SPN

Summary

SPN (sialophorin, HGNC:11249) is a protein-coding gene on chromosome 16p11.2, encoding Leukosialin (P16150). Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration.

This gene encodes a highly sialylated glycoprotein that functions in antigen-specific activation of T cells, and is found on the surface of thymocytes, T lymphocytes, monocytes, granulocytes, and some B lymphocytes. It contains a mucin-like extracellular domain, a transmembrane region and a carboxy-terminal intracellular region. The extracellular domain has a high proportion of serine and threonine residues, allowing extensive O-glycosylation, and has one potential N-glycosylation site, while the carboxy-terminal region has potential phosphorylation sites that may mediate transduction of activation signals. Different glycoforms of this protein have been described. In stimulated immune cells, proteolytic cleavage of the extracellular domain occurs in some cell types, releasing a soluble extracellular fragment. Defects in expression of this gene are associated with Wiskott-Aldrich syndrome.

Source: NCBI Gene 6693 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 92 total — 1 pathogenic
• MANE Select transcript: NM_003123

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11249
Approved symbol	SPN
Name	sialophorin
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	LSN, CD43, GPL115, LEU-22
Ensembl gene	ENSG00000197471
Ensembl biotype	protein_coding
OMIM	182160
Entrez	6693

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000360121, ENST00000395389, ENST00000436527, ENST00000561857, ENST00000563039, ENST00000652691, ENST00000858181, ENST00000858182, ENST00000963399

RefSeq mRNA: 2 — MANE Select: NM_003123 NM_001030288, NM_003123

CCDS: CCDS10650

Canonical transcript exons

ENST00000652691 — 2 exons

Exon	Start	End
ENSE00003846033	29663247	29663316
ENSE00003847658	29663695	29670876

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.65.

FANTOM5 (CAGE): breadth broad, TPM avg 30.2581 / max 1662.6495, expressed in 628 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153467	25.8183	621
153465	2.0471	224
153468	1.0126	122
153464	0.5631	146
153469	0.4107	112
153471	0.1569	94
153466	0.1556	72
153470	0.0938	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.65	gold quality
granulocyte	CL:0000094	97.63	gold quality
leukocyte	CL:0000738	94.41	gold quality
monocyte	CL:0000576	94.23	gold quality
mononuclear cell	CL:0000842	94.07	gold quality
tendon of biceps brachii	UBERON:0008188	93.98	gold quality
sperm	CL:0000019	92.30	silver quality
pancreatic ductal cell	CL:0002079	91.44	gold quality
male germ cell	CL:0000015	91.22	silver quality
bone marrow cell	CL:0002092	90.40	gold quality
vena cava	UBERON:0004087	90.38	silver quality
triceps brachii	UBERON:0001509	90.28	silver quality
medial globus pallidus	UBERON:0002477	90.21	gold quality
globus pallidus	UBERON:0001875	90.07	gold quality
bone marrow	UBERON:0002371	89.89	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.53	silver quality
ventral tegmental area	UBERON:0002691	89.47	silver quality
lateral globus pallidus	UBERON:0002476	89.29	silver quality
subthalamic nucleus	UBERON:0001906	89.06	silver quality
renal medulla	UBERON:0000362	89.04	silver quality
blood	UBERON:0000178	89.00	gold quality
pylorus	UBERON:0001166	88.96	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.88	silver quality
gluteal muscle	UBERON:0002000	88.88	silver quality
inferior vagus X ganglion	UBERON:0005363	88.70	silver quality
lymph node	UBERON:0000029	88.57	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.56	silver quality
superior surface of tongue	UBERON:0007371	88.39	gold quality
nipple	UBERON:0002030	88.33	gold quality
body of tongue	UBERON:0011876	88.17	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	202.81
E-MTAB-8205	yes	121.11
E-HCAD-6	yes	42.98
E-CURD-122	yes	41.68
E-MTAB-3929	yes	21.73
E-ANND-3	yes	14.60
E-MTAB-6701	yes	12.88
E-HCAD-1	yes	10.87
E-MTAB-8271	yes	9.48
E-CURD-112	yes	8.79
E-HCAD-10	yes	7.02
E-GEOD-100618	no	100.38
E-MTAB-9801	no	3.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

215 targeting SPN, 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-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-627-3P	99.90	71.42	3316

Literature-anchored findings (GeneRIF, showing 40)

• engagement of CD43 may, presumably through the repressing transcription, initiate a Bad-dependent apoptotic pathway. (PMID:11773067)
• CD43 can be seen as a co-stimulatory cell surface constituent that can modulate HIV-1 expression in T lymphocytes (PMID:12045189)
• down-regulation of CD43 mRNA levels occurs during activation of the cellline K562. This repression coincides with repression of the transcriptional activity of the CD43 gene promoter. (PMID:12411317)
• Examination of expression of CD43 in different human cell lines and tumor cell lines (PMID:12499775)
• Although ezrin-associated CD43 protein is excluded from the inhibitory, i.e., noncytolytic, NK cell immune synapse (IS), it is homogeneously distributed across the IS of activating conjugates. (PMID:12626536)
• It was also observed that the mucins from colon carcinoma patients had MUC1-type mucins that carried both sialyl-Lewis a and x epitopes and CD43-type sialyl-Lewis a mucins with only low levels of sialyl-Lewis x epitopes. (PMID:12820726)
• CD43 engagement on normal human T lymphocytes as well as in Jurkat cells results in transient phosphorylation of the zeta-chain and enhanced association of ZAP-70 and Vav to the zeta-chain. (PMID:12902492)
• Overexpression of SPN causes activation of the tumor suppressor proteins p53 and ARF 1. (PMID:14676827)
• Four phage antibodies were isolated and used in a preliminary immunohistochemistry study of CD43 expression on frozen colorectal adenoma and carcinoma tissue. (PMID:14719063)
• findings suggest that the CD43 molecules expressed on CD4+ memory T cells may be capable of enhancing the costimulatory signaling and hence providing accessory functions to TCR-mediated activation processes (PMID:15187099)
• Microarray analysis of inflammatory genes shows 1 group of genes coregulated by both stimuli and 2 further groups of target genes affected solely by costimulation or primarily by CD43. (PMID:15280197)
• CD43 is expressed by a variety of carcinoma cell lines, and plays a role in tumour cell-peritoneal adhesion probably via interactions with its putative ligand ICAM-1 (PMID:15449712)
• Data suggest that PKCtheta plays a critical role in the co-stimulatory functions of CD43 in human T cells. (PMID:15522211)
• CD43 is a T-cell E-selectin ligand distinct from PSGL-1 which expands the role of CD43 in the regulation of T-cell trafficking. (PMID:16269612)
• CD43 induces a signaling cascade that prolongs the duration of T cell receptor signaling, thereby supporting the temporality with which certain molecules are engaged as a mechanism to fine tune T cell signal quality, and ultimately immune function. (PMID:16751378)
• early progenitors committed to hematopoietic development could be identified by surface expression of leukosialin (PMID:16757688)
• Promotes cell growth and is a potential contributor to tumor development. (PMID:17891181)
• Lymphoepithelial lesions pattern, CD43 coexpression, and clonal plasma cell component in extranodal marginal zone B-cell lymphoma (EMZL) is site-dependent, and the differences may aid in the diagnosis of EMZLs at different anatomic sites. (PMID:17979485)
• triggering CD43 and the underlying signaling pathways enhance LFA-1 adhesiveness while CD43 also negatively regulates LFA-1 induction via other receptors by dynamic interaction with either LFA-1 or CD147. (PMID:17996943)
• CD43 seems to be selectively expressed in a subset of adenoid cystic carcinomas and its significance in salivary tumors is discussed. (PMID:18227725)
• The cleavage of neutrophil leukosialin (CD43) by cathepsin G releases its extracellular domain and triggers its intramembrane proteolysis by presenilin/gamma-secretase (PMID:18586676)
• Streptococcus gordonii DL1 surface protein Hsa binds to the host cell membrane glycoproteins CD11b, CD43, and CD50 (PMID:18678668)
• Expression of CD43 induces cell rounding, inhibition of cell re-attachment, augmentation of microvilli, and phosphorylation of Ezrin/Radixin/Moesin (ERM)in HEK293T cells. (PMID:21045567)
• identification of the tumor antigen UN1 as the transmembrane CD43 sialoglycoprotein (PMID:21372249)
• Data show that Pic, a class 2 SPATE protein produced by Shigella flexneri 2a targets a broad range of human leukocyte glycoproteins including CD43, CD44, CD45, CD93, CD162 and the surface-attached chemokine fractalkine. (PMID:21768350)
• CD43 regulates the threshold for T cell activation by targeting Cbl functions. (PMID:21905200)
• there exists a negative feedback loop between p53 and CD43: CD43-dependent signaling activates p53, which in turn downregulates the expression of CD43 (PMID:21947346)
• The anti-adhesive function of CD43 in colon carcinoma cells plays a role in the tumorigenesis and metastasis of colorectal carcinoma cells. (PMID:22075155)
• O-glycosylated CD43 and CD45 molecules on T cells regulates cell adhesion and favors the transmission of HTLV-1 from cell to cell. (PMID:22171268)
• The capping of CD43 on the cell surface is a strong signal for phagocytosis that allows phagocytes to differentiate between healthy and apoptotic cells without any additional membrane changes (PMID:22466560)
• CD43 localizes to the nucleus, where it binds chromatin, co-localizes and co-immunoprecipitates with beta-catenin, and enhances the reporter gene expression regulated by beta-catenin (PMID:22576689)
• Compared to healthy controls, both CD43 mRNA and protein expressions were reduced in T cells from patients with SLE, and were inversely correlated with IgG. (PMID:22613599)
• results suggest that, despite the high CD43 expression in both tumorous and nontumorous Langerhans cells (LCs), the JL1 epitope of CD43 is exposed in immature and neoplastic LCs. (PMID:22790855)
• Targeting CD43 in A549 lung cancer cells, increased homotypic adhesion, decreased heterotypic adhesion and transendothelial migration, increased susceptibility to apoptosis and increased vulnerability to lysis by NK cells (PMID:23015282)
• Taken together, these results show that elevated calcium levels induce CD43 capping, and macrophages remove the cells if their nucleolin receptors can bind to the poly-N-acetyllactosaminyl chains of capped CD43. (PMID:23400223)
• We conclude that CD43 is an adverse prognostic marker in DLBCL, and is preferentially expressed in the non-GCB subgroup. (PMID:23617469)
• CD43 promotes cells transformation by preventing merlin-mediated contact inhibition of growth. (PMID:24260485)
• When used as vaccine in mice, the 2/165 phagotope raised antibodies against the UN1/CD43 antigen, indicating that the 2/165 phagotope mimicked the UN1 antigen structure, and could represent a novel immunogen for cancer immunotherapy (PMID:24356816)
• CD43 polymorphisms are associated with TB susceptibility. (PMID:25078322)
• Host membrane protein PSGL-1, CD43, and CD44 association with assembling HIV-1 Gag is driven by polybasic sequences present in the cytoplasmic tails of the membrane proteins and in Gag. (PMID:25320329)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spn	ENSMUSG00000051457
rattus_norvegicus	Spnl1	ENSRNOG00000028414
rattus_norvegicus	Spn	ENSRNOG00000036711
rattus_norvegicus	Spnl2	ENSRNOG00000039282

Protein

Protein identifiers

Leukosialin — P16150 (reviewed: P16150)

Alternative names: GPL115, Galactoglycoprotein, Leukocyte sialoglycoprotein, Sialophorin

All UniProt accessions (2): C9JUK7, P16150

UniProt curated annotations — full annotation on UniProt →

Function. Predominant cell surface sialoprotein of leukocytes which regulates multiple T-cell functions, including T-cell activation, proliferation, differentiation, trafficking and migration. Positively regulates T-cell trafficking to lymph-nodes via its association with ERM proteins (EZR, RDX and MSN). Negatively regulates Th2 cell differentiation and predisposes the differentiation of T-cells towards a Th1 lineage commitment. Promotes the expression of IFN-gamma by T-cells during T-cell receptor (TCR) activation of naive cells and induces the expression of IFN-gamma by CD4(+) T-cells and to a lesser extent by CD8(+) T-cells. Plays a role in preparing T-cells for cytokine sensing and differentiation into effector cells by inducing the expression of cytokine receptors IFNGR and IL4R, promoting IFNGR and IL4R signaling and by mediating the clustering of IFNGR with TCR. Acts as a major E-selectin ligand responsible for Th17 cell rolling on activated vasculature and recruitment during inflammation. Mediates Th17 cells, but not Th1 cells, adhesion to E-selectin. Acts as a T-cell counter-receptor for SIGLEC1. Protects cells from apoptotic signals, promoting cell survival.

Subunit / interactions. Interacts with SIGLEC1. Monomer. Interacts with CTNNB1. Interacts with RDX (via FERM domain), EZR and MSN.

Subcellular location. Membrane. Cell projection. Microvillus. Uropodium Nucleus. Nucleus. PML body.

Tissue specificity. Cell surface of thymocytes, T-lymphocytes, neutrophils, plasma cells and myelomas.

Post-translational modifications. Glycosylated; has a high content of sialic acid and O-linked carbohydrate structures. Phosphorylation at Ser-355 is regulated by chemokines, requires its association with ERM proteins (EZR, RDX and MSN) and is essential for its function in the regulation of T-cell trafficking to lymph nodes. Has a high content of sialic acid and O-linked carbohydrate structures. Cleavage by CTSG releases its extracellular domain and triggers its intramembrane proteolysis by gamma-secretase releasing the CD43 cytoplasmic tail chain (CD43-ct) which translocates to the nucleus. Sumoylated.

RefSeq proteins (2): NP_001025459, NP_003114* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038829	Leukosialin	Family

UniProt features (54 total): glycosylation site 26, compositionally biased region 7, modified residue 7, region of interest 3, chain 2, topological domain 2, sequence variant 2, mutagenesis site 2, signal peptide 1, transmembrane region 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16150-F1	53.86	0.04

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 (7): 291, 336, 341, 351, 355, 368, 379

Glycosylation sites (26): 21, 22, 26, 28, 29, 35, 36, 37, 41, 42, 46, 47, 48, 50, 58, 69, 99, 103, 109, 113 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
282–283	reduced nuclear localization. loss of nuclear localization; when associated with 295-p-g-296.
295–296	reduced nuclear localization. loss of nuclear localization; when associated with 282-p-g-283.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-210991	Basigin interactions
R-HSA-109582	Hemostasis

MSigDB gene sets: 335 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GCM_MSN, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_THYMIC_T_CELL_SELECTION, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, MODULE_45

GO Biological Process (26): response to protozoan (GO:0001562), negative regulation of type IV hypersensitivity (GO:0001808), T-helper 1 cell lineage commitment (GO:0002296), chemotaxis (GO:0006935), immune response (GO:0006955), cellular defense response (GO:0006968), negative regulation of cell adhesion (GO:0007162), establishment or maintenance of cell polarity (GO:0007163), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), T cell costimulation (GO:0031295), positive regulation of tumor necrosis factor production (GO:0032760), T cell proliferation (GO:0042098), positive regulation of T cell proliferation (GO:0042102), negative regulation of T cell proliferation (GO:0042130), defense response to bacterium (GO:0042742), negative thymic T cell selection (GO:0045060), regulation of defense response to virus (GO:0050688), regulation of immune response (GO:0050776), leukocyte tethering or rolling (GO:0050901), apoptotic signaling pathway (GO:0097190), regulation of T cell migration (GO:2000404), positive regulation of T cell migration (GO:2000406), type II interferon production (GO:0032609), regulation of T cell activation (GO:0050863), negative regulation of T cell activation (GO:0050868)

GO Molecular Function (4): transmembrane signaling receptor activity (GO:0004888), Hsp70 protein binding (GO:0030544), heat shock protein binding (GO:0031072), protein binding (GO:0005515)

GO Cellular Component (12): uropod (GO:0001931), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), microvillus (GO:0005902), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), PML body (GO:0016605), extracellular exosome (GO:0070062), nucleus (GO:0005634), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Hemostasis	1
Cell surface interactions at the vascular wall	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
defense response	2
cellular process	2
positive regulation of T cell activation	2
T cell proliferation	2
regulation of T cell proliferation	2
response to other organism	1
type IV hypersensitivity	1
regulation of type IV hypersensitivity	1
negative regulation of T cell mediated immunity	1
negative regulation of hypersensitivity	1
T-helper cell lineage commitment	1
T-helper 1 cell differentiation	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
lymphocyte costimulation	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
T cell activation	1
lymphocyte proliferation	1
positive regulation of lymphocyte proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
response to bacterium	1
negative T cell selection	1
thymic T cell selection	1
regulation of response to biotic stimulus	1
regulation of defense response	1
regulation of response to external stimulus	1

Protein interactions and networks

STRING

2124 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPN	PTPRC	P08575	991
SPN	ICAM1	P05362	977
SPN	SELE	P16111	975
SPN	SELPLG	Q14242	969
SPN	EZR	P15311	966
SPN	RDX	P35241	952
SPN	MSN	P26038	942
SPN	CD5	P06127	932
SPN	CD44	P16070	926
SPN	CD19	P15391	923
SPN	SIGLEC1	Q9BZZ2	899
SPN	LGALS3	P17931	886
SPN	CD79A	P11912	823
SPN	CD34	P28906	809
SPN	SDC1	P18827	807

IntAct

39 interactions, top by confidence:

A	B	Type	Score
SPN	SGTA	psi-mi:“MI:0915”(physical association)	0.560
SPN	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
SPN	PLP2	psi-mi:“MI:0915”(physical association)	0.560
SPN	ERGIC3	psi-mi:“MI:0915”(physical association)	0.560
SPN	CYBC1	psi-mi:“MI:0915”(physical association)	0.560
CXCL16	SPN	psi-mi:“MI:0915”(physical association)	0.560
SPN	PPGB	psi-mi:“MI:0915”(physical association)	0.560
SPN	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
	SPN	psi-mi:“MI:0915”(physical association)	0.560
ICAM1	SPN	psi-mi:“MI:0407”(direct interaction)	0.440
SIGLEC1	SPN	psi-mi:“MI:0407”(direct interaction)	0.440
DICER1	SPN	psi-mi:“MI:0914”(association)	0.350
	CD63	psi-mi:“MI:0914”(association)	0.350
SPN	SPAG9	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SPN	LGALS8	psi-mi:“MI:0914”(association)	0.350
SPN	SGTA	psi-mi:“MI:0915”(physical association)	0.000
SPN	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
SPN	ERGIC3	psi-mi:“MI:0915”(physical association)	0.000
CYBC1	SPN	psi-mi:“MI:0915”(physical association)	0.000
CXCL16	SPN	psi-mi:“MI:0915”(physical association)	0.000
PPGB	SPN	psi-mi:“MI:0915”(physical association)	0.000
SPN	ARL13B	psi-mi:“MI:0915”(physical association)	0.000
	SPN	psi-mi:“MI:0915”(physical association)	0.000
PLP2	SPN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (65): SPN (Affinity Capture-RNA), SLC39A11 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), EIF2B3 (Affinity Capture-MS), EIF2B5 (Affinity Capture-MS), EIF2B4 (Affinity Capture-MS), EIF2B2 (Affinity Capture-MS), EIF2B3 (Affinity Capture-MS), SLC39A11 (Affinity Capture-MS), SPAG9 (Affinity Capture-MS), SPN (Two-hybrid), SPN (Two-hybrid), SPN (Two-hybrid), SPN (Two-hybrid), SPN (Two-hybrid)

ESM2 similar proteins: A0A2R8Y7Y5, A1KXC4, A6QLF8, J3KML8, O00592, O35188, O55145, O57604, P06484, P07141, P13838, P14220, P15702, P16150, P18827, P20934, P26260, P34740, P47951, P59647, P78423, P97808, Q08DZ5, Q1ECS6, Q28270, Q28645, Q29RT9, Q3MIW9, Q3TNW5, Q52S86, Q58Y74, Q5RAF8, Q62170, Q64314, Q6MG22, Q6P9X9, Q6UWI2, Q6UXF1, Q86YL7, Q8BHE4

Diamond homologs: P13838, P15702, P16150

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	62
Likely benign	14
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253525	GRCh37/hg19 16p11.2(chr16:29060171-30197341)x3	Pathogenic

SpliceAI

851 predictions. Top by Δscore:

Variant	Effect	Δscore
16:29664613:GC:G	donor_gain	0.9900
16:29664610:C:T	donor_gain	0.9800
16:29664625:G:GA	donor_gain	0.9800
16:29663077:TCAGG:T	donor_loss	0.9700
16:29663078:CAGG:C	donor_loss	0.9700
16:29663080:GGTGA:G	donor_loss	0.9700
16:29663082:T:G	donor_loss	0.9700
16:29664624:T:TA	donor_gain	0.9700
16:29664942:A:G	donor_gain	0.9700
16:29664618:ACGGG:A	donor_gain	0.9600
16:29664864:G:GG	donor_gain	0.9600
16:29663083:GA:G	donor_loss	0.9500
16:29664940:GAAT:G	donor_gain	0.9500
16:29664941:AATA:A	donor_gain	0.9500
16:29663313:GCCG:G	donor_gain	0.9400
16:29664863:A:AG	donor_gain	0.9400
16:29664596:C:G	donor_gain	0.9300
16:29664662:G:GT	donor_gain	0.9300
16:29664859:GGCC:G	donor_gain	0.9300
16:29663314:CCG:C	donor_loss	0.9200
16:29663315:CG:C	donor_loss	0.9200
16:29663316:GGTAA:G	donor_loss	0.9200
16:29663317:GTA:G	donor_loss	0.9200
16:29663753:G:A	acceptor_gain	0.9200
16:29664911:G:T	donor_gain	0.9200
16:29664928:T:G	donor_gain	0.9200
16:29663323:GG:G	donor_gain	0.9100
16:29663324:GG:G	donor_gain	0.9100
16:29664653:GTCCC:G	donor_gain	0.9100
16:29664654:TCCCT:T	donor_gain	0.9100

AlphaMissense

2509 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:29664761:T:C	F345L	0.983
16:29664763:C:A	F345L	0.983
16:29664763:C:G	F345L	0.983
16:29664637:G:C	W303C	0.977
16:29664637:G:T	W303C	0.977
16:29664635:T:A	W303R	0.968
16:29664635:T:C	W303R	0.968
16:29664764:T:C	F346L	0.938
16:29664766:T:A	F346L	0.938
16:29664766:T:G	F346L	0.938
16:29664641:G:T	G305W	0.936
16:29664753:T:A	L342H	0.921
16:29664759:C:T	T344I	0.920
16:29664641:G:A	G305R	0.912
16:29664641:G:C	G305R	0.912
16:29663753:G:A	G9R	0.907
16:29663753:G:C	G9R	0.907
16:29664557:T:A	W277R	0.904
16:29664557:T:C	W277R	0.904
16:29664582:C:T	T285I	0.899
16:29664639:C:A	A304D	0.897
16:29664762:T:C	F345S	0.894
16:29664638:G:C	A304P	0.891
16:29664642:G:A	G305E	0.891
16:29664516:C:A	A263D	0.887
16:29664534:T:A	V269D	0.887
16:29664584:G:T	G286W	0.881
16:29664762:T:G	F345C	0.874
16:29664636:G:T	W303L	0.873
16:29664531:T:A	I268K	0.870

dbSNP variants (sampled 300 via entrez): RS1000337145 (16:29666023 A>G), RS1000372600 (16:29666783 G>A,T), RS1000673115 (16:29662722 T>G), RS1000788807 (16:29662564 C>G,T), RS1000881500 (16:29670438 G>A), RS1001355506 (16:29667422 G>A,T), RS1001432402 (16:29666072 G>A,T), RS1001503868 (16:29670233 C>T), RS1001928301 (16:29670559 G>A), RS1002226499 (16:29665116 A>G), RS1002295022 (16:29662794 G>A), RS1002310255 (16:29668589 C>G,T), RS1002379497 (16:29670852 C>A), RS1002424879 (16:29668282 C>T), RS1002877878 (16:29667724 C>T)

Disease associations

OMIM: gene MIM:182160 | disease phenotypes: MIM:611913

GenCC curated gene-disease

Mondo (1): proximal 16p11.2 microdeletion syndrome (MONDO:0012756)

Orphanet (1): Proximal 16p11.2 microdeletion syndrome (Orphanet:261197)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C579850	16p11.2 Deletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, affects methylation, affects cotreatment, decreases reaction, increases expression	2
GSK-J4	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
tert-butylphenyl diphenyl phosphate	affects cotreatment, decreases reaction, increases expression	1
gadodiamide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
Bortezomib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Digitonin	affects cotreatment, decreases reaction, increases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Chlorpyrifos	affects cotreatment, decreases reaction, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Fluorouracil	increases expression, affects cotreatment, decreases reaction	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Mercuric Chloride	affects cotreatment, decreases reaction, increases expression	1
Methyl Methanesulfonate	decreases expression	1
Nickel	decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Zinc	decreases expression	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8Q3	Abcam HCT 116 SPN KO	Cancer cell line	Male
CVCL_B9BT	Abcam MCF-7 SPN KO	Cancer cell line	Female
CVCL_B9SJ	Abcam A-549 SPN KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04271332	PHASE2	ACTIVE_NOT_RECRUITING	Safety, Tolerability, and Efficacy of Arbaclofen in 16p11.2 Deletion
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight