SLAMF8

Summary

SLAMF8 (SLAM family member 8, HGNC:21391) is a protein-coding gene on chromosome 1q23.2, encoding SLAM family member 8 (Q9P0V8). May play a role in B-lineage commitment and/or modulation of signaling through the B-cell receptor.

This gene encodes a member of the CD2 family of cell surface proteins involved in lymphocyte activation. These proteins are characterized by Ig domains. This protein is expressed in lymphoid tissues, and studies of a similar protein in mouse suggest that it may function during B cell lineage commitment. The gene is found in a region of chromosome 1 containing many CD2 genes.

Source: NCBI Gene 56833 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 58 total
• MANE Select transcript: NM_020125

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21391
Approved symbol	SLAMF8
Name	SLAM family member 8
Location	1q23.2
Locus type	gene with protein product
Status	Approved
Aliases	BLAME, SBBI42, CD353
Ensembl gene	ENSG00000158714
Ensembl biotype	protein_coding
OMIM	606620
Entrez	56833

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000289707, ENST00000368104, ENST00000471286, ENST00000497141, ENST00000852919, ENST00000852920, ENST00000852921, ENST00000852922, ENST00000949529, ENST00000949530, ENST00000949531

RefSeq mRNA: 2 — MANE Select: NM_020125 NM_001330741, NM_020125

CCDS: CCDS1188, CCDS81387

Canonical transcript exons

ENST00000289707 — 5 exons

Exon	Start	End
ENSE00001040500	159829866	159830192
ENSE00001067952	159835184	159837492
ENSE00001511198	159826873	159826938
ENSE00003464386	159832876	159833181
ENSE00003601793	159833262	159833369

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 90.31.

FANTOM5 (CAGE): breadth broad, TPM avg 7.5415 / max 374.1842, expressed in 386 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6001	4.1074	277
6000	1.3227	190
5999	0.9926	161
5998	0.3589	117
5995	0.3012	113
5996	0.2244	84
5997	0.1883	79
5993	0.0236	9
5994	0.0183	4
5992	0.0041	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	90.31	gold quality
lymph node	UBERON:0000029	88.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.43	silver quality
caecum	UBERON:0001153	85.10	gold quality
lower lobe of lung	UBERON:0008949	84.05	gold quality
decidua	UBERON:0002450	80.45	gold quality
spleen	UBERON:0002106	80.42	gold quality
superficial temporal artery	UBERON:0001614	80.39	gold quality
amniotic fluid	UBERON:0000173	80.35	gold quality
gall bladder	UBERON:0002110	80.10	gold quality
rectum	UBERON:0001052	80.00	gold quality
granulocyte	CL:0000094	79.69	gold quality
right coronary artery	UBERON:0001625	76.78	gold quality
upper lobe of lung	UBERON:0008948	75.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	75.90	gold quality
smooth muscle tissue	UBERON:0001135	75.85	gold quality
diaphragm	UBERON:0001103	75.52	gold quality
upper lobe of left lung	UBERON:0008952	75.50	gold quality
palpebral conjunctiva	UBERON:0001812	74.77	gold quality
leukocyte	CL:0000738	74.48	gold quality
monocyte	CL:0000576	74.42	gold quality
olfactory bulb	UBERON:0002264	74.41	gold quality
mononuclear cell	CL:0000842	74.28	gold quality
lung	UBERON:0002048	74.13	gold quality
descending thoracic aorta	UBERON:0002345	74.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	73.46	gold quality
left coronary artery	UBERON:0001626	72.94	gold quality
colonic mucosa	UBERON:0000317	72.65	gold quality
coronary artery	UBERON:0001621	72.57	gold quality
small intestine	UBERON:0002108	72.56	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	7.22
E-ANND-3	yes	4.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting SLAMF8, 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-4673	100.00	66.64	1490
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-199A-5P	99.51	69.71	1107

Literature-anchored findings (GeneRIF, showing 7)

• Thus, SLAMF8 is involved in oncogenic KIT-mediated RAS-RAF- ERK signalling and the subsequent growth of human neoplastic mast cells mediated by SHP-2. (PMID:29498772)
• SLAM family member 8 is expressed in and enhances the growth of anaplastic large cell lymphoma. (PMID:32054954)
• Knockout of SLAMF8 attenuates collagen-induced rheumatoid arthritis in mice through inhibiting TLR4/NF-kappaB signaling pathway. (PMID:35259711)
• SLAMF8 Participates in Acute Renal Transplant Rejection via TLR4 Pathway on Pro-Inflammatory Macrophages. (PMID:35432371)
• SLAMF8 promotes the proliferation and migration of synovial fibroblasts by regulating the ERK/MMPs signalling pathway. (PMID:35506438)
• Upregulation of SLAMF8 aggravates ischemia/reperfusion-induced ferroptosis and injury in cardiomyocyte. (PMID:38158136)
• SLAMF8 can predict prognosis of pan-cancer and the immunotherapy response effectivity of gastric cancer. (PMID:38787377)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:cabz01074946.1	ENSDARG00000090396
mus_musculus	Slamf8	ENSMUSG00000053318
rattus_norvegicus	Slamf8	ENSRNOG00000008736

Paralogs (9): SLAMF7 (ENSG00000026751), CD84 (ENSG00000066294), CD2 (ENSG00000116824), SLAMF1 (ENSG00000117090), CD48 (ENSG00000117091), CD244 (ENSG00000122223), LY9 (ENSG00000122224), SLAMF9 (ENSG00000162723), SLAMF6 (ENSG00000162739)

Protein

Protein identifiers

SLAM family member 8 — Q9P0V8 (reviewed: Q9P0V8)

Alternative names: B-lymphocyte activator macrophage expressed, BCM-like membrane protein

All UniProt accessions (1): Q9P0V8

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in B-lineage commitment and/or modulation of signaling through the B-cell receptor.

Subcellular location. Membrane.

Tissue specificity. Expressed in lymph node, spleen, thymus and bone marrow.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P0V8-1	1	yes
Q9P0V8-2	2

RefSeq proteins (2): NP_001317670, NP_064510* (*=MANE)

Domains & families (InterPro)

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

UniProt features (13 total): sequence variant 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0V8-F1	81.35	0.57

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 (1): 152–201

Glycosylation sites (1): 85

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 277 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_REGULATION_OF_RESPIRATORY_BURST, GOBP_REGULATION_OF_CELL_ACTIVATION, CREL_01, GOBP_DENDRITIC_CELL_MIGRATION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_B_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_CHEMOTAXIS, NFKB_Q6

GO Biological Process (11): leukocyte chemotaxis involved in inflammatory response (GO:0002232), B-1 B cell lineage commitment (GO:0002336), immune response (GO:0006955), negative regulation of macrophage chemotaxis (GO:0010760), defense response to bacterium (GO:0042742), regulation of B cell differentiation (GO:0045577), negative regulation of respiratory burst involved in inflammatory response (GO:0060266), negative regulation of monocyte chemotaxis (GO:0090027), phagosome acidification (GO:0090383), negative regulation of neutrophil migration (GO:1902623), negative regulation of dendritic cell chemotaxis (GO:2000509)

GO Molecular Function (3): signaling receptor activity (GO:0038023), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (2): cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of leukocyte chemotaxis	3
negative regulation of mononuclear cell migration	2
cellular anatomical structure	2
leukocyte migration involved in inflammatory response	1
inflammatory response	1
leukocyte chemotaxis	1
B-1 B cell differentiation	1
B cell lineage commitment	1
immune system process	1
response to stimulus	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
negative regulation of macrophage migration	1
defense response	1
response to bacterium	1
B cell differentiation	1
regulation of lymphocyte differentiation	1
regulation of B cell activation	1
respiratory burst involved in inflammatory response	1
negative regulation of immune effector process	1
negative regulation of innate immune response	1
negative regulation of inflammatory response	1
negative regulation of multicellular organismal process	1
regulation of respiratory burst involved in inflammatory response	1
negative regulation of respiratory burst	1
regulation of cell development	1
monocyte chemotaxis	1
regulation of monocyte chemotaxis	1
intracellular pH reduction	1
phagosome maturation	1
negative regulation of leukocyte migration	1
regulation of neutrophil migration	1
neutrophil migration	1
dendritic cell chemotaxis	1
regulation of dendritic cell chemotaxis	1
molecular transducer activity	1
protein binding	1
binding	1

Protein interactions and networks

STRING

1976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLAMF8	SLAMF9	Q96A28	728
SLAMF8	LY9	Q9HBG7	627
SLAMF8	SLAMF6	Q96DU3	624
SLAMF8	KLHDC9	Q8NEP7	535
SLAMF8	SLAMF1	Q13291	532
SLAMF8	ARHGAP30	Q7Z6I6	527
SLAMF8	CD2	P06729	488
SLAMF8	CD58	P19256	483
SLAMF8	FCRL6	Q6DN72	478
SLAMF8	SH2D1A	O60880	448
SLAMF8	SH2D1B	O14796	435
SLAMF8	MFAP1	P55081	412
SLAMF8	NRROS	Q86YC3	407
SLAMF8	HABP4	Q5JVS0	406
SLAMF8	SLAMF7	Q9NQ25	389

IntAct

13 interactions, top by confidence:

A	B	Type	Score
EMP3	SLAMF8	psi-mi:“MI:0915”(physical association)	0.560
NINJ2	SLAMF8	psi-mi:“MI:0915”(physical association)	0.560
SLAMF8	SLAMF8	psi-mi:“MI:0407”(direct interaction)	0.440
SLAMF8	FBP1	psi-mi:“MI:0915”(physical association)	0.400
SLAMF8	GPD1L	psi-mi:“MI:0915”(physical association)	0.400
SLAMF8	HBD	psi-mi:“MI:0914”(association)	0.350
SLAMF8	TUBB8	psi-mi:“MI:0914”(association)	0.350
NINJ2	SLAMF8	psi-mi:“MI:0915”(physical association)	0.000
EMP3	SLAMF8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): FBP1 (Affinity Capture-MS), SLAMF8 (Synthetic Lethality), SLAMF8 (Two-hybrid), NINJ2 (Two-hybrid), GPD1L (Affinity Capture-MS), TNFSF9 (Affinity Capture-MS), HLA-F (Affinity Capture-MS), ULBP3 (Affinity Capture-MS), PVR (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), ITFG1 (Affinity Capture-MS), HBD (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), SAMM50 (Affinity Capture-MS)

ESM2 similar proteins: A6NMB1, A7LCJ3, G1T7E7, G1TR84, M3XWH1, O15389, O43699, O70540, P04217, P05362, P0DP72, P13597, P20138, P32942, P33729, Q00238, Q08ET2, Q14773, Q28125, Q28730, Q28806, Q2KJF1, Q5NKT8, Q5NKU6, Q5NKV4, Q5NKV6, Q5NKV9, Q60625, Q62230, Q64JA4, Q6DN72, Q7L513, Q80ZE3, Q91Y57, Q920A9, Q920G3, Q92154, Q95132, Q95LH0, Q96A28

Diamond homologs: A4FUY1, A6QQC6, A8MVW5, Q00888, Q14CZ8, Q4VAH7, Q640R3, Q9D780, Q9P0V8, Q9VN14, Q9D3G2, P42071, Q01965, Q18PI6, Q3KPI0, Q8BHK6, Q96A28, Q96DU3, Q9ET39, Q9HBG7, Q9NQ25, Q9UIB8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1241 predictions. Top by Δscore:

Variant	Effect	Δscore
1:159826934:GGAAG:G	donor_gain	1.0000
1:159826935:GAAGG:G	donor_gain	1.0000
1:159826937:AGG:A	donor_loss	1.0000
1:159826938:GGT:G	donor_loss	1.0000
1:159826939:GTA:G	donor_loss	1.0000
1:159826940:T:G	donor_loss	1.0000
1:159830189:TACGG:T	donor_loss	1.0000
1:159830190:ACGGT:A	donor_loss	1.0000
1:159830192:GGTG:G	donor_loss	1.0000
1:159830193:GTGA:G	donor_loss	1.0000
1:159830194:T:G	donor_loss	1.0000
1:159826935:GAAG:G	donor_gain	0.9900
1:159829882:A:AG	acceptor_gain	0.9900
1:159829883:G:GG	acceptor_gain	0.9900
1:159830188:GTACG:G	donor_gain	0.9900
1:159830193:G:GG	donor_gain	0.9900
1:159830195:G:GG	donor_loss	0.9900
1:159826939:G:GG	donor_gain	0.9800
1:159829865:GCCCT:G	acceptor_gain	0.9800
1:159830019:G:GC	acceptor_gain	0.9800
1:159833261:G:GC	acceptor_gain	0.9800
1:159834483:G:T	donor_gain	0.9800
1:159826872:G:GT	donor_gain	0.9700
1:159830185:GGT:G	donor_gain	0.9700
1:159830186:GTG:G	donor_gain	0.9700
1:159830187:TGT:T	donor_gain	0.9700
1:159830188:GTAC:G	donor_gain	0.9700
1:159830189:TACG:T	donor_gain	0.9700
1:159830196:A:AC	donor_loss	0.9700
1:159833257:TTCA:T	acceptor_loss	0.9700

AlphaMissense

1835 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:159833000:G:C	W164C	0.988
1:159833000:G:T	W164C	0.988
1:159830051:T:C	F76L	0.981
1:159830053:C:A	F76L	0.981
1:159830053:C:G	F76L	0.981
1:159833109:T:A	C201S	0.981
1:159833110:G:C	C201S	0.981
1:159829975:G:C	W50C	0.979
1:159829975:G:T	W50C	0.979
1:159829973:T:A	W50R	0.978
1:159829973:T:C	W50R	0.978
1:159832998:T:A	W164R	0.977
1:159832998:T:C	W164R	0.977
1:159830127:T:C	F101S	0.974
1:159833123:C:A	N205K	0.974
1:159833123:C:G	N205K	0.974
1:159833110:G:A	C201Y	0.973
1:159830084:A:C	S87R	0.972
1:159830086:C:A	S87R	0.972
1:159830086:C:G	S87R	0.972
1:159833111:C:G	C201W	0.972
1:159830126:T:C	F101L	0.971
1:159830128:C:A	F101L	0.971
1:159830128:C:G	F101L	0.971
1:159829977:G:C	R51P	0.969
1:159833109:T:C	C201R	0.968
1:159833130:A:C	S208R	0.966
1:159833132:C:A	S208R	0.966
1:159833132:C:G	S208R	0.966
1:159832963:G:A	C152Y	0.965

dbSNP variants (sampled 300 via entrez): RS1000063978 (1:159835694 A>C), RS1000118470 (1:159827992 C>T), RS1000265864 (1:159832736 A>T), RS1000436525 (1:159835455 C>G,T), RS1000629874 (1:159831249 C>T), RS1000720931 (1:159832532 A>G), RS1001321479 (1:159833789 G>A), RS1002200759 (1:159829097 C>G,T), RS1002628965 (1:159831241 A>C,T), RS1002814782 (1:159834283 T>C), RS1002933717 (1:159826684 C>A,G,T), RS1003203552 (1:159828256 C>G), RS1003424632 (1:159828031 A>G), RS1003612308 (1:159835661 T>C), RS1003664616 (1:159835351 A>T)

Disease associations

OMIM: gene MIM:606620 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004132_29	Crohn’s disease	1.000000e-08
GCST004132_51	Crohn’s disease	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
nickel sulfate	decreases expression	2
TL8-506	affects cotreatment, increases expression	1
bisphenol A	decreases methylation	1
sodium bichromate	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	decreases expression	1
Calcitriol	decreases expression	1
Dinitrochlorobenzene	decreases expression	1
Diuron	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Naled	affects expression	1
Nickel	increases expression	1
Oxazolone	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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