SLAMF1

Summary

SLAMF1 (signaling lymphocytic activation molecule family member 1, HGNC:10903) is a protein-coding gene on chromosome 1q23.3, encoding Signaling lymphocytic activation molecule (Q13291). Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family.

Enables SH2 domain binding activity; identical protein binding activity; and virus receptor activity. Involved in several processes, including negative regulation of CD40 signaling pathway; negative regulation of cytokine production; and positive regulation of MAPK cascade. Located in extracellular exosome. Is active in plasma membrane.

Source: NCBI Gene 6504 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_003037

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10903
Approved symbol	SLAMF1
Name	signaling lymphocytic activation molecule family member 1
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CD150, IPO-3, IPO3
Ensembl gene	ENSG00000117090
Ensembl biotype	protein_coding
OMIM	603492
Entrez	6504

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000302035, ENST00000494463, ENST00000538290, ENST00000878657, ENST00000878659

RefSeq mRNA: 2 — MANE Select: NM_003037 NM_001330754, NM_003037

CCDS: CCDS1207, CCDS81389

Canonical transcript exons

ENST00000302035 — 7 exons

Exon	Start	End
ENSE00001166196	160619776	160619849
ENSE00001166202	160624096	160624185
ENSE00001166212	160634613	160634897
ENSE00001166217	160637191	160637529
ENSE00001820545	160608106	160610798
ENSE00003596272	160612488	160612580
ENSE00003850569	160646870	160647044

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 92.38.

FANTOM5 (CAGE): breadth broad, TPM avg 11.4935 / max 903.6646, expressed in 343 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15520	8.1165	287
15521	3.1226	256
201781	0.1075	57
201780	0.1023	53
15517	0.0228	12
15518	0.0218	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
thymus	UBERON:0002370	92.38	gold quality
lymph node	UBERON:0000029	84.68	gold quality
granulocyte	CL:0000094	83.94	gold quality
vermiform appendix	UBERON:0001154	81.55	gold quality
caecum	UBERON:0001153	78.94	gold quality
heart right ventricle	UBERON:0002080	77.92	gold quality
blood	UBERON:0000178	77.62	gold quality
tonsil	UBERON:0002372	74.13	gold quality
bone marrow cell	CL:0002092	73.49	gold quality
spleen	UBERON:0002106	73.23	gold quality
rectum	UBERON:0001052	72.30	gold quality
pancreatic ductal cell	CL:0002079	71.09	silver quality
epithelium of nasopharynx	UBERON:0001951	70.50	silver quality
nasopharynx	UBERON:0001728	70.49	silver quality
bone marrow	UBERON:0002371	70.04	gold quality
gall bladder	UBERON:0002110	69.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.78	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.52	gold quality
mucosa of transverse colon	UBERON:0004991	68.99	gold quality
colonic epithelium	UBERON:0000397	68.51	silver quality
nasal cavity epithelium	UBERON:0005384	68.36	gold quality
small intestine	UBERON:0002108	68.15	gold quality
ileal mucosa	UBERON:0000331	66.84	silver quality
cerebellar vermis	UBERON:0004720	66.34	gold quality
myocardium	UBERON:0002349	65.80	gold quality
superficial temporal artery	UBERON:0001614	65.40	gold quality
upper arm skin	UBERON:0004263	64.58	gold quality
upper lobe of left lung	UBERON:0008952	64.25	gold quality
leukocyte	CL:0000738	64.10	gold quality
vastus lateralis	UBERON:0001379	64.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.01

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYB

Literature-anchored findings (GeneRIF, showing 40)

• SLAM contributes to the enhanced immunostimulatory functions of dendritic cells that are observed following the addition of IL-1 in vitro. (PMID:11489980)
• Susceptibility of human dendritic cells (DCs) to measles virus (MV) depends on their activation stages in conjunction with the level of CDw150: role of Toll stimulators in DC maturation and MV amplification (PMID:12270725)
• effect of X-linked lymphoproliferative syndrome gene product SAP/SH2D1A on signaling through signaling lymphocyte activation molecule family of immune receptors (PMID:12458214)
• direct correlation between the amount of hSLAM expressed on the cells’ surface and the degree of measles virus infection; MV infection induced downregulation of receptor hSLAM and inhibited cell division and proliferation of hSLAM(+)T cells (PMID:12610126)
• SLAM mRNA expression in PBMC is modulated during the course of specific immunotherapy, and an early and transient increase of SLAM mRNA expression is associated with clinical symptom improvement (PMID:14657878)
• SLAM expression correlates directly with T cell responsiveness to Mycobacterium tuberculosis antigen. (PMID:14707094)
• murine Measles virus-infected dendritic cells expressing hSLAM receptor downregulated B7-1, B7-2, CD40, MHC class I, and MHC class II expresssion on their surfaces, increased their rate of apoptosis, and inhibited T-cell proliferation. (PMID:15193925)
• binding site with measles virus hemagglutinin: attachment sites for MV receptors SLAM and CD46 overlap on the globular head (PMID:15308701)
• CD150 and SH2D1A are coexpressed during a narrow window of B-cell maturation and SH2D1A may be involved in regulation of B-cell differentiation via switching of CD150-mediated signaling pathways. (PMID:15315965)
• During ligation of SLAM in leprosy, signaling molecules and transcription factors participate in the induction or reinforcement of interferon-gamma production, promoting cell-mediated immune responses to mycobacterial infection. (PMID:15356162)
• activation of peripheral blood cells with agonistic anti-CD3 antibody and exogenous IL-2, as used for generation of cytokine-induced killer cells, results in significant SLAM and SAP activation 5 days after TCR stimulation (PMID:15661039)
• We have identified several novel SLAM binding sites at residues 429, 436 and 437 of measles virus haemagglutin (MVH) protein and MVH mutants in these residues dramatically decrease the ability to interaction with the cell surface SLAM. (PMID:16889684)
• SNPs present in both the SLAM and CD46 genes are associated with measurable and significant variations in antibody response after measles vaccination (PMID:17560639)
• Enhancement of anti-tumor activity in vitro and in vivo by CD150 and SAP (PMID:17692919)
• SLAM and CD46 do not have a role in measles virus growth and syncytium formation in tumor cell lines (PMID:17715217)
• Measles virus can infect and produce syncytia in human polarized epithelial cell lines independently of SLAM and CD46 by using distinctive receptor-binding sites on its hemagglutinin. (PMID:18287234)
• The functional roles of interleukin-17, SLAM and CREB on IFN-gamma production in persons with tuberculosis are reported. (PMID:19199539)
• Data show that measles virus infection of alveolar macrophages and subepithelial dendritic cells in the airways precedes infection of lymphocytes in lymphatic organs of mice expressing human SLAM with human-like tissue specificity. (PMID:20042501)
• CD150 may contribute to regulation of tumor cell maintenance in low-rate proliferating Hodgkin’s lymphoma (PMID:20231852)
• Apoptosis of measles virus-infected peripheral blood mononuclear cells is triggered by interaction between viral hemagglutinin protein and cellular receptor, SLAM. (PMID:20618687)
• Our findings suggest that -262A-188G haplotype in the SLAM gene promoter contributes to the risk of systemic lupus erythematosus by increasing the expression of SLAM. (PMID:20810499)
• A role for SLAM in controlling natural killer T (NKT) cell development is consistent with a role in both positive and negative thymic selection of NKT cells in NOD mice. (PMID:21357537)
• CD150 receptor could trigger PI3K-mediated Akt signaling pathway in normal, EBV-transformed and malignant B cells. (PMID:21423089)
• The simultaneous interaction of Measles virus glycoprotein-pseudotyped Lentivirus with both CD46 and SLAM is required to achieve efficient and stable transduction of B and T cells. (PMID:21450813)
• Subjects previously immunized with measles-mumps-rubella vaccine were genotyped for 66 candidate single nucleotide polymorphisms in the CD46, SLAM and CD209 genes. (PMID:22086389)
• Two genes were consistently retained in the models with clinical variables: SKI (v-SKI avian sarcoma viral oncogene homolog) and SLAMF1 (signaling lymphocytic activation molecule family member 1; CD150). (PMID:22194822)
• the study demonstrates that variants of SLAMF1 and ITLN1, both implicated in inflammation, are associated with type 2 diabetes in Indians. (PMID:22277902)
• conclude that Slamf1 recruits a subset of Vps34-associated proteins, which is involved in membrane fusion and NOX2 regulation (PMID:22493499)
• HIV-1 infection induces a high level of SLAM expression on CD4(+) T cells, which may enhance their susceptibility to measles virus and exacerbate measles in coinfected individuals. (PMID:22532682)
• Experimental adaptation of wild-type canine distemper virus (CDV) to the human entry receptor CD150 (PMID:23554862)
• Latent membrane protein 1 was responsible for the CD150 upregulation. (PMID:24238277)
• Signaling lymphocytic activation molecule (SLAM)/SLAM-associated protein pathway regulates human B-cell tolerance. (PMID:24373350)
• Molecular dynamics analysis revealed that mutant R32Q and T53I structures of SAP exhibited structural variation with respect to their backbone atoms before and after binding with the unphosphorylated SLAM peptide. (PMID:24770789)
• Upstream open reading frames regulate translation of the long isoform of SLAMF1 mRNA that encodes costimulatory receptor CD150 (PMID:25716736)
• Data suggest that SLAMF1 is another significant piece in the intricate defective immune-regulatory function of patients with SLE. (PMID:25920347)
• results indicate that loss of SLAMF1 expression in chronic lymphocytic leukemia modulates genetic pathways (PMID:26619119)
• Malignant B-cell lines at the different stages of maturation only partially resemble their normal counterparts by CD150 expression. In malignant B-cell lines, CD150 expression on mRNA level is much broader than on protein level. CD150 isoforms are differentially expressed in normal and malignant B cells with predominant expression of mCD150 isoform. (PMID:27356578)
• EBF1 is critical for transcriptional control of SLAMF1 gene in human B cells. (PMID:27424222)
• MeV can hijack SLAMF1 to drive endocytosis using a complex pathway that shares features with canonical viral macropinocytosis, phagocytosis, and mechanotransduction. This uptake pathway is specific to SLAMF1-positive cells and occurs within 60 min of viral attachment. (PMID:28100610)
• this paper shows that the X-linked lymphoproliferative disease gene product SAP regulates signals induced through the co-receptor SLAM (PMID:28827385)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:cabz01074946.1	ENSDARG00000090396
mus_musculus	Slamf1	ENSMUSG00000015316
rattus_norvegicus	Slamf1	ENSRNOG00000059073

Paralogs (9): SLAMF7 (ENSG00000026751), CD84 (ENSG00000066294), CD2 (ENSG00000116824), CD48 (ENSG00000117091), CD244 (ENSG00000122223), LY9 (ENSG00000122224), SLAMF8 (ENSG00000158714), SLAMF9 (ENSG00000162723), SLAMF6 (ENSG00000162739)

Protein

Protein identifiers

Signaling lymphocytic activation molecule — Q13291 (reviewed: Q13291)

Alternative names: CDw150, IPO-3, SLAM family member 1

All UniProt accessions (1): Q13291

UniProt curated annotations — full annotation on UniProt →

Function. Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. SLAMF1-induced signal-transduction events in T-lymphocytes are different from those in B-cells. Two modes of SLAMF1 signaling seem to exist: one depending on SH2D1A (and perhaps SH2D1B) and another in which protein-tyrosine phosphatase 2C (PTPN11)-dependent signal transduction operates. Initially it has been proposed that association with SH2D1A prevents binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2. However, signaling is also regulated by SH2D1A which can simultaneously interact with and recruit FYN which subsequently phosphorylates and activates SLAMF1. Mediates IL-2-independent proliferation of activated T-cells during immune responses and induces IFN-gamma production. Downstreaming signaling involves INPP5D, DOK1 and DOK2 leading to inhibited IFN-gamma production in T-cells, and PRKCQ, BCL10 and NFKB1 leading to increased T-cell activation and Th2 cytokine production. Promotes T-cell receptor-induced IL-4 secretion by CD4(+) cells. Inhibits antigen receptor-mediated production of IFN-gamma, but not IL-2, in CD4(-)/CD8(-) T-cells. Required for IL-4 production by germinal centers T follicular helper (T(Fh))cells. May inhibit CD40-induced signal transduction in monocyte-derived dendritic cells. May play a role in allergic responses and may regulate allergen-induced Th2 cytokine and Th1 cytokine secretion. In conjunction with SLAMF6 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage. Involved in the peripheral differentiation of indifferent natural killer T (iNKT) cells toward a regulatory NKT2 type. In macrophages involved in down-regulation of IL-12, TNF and nitric oxide in response to lipopolysaccharide (LPS). In B-cells activates the ERK signaling pathway independently of SH2D1A but implicating both, SYK and INPP5D, and activates Akt signaling dependent on SYK and SH2D1A. In B-cells also activates p38 MAPK and JNK1 and JNK2. In conjunction with CD84/SLAMF5 and SLAMF6 may be a negative regulator of the humoral immune response. Involved in innate immune response against Gram-negative bacteria in macrophages; probably recognizes OmpC and/or OmpF on the bacterial surface, regulates phagosome maturation and recruitment of the PI3K complex II (PI3KC3-C2) leading to accumulation of PdtIns(3)P and NOX2 activity in the phagosomes. (Microbial infection) Acts as a receptor for Measles virus; also including isoform 4.

Subunit / interactions. Interacts (via cytoplasmic domain) with SH2D1A and SH2D1B; SH2D1A mediates association with FYN; SH2D1A binds to phosphorylated and not phosphorylated ITSM 1. Interacts (via cytoplasmic domain phosphorylated on tyrosine residues) with INPP5D and PTPN11; presence of SH2D1A facilitates binding to INPP5D. Interacts with MAP4K1. Interacts with PIK3C3, BECN1 and UVRAG; indicative for an association with PI3K complex II (PI3KC3-C2). (Microbial infection) Interacts with measles hemagglutinin protein; this interaction allows attachment and viral entry into the CD150-expressing immune cells.

Subcellular location. Cell membrane Secreted Cell membrane.

Tissue specificity. Constitutively expressed on peripheral blood memory T-cells, T-cell clones, immature thymocytes and a proportion of B-cells, and is rapidly induced on naive T-cells after activation. Activated B-cells express isoform 1, isoform 3 and a cytoplasmic isoform. Isoform 4 is expressed in B-cells, primary T-cells, dendritic cells and macrophages. Isoform 4 is expressed in tumors of the central nervous system.

Post-translational modifications. Phosphorylated on tyrosine residues by FYN.

Domain organisation. The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. For SLAMF1 a ’two-out-of-three-pronged’ mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). SH2D1A binding is mediated by either three ‘prongs’ (for high affinity binding involving ITSM 1) or a combination of any two also including non-phosphorylated Tyr-281 of ITSM 1 thus providing a positive feedback loop implicating SH2D1A-dependent recruitment of activating FYN. ITSM 2 needs to be phosphorylated on Tyr-327 for SH2D1A binding.

Isoforms (4)

UniProt ID	Names	Canonical?
Q13291-1	1, Long, mCD150	yes
Q13291-2	2, Short, SURslam2, vmSLAM
Q13291-3	3, Secreted, SECslam, sSLAM
Q13291-4	4, nCD150

RefSeq proteins (2): NP_001317683, NP_003028* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007110	Ig-like_dom	Domain
IPR010407	Sig_lymph_act_molc_N	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015631	CD2/SLAM_rcpt	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF06214

UniProt features (41 total): mutagenesis site 9, glycosylation site 8, splice variant 4, modified residue 3, sequence variant 3, short sequence motif 3, topological domain 2, disulfide bond 2, domain 2, signal peptide 1, chain 1, site 1, transmembrane region 1, strand 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1D4T	X-RAY DIFFRACTION	1.1
1D4W	X-RAY DIFFRACTION	1.8
1I3Z	X-RAY DIFFRACTION	2.15
1M27	X-RAY DIFFRACTION	2.5
1KA6	SOLUTION NMR
1KA7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13291-F1	75.23	0.42

Functional residue map

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

Catalytic / active sites (1): 29 (interaction with measles hn protein)

Post-translational modifications (3): 281, 307, 327

Disulfide bonds (2): 158–228, 164–209

Glycosylation sites (8): 53, 57, 102, 125, 150, 155, 189, 217

Mutagenesis-validated functional residues (9):

Position	Phenotype
29	reduced infectivity.
269	no effect on interaction with inpp5d/ship-1, ptpn11/shp-2 and sh2d1a.
279	disrupts interaction with sh2d1a; when associated with a-325.
281	disrupts interaction with inpp5d/ship-1 and ptpn11/shp-2, no effect on interaction with sh2d1a.
281	disrupts interaction with sh2d1a; when associated with f-327.
307	no effect on interaction with ptpn11/shp-2 and sh2d1a.
325	disrupts interaction with sh2d1a; when associated with a-279.
327	disrupts interaction with inpp5d/ship-1 and ptpn11/shp-2, no effect on interaction with sh2d1a.
327	disrupts interaction with sh2d1a; when associated with f-281.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 457 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_VESICLE_FUSION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE

GO Biological Process (29): natural killer cell differentiation (GO:0001779), natural killer cell proliferation (GO:0001787), leukocyte chemotaxis involved in inflammatory response (GO:0002232), adaptive immune response (GO:0002250), myeloid dendritic cell activation involved in immune response (GO:0002277), negative regulation of T cell cytokine production (GO:0002725), phagocytosis (GO:0006909), immune response (GO:0006955), cell adhesion (GO:0007155), positive regulation of cell population proliferation (GO:0008284), positive regulation of macrophage chemotaxis (GO:0010759), regulation of vesicle fusion (GO:0031338), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-12 production (GO:0032695), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), positive regulation of type II interferon production (GO:0032729), positive regulation of activated T cell proliferation (GO:0042104), innate immune response (GO:0045087), positive regulation of JNK cascade (GO:0046330), positive regulation of ERK1 and ERK2 cascade (GO:0070374), negative regulation of CD40 signaling pathway (GO:2000349), positive regulation of dendritic cell chemotaxis (GO:2000510), positive regulation of T-helper 1 cell cytokine production (GO:2000556), negative regulation of cytokine production (GO:0001818), immune system process (GO:0002376), leukocyte activation (GO:0045321), lymphocyte activation (GO:0046649), symbiont entry into host cell (GO:0046718)

GO Molecular Function (7): virus receptor activity (GO:0001618), antigen binding (GO:0003823), transmembrane signaling receptor activity (GO:0004888), signaling receptor activity (GO:0038023), SH2 domain binding (GO:0042169), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), extracellular region (GO:0005576), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune response	3
negative regulation of cytokine production	3
cellular anatomical structure	3
natural killer cell activation	2
type II interferon production	2
regulation of type II interferon production	2
binding	2
lymphocyte differentiation	1
lymphocyte proliferation	1
leukocyte migration involved in inflammatory response	1
inflammatory response	1
leukocyte chemotaxis	1
myeloid dendritic cell activation	1
myeloid cell activation involved in immune response	1
T cell cytokine production	1
negative regulation of T cell mediated immunity	1
negative regulation of cytokine production involved in immune response	1
regulation of T cell cytokine production	1
endocytosis	1
immune system process	1
response to stimulus	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
vesicle fusion	1
regulation of organelle organization	1
regulation of vesicle-mediated transport	1
interleukin-12 production	1
regulation of interleukin-12 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1

Protein interactions and networks

STRING

2080 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLAMF1	SH2D1A	O60880	999
SLAMF1	MYBPH	Q13203	994
SLAMF1	SLAMF6	Q96DU3	970
SLAMF1	CD46	P15529	966
SLAMF1	BECN1	Q14457	950
SLAMF1	FYN	P06241	913
SLAMF1	PTPN11	Q06124	885
SLAMF1	MATK	P42679	875
SLAMF1	CD2	P06729	851
SLAMF1	NECTIN4	Q96NY8	845
SLAMF1	FLT3	P36888	832
SLAMF1	SH2D1B	O14796	824
SLAMF1	KIT	P10721	800
SLAMF1	LCK	P06239	794
SLAMF1	CD33	P20138	778

IntAct

41 interactions, top by confidence:

A	B	Type	Score
SLAMF1	SH2D1A	psi-mi:“MI:0914”(association)	0.940
SH2D1A	SLAMF1	psi-mi:“MI:0914”(association)	0.940
SH2D1A	SLAMF1	psi-mi:“MI:0407”(direct interaction)	0.940
SH2D1A	SLAMF1	psi-mi:“MI:0915”(physical association)	0.940
SLAMF1	SLAMF1	psi-mi:“MI:0407”(direct interaction)	0.720
SLAMF1	SLAMF1	psi-mi:“MI:0915”(physical association)	0.720
MAP4K1	SLAMF1	psi-mi:“MI:0915”(physical association)	0.580
SLAMF1	SH2D1A	psi-mi:“MI:0915”(physical association)	0.570
SH2D1A	SLAMF1	psi-mi:“MI:0915”(physical association)	0.570
H	SLAMF1	psi-mi:“MI:0407”(direct interaction)	0.560
RGS13	CIAO1	psi-mi:“MI:0914”(association)	0.530
INPP5D	SLAMF1	psi-mi:“MI:0914”(association)	0.460
PTPN11	SLAMF1	psi-mi:“MI:0914”(association)	0.460
H	SLAMF1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (177): SLC39A11 (Affinity Capture-MS), ATP1A3 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), ATP2B2 (Affinity Capture-MS), ATP2B3 (Affinity Capture-MS), NF1 (Affinity Capture-MS), HEATR1 (Affinity Capture-MS), CTPS2 (Affinity Capture-MS), INTS4 (Affinity Capture-MS), NUP188 (Affinity Capture-MS), UQCRC2 (Affinity Capture-MS), GK2 (Affinity Capture-MS), GK (Affinity Capture-MS), AHCTF1 (Affinity Capture-MS), INTS2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1G0, A0A0B4J1L0, A0A0G2KBC9, A1YIY0, A8MTB9, B6A8R8, C0HJX2, C0HJX3, E2RP87, H0VDZ8, P08637, P09326, P12314, P23505, P26151, P43626, P43627, P43628, P43631, P43632, P83555, P83556, Q01965, Q13291, Q14952, Q14953, Q14954, Q28942, Q2YHT5, Q61400, Q61450, Q640U3, Q68EV1, Q68SN8, Q6UX41, Q6UXE8, Q6UY09, Q6XJV4, Q6XPU4, Q7TST0

Diamond homologs: Q13291, Q95MM9, Q9QUM4, Q9HBG7, Q01965, Q18PI6, Q96A28, Q96DU3, Q9D780, Q9NQ25, Q9UIB8

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
LYN	unknown	SLAMF1	phosphorylation
MARCHF9	“down-regulates quantity by destabilization”	SLAMF1	ubiquitination
hsa-mir-146a-5p	“down-regulates quantity by repression”	SLAMF1	“post transcriptional regulation”
FYN	“up-regulates activity”	SLAMF1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1154 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160612482:CCTCA:C	donor_loss	1.0000
1:160612483:CTCAC:C	donor_loss	1.0000
1:160612484:TCA:T	donor_loss	1.0000
1:160612485:CACCT:C	donor_loss	1.0000
1:160612486:AC:A	donor_loss	1.0000
1:160612487:CC:C	donor_loss	1.0000
1:160612581:C:CC	acceptor_gain	1.0000
1:160637259:C:A	donor_gain	1.0000
1:160637272:T:TA	donor_gain	1.0000
1:160637280:T:A	donor_gain	1.0000
1:160612577:GAGG:G	acceptor_gain	0.9900
1:160612579:GG:G	acceptor_gain	0.9900
1:160612581:C:T	acceptor_loss	0.9900
1:160612582:T:C	acceptor_loss	0.9900
1:160619774:ACAC:A	donor_gain	0.9900
1:160619775:CA:C	donor_gain	0.9900
1:160619775:CACC:C	donor_gain	0.9900
1:160637203:A:C	donor_gain	0.9900
1:160637258:T:TA	donor_gain	0.9900
1:160637264:AT:A	donor_gain	0.9900
1:160637264:ATCCT:A	donor_gain	0.9900
1:160637265:T:TA	donor_gain	0.9900
1:160637268:T:TA	donor_gain	0.9900
1:160637451:AT:A	donor_gain	0.9900
1:160637530:C:CA	acceptor_loss	0.9900
1:160637531:T:G	acceptor_loss	0.9900
1:160612576:AGAGG:A	acceptor_gain	0.9800
1:160612578:AGG:A	acceptor_gain	0.9800
1:160619774:A:AC	donor_gain	0.9800
1:160619775:C:CC	donor_gain	0.9800

AlphaMissense

2190 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160634785:C:A	W176C	0.996
1:160634785:C:G	W176C	0.996
1:160634687:C:G	C209S	0.993
1:160634688:A:T	C209S	0.993
1:160634822:C:G	C164S	0.989
1:160634823:A:T	C164S	0.989
1:160634787:A:G	W176R	0.988
1:160634787:A:T	W176R	0.988
1:160634686:G:C	C209W	0.986
1:160634688:A:G	C209R	0.986
1:160634823:A:G	C164R	0.986
1:160634687:C:T	C209Y	0.985
1:160637254:A:C	Y118D	0.982
1:160634674:G:C	N213K	0.981
1:160634674:G:T	N213K	0.981
1:160634821:G:C	C164W	0.976
1:160634822:C:T	C164Y	0.975
1:160637253:T:G	Y118S	0.974
1:160637253:T:C	Y118C	0.970
1:160634687:C:A	C209F	0.969
1:160634688:A:C	C209G	0.965
1:160634841:A:G	C158R	0.961
1:160634630:C:G	C228S	0.960
1:160634631:A:T	C228S	0.960
1:160634786:C:G	W176S	0.960
1:160612528:A:T	I306K	0.959
1:160634840:C:G	C158S	0.959
1:160634841:A:T	C158S	0.959
1:160634665:G:C	S216R	0.956
1:160634665:G:T	S216R	0.956

dbSNP variants (sampled 300 via entrez): RS1000054579 (1:160645564 C>T), RS1000280750 (1:160640291 G>C), RS1000306251 (1:160635753 G>C,T), RS1000322931 (1:160610175 T>A), RS1000420125 (1:160627676 A>T), RS1000503145 (1:160641479 A>G), RS1000644527 (1:160641956 A>G), RS1000646458 (1:160647755 T>A), RS1000676212 (1:160635402 G>A), RS1000705469 (1:160635795 G>T), RS1000715737 (1:160640654 G>A,T), RS1000735041 (1:160643093 A>G), RS1000744769 (1:160642824 G>A), RS1000807 (1:160647238 G>T), RS1000827043 (1:160620954 T>C)

Disease associations

OMIM: gene MIM:603492 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001458_1	Schizophrenia (treatment resistant)	2.000000e-07
GCST001725_36	Inflammatory bowel disease	7.000000e-09
GCST003253_3	Microalbuminuria	9.000000e-07
GCST004861_31	Itch intensity from mosquito bite	2.000000e-08
GCST009597_305	Multiple sclerosis	1.000000e-09
GCST010679_2	Memory decline	4.000000e-08
GCST90002381_5	Eosinophil count	3.000000e-13
GCST90002382_13	Eosinophil percentage of white cells	4.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0004874	memory performance
EFO:0007710	cognitive decline measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
4-phenylenediamine	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
gardiquimod	increases expression, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Demecolcine	increases expression	1
Dinitrochlorobenzene	decreases expression	1
Eugenol	decreases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Tobacco Smoke Pollution	decreases methylation	1
Vincristine	increases expression	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	increases expression	1
Vitamin K 3	increases expression	1
Protein Kinase Inhibitors	decreases reaction, increases expression	1

Cellosaurus cell lines

5 cell lines: 2 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B4FH	MODE-K.CD150	Transformed cell line	Female
CVCL_B8PI	Abcam HCT 116 SLAMF1 KO	Cancer cell line	Male
CVCL_B9RX	Abcam A-549 SLAMF1 KO	Cancer cell line	Male
CVCL_C7UT	Vero PVR1/2 DKO hSLAM+	Spontaneously immortalized cell line	Female
CVCL_L037	Vero/hSLAM	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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