CD22

Summary

CD22 (CD22 molecule, HGNC:1643) is a protein-coding gene on chromosome 19q13.12, encoding B-cell receptor CD22 (P20273). Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and trafficking to bone marrow.

Predicted to enable CD4 receptor binding activity; protein phosphatase binding activity; and sialic acid binding activity. Involved in B cell activation; negative regulation of B cell receptor signaling pathway; and regulation of endocytosis. Located in early endosome and recycling endosome. Implicated in diffuse large B-cell lymphoma.

Source: NCBI Gene 933 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 148 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001771

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1643
Approved symbol	CD22
Name	CD22 molecule
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	SIGLEC-2, SIGLEC2
Ensembl gene	ENSG00000012124
Ensembl biotype	protein_coding
OMIM	107266
Entrez	933

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 20 protein_coding, 9 protein_coding_CDS_not_defined, 7 retained_intron, 4 nonsense_mediated_decay

ENST00000085219, ENST00000341773, ENST00000419549, ENST00000536635, ENST00000544992, ENST00000593704, ENST00000593867, ENST00000594125, ENST00000594250, ENST00000594349, ENST00000594954, ENST00000595419, ENST00000595780, ENST00000596492, ENST00000597433, ENST00000597916, ENST00000598028, ENST00000598138, ENST00000598537, ENST00000598815, ENST00000599717, ENST00000599799, ENST00000599811, ENST00000600131, ENST00000600424, ENST00000600655, ENST00000600905, ENST00000601329, ENST00000601414, ENST00000601732, ENST00000601769, ENST00000602123, ENST00000602224, ENST00000613136, ENST00000884225, ENST00000884226, ENST00000884227, ENST00000884228, ENST00000918678, ENST00000948629

RefSeq mRNA: 5 — MANE Select: NM_001771 NM_001185099, NM_001185100, NM_001185101, NM_001278417, NM_001771

CCDS: CCDS12457, CCDS54247, CCDS54248, CCDS54249, CCDS62634

Canonical transcript exons

ENST00000085219 — 14 exons

Exon	Start	End
ENSE00003006937	35329187	35329230
ENSE00003528089	35344829	35344925
ENSE00003528304	35346151	35346235
ENSE00003529118	35337755	35338021
ENSE00003546049	35338168	35338431
ENSE00003602356	35345602	35345720
ENSE00003630859	35341702	35341965
ENSE00003632030	35340881	35341138
ENSE00003651873	35332019	35332074
ENSE00003652433	35336036	35336341
ENSE00003675894	35341343	35341606
ENSE00003691466	35345051	35345126
ENSE00003751072	35332547	35332924
ENSE00003845039	35346566	35347361

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 97.88.

FANTOM5 (CAGE): breadth broad, TPM avg 8.0214 / max 693.0678, expressed in 370 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175316	6.6647	200
175305	1.1567	254
175306	0.0621	28
175312	0.0597	14
175315	0.0222	11
175314	0.0171	6
175310	0.0159	7
175311	0.0146	6
175313	0.0084	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	97.88	gold quality
left ovary	UBERON:0002119	97.21	gold quality
vermiform appendix	UBERON:0001154	97.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.77	gold quality
lymph node	UBERON:0000029	96.74	gold quality
right uterine tube	UBERON:0001302	96.31	gold quality
granulocyte	CL:0000094	96.27	gold quality
right ovary	UBERON:0002118	95.93	gold quality
sural nerve	UBERON:0015488	94.45	gold quality
spinal cord	UBERON:0002240	94.21	gold quality
ovary	UBERON:0000992	94.17	gold quality
caecum	UBERON:0001153	92.92	gold quality
corpus callosum	UBERON:0002336	92.81	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	91.05	gold quality
putamen	UBERON:0001874	90.28	gold quality
inferior olivary complex	UBERON:0002127	90.24	gold quality
caudate nucleus	UBERON:0001873	89.62	gold quality
amygdala	UBERON:0001876	88.99	gold quality
substantia nigra	UBERON:0002038	88.81	gold quality
blood	UBERON:0000178	88.66	gold quality
middle frontal gyrus	UBERON:0002702	88.63	gold quality
Ammon’s horn	UBERON:0001954	87.66	gold quality
ileal mucosa	UBERON:0000331	87.55	gold quality
ileum	UBERON:0002116	87.47	silver quality
midbrain	UBERON:0001891	87.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.81	gold quality
right frontal lobe	UBERON:0002810	86.78	gold quality
endometrium epithelium	UBERON:0004811	85.88	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.87	gold quality
medial globus pallidus	UBERON:0002477	85.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-32	yes	400.35
E-MTAB-8498	yes	150.07
E-HCAD-4	yes	116.07
E-CURD-122	yes	99.06
E-CURD-88	yes	47.04
E-ANND-3	yes	38.94
E-MTAB-9221	yes	22.17
E-MTAB-9067	yes	18.60
E-CURD-112	yes	10.23
E-MTAB-5061	yes	4.56
E-MTAB-9801	yes	3.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL6, FOXP1, SPI1, STAT1

miRNA regulators (miRDB)

40 targeting CD22, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-3945	98.68	64.21	553
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-8089	97.74	66.21	1698

Literature-anchored findings (GeneRIF, showing 40)

• The Lyn/CD22/SHP-1 pathway is important in autoimmunity. Naive and tolerant B-cells differ in their calcium signaling in response to antigenic stimulation. (PMID:11826756)
• Disulfide bonds and the resulting 3D conformation of the CD22 molecules may have important roles in the difference of antigenicity of CD22 beta in B cells and basophils (PMID:11882357)
• ligand-binding of CD22 influences its intracellular signaling domain and is needed for inhibition of the B cell receptor signal (PMID:11994426)
• masking of the alpha2-6-linked sialic acid binding site of CD22 involves many cell surface sialoglycoproteins, without requiring specific ligand(s) and/or is mediated by secondary interactions with Sias on CD45 and sIgM (PMID:15240561)
• Aberrant CD22 expression is a useful marker for detection of monoclonal B cells admixed with numerous benign polyclonal B cells (PMID:15899772)
• decreased CD22 expression may be associated with the activation of B cells in Bullous pemphigoid (BP), but not associated with BP-specific antibody production (PMID:17055225)
• study showed that a synonymous SNP in CD22, c.2304C > A, was significantly associated with susceptibility to limited cutaneous systemic sclerosis (PMID:17493148)
• The results suggest that these two siglec proteins have evolved distinct endocytic mechanisms consistent with roles in cell signaling and innate immunity. (PMID:17562860)
• a decrease in CD22(+) B cells and increase in CD5(+)CD22(-) B cells play critical roles in the pathogenesis of RA mediated by the activation of B cells (PMID:17585360)
• These results indicate that the alpha2-6-sialylated 6-sulfo-LacNAc determinant serves as an endogenous ligand for human CD22 and suggest the possibility that 6-GlcNAc sulfation as well as alpha2-6-sialylation may regulate Siglec-2 functions in humans. (PMID:17728258)
• SAP is inducibly expressed in the human BJAB cells, and co-localizes and interacts with CD22. SAP binding to the inhibitory immunoreceptor CD22 regulates calcium mobilization in B cells. (PMID:19150402)
• Data show that anti-CD22 autoantibodies were positive in 80% of TSK/+ mice and in 22% of SSc patients. (PMID:19919568)
• The B-cell receptor IgM was found to be a major in situ trans ligand of CD22. (PMID:20172905)
• B cell surface receptors CD20 and CD22 are significantly affected in patients with SLE, pointing to their possible involvement in the aetiopathogenesis of the disease and in the regulatory mechanisms in response to the immune disturbance. (PMID:20726320)
• These striking findings implicate CD22DeltaE12 as a previously undescribed pathogenic mechanism in human B-precursor leukemia. (PMID:20841423)
• The efficacy of a ligand-targeting approach to B cell-specific depletion therapy for cancer may be the ability of CD22 to recycle and accumulate ligand-decorated cargo intracellularly, as an endocytic receptor. (PMID:21178016)
• Taken together, these results suggest that negative regulation of TLR signaling of B cells is an intrinsic property of CD22. (PMID:21178327)
• Studies showed the qualitative and quantitative expression of four target surface antigens, CD19, CD20, CD22, and CD33, for which MoAbs are currently available for clinical use, in ALL. (PMID:21348573)
• This CD22-targeted polymer carrier may be useful for siRNA delivery to lymphoma cells. (PMID:21629223)
• Results obtained through a large cohort of European caucasian patients with systemic sclerosis do not support the contribution of CD19, CD20, CD22, CD24 variants to the genetic susceptibility. (PMID:21961844)
• Our study implicates the CD22DeltaE12 genetic defect in the aggressive biology of relapsed or therapy-refractory paediatric B-lineage ALL. (PMID:22017452)
• Anti-CD22 recombinant immunotoxin moxetumomab pasudotox has activity in relapsed/refractory hairy cell leukemia. (PMID:22355053)
• The finding that CD22 is expressed on lung cancer cells is significant in revealing a heretofore unknown mechanism of tumorigenesis and metastasis (PMID:22986740)
• In the absence of functional CD22, B cells have a “hyperactivated” phenotype, CD22 dysfunction could contribute to the pathogenesis of autoimmune diseases. (Review) (PMID:23083346)
• study detected the expression of CD22 and CD72 on B cells of myasthenia gravis, compared to multiple sclerosis patient controls and healthy controls y (PMID:23184497)
• By using integrative genomics and analysing the relationships of COPD phenotypes with SNPs and gene expression in lung tissue, we identified CST3 and CD22 as potential causal genes for airflow obstruction. (PMID:25182044)
• These results suggest that the in vivo mechanism of non-ligand-blocking epratuzumab may, in part, involve the unmasking of CD22 to facilitate the trans-interaction of B cells with vascular endothelium. (PMID:25484043)
• MicroRNA-19a and CD22 Comprise a Feedback Loop for B Cell Response in Sepsis. (PMID:26017478)
• Anti-CD22-magnetic nanoparticles-doxorubicin inhibited the proliferation of Raji cells, significantly increased the uptake of doxorubicin, and induced apoptosis. (PMID:26379425)
• results demonstrate that loss of high affinity CD22 ligands on GC B-cells occurs in both mice and humans through alternative mechanisms, unmasking CD22 relative to naive and memory B-cells (PMID:26507663)
• Siglec-1 and Siglec-2 are potential biomarkers in autoimmune disease. (Review) (PMID:26752092)
• We aimed to screen exons 9-14 of the CD22 gene, which is a mutational hot spot region in B-precursor acute lymphoblastic leukemia (pre-B ALL) patients. Nine variants, of which two novel, were found. Novel variants were in introns 10 and 13. Gly745Asp (rs10406069) variant was missense and Cys790Arg (rs79438722) variant was silent. (PMID:27486888)
• Diabody-based (177)Lu-radioimmunoconjugate for CD22-directed radioimmunotherapy reduced disease burden in a non-Hodgkin lymphoma mouse model. (PMID:27524505)
• This is the first time a NMR-based binding study of high affinity Siglec-2 (CD22) ligands in complex with whole Burkitt’s lymphoma Daudi cells has been described. (PMID:27808110)
• Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells (PMID:28829594)
• Here the authors structurally characterize the ectodomain of CD22 and present its crystal structure with the bound therapeutic antibody epratuzumab, which gives insights into the mechanism of inhibition of B-cell activation. (PMID:28970495)
• hCD22 transgenic mice develop normal humoral responses in a peanut allergy oral sensitization model. Homing of B cells to Peyer’s patches was partially rescued by expression of hCD22 compared with CD22(-/-) B cells, although not to wild-type levels. (PMID:28972089)
• Authors semi-quantitatively classified baseline expression of sCD19 and sCD22 in a large cohort of pediatric B-ALL. Dim CD19 and negative CD22 cases were correlated with common genetic abnormalities. (PMID:30058145)
• CD22 plays a key role in affecting B cell responses to antigens and innate immune signals, and CD22-CD22L interactions are essential for maintaining self-tolerance. The ability of CD22 to regulate both B cell receptor and toll-like receptors represents an attractive therapeutic strategy for manipulating B cell responses in autoimmunity. (PMID:30323814)
• up-regulation of siglec-2 in tumor tissues could predict better overall survival (OS) in hepatocellular carcinoma patients. Mechanisms of siglec-2 in hepatocellular carcinoma (HCC) development need further research. (PMID:30355653)

Cross-species orthologs

37 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:172106	ENSDARG00000017984
danio_rerio	si:ch211-152f2.2	ENSDARG00000034910
danio_rerio	si:ch211-152f2.3	ENSDARG00000043445
danio_rerio	cd22	ENSDARG00000053005
danio_rerio	si:dkey-33i11.1	ENSDARG00000053027
danio_rerio	si:ch211-1f22.5	ENSDARG00000054655
danio_rerio	zgc:171470	ENSDARG00000057844
danio_rerio	si:ch211-1f22.14	ENSDARG00000062309
danio_rerio	si:ch211-53m15.1	ENSDARG00000076539
danio_rerio	si:ch211-286b5.9	ENSDARG00000086166
danio_rerio	si:dkey-27j5.6	ENSDARG00000086301
danio_rerio	zmp:0000001289	ENSDARG00000089894
danio_rerio	si:ch211-152f2.1	ENSDARG00000092322
danio_rerio	si:ch211-1f22.12	ENSDARG00000093845
danio_rerio	si:dkey-27j5.10	ENSDARG00000094157
danio_rerio	si:ch211-1f22.11	ENSDARG00000094524
danio_rerio	si:ch211-1f22.8	ENSDARG00000096507
danio_rerio	si:ch73-94k4.5	ENSDARG00000096523
danio_rerio	si:dkey-27j5.8	ENSDARG00000096534
danio_rerio	si:ch211-1f22.7	ENSDARG00000096543
danio_rerio	si:dkey-27j5.7	ENSDARG00000096570
danio_rerio	si:ch211-152f2.4	ENSDARG00000096574
danio_rerio	si:ch211-286b5.6	ENSDARG00000096576
danio_rerio	si:ch211-1f22.9	ENSDARG00000096585
danio_rerio	si:ch211-1f22.10	ENSDARG00000096619
danio_rerio	si:ch211-1f22.4	ENSDARG00000096621
danio_rerio	si:ch211-1f22.13	ENSDARG00000096623
danio_rerio	si:ch211-286b5.8	ENSDARG00000096625
danio_rerio	si:ch73-94k4.1	ENSDARG00000096634
danio_rerio	si:dkey-27j5.11	ENSDARG00000096650
danio_rerio	si:ch211-1f22.6	ENSDARG00000096656
danio_rerio	si:ch211-1f22.16	ENSDARG00000096670
danio_rerio	si:ch73-94k4.3	ENSDARG00000096671
danio_rerio	si:ch211-1f22.3	ENSDARG00000101532
danio_rerio	si:dkey-4c23.5	ENSDARG00000115038
mus_musculus	Cd22	ENSMUSG00000030577
rattus_norvegicus	Cd22	ENSRNOG00000024000

Paralogs (16): SIGLEC1 (ENSG00000088827), SIGLEC8 (ENSG00000105366), CD33 (ENSG00000105383), SIGLEC6 (ENSG00000105492), MAG (ENSG00000105695), SIGLEC9 (ENSG00000129450), SIGLEC10 (ENSG00000142512), TMEM25 (ENSG00000149582), SIGLEC11 (ENSG00000161640), SIGLEC16 (ENSG00000161643), SIGLEC7 (ENSG00000168995), SIGLECL1 (ENSG00000179213), SIGLEC15 (ENSG00000197046), SIGLEC14 (ENSG00000254415), SIGLEC12 (ENSG00000254521), SIGLEC5 (ENSG00000268500)

Protein

Protein identifiers

B-cell receptor CD22 — P20273 (reviewed: P20273)

Alternative names: B-lymphocyte cell adhesion molecule, Sialic acid-binding Ig-like lectin 2, T-cell surface antigen Leu-14

All UniProt accessions (14): P20273, A0A087WZQ4, M0QY05, M0QY14, M0QYP4, M0QZ01, M0QZP5, M0QZR7, M0R0R6, M0R1M2, M0R2M0, M0R2R8, M0R3H1, Q0EAF5

UniProt curated annotations — full annotation on UniProt →

Function. Most highly expressed siglec (sialic acid-binding immunoglobulin-like lectin) on B-cells that plays a role in various aspects of B-cell biology including differentiation, antigen presentation, and trafficking to bone marrow. Binds to alpha 2,6-linked sialic acid residues of surface molecules such as CD22 itself, CD45 and IgM in a cis configuration. Can also bind to ligands on other cells as an adhesion molecule in a trans configuration. Acts as an inhibitory coreceptor on the surface of B-cells and inhibits B-cell receptor induced signaling, characterized by inhibition of the calcium mobilization and cellular activation. Mechanistically, the immunoreceptor tyrosine-based inhibitory motif domain is phosphorylated by the Src kinase LYN, which in turn leads to the recruitment of the protein tyrosine phosphatase 1/PTPN6, leading to the negative regulation of BCR signaling. If this negative signaling from is of sufficient strength, apoptosis of the B-cell can be induced.

Subunit / interactions. Predominantly monomer of isoform CD22-beta. Also found as heterodimer of isoform CD22-beta and a shorter isoform. Interacts with PTPN6/SHP-1, LYN, SYK, PIK3R1/PIK3R2 and PLCG1 upon phosphorylation. Interacts with GRB2, INPP5D and SHC1 upon phosphorylation. May form a complex with INPP5D/SHIP, GRB2 and SHC1.

Subcellular location. Cell membrane.

Tissue specificity. B-lymphocytes.

Post-translational modifications. Phosphorylation of Tyr-762, Tyr-807 and Tyr-822 are involved in binding to SYK, GRB2 and SYK, respectively. Phosphorylation of Tyr-842 is involved in binding to SYK, PLCG2 and PIK3R1/PIK3R2. Phosphorylated on tyrosine residues by LYN.

Domain organisation. Contains 4 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Similarity. Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.

Isoforms (5)

UniProt ID	Names	Canonical?
P20273-1	CD22-beta	yes
P20273-2	CD22-alpha
P20273-3	3
P20273-4	4
P20273-5	5

RefSeq proteins (5): NP_001172028, NP_001172029, NP_001172030, NP_001265346, NP_001762* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR056386	Ig_CD22	Domain

Pfam: PF08205, PF13895, PF13927, PF24518

UniProt features (111 total): strand 42, glycosylation site 11, helix 8, disulfide bond 8, sequence variant 8, domain 7, modified residue 7, splice variant 6, short sequence motif 4, topological domain 2, sequence conflict 2, turn 2, signal peptide 1, chain 1, binding site 1, transmembrane region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
5VKJ	X-RAY DIFFRACTION	2.12
5VKM	X-RAY DIFFRACTION	2.2
7O52	X-RAY DIFFRACTION	2.41
9ROB	X-RAY DIFFRACTION	2.7
9RM3	X-RAY DIFFRACTION	2.86
5VL3	X-RAY DIFFRACTION	3.1
9RO7	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20273-F1	79.33	0.51

Antibody-complex structures (SAbDab): 2 — 5VL3, 7O52

Functional residue map

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

Ligand- & substrate-binding residues (1): 120

Post-translational modifications (7): 725, 726, 729, 762, 807, 822, 842

Disulfide bonds (8): 39–167, 44–102, 161–219, 265–309, 353–396, 442–484, 529–571, 616–659

Glycosylation sites (11): 67, 101, 112, 135, 164, 231, 363, 445, 479, 574, 634

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-5690714	CD22 mediated BCR regulation
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983705	Signaling by the B Cell Receptor (BCR)

MSigDB gene sets: 310 (showing top): PID_BCR_5PATHWAY, GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, MODULE_52, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, MODULE_45, MODULE_64, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOCC_CELL_SURFACE, GOBP_B_CELL_PROLIFERATION

GO Biological Process (10): negative regulation of immunoglobulin production (GO:0002638), cell adhesion (GO:0007155), regulation of endocytosis (GO:0030100), regulation of B cell proliferation (GO:0030888), B cell activation (GO:0042113), regulation of immune response (GO:0050776), negative regulation of calcium-mediated signaling (GO:0050849), negative regulation of B cell receptor signaling pathway (GO:0050859), negative regulation of immune system process (GO:0002683), negative regulation of signal transduction (GO:0009968)

GO Molecular Function (7): IgM binding (GO:0001791), signaling receptor binding (GO:0005102), protein phosphatase binding (GO:0019903), carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691), CD4 receptor binding (GO:0042609), protein binding (GO:0005515)

GO Cellular Component (9): cytoplasm (GO:0005737), early endosome (GO:0005769), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), neuronal cell body membrane (GO:0032809), recycling endosome (GO:0055037), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Adaptive Immune System	2
Signaling by the B Cell Receptor (BCR)	2
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of immune system process	2
binding	2
endosome	2
immunoglobulin production	1
regulation of immunoglobulin production	1
negative regulation of production of molecular mediator of immune response	1
cellular process	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
B cell proliferation	1
regulation of lymphocyte proliferation	1
regulation of B cell activation	1
lymphocyte activation	1
immune response	1
regulation of response to stimulus	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
negative regulation of intracellular signal transduction	1
B cell receptor signaling pathway	1
regulation of B cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
immune system process	1
negative regulation of biological process	1
signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
immunoglobulin binding	1
protein binding	1
phosphatase binding	1
carboxylic acid binding	1
carbohydrate derivative binding	1
signaling receptor binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
plasma membrane	1

Protein interactions and networks

STRING

2102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD22	PTPRC	P08575	995
CD22	CD19	P15391	977
CD22	CD79A	P11912	945
CD22	CD200R1	Q8TD46	934
CD22	CD5	P06127	888
CD22	PTPN6	P29350	873
CD22	LYN	P07948	865
CD22	CD79B	P40259	860
CD22	SYK	P43405	849
CD22	MME	P08473	841
CD22	FFAR3	O14843	839
CD22	CD81	P18582	833
CD22	CR2	P20023	822
CD22	MS4A1	P08984	807
CD22	CD2	P06729	805

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CD22	SYK	psi-mi:“MI:0915”(physical association)	0.620
PTPN6	CD22	psi-mi:“MI:0915”(physical association)	0.500
CD22	PTPN6	psi-mi:“MI:0914”(association)	0.500
CD22	PLCG1	psi-mi:“MI:0914”(association)	0.500
PLCG1	CD22	psi-mi:“MI:0915”(physical association)	0.500
CD22	LYN	psi-mi:“MI:0914”(association)	0.500
LYN	CD22	psi-mi:“MI:0915”(physical association)	0.500
PTPRC	CD22	psi-mi:“MI:0915”(physical association)	0.400
CFTR	CD22	psi-mi:“MI:0915”(physical association)	0.370
ECE1	CD22	psi-mi:“MI:0915”(physical association)	0.370
CD22	S100A7	psi-mi:“MI:0914”(association)	0.350
cpxA	CD22	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (43): CPA4 (Affinity Capture-MS), S100A7 (Affinity Capture-MS), TYK2 (Negative Genetic), FABP4 (Negative Genetic), PRKAA1 (Negative Genetic), JAK3 (Negative Genetic), LIG1 (Negative Genetic), CD22 (Negative Genetic), STMN1 (Negative Genetic), CD22 (Negative Genetic), TPSAB1 (Negative Genetic), CD22 (Positive Genetic), PLA2G4C (Positive Genetic), PIK3CA (Positive Genetic), CD22 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, A6NMB1, A7LCJ3, A8E0Y8, D3YX43, D3YZF7, O70540, P01876, P01877, P01880, P04217, P0DP72, P13597, P20273, P20758, P43121, P50895, Q00238, Q14773, Q15109, Q28173, Q2KJF1, Q5BK54, Q5NKT8, Q61790, Q61826, Q62151, Q62230, Q63495, Q6UWB1, Q6UY09, Q80ZE3, Q86VR7, Q8R2Y2, Q920A9, Q920G3, Q92154, Q95KI3, Q96AP7

Diamond homologs: A0A8M2B818, B0JYH6, B4KPU0, P06731, P15151, P20273, P31997, P32506, P32507, Q15223, Q5FWR8, Q92692, Q9GL76, Q9JKF6, Q9JLB9, Q9N1E4, Q9N1E5, Q9N1E6, Q9NQS3, A0N0X6, A1KZ92, A2CG49, A3KN33, A4IGL7, A4IIW9, A8WGA3, B0BNK7, B4F785, D2HFT7, D4A1J9, D4ABX8, F1LW30, G5EBF1, G5EG78, O01761, O15146, O55005, O60229, O75325, O89026

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
LYN	“down-regulates activity”	CD22	phosphorylation
CD22	“up-regulates activity”	SH2B1	binding
ST6GAL1	“down-regulates activity”	CD22	glycosylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	107
Likely benign	18
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3242311	GRCh37/hg19 19q13.11-13.12(chr19:35223021-36895699)x1	Pathogenic

SpliceAI

2937 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35332693:A:AG	acceptor_gain	1.0000
19:35336128:G:A	acceptor_gain	1.0000
19:35336340:GC:G	donor_gain	1.0000
19:35337951:G:GT	donor_gain	1.0000
19:35337951:G:T	donor_gain	1.0000
19:35338020:GT:G	donor_gain	1.0000
19:35338219:G:GT	donor_gain	1.0000
19:35338306:G:T	donor_gain	1.0000
19:35340876:TCCA:T	acceptor_loss	1.0000
19:35340879:A:AG	acceptor_gain	1.0000
19:35340879:A:C	acceptor_loss	1.0000
19:35340880:G:GA	acceptor_gain	1.0000
19:35340880:GA:G	acceptor_gain	1.0000
19:35340880:GAT:G	acceptor_gain	1.0000
19:35340880:GATC:G	acceptor_gain	1.0000
19:35340880:GATCC:G	acceptor_gain	1.0000
19:35341087:GCTT:G	donor_gain	1.0000
19:35341137:GT:G	donor_gain	1.0000
19:35341602:GCTGT:G	donor_gain	1.0000
19:35341966:G:GG	donor_gain	1.0000
19:35344824:C:G	acceptor_gain	1.0000
19:35344827:A:AG	acceptor_gain	1.0000
19:35344828:G:GG	acceptor_gain	1.0000
19:35344828:GAT:G	acceptor_gain	1.0000
19:35344828:GATA:G	acceptor_gain	1.0000
19:35344924:CGGTG:C	donor_loss	1.0000
19:35344925:GGT:G	donor_loss	1.0000
19:35344926:G:GA	donor_loss	1.0000
19:35344927:T:A	donor_loss	1.0000
19:35345047:TCAGT:T	acceptor_loss	1.0000

AlphaMissense

5589 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35338382:C:A	N400K	0.994
19:35338382:C:G	N400K	0.994
19:35332617:G:C	W35C	0.992
19:35332617:G:T	W35C	0.992
19:35341464:G:C	W543C	0.992
19:35341464:G:T	W543C	0.992
19:35341420:T:A	C529S	0.991
19:35341421:G:C	C529S	0.991
19:35341560:C:A	N575K	0.990
19:35341560:C:G	N575K	0.990
19:35338239:T:A	C353S	0.988
19:35338240:G:C	C353S	0.988
19:35341420:T:C	C529R	0.988
19:35336149:T:A	W176R	0.987
19:35336149:T:C	W176R	0.987
19:35340955:T:A	C442S	0.987
19:35340956:G:C	C442S	0.987
19:35340999:G:C	W456C	0.987
19:35340999:G:T	W456C	0.987
19:35341905:T:A	C659S	0.987
19:35341906:G:C	C659S	0.987
19:35336104:T:C	C161R	0.986
19:35336151:G:C	W176C	0.986
19:35336151:G:T	W176C	0.986
19:35338278:T:A	W366R	0.986
19:35338278:T:C	W366R	0.986
19:35340956:G:A	C442Y	0.986
19:35341546:T:A	C571S	0.986
19:35341547:G:C	C571S	0.986
19:35337873:G:C	W279C	0.985

dbSNP variants (sampled 300 via entrez): RS1000009513 (19:35330986 A>G), RS1000022293 (19:35330043 A>G), RS1000087744 (19:35336082 G>A), RS1000151437 (19:35339279 G>A), RS1000176298 (19:35345822 C>A,G,T), RS1000526289 (19:35340386 G>A), RS1000617427 (19:35335306 A>G), RS1000683506 (19:35328517 C>T), RS1000962970 (19:35329997 G>A,C), RS1000988588 (19:35344062 G>A), RS1001029354 (19:35328741 C>T), RS1001049855 (19:35335151 A>C), RS1001197427 (19:35343715 G>A), RS1001465864 (19:35333757 C>T), RS1001528070 (19:35339088 T>C)

Disease associations

OMIM: gene MIM:107266 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002404_528	Red cell distribution width	7.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3218 (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 (2 total), top 2:

Ligand	Action	Affinity	Parameter
inotuzumab ozogamicin	Binding	9.7	pKd
moxetumomab pasudotox	Binding	8.22	pKd

ChEMBL bioactivities

37 potent at pChembl≥5 of 48 total, top 36 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.49	IC50	0.32	nM	CHEMBL5184174
9.41	IC50	0.39	nM	CHEMBL5185214
9.39	IC50	0.41	nM	CHEMBL5197497
7.16	IC50	70	nM	CHEMBL1684361
6.89	IC50	130	nM	CHEMBL1684360
6.64	IC50	230	nM	CHEMBL511111
6.62	IC50	240	nM	CHEMBL502862
6.47	Kd	335	nM	CHEMBL4788433
6.40	IC50	400	nM	CHEMBL509768
6.34	Kd	458	nM	CHEMBL4780037
6.33	IC50	470	nM	CHEMBL509633
6.28	IC50	530	nM	CHEMBL502862
6.21	Kd	620	nM	CHEMBL4760637
6.20	Kd	628	nM	CHEMBL4739978
6.13	Kd	740	nM	CHEMBL4761167
6.12	Kd	766	nM	CHEMBL4752379
6.09	IC50	820	nM	CHEMBL1684363
6.07	Kd	860	nM	CHEMBL4783164
6.05	IC50	900	nM	CHEMBL501599
6.02	Kd	952	nM	CHEMBL4797221
6.00	IC50	1000	nM	CHEMBL502788
5.96	IC50	1100	nM	CHEMBL503830
5.95	IC50	1120	nM	CHEMBL1684364
5.76	IC50	1730	nM	CHEMBL505326
5.75	IC50	1760	nM	CHEMBL504222
5.66	IC50	2200	nM	CHEMBL5197497
5.58	IC50	2600	nM	CHEMBL467951
5.43	IC50	3700	nM	CHEMBL451427
5.37	IC50	4300	nM	CHEMBL446730
5.26	IC50	5480	nM	CHEMBL453397
5.21	IC50	6220	nM	CHEMBL448298
5.15	IC50	7130	nM	CHEMBL508909
5.13	IC50	7480	nM	CHEMBL500461
5.12	IC50	7650	nM	CHEMBL499744
5.05	IC50	8850	nM	CHEMBL510261
5.01	IC50	9830	nM	CHEMBL460576

PubChem BioAssay actives

37 with measured affinity, of 117 total; 34 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
sodium (2R,4S,5R,6R)-5-acetamido-2-[3-(2-benzamidoethylsulfanyl)propoxy]-6-[(1R,2R)-1,2-dihydroxy-3-[(4-phenylbenzoyl)amino]propyl]-4-hydroxyoxane-2-carboxylate	1863566: Inhibition hFc tagged CD22 incubated for 4 hrs by ELISA	ic50	0.0003	uM
disodium;(2R,4S,5R,6R)-5-acetamido-2-[3-[2-[[4-[2-[3-[(2R,4S,5R,6R)-5-acetamido-2-carboxylato-4-hydroxy-6-[(1R,2R)-1,2,3-trihydroxypropyl]oxan-2-yl]oxypropylsulfanyl]ethylcarbamoyl]benzoyl]amino]ethylsulfanyl]propoxy]-6-[(1R,2R)-1,2-dihydroxy-3-[(4-phenylbenzoyl)amino]propyl]-4-hydroxyoxane-2-carboxylate	1863566: Inhibition hFc tagged CD22 incubated for 4 hrs by ELISA	ic50	0.0004	uM
disodium;(2R,4S,5R,6R)-5-acetamido-2-[3-[2-[[4-[2-[3-[(2R,4S,5R,6R)-5-acetamido-2-carboxylato-6-[(1R,2R)-1,2-dihydroxy-3-[(4-phenylbenzoyl)amino]propyl]-4-hydroxyoxan-2-yl]oxypropylsulfanyl]ethylcarbamoyl]benzoyl]amino]ethylsulfanyl]propoxy]-6-[(1R,2R)-1,2-dihydroxy-3-[(4-phenylbenzoyl)amino]propyl]-4-hydroxyoxane-2-carboxylate	1863566: Inhibition hFc tagged CD22 incubated for 4 hrs by ELISA	ic50	0.0004	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[(4-phenylphenyl)methoxy]oxane-2-carboxylic acid	578486: Antagonist activity at human CD22 after 1 hr by competitive ELISA	ic50	0.0700	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-phenylmethoxyoxane-2-carboxylic acid	578486: Antagonist activity at human CD22 after 1 hr by competitive ELISA	ic50	0.1300	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(2-hydroxyphenyl)phenyl]methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	0.2300	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(4-hydroxyphenyl)phenyl]methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	0.2400	uM
sodium (2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-(4-phenyltriazol-1-yl)oxane-2-carboxylate	1705724: Binding affinity to recombinant human CD22d1-3-Fc expressed in 293T cells by surface plasmon resonance assay	kd	0.3350	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(4-hydroxyphenyl)benzoyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	0.4000	uM
sodium (2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-phenylmethoxyoxane-2-carboxylate	1705724: Binding affinity to recombinant human CD22d1-3-Fc expressed in 293T cells by surface plasmon resonance assay	kd	0.4580	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[(4-phenylphenyl)methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	0.4700	uM
sodium (2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[4-(4-phenylphenyl)triazol-1-yl]oxane-2-carboxylate	1705724: Binding affinity to recombinant human CD22d1-3-Fc expressed in 293T cells by surface plasmon resonance assay	kd	0.6200	uM
sodium (2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-2-[(4-ethynylphenyl)methoxy]-4-hydroxy-5-[(2-hydroxyacetyl)amino]oxane-2-carboxylate	1705724: Binding affinity to recombinant human CD22d1-3-Fc expressed in 293T cells by surface plasmon resonance assay	kd	0.6280	uM
sodium (2R,4S,5R,6R)-2-[[4-[1-[2-[2-[2-[2-[5-[(3aR,4R,6aS)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]phenyl]methoxy]-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]oxane-2-carboxylate	1705724: Binding affinity to recombinant human CD22d1-3-Fc expressed in 293T cells by surface plasmon resonance assay	kd	0.7400	uM
sodium (2R,4S,5R,6R)-2-[4-(cyclohexylmethyl)triazol-1-yl]-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]oxane-2-carboxylate	1705724: Binding affinity to recombinant human CD22d1-3-Fc expressed in 293T cells by surface plasmon resonance assay	kd	0.7660	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(4-hydroxyphenyl)phenyl]methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-phenylmethoxyoxane-2-carboxylic acid	578486: Antagonist activity at human CD22 after 1 hr by competitive ELISA	ic50	0.8200	uM
sodium (2R,4S,5R,6R)-2-[4-(cyclohexylmethoxy)triazol-1-yl]-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]oxane-2-carboxylate	1705724: Binding affinity to recombinant human CD22d1-3-Fc expressed in 293T cells by surface plasmon resonance assay	kd	0.8600	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	0.9000	uM
sodium (2R,4S,5R,6R)-2-(4-benzyltriazol-1-yl)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(4-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]oxane-2-carboxylate	1705724: Binding affinity to recombinant human CD22d1-3-Fc expressed in 293T cells by surface plasmon resonance assay	kd	0.9520	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[(2-naphthalen-2-ylacetyl)amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	1.0000	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[(4-phenylbenzoyl)amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	1.1000	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(4-hydroxyphenyl)phenyl]methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[(4-phenylphenyl)methoxy]oxane-2-carboxylic acid	578486: Antagonist activity at human CD22 after 1 hr by competitive ELISA	ic50	1.1200	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(3-hydroxyphenyl)phenyl]methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	1.7300	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(4-methoxyphenyl)phenyl]methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	1.7600	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-(naphthalene-2-carbonylamino)propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	2.6000	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-(4-phenylphenyl)acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	3.7000	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[2-[4-(3-hydroxyphenyl)phenyl]acetyl]amino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	4.3000	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[2-(4-phenylphenyl)ethylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	5.4800	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[4-(4-phenylphenyl)butylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	6.2200	uM
(2R,4S,5R,6R)-6-[(1R,2R)-3-[[4-(3-carboxyphenyl)benzoyl]amino]-1,2-dihydroxypropyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	7.1300	uM
(2R,4S,5R,6R)-6-[(1R,2R)-3-[[4-(3-carboxyphenyl)phenyl]methylamino]-1,2-dihydroxypropyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	7.4800	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[3-(4-hydroxyphenyl)propanoylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	7.6500	uM
(2R,4S,5R,6R)-6-[(1R,2R)-3-[(2,2-diphenylacetyl)amino]-1,2-dihydroxypropyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	8.8500	uM
(2R,4S,5R,6R)-6-[(1R,2R)-1,2-dihydroxy-3-[[4-(4-methylphenyl)phenyl]methylamino]propyl]-4-hydroxy-5-[(2-hydroxyacetyl)amino]-2-[[(2R,3R,4S,5R,6S)-3,4,5-trihydroxy-6-(4-methoxyphenoxy)oxan-2-yl]methoxy]oxane-2-carboxylic acid	389258: Binding affinity to biotinylated human CD22-human IgG1 chimeric protein expressed in mouse J558LST6 cells by flow cytometry	ic50	9.8300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects expression, increases expression	3
Estradiol	affects binding, increases expression	2
Formaldehyde	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
kojic acid	decreases expression	1
terbufos	decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	increases acetylation, increases expression	1
aflatoxin B2	increases methylation	1
bryostatin 1	increases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1

ChEMBL screening assays

16 unique, capped per target: 15 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1169089	Binding	Binding affinity to human SIGLEC2 by saturation transfer difference-titration assay	Synthesis and binding analysis of unique AG2 pentasaccharide to human Siglec-2 using NMR techniques. — Bioorg Med Chem
CHEMBL1686886	Functional	Antagonist activity at human CD22 after 1 hr by competitive ELISA	CD22-antagonists with nanomolar potency: the synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1GD	Abcam Raji CD22 KO	Cancer cell line	Male
CVCL_E6PB	Genomeditech CHO-K1 H_CD22	Spontaneously immortalized cell line	Female
CVCL_F1SV	HyCyte Ramos KO-hCD22	Cancer cell line	Male
CVCL_F1TV	HyCyte THP-1 KO-hCD22	Cancer cell line	Male
CVCL_UE23	293T human CD22	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery