ALCAM

Summary

ALCAM (activated leukocyte cell adhesion molecule, HGNC:400) is a protein-coding gene on chromosome 3q13.11, encoding CD166 antigen (Q13740). Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts. In precision oncology, ALCAM EXPRESSION is associated with resistance to Fluorouracil in Colorectal Cancer (CIViC Level B).

This gene encodes activated leukocyte cell adhesion molecule (ALCAM), also known as CD166 (cluster of differentiation 166), which is a member of a subfamily of immunoglobulin receptors with five immunoglobulin-like domains (VVC2C2C2) in the extracellular domain. This protein binds to T-cell differentiation antigene CD6, and is implicated in the processes of cell adhesion and migration. Multiple alternatively spliced transcript variants encoding different isoforms have been found.

Source: NCBI Gene 214 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 113 total
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_001627

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:400
Approved symbol	ALCAM
Name	activated leukocyte cell adhesion molecule
Location	3q13.11
Locus type	gene with protein product
Status	Approved
Aliases	CD166, MEMD
Ensembl gene	ENSG00000170017
Ensembl biotype	protein_coding
OMIM	601662
Entrez	214

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000306107, ENST00000460954, ENST00000465413, ENST00000470756, ENST00000472644, ENST00000481337, ENST00000486979, ENST00000489178, ENST00000491388, ENST00000880065, ENST00000880066, ENST00000932235

RefSeq mRNA: 4 — MANE Select: NM_001627 NM_001243280, NM_001243281, NM_001243283, NM_001627

CCDS: CCDS33810, CCDS58841

Canonical transcript exons

ENST00000306107 — 16 exons

Exon	Start	End
ENSE00001151818	105545223	105545335
ENSE00001878770	105574477	105576900
ENSE00001938712	105366909	105367481
ENSE00003465269	105552468	105552585
ENSE00003466834	105539975	105540102
ENSE00003491728	105547149	105547284
ENSE00003514640	105571852	105571964
ENSE00003517275	105534663	105534845
ENSE00003543620	105541633	105541765
ENSE00003564076	105532002	105532066
ENSE00003602326	105552144	105552182
ENSE00003633089	105533603	105533690
ENSE00003633421	105520067	105520167
ENSE00003652780	105550127	105550259
ENSE00003659444	105547390	105547523
ENSE00003667569	105524289	105524508

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.0058 / max 596.1041, expressed in 1746 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37742	45.2687	1730
37740	6.8254	1520
37741	3.9115	1227
37743	2.2757	1026
37739	1.2014	675
37738	0.7759	299
37737	0.7472	278

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.66	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.60	gold quality
epithelium of bronchus	UBERON:0002031	99.56	gold quality
endothelial cell	CL:0000115	99.54	gold quality
bronchus	UBERON:0002185	99.52	gold quality
palpebral conjunctiva	UBERON:0001812	99.30	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.07	gold quality
corpus callosum	UBERON:0002336	99.04	gold quality
visceral pleura	UBERON:0002401	98.96	gold quality
lateral globus pallidus	UBERON:0002476	98.94	gold quality
substantia nigra pars compacta	UBERON:0001965	98.91	gold quality
trigeminal ganglion	UBERON:0001675	98.81	gold quality
inferior vagus X ganglion	UBERON:0005363	98.80	gold quality
epithelium of nasopharynx	UBERON:0001951	98.75	gold quality
lower lobe of lung	UBERON:0008949	98.62	gold quality
superior vestibular nucleus	UBERON:0007227	98.53	gold quality
nasal cavity mucosa	UBERON:0001826	98.32	gold quality
subthalamic nucleus	UBERON:0001906	98.32	gold quality
medulla oblongata	UBERON:0001896	98.30	gold quality
cranial nerve II	UBERON:0000941	98.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.11	gold quality
dorsal root ganglion	UBERON:0000044	97.99	gold quality
nasal cavity epithelium	UBERON:0005384	97.94	gold quality
ventral tegmental area	UBERON:0002691	97.78	gold quality
pons	UBERON:0000988	97.72	gold quality
descending thoracic aorta	UBERON:0002345	97.70	gold quality
germinal epithelium of ovary	UBERON:0001304	97.62	gold quality
inferior olivary complex	UBERON:0002127	97.56	gold quality
periodontal ligament	UBERON:0008266	97.37	gold quality
islet of Langerhans	UBERON:0000006	97.31	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-9154	yes	970.09
E-HCAD-35	yes	78.28
E-CURD-114	yes	50.45
E-HCAD-10	yes	17.97
E-MTAB-5061	yes	16.90
E-GEOD-83139	yes	8.19
E-GEOD-130148	yes	8.05
E-GEOD-93593	yes	4.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GDNF, GLI1, NFKB, REL, SP1

miRNA regulators (miRDB)

175 targeting ALCAM, 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-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
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-6740-5P	100.00	65.64	932
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Literature-anchored findings (GeneRIF, showing 40)

• ALCAM expression up-regulated in low-grade prostate tumors and down-regulated in high-grade tumors; may play role in progression of prostate cancer (PMID:12481253)
• ALCAM is expressed on human endometrial epithelial cells and blastocysts. (PMID:12843199)
• the intact cell adhesion function of ALCAM may both favor primary tumor growth and represent a rate-limiting step for tissue invasion from vertical growth phase melanoma. (PMID:15140234)
• PKCA has a major role in cytoskeleton-dependent avidity modulation of ALCAM. (PMID:15169840)
• a novel soluble isoform of ALCAM may have ALCAM-dependent and ALCAM-independent functions (PMID:15496415)
• Overexpression of activated leukocyte cell adhesion molecule is associated with tumor invasion and nodal metastasis in esophageal squamous cell carcinoma (PMID:16024937)
• Data attribute a novel signaling role to ALCAM in regulation of proteolysis and support its previously postulated sensor function in invasive growth. (PMID:16204050)
• Localization of ALCAM specifically at cell-cell junctions in endothelial cells supported its role in transendothelial migration (PMID:16650408)
• Engagement of CD6 with CD166 on tumor cells plays an important role in gammadelta T cell activation by tumor cells sensitized with nonpeptide antigens endogenously or exogenously. (PMID:16818742)
• the CD6-ALCAM interaction results in activation of the three MAP kinase cascades, likely influencing the dynamic balance that determines whether resting or activated lymphocytes survive or undergo apoptosis. (PMID:16818773)
• The above results indicate that ALCAM-ALCAM interactions are crucial to the survival and primary site maintenance of breast cancer cells. (PMID:16865058)
• HLA-A *0201 restricted ALCAM peptides primed autologous CD8(+) T cells to elicit cytotoxic response against ALCAM(+) human cancer cells. (PMID:17624664)
• These results indicate that homotypic and heterotypic ALCAM-mediated adhesion are governed by significantly distinct kinetic and mechanical properties. (PMID:17971418)
• These findings indicate an important function for ALCAM in the recruitment of leukocytes into the brain. (PMID:18157132)
• disruption of ALCAM-mediated adhesion is a relevant step in ovarian cancer cell motility, and ADAM17/TACE takes part in this process, which may be relevant to invasive potential (PMID:18171982)
• activated leukocyte cell adhesion molecule (ALCAM/CD166) may have a role in breast cancer (PMID:18172759)
• This study has, for the first time, shown that patients who develop skeletal metastasis tend to have the lowest levels of ALCAM transcripts in their breast cancers. (PMID:18202807)
• Over the past decade, alterations in expression of ALCAM have been reported in several human tumors (melanoma, prostate cancer, breast cancer, colorectal carcinoma, bladder cancer, and esophageal squamous cell carcinoma). (PMID:18279810)
• Decreased/lost ALCAM membrane expression is a marker of poorer outcome in epithelial ovarian cancer. (PMID:18347173)
• ALCAM coordinates tissue growth and cell migration in a process involvnig L1CAM (PMID:18483249)
• Higher ALCAM expression showed a positive correlation with estrogen receptor status and is a useful predictive marker for the response to taxane-free chemotherapy. (PMID:18810438)
• Increased ALCAM expression in the cytoplasm is associated with oral cancer (PMID:19142865)
• Elevated levels of ALCAM in serum is associated with breast cancer. (PMID:19322904)
• upregulation of CD166 in a von Hippel-Lindau tumour suppressor gene defective renal cell carcinoma cell line. (PMID:19337990)
• ALCAM overexpression is a relevant independent prognostic marker for poor survival and early tumour relapse in pancreatic cancer. (PMID:19603023)
• Report prognostic significance of the cancer stem cell markers CD133, CD44, and CD166 in colorectal cancer. (PMID:19626493)
• Data show that compounds 17 and 18 were discovered as new potential inhibitors, with a nanomolar activity for ADAM-17 isolated enzyme and soluble ALCAM release in cancer cells. (PMID:20180536)
• ALCAM is expressed in neuroblastoma primary tumors with diverse patterns of subcellular localization. (PMID:20208136)
• examined ALCAM expression levels in primary breast cancer and distant metastases of the same patient within 29 autopsy cases to better understand the underlying mechanisms of metastases and the role of adhesion molecules in this process (PMID:20364042)
• Loss of ALCAM in breast cancer cells facilitates the invasive behaviour of breast cancer and high levels of ALCAM in the cells have a suppressive role in the aggressive nature of breast cancer cells. (PMID:20530423)
• Prognostic impact of this and other cancer stem cell markers expression in colorectal cancer. (PMID:20606680)
• Data show that CD6-ALCAM interaction in vitro induced a synergistic co-stimulation of normal peripheral blood mononuclear cells. (PMID:20726988)
• CD166 is highly expressed within the endogenous intestinal stem cell niche (PMID:20826154)
• Data suggests that loss of ALCAM expression, due in part to DNA methylation of extensive segments of the promoter, significantly impairs the ability of circulating tumor cells to adhere to each other, and may therefore promote metastasis. (PMID:20929568)
• involvement of ALCAM in the pathogenesis of different types of tumors [review] (PMID:20952758)
• ALCAM expression was associated with estrogen receptor-positive phenotype, nodal involvement and breast tumor cells in bone marrow. Strong ALCAM expression in ductal carcinomas correlated with shorter recurrence-free intervals/overall survival. (PMID:20972617)
• Both transfection of mimics of microRNA-192 or -215 and ALCAM knockdown by an ALCAM-specific siRNA significantly increased the migration of HFE145 cells (PMID:21119604)
• There is a lineage-specific silencing of ALCAM in bi-potential erythromegakaryocytic progenitor cell lines. (PMID:21126364)
• polymorphisms in ALCAM gene is associated with breast cancer. (PMID:21293922)
• ALCAM may have an important role in thyroid tumor biology. (PMID:21364949)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	alcama	ENSDARG00000026531
danio_rerio	alcamb	ENSDARG00000058538
mus_musculus	Alcam	ENSMUSG00000022636
rattus_norvegicus	Alcam	ENSRNOG00000001989

Paralogs (3): MCAM (ENSG00000076706), BCAM (ENSG00000187244), AGER (ENSG00000204305)

Protein

Protein identifiers

CD166 antigen — Q13740 (reviewed: Q13740)

Alternative names: Activated leukocyte cell adhesion molecule

All UniProt accessions (3): Q13740, F5GXJ9, H7C543

UniProt curated annotations — full annotation on UniProt →

Function. Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts. Promotes T-cell activation and proliferation via its interactions with CD6. Contributes to the formation and maturation of the immunological synapse via its interactions with CD6. Mediates homotypic interactions with cells that express ALCAM. Acts as a ligand for the LILRB4 receptor, enhancing LILRB4-mediated inhibition of T cell proliferation. Required for normal hematopoietic stem cell engraftment in the bone marrow. Mediates attachment of dendritic cells onto endothelial cells via homotypic interaction. Inhibits endothelial cell migration and promotes endothelial tube formation via homotypic interactions. Required for normal organization of the lymph vessel network. Required for normal hematopoietic stem cell engraftment in the bone marrow. Plays a role in hematopoiesis; required for normal numbers of hematopoietic stem cells in bone marrow. Promotes in vitro osteoblast proliferation and differentiation. Promotes neurite extension, axon growth and axon guidance; axons grow preferentially on surfaces that contain ALCAM. Mediates outgrowth and pathfinding for retinal ganglion cell axons. Inhibits activities of membrane-bound isoforms by competing for the same interaction partners. Inhibits cell attachment via homotypic interactions. Promotes endothelial cell migration. Inhibits endothelial cell tube formation.

Subunit / interactions. Homodimer. Interacts (via extracellular domain) with CD6 (via extracellular domain). Homodimerization and interaction with CD6 involve the same region and cannot occur simultaneously. The affinity for CD6 is much higher than the affinity for self-association. Interacts (via glycosylated extracellular domain) with LGALS1 and LGALS3. Interaction with LGALS1 or LGALS3 inhibits interaction with CD6.

Subcellular location. Cell membrane. Cell projection. Axon. Dendrite Secreted.

Tissue specificity. Detected on hematopoietic stem cells derived from umbilical cord blood. Detected on lymph vessel endothelial cells, skin and tonsil. Detected on peripheral blood monocytes. Detected on monocyte-derived dendritic cells (at protein level). Detected at low levels in spleen, placenta, liver. Expressed by activated T-cells, B-cells, monocytes and thymic epithelial cells. Isoform 1 and isoform 3 are detected in vein and artery endothelial cells, astrocytes, keratinocytes and artery smooth muscle cells. Expressed by neurons in the brain. Restricted expression in tumor cell lines. Detected in highly metastasizing melanoma cell lines.

Post-translational modifications. Glycosylated.

Domain organisation. The CD6 binding site is located in the N-terminal Ig-like domain.

Induction. Up-regulated by TNF and IFNG (at protein level).

Miscellaneous. Secreted form, inhibits isoform 1 homophilic interaction.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13740-1	1	yes
Q13740-2	2
Q13740-3	3, sALCAM
Q13740-4	4

RefSeq proteins (3): NP_001230209, NP_001230210, NP_001618* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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
IPR051116	Surface_Rcpt/Adhesion_Mol	Family

Pfam: PF08205, PF13927

UniProt features (62 total): strand 18, glycosylation site 9, sequence variant 6, disulfide bond 5, splice variant 5, domain 5, turn 4, helix 3, topological domain 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5A2F	X-RAY DIFFRACTION	1.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13740-F1	86.13	0.72

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 (5): 43–113, 157–220, 270–313, 354–392, 435–485

Glycosylation sites (9): 91, 95, 167, 265, 306, 361, 457, 480, 499

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-373760	L1CAM interactions
R-HSA-1266738	Developmental Biology
R-HSA-422475	Axon guidance
R-HSA-9675108	Nervous system development

MSigDB gene sets: 544 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, WENDT_COHESIN_TARGETS_UP, GCACCTT_MIR18A_MIR18B, MODULE_97, MODULE_52, TAATAAT_MIR126, WANG_CLIM2_TARGETS_UP, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, FARMER_BREAST_CANCER_CLUSTER_7, ZHAN_MULTIPLE_MYELOMA_PR_DN, GOBP_NEURON_PROJECTION_EXTENSION, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_RETINAL_GANGLION_CELL_AXON_GUIDANCE, GOBP_NEURON_PROJECTION_EXTENSION_INVOLVED_IN_NEURON_PROJECTION_GUIDANCE

GO Biological Process (10): adaptive immune response (GO:0002250), cell adhesion (GO:0007155), heterophilic cell-cell adhesion (GO:0007157), signal transduction (GO:0007165), motor neuron axon guidance (GO:0008045), retinal ganglion cell axon guidance (GO:0031290), axon extension involved in axon guidance (GO:0048846), neuron projection extension (GO:1990138), immune system process (GO:0002376), axon guidance (GO:0007411)

GO Molecular Function (3): signaling receptor binding (GO:0005102), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (12): immunological synapse (GO:0001772), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), axon (GO:0030424), dendrite (GO:0030425), neuronal cell body (GO:0043025), extracellular exosome (GO:0070062), extracellular region (GO:0005576), membrane (GO:0016020), T cell receptor complex (GO:0042101), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
axon guidance	3
cellular process	2
protein binding	2
plasma membrane	2
neuron projection	2
immune response	1
cell-cell adhesion	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
axon extension	1
developmental cell growth	1
neuron projection morphogenesis	1
developmental growth involved in morphogenesis	1
biological_process	1
axonogenesis	1
neuron projection guidance	1
binding	1
membrane	1
cell periphery	1
cell-substrate junction	1
cell surface	1
side of membrane	1
dendritic tree	1
somatodendritic compartment	1
cell body	1
extracellular vesicle	1
plasma membrane signaling receptor complex	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALCAM	CD6	P30203	999
ALCAM	LGALS8	O00214	956
ALCAM	ENG	P17813	878
ALCAM	THY1	P04216	855
ALCAM	NT5E	P21589	854
ALCAM	CD44	P16070	851
ALCAM	S100B	P04271	844
ALCAM	ITGB1	P05556	821
ALCAM	LILRB4	Q8NHJ6	812
ALCAM	CNTN6	Q9UQ52	802
ALCAM	L1CAM	P32004	799
ALCAM	CD34	P28906	798
ALCAM	PROM1	O43490	772
ALCAM	PTPRC	P08575	772
ALCAM	CD24	P25063	762

IntAct

73 interactions, top by confidence:

A	B	Type	Score
CD6	ALCAM	psi-mi:“MI:0407”(direct interaction)	0.850
ALCAM	CD6	psi-mi:“MI:0407”(direct interaction)	0.850
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
ALCAM	LGALS1	psi-mi:“MI:0914”(association)	0.770
ALCAM	LGALS1	psi-mi:“MI:0915”(physical association)	0.770
ALCAM	LGALS1	psi-mi:“MI:0407”(direct interaction)	0.770
LGALS1	ALCAM	psi-mi:“MI:0407”(direct interaction)	0.770
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
LGALS3	ALCAM	psi-mi:“MI:0407”(direct interaction)	0.740
ALCAM	LGALS3	psi-mi:“MI:0407”(direct interaction)	0.740
ALCAM	ALCAM	psi-mi:“MI:0407”(direct interaction)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
APOD	CCN1	psi-mi:“MI:0914”(association)	0.530

BioGRID (126): ALCAM (Affinity Capture-MS), ALCAM (Affinity Capture-MS), ALCAM (Affinity Capture-MS), ALCAM (Affinity Capture-MS), ALCAM (Affinity Capture-MS), ALCAM (Affinity Capture-MS), ALCAM (Affinity Capture-MS), ALCAM (Affinity Capture-MS), LGALS1 (Affinity Capture-MS), ALCAM (Affinity Capture-MS), ALCAM (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), ALCAM (Affinity Capture-RNA), ALCAM (Affinity Capture-MS), ALCAM (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IGV4, A0A8M2B818, B0JYH6, F1LW30, O35112, O46634, O46651, P0C673, P17948, P26453, P35969, P42292, P53767, Q08DK1, Q13740, Q15198, Q1WIM2, Q2PFX1, Q504C1, Q58EG3, Q5DX21, Q5FWR8, Q5R412, Q5RJP7, Q5U2P2, Q5VJ70, Q61490, Q6DJ83, Q6PE55, Q6UXZ4, Q6X936, Q7T2Z5, Q7TSN7, Q80W68, Q8BLQ9, Q8BR86, Q8IZU9, Q8K1S2, Q8N3J6, Q8QHL3

Diamond homologs: O35112, O46634, O46651, P42292, Q13740, Q61490, Q90304, Q90460, Q9BH13, Q3U0X8, Q9R069, P79701, O00533, Q90773, Q98892, Q99PJ0, P70232, Q58DA5, Q9P121, P50895, P43121, Q5GIT4, Q62718, Q9ESS6, Q9MZ08

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GDNF	“up-regulates quantity by expression”	ALCAM	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	7
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

3543 predictions. Top by Δscore:

Variant	Effect	Δscore
3:105520165:TAT:T	donor_gain	1.0000
3:105520168:G:GG	donor_gain	1.0000
3:105524288:GGAAA:G	acceptor_gain	1.0000
3:105524509:G:GG	donor_gain	1.0000
3:105532000:A:AG	acceptor_gain	1.0000
3:105532001:G:GG	acceptor_gain	1.0000
3:105533601:AGTTG:A	acceptor_gain	1.0000
3:105533602:GTT:G	acceptor_gain	1.0000
3:105533602:GTTGG:G	acceptor_gain	1.0000
3:105533688:G:GT	donor_gain	1.0000
3:105534661:A:AG	acceptor_gain	1.0000
3:105534661:AGC:A	acceptor_gain	1.0000
3:105534662:G:GA	acceptor_gain	1.0000
3:105534662:GC:G	acceptor_gain	1.0000
3:105534662:GCG:G	acceptor_gain	1.0000
3:105534662:GCGGT:G	acceptor_gain	1.0000
3:105534827:G:GT	donor_gain	1.0000
3:105534841:TTACT:T	donor_gain	1.0000
3:105534843:ACTGT:A	donor_loss	1.0000
3:105534844:CT:C	donor_gain	1.0000
3:105534845:TGTA:T	donor_loss	1.0000
3:105534846:G:GA	donor_loss	1.0000
3:105534846:G:GG	donor_gain	1.0000
3:105534847:T:G	donor_loss	1.0000
3:105540103:G:GG	donor_gain	1.0000
3:105540705:G:GT	donor_gain	1.0000
3:105540759:G:T	donor_gain	1.0000
3:105547280:AGAAG:A	donor_loss	1.0000
3:105547282:AAG:A	donor_loss	1.0000
3:105547283:AGGT:A	donor_loss	1.0000

AlphaMissense

3839 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:105547452:T:C	C435R	1.000
3:105547488:T:A	W447R	1.000
3:105547488:T:C	W447R	1.000
3:105520159:T:A	W56R	0.999
3:105520159:T:C	W56R	0.999
3:105520161:G:C	W56C	0.999
3:105520161:G:T	W56C	0.999
3:105524451:T:A	C113S	0.999
3:105524451:T:C	C113R	0.999
3:105524452:G:C	C113S	0.999
3:105533651:T:A	W170R	0.999
3:105533651:T:C	W170R	0.999
3:105533653:G:C	W170C	0.999
3:105533653:G:T	W170C	0.999
3:105534773:T:A	C220S	0.999
3:105534774:G:C	C220S	0.999
3:105540052:T:A	C270S	0.999
3:105540052:T:C	C270R	0.999
3:105540053:G:C	C270S	0.999
3:105541711:T:A	C313S	0.999
3:105541712:G:C	C313S	0.999
3:105545327:T:A	W366R	0.999
3:105545327:T:C	W366R	0.999
3:105545329:G:C	W366C	0.999
3:105545329:G:T	W366C	0.999
3:105547218:T:A	C392S	0.999
3:105547218:T:C	C392R	0.999
3:105547219:G:A	C392Y	0.999
3:105547219:G:C	C392S	0.999
3:105547273:T:C	L410P	0.999

dbSNP variants (sampled 300 via entrez): RS1000003842 (3:105546112 A>G), RS1000016912 (3:105475835 A>G), RS1000038754 (3:105409820 T>G), RS1000039234 (3:105452075 T>C), RS1000050573 (3:105454442 C>T), RS1000088359 (3:105475574 T>G), RS1000091504 (3:105556850 A>G), RS1000127225 (3:105441905 A>G), RS1000130951 (3:105406248 T>C), RS1000136510 (3:105409530 A>T), RS1000156716 (3:105492993 G>T), RS1000157506 (3:105385641 T>C), RS1000160522 (3:105406053 T>C), RS1000163476 (3:105462252 G>A), RS1000205099 (3:105471867 C>T)

Disease associations

OMIM: gene MIM:601662 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST001572_1	Erectile dysfunction in type 1 diabetes	7.000000e-07
GCST002337_52	Amyotrophic lateral sclerosis (sporadic)	4.000000e-08
GCST002444_2	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	2.000000e-06
GCST002783_379	Body mass index	4.000000e-06
GCST002783_536	Body mass index	8.000000e-06
GCST003139_15	Glomerular filtration rate in chronic kidney disease	6.000000e-06
GCST004369_4	Ovarian disease with few adhesions	8.000000e-07
GCST005023_54	Initial pursuit acceleration	5.000000e-06
GCST005580_4	Intraocular pressure	2.000000e-15
GCST005580_98	Intraocular pressure	7.000000e-11
GCST006585_2480	Blood protein levels	7.000000e-07
GCST006941_63	Irritable mood	2.000000e-08
GCST007576_233	Chronotype	1.000000e-08
GCST008473_19	Visceral fat	6.000000e-06
GCST009368_54	HDL cholesterol levels x long total sleep time interaction (2df test)	4.000000e-08
GCST009391_1240	Metabolite levels	6.000000e-06
GCST009441_17	Age-related cognitive decline (memory) (slope of z-scores)	7.000000e-06
GCST009665_13	Breast cancer	1.000000e-08
GCST010225_11	Cortical surface area (visual PC2)	3.000000e-17
GCST010225_12	Cortical surface area (visual PC2)	1.000000e-08
GCST010225_14	Cortical surface area (visual PC2)	2.000000e-15
GCST010225_15	Cortical surface area (visual PC2)	1.000000e-10
GCST010225_22	Cortical surface area (visual PC2)	5.000000e-08
GCST010225_6	Cortical surface area (visual PC2)	1.000000e-09
GCST010241_348	Apolipoprotein A1 levels	4.000000e-08
GCST010988_108	Adult body size	4.000000e-12
GCST011616_33	Cortical volume	2.000000e-10
GCST011616_44	Cortical volume	1.000000e-09
GCST011617_34	Cortical surface area	4.000000e-15
GCST011696_2	Alzheimer’s disease	9.000000e-07

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0004340	body mass index
EFO:0008434	initial pursuit acceleration
EFO:0004695	intraocular pressure measurement
EFO:0009594	irritability measurement
EFO:0008328	chronotype measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010422	triacylglycerol 54:4 measurement
EFO:0007710	cognitive decline measurement
EFO:0004771	visual cortical surface area measurement
EFO:0004614	apolipoprotein A 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4665584 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
ALCAM EXPRESSION	Fluorouracil	Colorectal Cancer	Resistance	CIViC B	EID853

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
sodium arsenite	increases abundance, affects cotreatment, increases expression, decreases expression	4
trichostatin A	increases expression, affects cotreatment	3
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression, decreases reaction	3
Tetrachlorodibenzodioxin	increases expression, affects expression, decreases expression, affects cotreatment	3
methylmercuric chloride	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Tretinoin	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
Medroxyprogesterone Acetate	increases expression	2
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
napabucasin	decreases expression	1
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
terbufos	increases methylation	1
sulforaphane	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
nickel sulfate	increases expression	1
1-nitropyrene	increases expression	1
di-n-butylphosphoric acid	affects expression	1

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7VX	Abcam Raji ALCAM KO	Cancer cell line	Male
CVCL_B9WF	Abcam THP-1 ALCAM KO	Cancer cell line	Male
CVCL_C6YG	Abcam PC-3 ALCAM KO	Cancer cell line	Male
CVCL_E6P1	Genomeditech CHO-K1 H_ALCAM(CD166)	Spontaneously immortalized cell line	Female
CVCL_SC21	HAP1 ALCAM (-) 1	Cancer cell line	Male
CVCL_XL23	HAP1 ALCAM (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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