CD33

Summary

CD33 (CD33 molecule, HGNC:1659) is a protein-coding gene on chromosome 19q13.41, encoding Myeloid cell surface antigen CD33 (P20138). Sialic-acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and in maintaining immune cells in a resting state.

Enables protein phosphatase binding activity; protein tyrosine phosphatase activator activity; and sialic acid binding activity. Involved in several processes, including immune response-regulating signaling pathway; negative regulation of cytokine production; and negative regulation of monocyte activation. Located in Golgi apparatus; external side of plasma membrane; and peroxisome.

Source: NCBI Gene 945 — RefSeq curated summary.

At a glance

• GWAS associations: 28
• Clinical variants (ClinVar): 73 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001772

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1659
Approved symbol	CD33
Name	CD33 molecule
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	SIGLEC3, SIGLEC-3, p67, FLJ00391, CD33rSiglec
Ensembl gene	ENSG00000105383
Ensembl biotype	protein_coding
OMIM	159590
Entrez	945

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 2 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000262262, ENST00000391796, ENST00000421133, ENST00000436584, ENST00000598473, ENST00000600557, ENST00000601785, ENST00000850910, ENST00000850911, ENST00000896216, ENST00000921670, ENST00000945453

RefSeq mRNA: 3 — MANE Select: NM_001772 NM_001082618, NM_001177608, NM_001772

CCDS: CCDS33084, CCDS46157, CCDS54299

Canonical transcript exons

ENST00000262262 — 7 exons

Exon	Start	End
ENSE00000954679	51225218	51225598
ENSE00003091543	51239518	51240016
ENSE00003498932	51235595	51235676
ENSE00003520712	51235157	51235253
ENSE00003625145	51225803	51226081
ENSE00003625446	51226309	51226356
ENSE00003845850	51225080	51225155

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 97.58.

FANTOM5 (CAGE): breadth broad, TPM avg 12.1235 / max 394.1960, expressed in 587 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177204	12.0147	586
177205	0.0930	59
177206	0.0158	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.58	gold quality
mononuclear cell	CL:0000842	97.16	gold quality
leukocyte	CL:0000738	97.15	gold quality
granulocyte	CL:0000094	97.13	gold quality
spleen	UBERON:0002106	92.22	gold quality
blood	UBERON:0000178	88.60	gold quality
bone marrow cell	CL:0002092	86.90	gold quality
diaphragm	UBERON:0001103	85.16	gold quality
bone marrow	UBERON:0002371	84.29	gold quality
right coronary artery	UBERON:0001625	83.58	gold quality
upper lobe of left lung	UBERON:0008952	83.11	gold quality
right lung	UBERON:0002167	82.36	gold quality
upper lobe of lung	UBERON:0008948	81.86	gold quality
omental fat pad	UBERON:0010414	81.61	gold quality
bone element	UBERON:0001474	81.56	gold quality
peritoneum	UBERON:0002358	81.54	gold quality
vermiform appendix	UBERON:0001154	81.15	gold quality
right adrenal gland cortex	UBERON:0035827	80.60	gold quality
gall bladder	UBERON:0002110	80.55	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.34	gold quality
right adrenal gland	UBERON:0001233	79.74	gold quality
lymph node	UBERON:0000029	79.00	gold quality
smooth muscle tissue	UBERON:0001135	78.74	gold quality
left coronary artery	UBERON:0001626	78.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.10	gold quality
coronary artery	UBERON:0001621	77.94	gold quality
left adrenal gland	UBERON:0001234	77.86	gold quality
left adrenal gland cortex	UBERON:0035825	77.79	gold quality
olfactory bulb	UBERON:0002264	77.77	gold quality
descending thoracic aorta	UBERON:0002345	77.71	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	24.73
E-ANND-3	yes	10.70
E-MTAB-6678	yes	8.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, HLF, MYC, SP1, SPI1

miRNA regulators (miRDB)

14 targeting CD33, 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-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-374C-3P	98.47	67.93	451
HSA-MIR-3144-3P	98.15	67.34	677
HSA-MIR-6514-3P	97.52	66.50	808
HSA-MIR-4327	97.21	67.71	676
HSA-MIR-6747-5P	96.17	64.99	743
HSA-MIR-324-5P	95.68	65.20	560

Literature-anchored findings (GeneRIF, showing 40)

• Regulation of myeloid cell proliferation and survival by p75/AIRM1 and CD33 surface receptors. (PMID:11774609)
• Sites of serine/threonine phosphorylation by protein kinase C and the effect on its lectin activity (PMID:11964282)
• effectiveness of in vivo ablation of CD33+ cells to treat patients with aacaute myeloid leukemia. (PMID:11970770)
• review of structure, function, expression and clinical application (PMID:12144127)
• Expression of CD33 on CD4(+)CD56(+) lineage-negative cells should not exclude the diagnosis of plasmacytoid dendritic cell leukemia. (PMID:15388576)
• Amount of internalization of CD33 following antibody binding for gemtuzumab ozogamicin induced cytotoxicity suggest novel therapeutic approaches for improvement of clinical outcome of leukemia patients. (PMID:15454492)
• incubation of leukemia cells with anti-CD33 mAb and anticancer agents leads to additive antiproliferative effects and enhanced cytotoxicity. (PMID:15676214)
• Expression is rarely decreased in association with chromic myelogenous leukemia. (PMID:17662271)
• The results demonstrate that phosphorylation-dependent ubiquitylation of the immunoreceptor tyrosine-based inhibitory motif (ITIM) of CD33 regulates cell surface expression and internalization of this immunoreceptor. (PMID:18062779)
• CD13 was expressed in 73% of acute myeloid leukemia patients, CD15 was expressed in 43% of patients, CD33 was expressed in 64% of patients, and CD34 was expressed in 66% of patients. (PMID:18085638)
• The species-specific differences in the expression expression of Siglecs in SIV infection was studied. (PMID:18331725)
• determined the association of the genotype of each of the CD33 single nucleotide polymorphisms with changes in MRD during treatment with GO for AML (PMID:18615103)
• the CD33+ CD14- phenotype is characteristic of multinuclear osteoclast-like cells in giant cell tumor of bone (PMID:18767926)
• CD13 and/or CD33 are sensitive but not entirely specific markers of anaplastic lymphoma kinase anaplastic large cell lymphomas and should not be misinterpreted as indicating myeloid sarcoma. (PMID:18794057)
• IL-6 can reverse the expression level of CD33 by up-regulating MYC followed by the down-regulation of CEBPA expression (PMID:19259613)
• Findings suggest the important role of the CD11b+/CD14/CD15+/CD33+ MDSCs in mediating immunosuppression in NSCLC. (PMID:19572148)
• Specific induction of CD33 expression by E2A-HLF is associated with acute Lymphoblastic Leukemia. (PMID:20147975)
• Results indicate that anti-CD33 chimeric receptors strongly enhance anti-leukemic cytokine-induced killer cell functions. (PMID:20713459)
• Data suggest that CD19 and CD33 are present on the surface of the leukemic cell lines such that they can be connected by a single sctb molecule. (PMID:21081841)
• expression and localization of the two CD33 isoforms on several hematopoietic cell lines (PMID:21278227)
• Studies indicate that CD33 is expressed on hepatocytes, which makes them susceptible for targeted CD33 chemotherapy. (PMID:21329979)
• 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)
• found independent evidence for association for Alzheimer’s disease susceptibility loci at EPHA1, CD33 and CD2AP (PMID:21460840)
• Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. (PMID:21460841)
• CD33 is expressed abundantly on immature CD34(+)/CD38(-) stem cells and may serve as a stem cell target in chronic myeloid leukemia. (PMID:21993666)
• results support the view that single-nucleotide polymorphisms in GOLPH2 and in near gene 5’ region of CD33 are significantly associated with sporadic Alzheimer’s disease in the north Chinese Han population. (PMID:22167654)
• data revealed the allele (T) of the rs3865444 polymorphism of the CD33 gene and the allele (C) of the rs610932 polymorphism of the MS4A6A gene may contribute to Alzheimer’s disease risk in the Chinese Han population (PMID:22382309)
• Our data suggest that genetic variations in CD33 could impact clinical outcome of GO-based therapy in pediatric acute myeloid leukemia . (PMID:23444229)
• The minor allele of the CD33 SNP rs3865444, which confers protection against Alzheimer disease, was associated with reductions in both CD33 expression and insoluble amyloid beta 42 (Abeta42) levels in AD brain. (PMID:23623698)
• This study showed that the rs3865444(C) risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P(joint) = 1.3 x 10(-13)) of young and older individuals. (PMID:23708142)
• these results suggest a novel model wherein single nucleotide polymorphism-modulated RNA splicing modulates CD33 function and, thereby, Alzheimer disease risk. (PMID:23946390)
• This review discusses the recent epidemiological findings of CD33 that relate to Alzheimer’s disease and the pathogenic roles played by CD33 in this disease. (PMID:23982747)
• The rs3865444(C) risk allele is strongly associated with greater expression of CD33 exon 2 and increased Alzheimer’s disease susceptibility. [Meta-analysis] (PMID:24381305)
• Case Report: indolent T-lymphoblastic proliferation with disseminated multinodal involvement with partial CD33 expression on T cells. (PMID:24618611)
• Data suggest that the CD16xCD33 bispecific killer cell engager (BiKE) functions against both CD33(+) myelodysplastic syndromes (MDS) and myeloid-derived suppressor cells (MDSCs) targets and may be therapeutically beneficial for MDS patients. (PMID:24652987)
• Dasatinib enhances migration of monocyte-derived dendritic cells by reducing phosphorylation of inhibitory immune receptors Siglec-9 and Siglec-3. (PMID:24882272)
• 87.8% of AMLs express CD33. Additionally, 9.4% of AMLs express CD123 without concomitant CD33 expression. (PMID:24927407)
• This study showed that CD13 and CD33 expression associated with poor prognosis in patients with MM implicating the need of analysis of these markers in MM diagnosis. (PMID:24991573)
• Data indicate that glycosylphosphatidylinositol-anchored glycoprotein CD14 controls Toll-like receptor-4 (TLR4)-mediated signaling through the ligation with sialic acid-binding lectin 3 (CD33). (PMID:25059667)
• the CD33 rs3865444 polymorphism is associated with Alzheimer’s disease susceptibility in Chinese, European, and North American populations. (PMID:25186233)

Cross-species orthologs

0 orthologs

Paralogs (16): CD22 (ENSG00000012124), SIGLEC1 (ENSG00000088827), SIGLEC8 (ENSG00000105366), 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

Myeloid cell surface antigen CD33 — P20138 (reviewed: P20138)

Alternative names: Sialic acid-binding Ig-like lectin 3, gp67

All UniProt accessions (4): P20138, A0A173G4N9, B4DF51, Q546G0

UniProt curated annotations — full annotation on UniProt →

Function. Sialic-acid-binding immunoglobulin-like lectin (Siglec) that plays a role in mediating cell-cell interactions and in maintaining immune cells in a resting state. Preferentially recognizes and binds alpha-2,3- and more avidly alpha-2,6-linked sialic acid-bearing glycans. Upon engagement of ligands such as C1q or syalylated glycoproteins, two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) located in CD33 cytoplasmic tail are phosphorylated by Src-like kinases such as LCK. These phosphorylations provide docking sites for the recruitment and activation of protein-tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2. In turn, these phosphatases regulate downstream pathways through dephosphorylation of signaling molecules. One of the repressive effect of CD33 on monocyte activation requires phosphoinositide 3-kinase/PI3K.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with PTPN6/SHP-1 and PTPN11/SHP-2 upon phosphorylation. Interacts with C1QA (via C-terminus); this interaction activates CD33 inhibitory motifs.

Subcellular location. Cell membrane Peroxisome.

Tissue specificity. Monocytic/myeloid lineage cells. In the brain, CD33 is mainly expressed on microglial cells.

Post-translational modifications. Glycosylated. Glycosylation at Asn-100 is critical for regulating ligand recognition. Phosphorylation of Tyr-340 is involved in binding to PTPN6 and PTPN11. Phosphorylation of Tyr-358 is involved in binding to PTPN6. LCK phosphorylates Tyr-340 efficiently and Tyr-358 to a lesser extent.

Domain organisation. Contains 2 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.

Miscellaneous. Mostly detected on NKL and myeloid cell lines but poorly expressed on B-cell lines and T-lymphocytes.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P20138-1	CD33M	yes
P20138-2	3
P20138-3	CD33m

RefSeq proteins (3): NP_001076087, NP_001171079, NP_001763* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051036	SIGLEC	Family

Pfam: PF00047, PF07686

UniProt features (64 total): strand 18, sequence variant 11, glycosylation site 5, mutagenesis site 5, helix 4, disulfide bond 3, binding site 2, modified residue 2, topological domain 2, splice variant 2, turn 2, domain 2, short sequence motif 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6D4A	X-RAY DIFFRACTION	1.75
6D48	X-RAY DIFFRACTION	1.78
6D49	X-RAY DIFFRACTION	1.8
7AW6	X-RAY DIFFRACTION	1.95
5IHB	X-RAY DIFFRACTION	2.24
5J0B	X-RAY DIFFRACTION	2.48
5J06	X-RAY DIFFRACTION	2.66
6TL8	X-RAY DIFFRACTION	2.8
9VL2	X-RAY DIFFRACTION	3.18
9BET	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20138-F1	78.30	0.57

Functional residue map

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

Ligand- & substrate-binding residues (2): 119; 154

Post-translational modifications (2): 340, 358

Disulfide bonds (3): 36–169, 41–101, 163–212

Glycosylation sites (5): 100, 113, 160, 209, 230

Mutagenesis-validated functional residues (5):

Position	Phenotype
100	significant loss of binding to peripheral blood granulocytes.
340	abolishes binding to ptpn6 and ptpn11. increases binding of red blood cells.
340	complete loss of phosphorylation by lck.
358	reduces binding to ptpn6.
358	more than 50% loss of phosphorylation by lck.

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-6798695	Neutrophil degranulation
R-HSA-9918485	Dengue Virus Attachment and Entry
R-HSA-1280218	Adaptive Immune System
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 233 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, MODULE_16, GOBP_INTERLEUKIN_1_PRODUCTION, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_CELL_ADHESION, MODULE_118, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (12): immune response-inhibiting signal transduction (GO:0002765), cell adhesion (GO:0007155), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), negative regulation of cell population proliferation (GO:0008285), negative regulation of interleukin-1 beta production (GO:0032691), negative regulation of interleukin-8 production (GO:0032717), negative regulation of tumor necrosis factor production (GO:0032720), Fc-gamma receptor signaling pathway (GO:0038094), positive regulation of protein secretion (GO:0050714), cell-cell adhesion (GO:0098609), negative regulation of monocyte activation (GO:0150102)

GO Molecular Function (6): protein tyrosine phosphatase activator activity (GO:0008160), protein phosphatase binding (GO:0019903), carbohydrate binding (GO:0030246), sialic acid binding (GO:0033691), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (8): peroxisome (GO:0005777), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), specific granule membrane (GO:0035579), tertiary granule membrane (GO:0070821), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Immune System	2
Adaptive Immune System	1
Innate Immune System	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cell communication	2
signaling	2
binding	2
cellular anatomical structure	2
secretory granule membrane	2
immune response-regulating signaling pathway	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
negative regulation of interleukin-1 production	1
negative regulation of cytokine production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
Fc receptor signaling pathway	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
cell adhesion	1
negative regulation of leukocyte activation	1
monocyte activation	1
protein tyrosine phosphatase activity	1
protein phosphatase activator activity	1
phosphatase binding	1
carboxylic acid binding	1
carbohydrate derivative binding	1
molecular transducer activity	1
microbody	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1

Protein interactions and networks

STRING

2618 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD33	FCGR3A	P08637	973
CD33	FCGR3B	O75015	959
CD33	TREM2	Q9NZC2	953
CD33	ANPEP	P15144	952
CD33	CD34	P28906	951
CD33	KIT	P10721	897
CD33	FUT4	P22083	879
CD33	TYROBP	O43914	873
CD33	CD19	P15391	871
CD33	CD7	P09564	870
CD33	NCAM1	P13591	852
CD33	CD4	P01730	843
CD33	ITGAM	P11215	814
CD33	IL3RA	P26951	813
CD33	CD38	P28907	810

IntAct

106 interactions, top by confidence:

A	B	Type	Score
CD33	PTPN6	psi-mi:“MI:0915”(physical association)	0.820
PTPN6	CD33	psi-mi:“MI:0914”(association)	0.820
CD33	KRT31	psi-mi:“MI:0915”(physical association)	0.720
KRT31	CD33	psi-mi:“MI:0915”(physical association)	0.720
PTPN11	CD33	psi-mi:“MI:0914”(association)	0.680
PTPN11	CD33	psi-mi:“MI:0915”(physical association)	0.680
CD33	PEX19	psi-mi:“MI:0914”(association)	0.640
CD33	S100A9	psi-mi:“MI:0915”(physical association)	0.590
CD33	S100A9	psi-mi:“MI:2364”(proximity)	0.590
CD33	S100A9	psi-mi:“MI:0403”(colocalization)	0.590
KRT40	CD33	psi-mi:“MI:0915”(physical association)	0.560
CD33	KRT40	psi-mi:“MI:0915”(physical association)	0.560
TTMP	CD33	psi-mi:“MI:0915”(physical association)	0.560
CD33	KRT35	psi-mi:“MI:0915”(physical association)	0.560
CD33	GIMAP5	psi-mi:“MI:0915”(physical association)	0.560
CD33	EMD	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (38): KRT31 (Two-hybrid), KRT40 (Two-hybrid), SLC39A11 (Affinity Capture-MS), PEX19 (Affinity Capture-MS), COMMD3 (Affinity Capture-MS), SAAL1 (Affinity Capture-MS), CALM3 (Affinity Capture-MS), PEX19 (Affinity Capture-MS), SLC39A11 (Affinity Capture-MS), COMMD3 (Affinity Capture-MS), CD33 (Two-hybrid), CD33 (Two-hybrid), CD33 (Two-hybrid), CD33 (Two-hybrid), CD33 (Two-hybrid)

ESM2 similar proteins: A0A0K2S4Q6, A2A7V7, A6NI73, A8K4G0, O43699, O75019, O75022, O75023, O75871, O76036, P0C191, P20138, P24071, P40198, P59901, P80943, Q08708, Q13410, Q28110, Q3U497, Q496F6, Q64JA4, Q6GTX8, Q6ISS4, Q6PI73, Q6UXZ3, Q7TSN2, Q863H2, Q8C567, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8NHJ6, Q8NHL6, Q8VBT3, Q8VCH2, Q95JB9

Diamond homologs: A6NMB1, D3YXG0, O15389, O43699, O60469, P20138, P35329, Q08ET2, Q63994, Q64JA4, Q80ZE3, Q8N441, Q8VHZ8, Q91Y57, Q920G3, Q95LH0, Q96LC7, Q96PQ1, Q96RL6, Q96RW7, Q9ERC8, Q9NYZ4, Q9Y286, Q9Y336, Q460M5, Q6ZMC9, Q80TG9, Q8N7X8, Q9BE71, Q9ULH4, A1KZ92, A2AJ76, A2ASS6, P98160, Q28173, Q62151, Q63495, Q8BQC3, Q8NDA2, Q9QZS7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
blinatumomab	“down-regulates activity”	CD33	binding
“gemtuzumab ozogamicin”	“down-regulates activity”	CD33	binding
LCK	up-regulates	CD33	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	7	17.9×	2e-05
Adaptive Immune System	9	7.9×	9e-05
Neutrophil degranulation	9	6.1×	4e-04
Innate Immune System	8	6.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell adhesion	9	8.0×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	11
Benign	19

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2424337	NC_000019.9:g.(?51727962)(51890697_?)del	Pathogenic

SpliceAI

1033 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51226079:CCT:C	donor_gain	1.0000
19:51226080:CT:C	donor_gain	1.0000
19:51226080:CTGT:C	donor_loss	1.0000
19:51226081:TG:T	donor_loss	1.0000
19:51226082:G:GG	donor_gain	1.0000
19:51226082:GTA:G	donor_loss	1.0000
19:51226083:TAAG:T	donor_loss	1.0000
19:51239516:A:G	acceptor_gain	1.0000
19:51226077:CACCT:C	donor_gain	0.9900
19:51226078:ACCT:A	donor_gain	0.9900
19:51239513:A:AG	acceptor_gain	0.9900
19:51239514:T:G	acceptor_gain	0.9900
19:51239515:A:AG	acceptor_gain	0.9900
19:51239517:G:GG	acceptor_gain	0.9900
19:51225548:G:GT	donor_gain	0.9800
19:51225800:TAGAC:T	acceptor_loss	0.9800
19:51225801:A:AG	acceptor_gain	0.9800
19:51225801:A:AT	acceptor_loss	0.9800
19:51225802:G:GG	acceptor_gain	0.9800
19:51225802:GACTT:G	acceptor_gain	0.9800
19:51226084:AAGT:A	donor_loss	0.9800
19:51235254:G:GG	donor_gain	0.9800
19:51225153:CAG:C	donor_loss	0.9700
19:51225154:AGG:A	donor_loss	0.9700
19:51225155:GG:G	donor_loss	0.9700
19:51225156:G:A	donor_loss	0.9700
19:51225157:T:A	donor_loss	0.9700
19:51225548:G:T	donor_gain	0.9700
19:51225564:T:G	donor_gain	0.9700
19:51225631:G:T	donor_gain	0.9700

AlphaMissense

2347 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51225448:T:C	F90L	0.980
19:51225450:C:A	F90L	0.980
19:51225450:C:G	F90L	0.980
19:51225361:T:C	F61L	0.972
19:51225363:C:A	F61L	0.972
19:51225363:C:G	F61L	0.972
19:51225360:G:C	W60C	0.969
19:51225360:G:T	W60C	0.969
19:51225449:T:G	F90C	0.963
19:51225919:T:A	W179R	0.961
19:51225919:T:C	W179R	0.961
19:51225358:T:A	W60R	0.959
19:51225358:T:C	W60R	0.959
19:51225449:T:C	F90S	0.958
19:51225921:G:C	W179C	0.956
19:51225921:G:T	W179C	0.956
19:51225536:G:C	R119P	0.953
19:51225481:T:A	C101S	0.949
19:51225482:G:C	C101S	0.949
19:51225533:T:C	F118S	0.947
19:51225400:G:C	A74P	0.945
19:51225515:A:C	D112A	0.941
19:51225871:T:C	C163R	0.940
19:51226018:T:C	C212R	0.937
19:51225362:T:C	F61S	0.935
19:51225913:T:C	F177L	0.934
19:51225915:C:A	F177L	0.934
19:51225915:C:G	F177L	0.934
19:51226013:T:C	L210P	0.931
19:51226018:T:A	C212S	0.931

dbSNP variants (sampled 300 via entrez): RS1000041874 (19:51233189 T>C), RS1000106922 (19:51216929 A>G), RS1000171072 (19:51238057 G>T), RS1000293701 (19:51223470 A>G), RS1000368114 (19:51231828 G>A), RS1000554517 (19:51226089 C>T), RS1000589489 (19:51210719 C>T), RS1000757817 (19:51237673 G>A,T), RS1000994690 (19:51234233 C>G,T), RS1000998024 (19:51217931 A>C,G), RS1001224039 (19:51215844 C>T), RS1001232835 (19:51239912 T>C), RS1001504137 (19:51227461 T>C), RS1001519362 (19:51211456 C>G,T), RS1001588057 (19:51211744 G>A,T)

Disease associations

OMIM: gene MIM:159590 | disease phenotypes: MIM:231680

GenCC curated gene-disease

Mondo (1): multiple acyl-CoA dehydrogenase deficiency (MONDO:0009282)

Orphanet (1): Multiple acyl-CoA dehydrogenase deficiency (Orphanet:26791)

HPO phenotypes

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

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000255_2	Alzheimer’s disease	6.000000e-06
GCST001026_8	Alzheimer’s disease (late onset)	2.000000e-09
GCST002245_1	Alzheimer’s disease (late onset)	3.000000e-06
GCST002818_2	HIV-1 susceptibility	5.000000e-06
GCST004603_278	Platelet count	7.000000e-09
GCST004607_23	Plateletcrit	1.000000e-10
GCST004610_96	White blood cell count	2.000000e-10
GCST005549_3	Alzheimer’s disease (late onset)	2.000000e-06
GCST006585_528	Blood protein levels	0.000000e+00
GCST007319_6	Alzheimer’s disease (late onset)	4.000000e-08
GCST007320_73	Alzheimer’s disease or family history of Alzheimer’s disease	6.000000e-09
GCST008922_18	Triacylglyceride levels	9.000000e-09
GCST008922_4	Triacylglyceride levels	3.000000e-08
GCST008922_9	Triacylglyceride levels	5.000000e-08
GCST009019_5	Alzheimer’s disease	7.000000e-06
GCST009021_8	Alzheimer’s disease	4.000000e-08
GCST009268_6	Dental caries (decayed, missing and filled tooth surfaces)	3.000000e-06
GCST90002379_156	Basophil count	2.000000e-12
GCST90002381_354	Eosinophil count	8.000000e-13
GCST90002386_216	High light scatter reticulocyte percentage of red cells	4.000000e-10
GCST90002388_379	Lymphocyte count	1.000000e-24
GCST90002393_668	Monocyte count	9.000000e-15
GCST90002398_92	Neutrophil count	5.000000e-12
GCST90002400_94	Plateletcrit	1.000000e-26
GCST90002402_571	Platelet count	2.000000e-23
GCST90002405_433	Reticulocyte count	3.000000e-10
GCST90002406_536	Reticulocyte fraction of red cells	7.000000e-13
GCST90002407_635	White blood cell count	7.000000e-30

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:1001870	late-onset Alzheimers disease
EFO:0009268	family history of Alzheimer’s disease
EFO:0004530	triglyceride measurement
EFO:0005090	basophil count
EFO:0004842	eosinophil count
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1842 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs35112940	Efficacy	3	gemtuzumab ozogamicin	Leukemia;Myeloid;Acute

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1803254	CD33		0.00	0
rs12459419	CD33		0.00	0
rs35112940	CD33	3	2.00	1	gemtuzumab ozogamicin

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
lintuzumab	Binding	10.0	pKd
vadastuximab talirine	Binding	9.3	pKd

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
tanshinone	decreases expression	1
diallyl disulfide	decreases expression, affects reaction	1
tesmilifene	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Aripiprazole	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Carcinogens	decreases expression	1
Chlorpyrifos	decreases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Mutagens	decreases expression	1
Ozone	affects cotreatment, increases expression	1
Theophylline	decreases expression, affects cotreatment	1
Tretinoin	increases reaction, increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

27 cell lines: 24 induced pluripotent stem cell, 1 spontaneously immortalized cell line, 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C6QH	LBi001-A	Induced pluripotent stem cell	Female
CVCL_C6QI	LBi001-B	Induced pluripotent stem cell	Female
CVCL_C6QJ	LBi002-A	Induced pluripotent stem cell	Female
CVCL_C6QK	LBi002-B	Induced pluripotent stem cell	Female
CVCL_C6QL	LBi003-A	Induced pluripotent stem cell	Male
CVCL_C6QM	LBi003-B	Induced pluripotent stem cell	Male
CVCL_C6QN	LBi004-A	Induced pluripotent stem cell	Female
CVCL_C6QP	LBi004-B	Induced pluripotent stem cell	Female
CVCL_C6QQ	LBi005-A	Induced pluripotent stem cell	Male
CVCL_C6QR	LBi005-B	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
NCT05892692	Not specified	COMPLETED	Nexus of Risk: Sexual Assault, Alcohol Use, and Risky Sex Among College Women
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan