SLAMF7

Summary

SLAMF7 (SLAM family member 7, HGNC:21394) is a protein-coding gene on chromosome 1q23.3, encoding SLAM family member 7 (Q9NQ25). Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family.

Enables identical protein binding activity. Predicted to be involved in T cell activation and immune response. Predicted to act upstream of or within regulation of natural killer cell activation. Located in endoplasmic reticulum.

Source: NCBI Gene 57823 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 31 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_021181

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21394
Approved symbol	SLAMF7
Name	SLAM family member 7
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CRACC, 19A, CS1, CD319
Ensembl gene	ENSG00000026751
Ensembl biotype	protein_coding
OMIM	606625
Entrez	57823

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000359331, ENST00000368042, ENST00000368043, ENST00000441662, ENST00000444090, ENST00000458104, ENST00000458602, ENST00000484221, ENST00000488819, ENST00000495334, ENST00000621377, ENST00000865347, ENST00000865348

RefSeq mRNA: 10 — MANE Select: NM_021181 NM_001282588, NM_001282589, NM_001282590, NM_001282591, NM_001282592, NM_001282593, NM_001282594, NM_001282595, NM_001282596, NM_021181

CCDS: CCDS1209, CCDS60321, CCDS60322, CCDS60323, CCDS60324, CCDS60325, CCDS72956, CCDS72957

Canonical transcript exons

ENST00000368043 — 7 exons

Exon	Start	End
ENSE00000789184	160751345	160751448
ENSE00000829161	160750304	160750423
ENSE00001882185	160739247	160739356
ENSE00003305488	160748194	160748514
ENSE00003340475	160749821	160750093
ENSE00003570511	160753106	160754821
ENSE00003682756	160752186	160752248

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 97.48.

FANTOM5 (CAGE): breadth broad, TPM avg 73.7790 / max 6552.0021, expressed in 527 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6157	54.0482	343
6158	15.9487	473
6159	2.0298	305
6175	0.5239	109
6171	0.5014	106
6169	0.3654	92
6172	0.1565	69
6168	0.1169	55
6170	0.0883	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.48	gold quality
type B pancreatic cell	CL:0000169	95.68	gold quality
olfactory bulb	UBERON:0002264	95.67	gold quality
diaphragm	UBERON:0001103	93.67	gold quality
lymph node	UBERON:0000029	93.03	gold quality
colonic epithelium	UBERON:0000397	92.60	gold quality
rectum	UBERON:0001052	92.14	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.63	gold quality
bone marrow cell	CL:0002092	91.19	gold quality
spleen	UBERON:0002106	90.34	gold quality
leukocyte	CL:0000738	89.91	gold quality
monocyte	CL:0000576	89.62	gold quality
mononuclear cell	CL:0000842	89.36	gold quality
palpebral conjunctiva	UBERON:0001812	89.19	gold quality
blood	UBERON:0000178	88.55	gold quality
epithelium of nasopharynx	UBERON:0001951	87.61	gold quality
tonsil	UBERON:0002372	87.23	gold quality
vermiform appendix	UBERON:0001154	87.20	gold quality
colonic mucosa	UBERON:0000317	86.33	gold quality
superficial temporal artery	UBERON:0001614	86.31	gold quality
jejunal mucosa	UBERON:0000399	85.92	gold quality
duodenum	UBERON:0002114	85.64	gold quality
caecum	UBERON:0001153	84.51	gold quality
hair follicle	UBERON:0002073	83.85	gold quality
mucosa of transverse colon	UBERON:0004991	82.94	gold quality
pylorus	UBERON:0001166	82.88	gold quality
trachea	UBERON:0003126	82.49	gold quality
parotid gland	UBERON:0001831	82.24	gold quality
gall bladder	UBERON:0002110	82.06	gold quality
orbitofrontal cortex	UBERON:0004167	81.65	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-HCAD-29	yes	441.18
E-CURD-88	yes	99.24
E-CURD-122	yes	46.18
E-HCAD-4	yes	40.51
E-CURD-46	yes	36.40
E-ANND-3	yes	35.66
E-MTAB-8410	yes	34.35
E-HCAD-11	yes	21.90
E-MTAB-8142	yes	18.10
E-HCAD-1	yes	13.60
E-MTAB-9543	yes	13.26
E-MTAB-10553	yes	9.44
E-MTAB-6678	yes	9.17
E-MTAB-7606	no	1000.49
E-MTAB-5061	no	3.86

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NSD2, YY1

miRNA regulators (miRDB)

64 targeting SLAMF7, 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-3120-5P	100.00	65.56	965
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-6071	99.16	67.77	1780

Literature-anchored findings (GeneRIF, showing 36)

• CS1-L and CS1-S may differentially regulate human NK cell functions (PMID:15368295)
• 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)
• CS1 may play a role in the regulation of B lymphocyte proliferation during immune responses (PMID:17878365)
• CS1 was expressed at adhesion-promoting uropod membranes of polarized Multiple Myeloma cells, andis required for MM cell adhesion to bone marrow stromal cells (PMID:17906076)
• 2B4, NTB-A and CRACC have roles in the regulation of Natural Killer cell function [review] (PMID:17981603)
• HuLuc63 eliminates myeloma cells, at least in part, via NK-mediated ADCC and shows the therapeutic potential of targeting CS1 with HuLuc63 for the treatment of multiple myeloma. (PMID:18451245)
• Data show that pair-wise ligations of 2B4 with DNAM-1 and/or NKG2D lead to increased effector functions of primary CD4(+)CD28(-) T cells to suboptimal levels of anti-CD3 stimulation. (PMID:19904767)
• altered expression of splice variants of CS1 and 2B4 that mediate differential signalling in PBMC from patients with SLE. (PMID:20345977)
• These data suggest an involvement of CRACC-mediated NK cell activation in periodontal tissue destruction and point to a plausible distinction in the pathobiology of aggressive and chronic periodontitis. (PMID:23250953)
• SLAMF7 plays an inhibitory role in human monocytes to control proinflammatory immune responses. (PMID:23695528)
• These results suggest a role for CD319 and CD229 in the systemic lupus erythematosus disease process. (PMID:23956418)
• Our data highlight the therapeutic potential of targeting CD319 in rheumatoid arthritis (PMID:24299175)
• SLAMF7-triggered inhibition is mediated by a mechanism involving Src kinases, CD45, and SHIP-1 that is defective in MM cells (PMID:25312647)
• Blimp-1 regulates the transcription of CS1 gene in NK and B cell lines from multiple myeloma and diffuse large B cell lymphoma patients. (PMID:26310579)
• Cohort statistics revealed a significant increase of circulating sSLAMF7 in multiple myeloma patients versus normal controls (PMID:27116021)
• Memory CD8+ T cells from SLE patients displayed decreased amounts of SLAMF7, a surface receptor that characterizes effector CD8+ T cells. Ligation of SLAMF7 increased CD8+ T cell degranulation capacity and the percentage of IFNgamma-producing cells in response to antigen challenge in SLE patients and healthy controls. SLAMF7 engagement promoted cytotoxic lysis of target cells in response to stimulation with viral antig… (PMID:28076903)
• phagocytosis of haematopoietic tumour cells during SIRPalpha-CD47 blockade was strictly dependent on SLAM family receptors in vitro and in vivo; in both mouse and human cells, this function required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319), expressed on macrophages and tumour cell targets (PMID:28424516)
• The data show that the great majority of primary patient plasmablastic lymphoma (PBL) cases from a variety of subtypes express SLAMF7. From a diagnostic histopathology perspective, SLAMF7 may be a useful addition to a panel of markers for the diagnosis and characterization of PBL (PMID:29785767)
• These data provide emerging evidence that SLAMF7 could be a target of potential therapeutic intervention in carotid atherosclerosis. (PMID:29905534)
• this study shows that SLAMF7 is a critical negative regulator of IFN-alpha-mediated CXCL10 production in chronic HIV infection (PMID:30530590)
• cancer cell expression of SLAMF7 is not required for phagocytosis and, in contrast to CD47 expression, should not be used as selection criterion for CD47-targeted therapy. (PMID:30710089)
• Down-regulation of SLAMF7 and up-regulation of TREM1 occur in primary and metastatic stage IV colorectal cancer tissues. (PMID:30918427)
• immune receptor CD48 is overexpressed on MM cells together with SLAMF7, and that CD48 may be considered as an alternative target for treatment of MM in cases showing weak expression of SLAMF7. (PMID:31115879)
• Strong expression of SLAMF7 in natural killer/T-cell lymphoma and large granular lymphocyte leukemia - a prominent biomarker and potential target for anti-SLAMF7 antibody therapy. (PMID:31164030)
• Advanced systemic mastocytosis with strong expression of signaling lymphocyte activation marker family member 7 (SLAMF7) responsive to therapy with elotuzumab and lenalidomide. (PMID:31566043)
• Association of circulating SLAMF7(+)Tfh1 cells with IgG4 levels in patients with IgG4-related disease. (PMID:32487061)
• CD319 (SLAMF7) an alternative marker for detecting plasma cells in the presence of daratumumab or elotuzumab. (PMID:33017079)
• SLAMF7 Signaling Reprograms T Cells toward Exhaustion in the Tumor Microenvironment. (PMID:33288545)
• SLAMF7 and IL-6R define distinct cytotoxic versus helper memory CD8(+) T cells. (PMID:33311473)
• Combinatorial targeting of multiple myeloma by complementing T cell engaging antibody fragments. (PMID:33420283)
• SLAMF7 selectively favors degranulation to promote cytotoxicity in human NK cells. (PMID:34693521)
• SLAMF7 and TREM1 Mediate Immunogenic Cell Death in Colorectal Cancer Cells: Focus on Microsatellite Stability. (PMID:34732412)
• SLAMF7 engagement superactivates macrophages in acute and chronic inflammation. (PMID:35148199)
• SLAMF7 modulates B cells and adaptive immunity to regulate susceptibility to CNS autoimmunity. (PMID:36199066)
• Identification and elucidation of cross talk between SLAM Family Member 7 (SLAMF7) and Toll-like receptor (TLR) pathways in monocytes and macrophages. (PMID:37420084)
• SLAMF7 as a Promising Immunotherapeutic Target in Multiple Myeloma Treatments. (PMID:37754488)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:cabz01074946.1	ENSDARG00000090396
mus_musculus	Slamf7	ENSMUSG00000038179
rattus_norvegicus	Slamf7	ENSRNOG00000023209

Paralogs (9): CD84 (ENSG00000066294), CD2 (ENSG00000116824), SLAMF1 (ENSG00000117090), CD48 (ENSG00000117091), CD244 (ENSG00000122223), LY9 (ENSG00000122224), SLAMF8 (ENSG00000158714), SLAMF9 (ENSG00000162723), SLAMF6 (ENSG00000162739)

Protein

Protein identifiers

SLAM family member 7 — Q9NQ25 (reviewed: Q9NQ25)

Alternative names: CD2 subset 1, CD2-like receptor-activating cytotoxic cells, Membrane protein FOAP-12, Novel Ly9, Protein 19A

All UniProt accessions (4): B4DVL7, B4DW98, Q9NQ25, R4GND0

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. Isoform 1 mediates NK cell activation through a SH2D1A-independent extracellular signal-regulated ERK-mediated pathway. Positively regulates NK cell functions by a mechanism dependent on phosphorylated SH2D1B. Downstream signaling implicates PLCG1, PLCG2 and PI3K. In addition to heterotypic NK cells-target cells interactions also homotypic interactions between NK cells may contribute to activation. However, in the absence of SH2D1B, inhibits NK cell function. Also acts inhibitory in T-cells. May play a role in lymphocyte adhesion. In LPS-activated monocytes negatively regulates production of pro-inflammatory cytokines. Isoform 3 does not mediate any NK cell activation.

Subunit / interactions. Isoform 1 binds to SH2D1A when its cytoplasmic tail is phosphorylated in the presence of FYN (in vitro); low affinity binding, the physiological relevance of the interaction is questioned. Interacts with SH2D1B; in NK cells. Interacts (via ITSM phosphorylated on Tyr-302) with SH2D1B, PTPN6/SHP-1, PTPN11/SHP-2, INPP5D/SHIP1, CSK and FYN.

Subcellular location. Membrane.

Tissue specificity. Expressed in spleen, lymph node, peripheral blood leukocytes, bone marrow, small intestine, stomach, appendix, lung and trachea. Expression was detected in NK cells, activated B-cells, NK-cell line but not in promyelocytic, B-, or T-cell lines. Expressed in monocytes. Isoform 3 is expressed at much lower level than isoform 1.

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. A ’three-pronged’ mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3).

Miscellaneous. Proposed to be involved in systemic lupus erythematosus (SLE) disease process.

Isoforms (7)

UniProt ID	Names	Canonical?
Q9NQ25-1	1, 19A, CS1-L	yes
Q9NQ25-2	2
Q9NQ25-3	3, 19A24, CS1-S
Q9NQ25-4	4
Q9NQ25-5	5
Q9NQ25-6	6
Q9NQ25-7	7

RefSeq proteins (10): NP_001269517, NP_001269518, NP_001269519, NP_001269520, NP_001269521, NP_001269522, NP_001269523, NP_001269524, NP_001269525, NP_067004* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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 (27 total): splice variant 7, glycosylation site 6, disulfide bond 2, topological domain 2, sequence variant 2, domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ25-F1	78.44	0.45

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 (2): 145–215, 151–195

Glycosylation sites (6): 142, 148, 172, 176, 204, 98

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: 290 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_255, MODULE_317, GOCC_CELL_SURFACE, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, SHAFFER_IRF4_TARGETS_IN_PLASMA_CELL_VS_MATURE_B_LYMPHOCYTE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, ROZANOV_MMP14_TARGETS_UP, GOBP_ADAPTIVE_IMMUNE_RESPONSE, GOBP_NATURAL_KILLER_CELL_MEDIATED_IMMUNITY, GOBP_NATURAL_KILLER_CELL_ACTIVATION

GO Biological Process (8): adaptive immune response (GO:0002250), immune response (GO:0006955), cell adhesion (GO:0007155), natural killer cell activation (GO:0030101), T cell activation (GO:0042110), natural killer cell mediated cytotoxicity (GO:0042267), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (1): identical protein binding (GO:0042802)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), endoplasmic reticulum (GO:0005783), 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
immune response	2
lymphocyte activation	2
immune system process	1
response to stimulus	1
cellular process	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
biological_process	1
defense response to symbiont	1
protein binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLAMF7	CD48	P09326	854
SLAMF7	FCGR3A	P08637	810
SLAMF7	FCGR3B	O75015	788
SLAMF7	CD2	P06729	788
SLAMF7	SH2D1B	O14796	783
SLAMF7	CD38	P28907	730
SLAMF7	KLRK1	P26718	714
SLAMF7	NCR1	O76036	708
SLAMF7	GPRC5D	Q9NZD1	696
SLAMF7	SH2D1A	O60880	684
SLAMF7	SLAMF1	Q13291	659
SLAMF7	SDC1	P18827	651
SLAMF7	CD244	Q9BZW8	626
SLAMF7	KLRF1	Q9NZS2	623
SLAMF7	TNFRSF17	Q02223	622

IntAct

14 interactions, top by confidence:

A	B	Type	Score
SLAMF7	SLAMF7	psi-mi:“MI:0915”(physical association)	0.710
SLAMF7	SLAMF7	psi-mi:“MI:0407”(direct interaction)	0.710
SH2D1A	SLAMF7	psi-mi:“MI:0407”(direct interaction)	0.440
SH2D1B	SLAMF7	psi-mi:“MI:0407”(direct interaction)	0.440
SLAMF7	NCR3	psi-mi:“MI:0915”(physical association)	0.400
SLAMF7	CLK3	psi-mi:“MI:0915”(physical association)	0.370
SLAMF7	MAK	psi-mi:“MI:0915”(physical association)	0.370
TRIB2	SLAMF7	psi-mi:“MI:0915”(physical association)	0.370
SLAMF7	HUS1	psi-mi:“MI:0914”(association)	0.350
SLAMF7	TNFSF9	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
S1PR3	STXBP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): LEMD3 (Affinity Capture-MS), HUS1 (Affinity Capture-MS), APBB1 (Affinity Capture-MS), TBC1D23 (Affinity Capture-MS), PTCD2 (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), NAGPA (Affinity Capture-MS), YIF1A (Affinity Capture-MS), LGALS1 (Affinity Capture-MS), DAGLB (Affinity Capture-MS), TBC1D23 (Affinity Capture-MS), PTCD2 (Affinity Capture-MS), HUS1 (Affinity Capture-MS), NAGPA (Affinity Capture-MS), FBXO2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E4BZH1, A4QPC6, A5D7V5, A7TZE6, A7TZF0, A7TZF3, A7XUX6, A7XV04, A7XV07, A8K4G0, A8MVZ5, O70355, P08508, P18892, P24071, P31994, P55803, P78410, P79391, Q13410, Q16653, Q29ZQ1, Q3KPI0, Q58DF9, Q5R7W8, Q5R960, Q5R996, Q61885, Q62556, Q63345, Q6Q8B3, Q6UXZ3, Q6XJV4, Q6XJV6, Q7KYR7, Q7TST0, Q7YR73, Q8BTP3, Q8K249, Q8TD46

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

SIGNOR signaling

0 interactions.

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	22
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

952 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160751449:G:GG	donor_gain	1.0000
1:160752181:A:AG	acceptor_gain	1.0000
1:160752182:A:G	acceptor_gain	1.0000
1:160752183:A:G	acceptor_gain	1.0000
1:160752184:A:G	acceptor_gain	1.0000
1:160752185:GA:G	acceptor_gain	1.0000
1:160748492:GGA:G	donor_gain	0.9900
1:160748493:GAG:G	donor_gain	0.9900
1:160749949:C:T	donor_gain	0.9900
1:160750080:G:GT	donor_gain	0.9900
1:160751343:A:AG	acceptor_gain	0.9900
1:160751344:G:GG	acceptor_gain	0.9900
1:160751344:GA:G	acceptor_gain	0.9900
1:160752174:T:TA	acceptor_gain	0.9900
1:160752185:G:GG	acceptor_gain	0.9900
1:160752185:GAGAA:G	acceptor_gain	0.9900
1:160752246:AAGGT:A	donor_loss	0.9900
1:160752248:GGT:G	donor_loss	0.9900
1:160752249:G:T	donor_loss	0.9900
1:160752250:T:A	donor_loss	0.9900
1:160739353:ACAGG:A	donor_loss	0.9800
1:160739354:CAGGT:C	donor_loss	0.9800
1:160739355:AGGTG:A	donor_loss	0.9800
1:160739356:GGT:G	donor_loss	0.9800
1:160739357:G:C	donor_loss	0.9800
1:160739358:T:G	donor_loss	0.9800
1:160748192:A:AC	acceptor_loss	0.9800
1:160748192:A:AG	acceptor_gain	0.9800
1:160748192:AG:A	acceptor_gain	0.9800
1:160748193:G:C	acceptor_loss	0.9800

AlphaMissense

2182 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:160749936:G:C	W164C	0.993
1:160749936:G:T	W164C	0.993
1:160749934:T:A	W164R	0.986
1:160749934:T:C	W164R	0.986
1:160748295:T:A	W53R	0.984
1:160748295:T:C	W53R	0.984
1:160749890:T:C	L149P	0.983
1:160750027:T:A	C195S	0.982
1:160750028:G:C	C195S	0.982
1:160748445:T:G	Y103D	0.978
1:160748297:G:C	W53C	0.977
1:160748297:G:T	W53C	0.977
1:160750027:T:C	C195R	0.974
1:160750028:G:A	C195Y	0.974
1:160750029:C:G	C195W	0.971
1:160748254:T:C	F39S	0.968
1:160748503:T:C	L122P	0.967
1:160748509:T:A	V124D	0.966
1:160749836:C:A	P131H	0.963
1:160748254:T:G	F39C	0.959
1:160748434:A:C	D99A	0.958
1:160749895:T:A	C151S	0.958
1:160749896:G:C	C151S	0.958
1:160748434:A:G	D99G	0.957
1:160750041:C:A	N199K	0.953
1:160750041:C:G	N199K	0.953
1:160748434:A:T	D99V	0.952
1:160748439:G:T	G101W	0.952
1:160749895:T:C	C151R	0.952
1:160749935:G:C	W164S	0.952

dbSNP variants (sampled 300 via entrez): RS1000148474 (1:160753860 T>C), RS1000518232 (1:160750765 C>A,T), RS1000831401 (1:160751002 T>G), RS1000924867 (1:160746028 C>T), RS1000934181 (1:160744928 G>T), RS1000985097 (1:160745220 T>A,C), RS1001225453 (1:160752725 G>A), RS1001435685 (1:160749490 C>T), RS1001937388 (1:160746153 A>C,G), RS1002561122 (1:160741871 C>T), RS1002870448 (1:160752675 T>A,C), RS1003119621 (1:160755123 G>A), RS1003121872 (1:160737692 A>AT), RS1003616443 (1:160754313 G>A), RS1003654137 (1:160754685 G>A)

Disease associations

OMIM: gene MIM:606625 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001725_36	Inflammatory bowel disease	7.000000e-09
GCST003253_3	Microalbuminuria	9.000000e-07
GCST005531_31	Multiple sclerosis	4.000000e-11
GCST006585_1128	Blood protein levels	4.000000e-208
GCST008575_11	IgM levels	4.000000e-09
GCST008575_12	IgM levels	2.000000e-08

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3559386 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — CD molecules

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
elotuzumab	Binding	8.05	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	5
Benzo(a)pyrene	increases expression, increases methylation	3
Nickel	decreases expression, increases expression	3
(+)-JQ1 compound	decreases expression	2
Formaldehyde	decreases expression, increases expression	2
Aflatoxin B1	increases expression	2
bufotalin	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
gardiquimod	increases expression, decreases reaction	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Aldehydes	increases expression	1
Allergens	affects cotreatment, decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	affects cotreatment, decreases expression, increases expression	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Demecolcine	increases expression	1
Diuron	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1DB	Ubigene THP-1 SLAMF7 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms