule, Tumor suppressor in lung cancer 1

All UniProt accessions (12): A0A087X0T8, A0A0A0MTJ8, Q9BY67, F5H0H5, F5H125, F5H372, F5H8J9, H0YG94, X5D7A8, X5D8W0, X5DQR8, X5DQS5

UniProt curated annotations — full annotation on UniProt →

Function. Mediates homophilic cell-cell adhesion in a Ca(2+)-independent manner. Also mediates heterophilic cell-cell adhesion with CADM3 and NECTIN3 in a Ca(2+)-independent manner. Interaction with CRTAM promotes natural killer (NK) cell cytotoxicity and interferon-gamma (IFN-gamma) secretion by CD8+ cells in vitro as well as NK cell-mediated rejection of tumors expressing CADM1 in vivo. In mast cells, may mediate attachment to and promote communication with nerves. CADM1, together with MITF, is essential for development and survival of mast cells in vivo. By interacting with CRTAM and thus promoting the adhesion between CD8+ T-cells and CD8+ dendritic cells, regulates the retention of activated CD8+ T-cell within the draining lymph node. Required for the intestinal retention of intraepithelial CD4+ CD8+ T-cells and, to a lesser extent, intraepithelial and lamina propria CD8+ T-cells and CD4+ T-cells. Interaction with CRTAM promotes the adhesion to gut-associated CD103+ dendritic cells, which may facilitate the expression of gut-homing and adhesion molecules on T-cells and the conversion of CD4+ T-cells into CD4+ CD8+ T-cells. Acts as a synaptic cell adhesion molecule and plays a role in the formation of dendritic spines and in synapse assembly. May be involved in neuronal migration, axon growth, pathfinding, and fasciculation on the axons of differentiating neurons. May play diverse roles in the spermatogenesis including in the adhesion of spermatocytes and spermatids to Sertoli cells and for their normal differentiation into mature spermatozoa. Acts as a tumor suppressor in non-small-cell lung cancer (NSCLC) cells. May contribute to the less invasive phenotypes of lepidic growth tumor cells. (Microbial infection) Induces cell fusion in neuron infected by a neuropathogenic strain of measles. Interacts with measles hemagglutinin to trigger hyperfusogenic F-mediated membrane fusion and presumably transsynaptic cell-to-cell transmission of the virus.

Subunit / interactions. Homodimer (via Ig-like V-type domain). Interacts with FARP1. Interacts (via Ig-like V-type domain) with CRTAM (via Ig-like V-type domain); the interaction competes with CRTAM homodimerization and CADM1 homodimerization. Interacts (via C-terminus) with EPB41L3/DAL1. The interaction with EPB41L3/DAL1 may act to anchor CADM1 to the actin cytoskeleton. Interacts (via C-terminus) with MPP2 (via PDZ domain). Interacts (via C-terminus) with MPP3 (via PDZ domain); this interaction connects CADM1 with DLG1. Interacts (via C-terminus) with PALS2 (via PDZ domain). (Microbial infection) Interacts with herpes virus 8 proteins vFLIP and vGPCR; these interactions are essential for NF-kappa-B activation.

Subcellular location. Cell membrane. Synapse.

Post-translational modifications. Glycosylation at Asn-67 and Asn-101 promotes adhesive binding and synapse induction.

Domain organisation. The cytoplasmic domain appears to play a critical role in proapoptosis and tumor suppressor activity in NSCLC.

Similarity. Belongs to the nectin family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BY67-1	1	yes
Q9BY67-2	2
Q9BY67-3	3
Q9BY67-4	4
Q9BY67-5	5, E

RefSeq proteins (5): NP_001091987, NP_001287972, NP_001287973, NP_001287974, NP_055148 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003585	Neurexin-like	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07686, PF08205, PF13927

UniProt features (41 total): strand 10, glycosylation site 6, splice variant 5, disulfide bond 3, sequence conflict 3, domain 3, topological domain 2, mutagenesis site 2, modified residue 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4H5S	X-RAY DIFFRACTION	1.7
3BIN	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BY67-F1	81.63	0.65

Functional residue map

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

Post-translational modifications (2): 422, 434

Disulfide bonds (3): 64–124, 166–220, 267–313

Glycosylation sites (6): 67, 101, 113, 165, 304, 308

Mutagenesis-validated functional residues (2):

Position	Phenotype
406	nearly abolishes epb41l3 binding.
408	strongly reduced affinity for epb41l3.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-418990	Adherens junctions interactions
R-HSA-420597	Nectin/Necl trans heterodimerization
R-HSA-1500931	Cell-Cell communication
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization

MSigDB gene sets: 482 (showing top): FREAC2_01, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GGTGTGT_MIR329, MYOGENIN_Q6, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GGGNRMNNYCAT_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_MALE_GAMETE_GENERATION, LHX3_01, GGGTGGRR_PAX4_03

GO Biological Process (12): positive regulation of cytokine production (GO:0001819), immune system process (GO:0002376), apoptotic process (GO:0006915), homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), spermatogenesis (GO:0007283), cell recognition (GO:0008037), cell differentiation (GO:0030154), susceptibility to natural killer cell mediated cytotoxicity (GO:0042271), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), detection of stimulus (GO:0051606), cell adhesion (GO:0007155)

GO Molecular Function (4): signaling receptor binding (GO:0005102), PDZ domain binding (GO:0030165), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), basolateral plasma membrane (GO:0016323), neuron projection (GO:0043005), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cell-cell junction organization	1
Adherens junctions interactions	1
Cell junction organization	1
Cell-Cell communication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	2
cellular process	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
biological_process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
positive regulation of natural killer cell mediated cytotoxicity	1
positive regulation of leukocyte mediated cytotoxicity	1
positive regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
response to stimulus	1
protein binding	1
protein domain specific binding	1
identical protein binding	1
protein dimerization activity	1
binding	1
membrane	1
cell periphery	1
anchoring junction	1
basal plasma membrane	1
plasma membrane region	1
plasma membrane bounded cell projection	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2594 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CADM1	CRTAM	O95727	988
CADM1	HAVCR2	Q8TDQ0	988
CADM1	EPB41	P11171	917
CADM1	MPP3	Q13368	896
CADM1	PALS2	Q9NZW5	895
CADM1	SDCBP	O00560	895
CADM1	EPB41L3	Q9Y2J2	857
CADM1	ITGB2	P05107	810
CADM1	NLGN1	Q8N2Q7	794
CADM1	DLG3	Q92796	774
CADM1	ICAM1	P05362	773
CADM1	IL6	P05231	771
CADM1	THBD	P07204	763
CADM1	CD8A	P01732	740
CADM1	NLGN2	Q8NFZ4	721

IntAct

50 interactions, top by confidence:

A	B	Type	Score
LIN7A	CASK	psi-mi:“MI:0914”(association)	0.830
CRTAM	CADM1	psi-mi:“MI:0407”(direct interaction)	0.650
CADM1	CADM1	psi-mi:“MI:0407”(direct interaction)	0.620
CRTAM	CADM1	psi-mi:“MI:0915”(physical association)	0.610
CADM1	CRTAM	psi-mi:“MI:0407”(direct interaction)	0.610
CADM1	PSMA6	psi-mi:“MI:0915”(physical association)	0.560
PSMA6	CADM1	psi-mi:“MI:0915”(physical association)	0.560
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
St8sia2	CADM1	psi-mi:“MI:0559”(glycosylation reaction)	0.440
ST8SIA4	CADM1	psi-mi:“MI:0559”(glycosylation reaction)	0.440
GSK3B	SEC16A	psi-mi:“MI:0914”(association)	0.420
CADM1	CADM2	psi-mi:“MI:0915”(physical association)	0.400
CADM2	CADM1	psi-mi:“MI:0915”(physical association)	0.400
ATF7IP	CADM1	psi-mi:“MI:0915”(physical association)	0.370
PTPN4	TPR	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
incE	STX7	psi-mi:“MI:0914”(association)	0.350
PTPN4	GOLIM4	psi-mi:“MI:0914”(association)	0.350
RIPK4	TBCA	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): CADM1 (Two-hybrid), CADM1 (Affinity Capture-MS), CADM1 (Affinity Capture-MS), CADM1 (Affinity Capture-MS), CNBP (Co-fractionation), RPS15 (Co-fractionation), MPP3 (Two-hybrid), CADM1 (Affinity Capture-MS), CADM1 (Proximity Label-MS), CADM1 (Affinity Capture-MS), CADM1 (Affinity Capture-MS), CADM1 (Affinity Capture-MS), CADM1 (Affinity Capture-MS), CADM1 (Proximity Label-MS), MPP3 (Affinity Capture-Western)

ESM2 similar proteins: A0A5B9, A6NDV4, A6QLK4, B1AWJ5, E9PTA2, O75051, O94759, P01850, P01851, P01852, P01857, P01859, P01860, P01861, P01869, P01870, P01906, P01909, P03987, P06333, P0DSE2, P0DTU4, P11364, P15151, P15981, P20759, P20762, P32506, P54900, Q1WIM1, Q1WIM3, Q3TMX7, Q6P767, Q6ZRP7, Q7TQ33, Q812F8, Q8N126, Q8NFZ8, Q8R143, Q8R464

Diamond homologs: B0X4T2, B3N666, B4GKZ8, B4HY03, B4KPU0, B4Q599, O00533, O42414, O75325, O94856, P11627, P32004, P35331, P70232, P97685, P97686, Q01974, Q03696, Q05695, Q21038, Q23551, Q26614, Q29JX6, Q60625, Q6AYP5, Q810U3, Q810U4, Q8AXY6, Q8BXA0, Q8R5M8, Q8WZ75, Q90478, Q90479, Q91664, Q92823, Q96NI6, Q98902, Q9BY67, Q9Z109, Q9Z138

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SP1	“up-regulates quantity by expression”	CADM1	“transcriptional regulation”
SP3	“up-regulates quantity by expression”	CADM1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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.

GO biological processes:

GO term	Partners	Fold	FDR
Ras protein signal transduction	5	23.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	10
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

4478 predictions. Top by Δscore:

Variant	Effect	Δscore
11:115176485:A:AC	donor_gain	1.0000
11:115176486:C:CC	donor_gain	1.0000
11:115176486:CT:C	donor_gain	1.0000
11:115176491:T:A	donor_gain	1.0000
11:115178639:CTTA:C	donor_loss	1.0000
11:115178640:TTA:T	donor_loss	1.0000
11:115178641:TACCT:T	donor_loss	1.0000
11:115178642:A:AC	donor_gain	1.0000
11:115178643:C:CC	donor_gain	1.0000
11:115178643:C:CT	donor_loss	1.0000
11:115178772:GAAT:G	acceptor_gain	1.0000
11:115178776:C:CC	acceptor_gain	1.0000
11:115178786:C:CT	acceptor_gain	1.0000
11:115178787:A:T	acceptor_gain	1.0000
11:115214776:CAGGC:C	acceptor_gain	1.0000
11:115214777:AGGC:A	acceptor_gain	1.0000
11:115214777:AGGCC:A	acceptor_loss	1.0000
11:115214778:GGC:G	acceptor_gain	1.0000
11:115214778:GGCCT:G	acceptor_loss	1.0000
11:115214779:GC:G	acceptor_gain	1.0000
11:115214779:GCCT:G	acceptor_loss	1.0000
11:115214780:CC:C	acceptor_gain	1.0000
11:115214780:CCTGC:C	acceptor_loss	1.0000
11:115214781:C:CC	acceptor_gain	1.0000
11:115214781:CTGC:C	acceptor_loss	1.0000
11:115214782:T:A	acceptor_loss	1.0000
11:115217890:A:AC	donor_gain	1.0000
11:115217891:C:CT	donor_gain	1.0000
11:115229104:GGTAC:G	donor_loss	1.0000
11:115229106:TACT:T	donor_loss	1.0000

AlphaMissense

3074 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:115214651:G:C	N317K	1.000
11:115214651:G:T	N317K	1.000
11:115214667:C:G	R312P	1.000
11:115214671:A:C	Y311D	1.000
11:115214762:C:A	W280C	1.000
11:115214762:C:G	W280C	1.000
11:115214764:A:G	W280R	1.000
11:115214764:A:T	W280R	1.000
11:115229174:G:C	C220W	1.000
11:115229175:C:G	C220S	1.000
11:115229175:C:T	C220Y	1.000
11:115229176:A:G	C220R	1.000
11:115229176:A:T	C220S	1.000
11:115231378:C:A	W179C	1.000
11:115231378:C:G	W179C	1.000
11:115231380:A:G	W179R	1.000
11:115231380:A:T	W179R	1.000
11:115231417:G:C	C166W	1.000
11:115231419:A:G	C166R	1.000
11:115238505:A:T	V140D	1.000
11:115238552:G:C	C124W	1.000
11:115238553:C:G	C124S	1.000
11:115238553:C:T	C124Y	1.000
11:115238554:A:G	C124R	1.000
11:115238554:A:T	C124S	1.000
11:115238559:T:C	Y122C	1.000
11:115238560:A:C	Y122D	1.000
11:115238571:T:A	D118V	1.000
11:115238604:A:G	L107P	1.000
11:115238637:C:A	R96M	1.000

dbSNP variants (sampled 300 via entrez): RS1000003478 (11:115411323 C>G), RS1000007972 (11:115168892 C>T), RS1000020827 (11:115317274 G>A), RS1000023878 (11:115458682 C>T), RS1000028413 (11:115280648 G>A), RS1000036251 (11:115366232 G>A), RS1000050136 (11:115410893 T>C), RS1000051100 (11:115373223 C>G), RS1000071582 (11:115409611 A>C,T), RS1000080555 (11:115418264 C>T), RS1000080558 (11:115289119 C>T), RS1000084280 (11:115462024 G>A), RS1000085260 (11:115324565 G>A), RS1000090317 (11:115504825 C>T), RS1000098699 (11:115198809 A>G)

Disease associations

OMIM: gene MIM:605686 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
autism spectrum disorder	Limited	Autosomal dominant

Mondo (1): autism spectrum disorder (MONDO:0005258)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST000789_1	Cardiovascular risk factors (age interaction)	8.000000e-06
GCST001762_225	Obesity-related traits	6.000000e-06
GCST002541_90	Menarche (age at onset)	7.000000e-11
GCST002783_15	Body mass index	9.000000e-08
GCST002783_361	Body mass index	5.000000e-13
GCST002783_496	Body mass index	1.000000e-12
GCST002783_92	Body mass index	4.000000e-08
GCST003655_9	Cutaneous squamous cell carcinoma	9.000000e-09
GCST003993_38	Menarche (age at onset)	1.000000e-09
GCST004125_1	Type 2 diabetes (age of onset)	6.000000e-07
GCST004125_25	Type 2 diabetes (age of onset)	9.000000e-06
GCST004735_11	Epstein-Barr virus copy number in lymphoblastoid cell lines	5.000000e-06
GCST004904_240	Body mass index	1.000000e-15
GCST005950_1	Body mass index x sex x age interaction (4df test)	2.000000e-187
GCST005951_192	Body mass index	4.000000e-188
GCST005952_1	Body mass index (age>50)	1.000000e-97
GCST006288_1	Heel bone mineral density	2.000000e-33
GCST006288_191	Heel bone mineral density	3.000000e-19
GCST006288_379	Heel bone mineral density	4.000000e-14
GCST006899_12	Thyroid stimulating hormone levels	4.000000e-12
GCST006979_226	Heel bone mineral density	2.000000e-20
GCST006979_423	Heel bone mineral density	3.000000e-76
GCST006979_424	Heel bone mineral density	9.000000e-11
GCST006979_425	Heel bone mineral density	4.000000e-17
GCST007576_392	Chronotype	6.000000e-08
GCST008151_18	Waist circumference	7.000000e-06
GCST008158_121	Body mass index	7.000000e-06
GCST008158_64	Body mass index	5.000000e-08
GCST008160_2	Waist circumference	7.000000e-06
GCST008465_2	Anorexia nervosa	6.000000e-11

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008007	age at assessment
EFO:0004736	aspartate aminotransferase measurement
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:1001927	cutaneous squamous cell carcinoma
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0006781	coffee consumption measurement
EFO:0006807	linoleic acid measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0009902	handedness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

65 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, increases expression, affects expression, affects cotreatment	5
sodium arsenite	decreases expression, increases abundance, increases expression, affects methylation	4
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
Cyclosporine	increases methylation, decreases expression	4
Tretinoin	increases expression	3
Valproic Acid	affects expression, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Temozolomide	increases expression, affects response to substance	2
Arsenic	increases response to substance, decreases expression, increases abundance	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Tunicamycin	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
methylselenic acid	affects expression	1
sodium arsenate	decreases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
benzo(k)fluoranthene	decreases expression	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
nivalenol	decreases expression	1
indeno(1,2,3-cd)pyrene	decreases expression	1
tamibarotene	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
U 0126	increases expression, decreases reaction	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F1LV	HyCyte A-549 KO-hCADM1	Cancer cell line	Male

Clinical trials (associated diseases)

300 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
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
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder