SLAMF6

Summary

SLAMF6 (SLAM family member 6, HGNC:21392) is a protein-coding gene on chromosome 1q23.2-q23.3, encoding SLAM family member 6 (Q96DU3). Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family.

The protein encoded by this gene is a type I transmembrane protein, belonging to the CD2 subfamily of the immunoglobulin superfamily. This encoded protein is expressed on Natural killer (NK), T, and B lymphocytes. It undergoes tyrosine phosphorylation and associates with the Src homology 2 domain-containing protein (SH2D1A) as well as with SH2 domain-containing phosphatases (SHPs). It functions as a coreceptor in the process of NK cell activation. It can also mediate inhibitory signals in NK cells from X-linked lymphoproliferative patients. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 114836 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_001184714

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21392
Approved symbol	SLAMF6
Name	SLAM family member 6
Location	1q23.2-q23.3
Locus type	gene with protein product
Status	Approved
Aliases	KALI, NTBA, KALIb, Ly108, SF2000, NTB-A, CD352
Ensembl gene	ENSG00000162739
Ensembl biotype	protein_coding
OMIM	606446
Entrez	114836

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000368055, ENST00000368057, ENST00000368059, ENST00000873202, ENST00000873203, ENST00000960639

RefSeq mRNA: 4 — MANE Select: NM_001184714 NM_001184714, NM_001184715, NM_001184716, NM_052931

CCDS: CCDS1205, CCDS53393, CCDS53394

Canonical transcript exons

ENST00000368057 — 8 exons

Exon	Start	End
ENSE00001068148	160490198	160490236
ENSE00001068151	160496061	160496393
ENSE00001068152	160487104	160487175
ENSE00001068154	160491125	160491388
ENSE00001068155	160490575	160490685
ENSE00001446213	160489088	160489170
ENSE00001885693	160485036	160486754
ENSE00001935440	160523144	160523255

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 94.09.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3551 / max 262.4147, expressed in 298 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15498	5.2288	295
15499	0.1264	71

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	94.09	gold quality
lymph node	UBERON:0000029	89.94	gold quality
spleen	UBERON:0002106	88.73	gold quality
vermiform appendix	UBERON:0001154	87.94	gold quality
blood	UBERON:0000178	83.95	gold quality
bone marrow cell	CL:0002092	81.71	gold quality
caecum	UBERON:0001153	80.68	gold quality
superficial temporal artery	UBERON:0001614	79.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.33	gold quality
gall bladder	UBERON:0002110	75.30	gold quality
small intestine	UBERON:0002108	72.73	gold quality
mucosa of transverse colon	UBERON:0004991	72.50	gold quality
rectum	UBERON:0001052	72.28	gold quality
bone marrow	UBERON:0002371	70.63	gold quality
leukocyte	CL:0000738	70.32	gold quality
tonsil	UBERON:0002372	69.61	gold quality
upper lobe of left lung	UBERON:0008952	69.24	gold quality
colonic epithelium	UBERON:0000397	68.99	silver quality
upper lobe of lung	UBERON:0008948	68.76	gold quality
monocyte	CL:0000576	67.88	gold quality
smooth muscle tissue	UBERON:0001135	66.47	gold quality
epithelium of nasopharynx	UBERON:0001951	66.14	gold quality
left uterine tube	UBERON:0001303	65.37	gold quality
right lung	UBERON:0002167	64.86	gold quality
body of stomach	UBERON:0001161	64.85	gold quality
transverse colon	UBERON:0001157	64.48	gold quality
right coronary artery	UBERON:0001625	63.80	gold quality
omental fat pad	UBERON:0010414	63.24	gold quality
peritoneum	UBERON:0002358	63.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR2, MYB, ZBTB16

miRNA regulators (miRDB)

67 targeting SLAMF6, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6808-5P	99.31	66.23	2150

Literature-anchored findings (GeneRIF, showing 21)

• regulation of interferon-gamma secretion, and not interleukin-4 in vitro, as well as inhibition of Th1 cell-induced isotype switching and attenuation of experimental allergic encephalomyelitis identifies NTB-A as a regulator of T cell response (PMID:14988414)
• NTB-A is an interlymphocyte signaling molecule, which serves to orchestrate the activities of immune cells. (PMID:15153464)
• blocking the engagement of 2B4, NTB-A and CRACC has no effect on the proliferation or development of the cytotoxic potential of NK cells but triggering by their physiological ligands on MHC class I-negative target cells induces potent NK cell cytotoxicity (PMID:16410313)
• NTB-A-mediated IFN-gamma production was greatly reduced in the absence of SLAM-associated protein (SAP), demonstrating that cytokine production and cytotoxicity are differentially dependent on SAP and possibly EAT-2 (PMID:16920955)
• The 3.0 A crystal structure of the complete NTB-A ectodomain revealed a rod-like monomer that self-associates to form a highly kinked dimer spanning an end-to-end distance of approximately 100 A. (PMID:17045824)
• HTLV-1-infected CD4+ T cells did not express ligands for NK cell activating receptors, NCR and NKG2D, although they did express ligands for NK cell coactivating receptors, NTB-A and 2B4. (PMID:17609265)
• 2B4, NTB-A and CRACC have roles in the regulation of Natural Killer cell function [review] (PMID:17981603)
• Vpu downmodulation of NTB-A protects the infected cell from lysis by NK cells. (PMID:21075351)
• Although the expression of SLAMF6 on the surface of T cells from patients with systemic lupus erythematosus (SLE) T cells is comparable to that on the normal T cells, engagement of SLAMF6 results in severely reduced Th1 and IL-2 cytokine production (PMID:21231893)
• SLAMF3 and SLAMF6 T cell surface expression and IL-17 levels significantly correlate with disease activity in systemic lupus erythematosus patients (PMID:22184727)
• Data indicate that the dominance of the SLAMF3/SLAMF6 pathway in inducing IL-17A production can be attributed to an increased nuclear abundance and recruitment of RORgammat to the IL17A promoter. (PMID:22989874)
• Together, these results suggest that the reduction of NTB-A from the cell surface is associated with the Vpu-mediated effect on the glycosylation pattern of newly synthesized NTB-A molecules. (PMID:23528733)
• our data reveal how SAP nucleates a previously unknown signaling complex involving NTB-A and LCK to potentiate restimulation-induced cell death of activated human T cells. (PMID:24688028)
• In addition to their role in NK cell activation by hematopoietic cells, the SLAM-SAP-SHP1 pathways influence responsiveness toward nonhematopoietic targets by a process akin to NK cell ’education’. (PMID:26878112)
• in addition to its established role in Invariant NKT(iNKT) cell ontogeny, Ly108 regulates iNKT cell function in mice and humans (PMID:28373584)
• these results showed that the NTB-A/SAP pathway regulates T-cell activation and restimulation-induced cell death during human tuberculosis (PMID:28546549)
• Authors found that seSLAMF6 reduced activation-induced cell death and had an antiapoptotic effect on tumor-infiltrating lymphocytes. (PMID:29305520)
• SLAMF6 is an important regulator of T cell activation where both its ectodomain and its endodomain contribute differentially to T cell functions. (PMID:31199820)
• Expression and function of SLAMF6 in CD8(+) T lymphocytes of patients with severe aplastic anemia. (PMID:33774556)
• SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population. (PMID:35016729)
• Clinical and immunological relevance of SLAMF6 expression in the tumor microenvironment of breast cancer and melanoma. (PMID:38287061)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:cabz01074946.1	ENSDARG00000090396
mus_musculus	Slamf6	ENSMUSG00000015314
rattus_norvegicus	Slamf6	ENSRNOG00000038286

Paralogs (9): SLAMF7 (ENSG00000026751), CD84 (ENSG00000066294), CD2 (ENSG00000116824), SLAMF1 (ENSG00000117090), CD48 (ENSG00000117091), CD244 (ENSG00000122223), LY9 (ENSG00000122224), SLAMF8 (ENSG00000158714), SLAMF9 (ENSG00000162723)

Protein

Protein identifiers

SLAM family member 6 — Q96DU3 (reviewed: Q96DU3)

Alternative names: Activating NK receptor, NK-T-B-antigen

All UniProt accessions (1): Q96DU3

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. Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors. Positive signaling in NK cells implicates phosphorylation of VAV1. NK cell activation seems to depend on SH2D1B and not on SH2D1A. In conjunction with SLAMF1 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage. Promotes T-cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A. Promotes recruitment of RORC to the IL-17 promoter. In conjunction with SLAMF1 and CD84/SLAMF5 may be a negative regulator of the humoral immune response. In the absence of SH2D1A/SAP can transmit negative signals to CD4(+) T-cells and NKT cells. Negatively regulates germinal center formation by inhibiting T-cell:B-cell adhesion; the function probably implicates increased association with PTPN6/SHP-1 via ITSMs in absence of SH2D1A/SAP. However, reported to be involved in maintaining B-cell tolerance in germinal centers and in preventing autoimmunity.

Subunit / interactions. Homodimer. Interacts with PTN6. Interacts (phosphorylated) with PTN11. Interacts (phosphorylated on tyrosine residues) with SH2D1A/SAP and SH2D1B/EAT2; SH2D1A and SH2D1B can associate with the same SLAMF6 molecule; interaction with SH2D1B is mediated by ITSM 2.

Subcellular location. Cell membrane.

Tissue specificity. Expressed by all (resting and activated) natural killer cells (NK), T- and B-lymphocytes. Increased surface expression on T-cells of systemic lupus erythematosus (SLE) patients.

Post-translational modifications. Phosphorylation in NK cells upon engagment by SLAMF6-expressing target cells is leading to receptor activation.

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-containingbinding partners. Especially they mediate the with the SH2 domain of SH2D1A and SH2D1B. A ’two-out-of-three-pronged’ mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3).

Isoforms (3)

UniProt ID	Names	Canonical?
Q96DU3-1	1	yes
Q96DU3-2	2
Q96DU3-3	3

RefSeq proteins (4): NP_001171643, NP_001171644, NP_001171645, NP_443163 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015631	CD2/SLAM_rcpt	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF07686

UniProt features (50 total): strand 16, glycosylation site 7, mutagenesis site 7, modified residue 3, helix 3, disulfide bond 2, topological domain 2, splice variant 2, domain 2, short sequence motif 2, signal peptide 1, chain 1, transmembrane region 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2IF7	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DU3-F1	77.15	0.50

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 (3): 278, 309, 274

Disulfide bonds (2): 147–214, 153–195

Glycosylation sites (7): 58, 87, 137, 144, 161, 178, 203

Mutagenesis-validated functional residues (7):

Position	Phenotype
108	inhibits dimerization.
110	inhibits dimerization.
112	inhibits dimerization.
274	retains reduced slamf6-mediated cytotoxicity, disrupts interaction with sh2d1a and retains interaction with sh2d1b; when
285	abolishes slamf6-mediated cytotoxicity, disrupts interaction with sh2d1b and retains interaction with sh2d1a.
309	reduced slamf6-mediated cytotoxicity.
309	retains reduced slamf6-mediated cytotoxicity, disrupts interaction with sh2d1a and retains interaction with sh2d1b; when

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 254 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, CAGCAGG_MIR370, GOBP_CD4_POSITIVE_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_T_CELL_DIFFERENTIATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY

GO Biological Process (9): immune response (GO:0006955), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-17 production (GO:0032740), T cell activation (GO:0042110), innate immune response (GO:0045087), positive regulation of natural killer cell mediated cytotoxicity (GO:0045954), T-helper 17 cell lineage commitment (GO:0072540), adaptive immune response (GO:0002250), immune system process (GO:0002376)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cytokine production	2
immune response	2
immune system process	1
response to stimulus	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-17 production	1
regulation of interleukin-17 production	1
lymphocyte activation	1
defense response to symbiont	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
T-helper cell lineage commitment	1
T-helper 17 cell differentiation	1
biological_process	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLAMF6	SLAMF1	Q13291	970
SLAMF6	SH2D1A	O60880	968
SLAMF6	KLRF1	Q9NZS2	928
SLAMF6	CD48	P09326	924
SLAMF6	CD244	Q9BZW8	902
SLAMF6	NCR3	O14931	863
SLAMF6	CD226	Q15762	848
SLAMF6	NCR1	O76036	821
SLAMF6	SH2D1B	O14796	813
SLAMF6	KLRK1	P26718	800
SLAMF6	NCR2	O95944	794
SLAMF6	CLEC2B	Q92478	783
SLAMF6	CD2	P06729	757
SLAMF6	PTPN11	Q06124	746
SLAMF6	PVR	P15151	741

IntAct

41 interactions, top by confidence:

A	B	Type	Score
SLAMF6	SH2D1A	psi-mi:“MI:0915”(physical association)	0.870
SLAMF6	SH2D1A	psi-mi:“MI:0914”(association)	0.870
SH2D1A	SLAMF6	psi-mi:“MI:0915”(physical association)	0.870
SLAMF6	SH2D1B	psi-mi:“MI:0914”(association)	0.620
SH2D1A	CD247	psi-mi:“MI:0914”(association)	0.620
SH2D1B	SLAMF6	psi-mi:“MI:0915”(physical association)	0.620
SLAMF6	SLAMF6	psi-mi:“MI:0915”(physical association)	0.610
SLAMF6	SLAMF6	psi-mi:“MI:0407”(direct interaction)	0.610
BRICD5	SLAMF6	psi-mi:“MI:0915”(physical association)	0.560
SLAMF6	RABAC1	psi-mi:“MI:0915”(physical association)	0.560
TMPPE	SLAMF6	psi-mi:“MI:0915”(physical association)	0.560
CLDN19	SLAMF6	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	SLAMF6	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	SLAMF6	psi-mi:“MI:0915”(physical association)	0.560
SH2D1A	LCK	psi-mi:“MI:0914”(association)	0.550
SLAMF6	HA	psi-mi:“MI:0407”(direct interaction)	0.440
SLAMF6	LCK	psi-mi:“MI:0915”(physical association)	0.400
SLAMF6	NCR3	psi-mi:“MI:0915”(physical association)	0.400
HAVCR1	SLAMF6	psi-mi:“MI:0915”(physical association)	0.400
SLAMF6	PTPN6	psi-mi:“MI:0914”(association)	0.350
SH2D1A	SH2D1B	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
SLAMF6	FPGT	psi-mi:“MI:0914”(association)	0.350
BRICD5	SLAMF6	psi-mi:“MI:0915”(physical association)	0.000
RABAC1	SLAMF6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): CXCL14 (Reconstituted Complex), SLAMF6 (Two-hybrid), SLAMF6 (Two-hybrid), CLDN19 (Two-hybrid), JAGN1 (Two-hybrid), BRICD5 (Two-hybrid), TMPPE (Two-hybrid), SH2D1A (Affinity Capture-Western), PTPN11 (Affinity Capture-Western), PTPN6 (Affinity Capture-Western), CSNK1D (Affinity Capture-MS), DGAT1 (Affinity Capture-MS), SELENBP1 (Affinity Capture-MS), DUSP14 (Affinity Capture-MS), FPGT (Affinity Capture-MS)

ESM2 similar proteins: A5D7V5, A7TZE6, A7TZF3, A7XUX6, A7XV04, A7XV07, C0HJX2, C0HJX3, P08101, P08508, P0C1X9, P12318, P20138, P27645, P31994, P31995, P42070, P43629, P43630, P97484, Q49BZ4, Q60513, Q63203, Q68SN8, Q6Q8B3, Q6QLQ4, Q6SJQ5, Q6XJV4, Q6XJV6, Q8BG84, Q8BTP3, Q8HZR8, Q8N109, Q8NC01, Q8NHK3, Q8R4Y0, Q8SPV8, Q8TD46, Q8VCH2, Q921W8

Diamond homologs: Q01965, Q18PI6, Q8BHK6, Q96A28, Q96DU3, Q9D780, Q9HBG7, Q9NQ25, Q9UIB8, Q9ET39, P42071, Q3KPI0, Q4VAH7, Q9P0V8, A4FUY1, Q14CZ8, Q640R3, Q13291

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
hsa-mir-146a-5p	“down-regulates quantity by repression”	SLAMF6	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1123 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160486753:CT:C	acceptor_gain	1.0000
1:160487098:GCTTA:G	donor_loss	1.0000
1:160487099:CTTA:C	donor_loss	1.0000
1:160487100:TTA:T	donor_loss	1.0000
1:160487101:TA:T	donor_loss	1.0000
1:160487102:A:AG	donor_loss	1.0000
1:160487103:CCT:C	donor_gain	1.0000
1:160486750:TTACT:T	acceptor_gain	0.9900
1:160486751:TACT:T	acceptor_gain	0.9900
1:160486755:C:CC	acceptor_gain	0.9900
1:160487097:GGCTT:G	donor_loss	0.9900
1:160487175:CCTG:C	acceptor_loss	0.9900
1:160487176:C:CC	acceptor_gain	0.9900
1:160487176:C:CG	acceptor_loss	0.9900
1:160489166:CTCTG:C	acceptor_gain	0.9900
1:160491165:A:AC	donor_gain	0.9900
1:160491166:C:CC	donor_gain	0.9900
1:160496059:A:AC	donor_gain	0.9900
1:160496060:C:CC	donor_gain	0.9900
1:160496063:AATAT:A	donor_gain	0.9900
1:160523139:TTTA:T	donor_loss	0.9900
1:160523140:TTA:T	donor_loss	0.9900
1:160523141:TACCT:T	donor_loss	0.9900
1:160486754:TCTGT:T	acceptor_loss	0.9800
1:160486755:C:T	acceptor_loss	0.9800
1:160486752:ACT:A	acceptor_gain	0.9700
1:160486753:CTC:C	acceptor_gain	0.9700
1:160486754:TCT:T	acceptor_gain	0.9700
1:160487172:TTTC:T	acceptor_gain	0.9700
1:160489168:CTG:C	acceptor_gain	0.9700

AlphaMissense

2173 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160491273:C:A	W166C	0.987
1:160491273:C:G	W166C	0.987
1:160491275:A:G	W166R	0.977
1:160491275:A:T	W166R	0.977
1:160491187:C:G	C195S	0.971
1:160491188:A:T	C195S	0.971
1:160496124:A:C	Y107D	0.969
1:160496280:A:G	W55R	0.968
1:160496280:A:T	W55R	0.968
1:160491319:A:G	L151P	0.967
1:160496278:C:A	W55C	0.962
1:160496278:C:G	W55C	0.962
1:160491188:A:G	C195R	0.955
1:160491186:G:C	C195W	0.952
1:160491314:A:G	C153R	0.952
1:160491182:C:G	A197P	0.947
1:160491313:C:G	C153S	0.941
1:160491314:A:T	C153S	0.941
1:160491312:G:C	C153W	0.938
1:160496117:G:T	A109D	0.934
1:160491187:C:T	C195Y	0.932
1:160491174:A:C	N199K	0.928
1:160491174:A:T	N199K	0.928
1:160491274:C:G	W166S	0.928
1:160491181:G:T	A197E	0.927
1:160496072:A:G	L124P	0.927
1:160491130:C:G	C214S	0.923
1:160491131:A:T	C214S	0.923
1:160491313:C:T	C153Y	0.913
1:160496114:T:G	Q110P	0.911

dbSNP variants (sampled 300 via entrez): RS1000023641 (1:160507285 A>G), RS1000061811 (1:160488105 A>C,G), RS1000125259 (1:160506776 A>G), RS1000238990 (1:160520557 T>C), RS1000288483 (1:160490738 G>C), RS1000305215 (1:160513892 T>G), RS1000331179 (1:160518525 T>C), RS1000376398 (1:160508096 T>C), RS1000384582 (1:160493181 C>A,T), RS1000407530 (1:160507948 A>C), RS1000499650 (1:160522455 G>A), RS1000664879 (1:160517501 G>A,T), RS1000669351 (1:160489418 T>G), RS1000800401 (1:160514132 G>A), RS1000827621 (1:160523526 A>G)

Disease associations

OMIM: gene MIM:606446 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001984_5	Graves’ disease	2.000000e-18
GCST005531_85	Multiple sclerosis	5.000000e-06
GCST006585_2669	Blood protein levels	5.000000e-07
GCST011389_9	Rheumatoid arthritis	5.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
sulforaphane	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
Aripiprazole	affects cotreatment, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cisplatin	increases expression	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Ozone	affects cotreatment, increases expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D2M4	Abcam Raji SLAMF6 KO	Cancer cell line	Male
CVCL_WQ53	Abcam Jurkat SLAMF6 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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