CD52

Summary

CD52 (CD52 molecule, HGNC:1804) is a protein-coding gene on chromosome 1p36.11, encoding CAMPATH-1 antigen (P31358). May play a role in carrying and orienting carbohydrate, as well as having a more specific role.

Involved in positive regulation of cytosolic calcium ion concentration. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in sperm midpiece.

Source: NCBI Gene 1043 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 16 total
• Druggable target: yes
• MANE Select transcript: NM_001803

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1804
Approved symbol	CD52
Name	CD52 molecule
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	HE5, EDDM5
Ensembl gene	ENSG00000169442
Ensembl biotype	protein_coding
OMIM	114280
Entrez	1043

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000374213, ENST00000470468, ENST00000492808

RefSeq mRNA: 1 — MANE Select: NM_001803 NM_001803

CCDS: CCDS30647

Canonical transcript exons

ENST00000374213 — 2 exons

Exon	Start	End
ENSE00001231714	26320171	26320523
ENSE00001878102	26317958	26318071

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 100.00.

FANTOM5 (CAGE): breadth broad, TPM avg 203.0901 / max 13755.5005, expressed in 747 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1599	187.1837	727
1598	15.9064	534

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	100.00	gold quality
cauda epididymis	UBERON:0004360	99.89	gold quality
granulocyte	CL:0000094	99.87	gold quality
leukocyte	CL:0000738	99.63	gold quality
monocyte	CL:0000576	99.62	gold quality
mononuclear cell	CL:0000842	99.62	gold quality
spleen	UBERON:0002106	99.52	gold quality
thymus	UBERON:0002370	99.20	gold quality
right lung	UBERON:0002167	98.98	gold quality
lymph node	UBERON:0000029	98.80	gold quality
vermiform appendix	UBERON:0001154	98.79	gold quality
blood	UBERON:0000178	98.72	gold quality
upper lobe of left lung	UBERON:0008952	98.48	gold quality
upper lobe of lung	UBERON:0008948	98.21	gold quality
gall bladder	UBERON:0002110	97.79	gold quality
lower lobe of lung	UBERON:0008949	97.79	gold quality
bone marrow	UBERON:0002371	97.66	gold quality
superficial temporal artery	UBERON:0001614	97.62	gold quality
rectum	UBERON:0001052	97.35	gold quality
bone marrow cell	CL:0002092	96.43	gold quality
trabecular bone tissue	UBERON:0002483	96.28	gold quality
caecum	UBERON:0001153	96.07	gold quality
epithelium of nasopharynx	UBERON:0001951	95.54	gold quality
mucosa of transverse colon	UBERON:0004991	95.48	gold quality
lung	UBERON:0002048	95.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.16	gold quality
adult organism	UBERON:0007023	94.53	gold quality
small intestine	UBERON:0002108	92.64	gold quality
periodontal ligament	UBERON:0008266	91.89	gold quality
smooth muscle tissue	UBERON:0001135	91.65	gold quality

Single-cell (SCXA)

Detected in 57 experiment(s), a significant marker in 46.

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	3831.98
E-MTAB-7606	yes	3765.60
E-HCAD-36	yes	3653.91
E-HCAD-4	yes	3429.35
E-MTAB-7407	yes	3154.53
E-MTAB-6701	yes	3041.92
E-MTAB-9906	yes	2997.65
E-GEOD-111727	yes	2784.70
E-HCAD-15	yes	2741.45
E-HCAD-8	yes	2724.25
E-MTAB-8410	yes	2630.46
E-MTAB-8221	yes	2559.99
E-CURD-79	yes	2415.74
E-HCAD-10	yes	2147.98
E-MTAB-8530	yes	2137.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NKX2-2, SATB1

miRNA regulators (miRDB)

7 targeting CD52, 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-6887-3P	99.66	67.83	1778
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-6859-3P	97.26	64.69	428
HSA-MIR-6798-3P	94.55	68.78	325

Literature-anchored findings (GeneRIF, showing 23)

• A review on CD52 expression and function (PMID:11257744)
• Review article on CD52 structure and function. (PMID:11860230)
• HE5(CD52) mRNA and protein, expressed in epithelial cells of the distal epididymis, were not affected by the obstruction of the vas deferens. (PMID:14662784)
• The relationship between this differential insertion and differences in glycosylation of rat and human CD52 is discussed. (PMID:16266689)
• CD52 is widely expressed on human mast cells (MCs) and Waldenstrom’s Macroglobulinemia bone marrow lymphoplasmacytic cells and provide the preclinical rationale for the use of alemtuzumab in the treatment of WM and possibly other MC-related disorders. (PMID:16796779)
• In this study, we identified the antigen of 4C8 mAb as CD52. CD52 is a costimulatory molecule for induction of CD4-positive T cells. (PMID:16797237)
• In contrast with CLL, the variable expression of CD52 among other hematologic malignancies suggests that target validation on a case-by-case basis will likely be necessary to guide the rational analysis of CAMPATH therapy. (PMID:17145843)
• Our data demonstrate differences in the intensity of the CD52 antigen expression between B-lymphocytes and tumor lymphocytes of B-CLL patients, and between B-CLL and SLL tumor cells. CD52 antigen is expressed at low level on CD34(+) cells. (PMID:17428002)
• The semenogelin-CD52 soluble form is a direct consequence of the liquefaction process in human semen. (PMID:17624925)
• We first showed the expression of CD52 in human cumulus cells. CD52 has some functional roles around fertilization in females as well as in males. (PMID:18647288)
• Clonal large granular lymphocytes exhibited decreased CD52 expression post-therapy in patients refractory to treatment. (PMID:19794084)
• Our bioinformatics findings suggest that CD52 polymorphism may affect the efficiency of GPI anchor formation and thus may indirectly alter the response to anti-CD52 agents like alemtuzumabin renal transplantation. (PMID:20349607)
• CT60 single-nucleotide polymorphism of CTLA4 is a surrogate marker for donor lymphocyte infusion outcome after allogeneic cell transplantation for acute leukemia (PMID:21552305)
• carbohydrate moiety of sperm protein interferes with the complement system via binding to C1q (PMID:22386526)
• A molecular and computational diagnostic approach identifies FOXP3, ICOS, CD52 and CASP1 as the most informative biomarkers in acute graft-versus-host disease. (PMID:22491736)
• CD52 is a novel prognostic NSC marker and a potential NSC target in a subset of patients with MDS and AML, which may have clinical implications and may explain clinical effects produced by alemtuzumab in these patients. (PMID:24799522)
• This polyclonal mutational landscape in the PIGA gene was also found in CD52(-) T cells present. (PMID:29427418)
• soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR. (PMID:29997173)
• Mutations in PIGA cause a CD52-/GPI-anchor-deficient phenotype complicating alemtuzumab treatment in T-cell prolymphocytic leukemia. (PMID:32875608)
• CD52 Is Elevated on B cells of SLE Patients and Regulates B Cell Function. (PMID:33658999)
• High expression of CD52 in adipocytes: a potential therapeutic target for obesity with type 2 diabetes. (PMID:33705353)
• Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia. (PMID:37314354)
• CD52 mRNA expression predicts prognosis and response to immune checkpoint blockade in melanoma. (PMID:37975535)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd52	ENSMUSG00000000682
rattus_norvegicus	Cd52	ENSRNOG00000015403

Protein

Protein identifiers

CAMPATH-1 antigen — P31358 (reviewed: P31358)

Alternative names: CDw52, Cambridge pathology 1 antigen, Epididymal secretory protein E5, Human epididymis-specific protein 5

All UniProt accessions (2): P31358, V9HWN9

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in carrying and orienting carbohydrate, as well as having a more specific role.

Subcellular location. Cell membrane.

RefSeq proteins (1): NP_001794* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026643	CAMPATH-1	Family

Pfam: PF15116

UniProt features (8 total): glycosylation site 2, sequence variant 2, signal peptide 1, peptide 1, propeptide 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6OBD	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31358-F1	68.22	0.00

Antibody-complex structures (SAbDab): 1 — 6OBD

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 (1): 36

Glycosylation sites (2): 27, 40

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 259 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, MODULE_45, GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_DN, BOYLAN_MULTIPLE_MYELOMA_D_DN, FINAK_BREAST_CANCER_SDPP_SIGNATURE, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOBP_RESPIRATORY_BURST, HAHTOLA_CTCL_PATHOGENESIS, BROWN_MYELOID_CELL_DEVELOPMENT_UP, SANSOM_APC_TARGETS_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, KANG_IMMORTALIZED_BY_TERT_DN, VALK_AML_CLUSTER_15, MODULE_60

GO Biological Process (2): positive regulation of cytosolic calcium ion concentration (GO:0007204), respiratory burst (GO:0045730)

GO Molecular Function (0):

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), sperm midpiece (GO:0097225), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
regulation of biological quality	1
metabolic process	1
cell periphery	1
sperm flagellum	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD52	SIGLEC10	Q96LC7	874
CD52	CD2	P06729	701
CD52	CD19	P15391	662
CD52	CD22	P20273	660
CD52	CD48	P09326	629
CD52	IL10	P22301	625
CD52	IL2RA	P01589	623
CD52	CD4	P01730	622
CD52	CD27	P26842	603
CD52	TNFRSF8	P28908	598
CD52	CD8A	P01732	598
CD52	IL7R	P16871	581
CD52	CD5	P06127	580
CD52	CD33	P20138	576
CD52	CD1B	P29016	576

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CD52	SIGLEC10	psi-mi:“MI:0407”(direct interaction)	0.610
CD52	SIGLEC10	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (6): CD52 (Two-hybrid), CD52 (Two-hybrid), CD52 (Two-hybrid), CD52 (Two-hybrid), CD52 (Affinity Capture-RNA), CD52 (Affinity Capture-Western)

ESM2 similar proteins: A0A0K8RG61, A0A0N7CSQ4, A0A144LVM3, A0A6G9KHD1, A0A6G9KIT6, A0A6M3Z541, A1ZB62, A1ZB63, B1NWT4, C0HJQ5, C0HLG4, D2Y168, D2Y2R4, E4VP43, I0B6F2, I6R1R9, P01076, P0C636, P0CC12, P0CY86, P0DJ33, P0DJ34, P0DQB4, P0DQB5, P0DQB8, P0DSJ8, P0DSJ9, P0DSK1, P0DTX5, P0DUS1, P0DXW7, P0DXW8, P0DXZ5, P0DY25, P31358, P86271, P86400, Q28896, Q3YEH0, Q64389

Diamond homologs: P31358, P32763, Q28896, Q64389

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SATB1	“up-regulates quantity by expression”	CD52	“transcriptional regulation”
alemtuzumab	“down-regulates activity”	CD52	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

179 predictions. Top by Δscore:

Variant	Effect	Δscore
1:26318069:CAG:C	donor_gain	0.9900
1:26318072:G:GA	donor_loss	0.9900
1:26318073:T:G	donor_loss	0.9900
1:26318771:G:GT	donor_gain	0.9900
1:26318772:A:T	donor_gain	0.9900
1:26320165:CTACA:C	acceptor_loss	0.9900
1:26320166:TACA:T	acceptor_loss	0.9900
1:26320167:ACAGA:A	acceptor_loss	0.9900
1:26320168:CAG:C	acceptor_loss	0.9900
1:26320169:A:AG	acceptor_gain	0.9900
1:26320170:G:GG	acceptor_gain	0.9900
1:26318763:GCAT:G	donor_gain	0.9800
1:26320170:GATAC:G	acceptor_gain	0.9800
1:26318067:TAC:T	donor_gain	0.9700
1:26318068:ACA:A	donor_gain	0.9700
1:26320170:GAT:G	acceptor_gain	0.9700
1:26318072:G:GG	donor_gain	0.9600
1:26318766:T:TG	donor_gain	0.9500
1:26320170:GA:G	acceptor_gain	0.9500
1:26320170:GATA:G	acceptor_gain	0.9500
1:26318919:G:T	donor_gain	0.9400
1:26318630:T:TA	donor_gain	0.9200
1:26318631:A:AA	donor_gain	0.9200
1:26318617:G:GT	donor_gain	0.9100
1:26318923:C:G	donor_gain	0.9100
1:26318652:G:T	donor_gain	0.9000
1:26318721:C:G	donor_gain	0.8900
1:26318919:G:GT	donor_gain	0.8600
1:26320167:A:AG	acceptor_gain	0.8500
1:26318944:G:GT	donor_gain	0.8400

AlphaMissense

404 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:26318051:A:C	S12R	0.988
1:26318053:C:A	S12R	0.988
1:26318053:C:G	S12R	0.988
1:26318055:T:G	L13R	0.850
1:26318061:T:A	V15D	0.841
1:26318058:T:G	L14R	0.840
1:26318055:T:C	L13P	0.828
1:26320277:T:A	I54K	0.821
1:26318055:T:A	L13H	0.789
1:26320268:C:A	A51D	0.783
1:26318027:T:C	F4L	0.774
1:26318029:C:A	F4L	0.774
1:26318029:C:G	F4L	0.774
1:26320277:T:G	I54R	0.765
1:26320172:T:A	I19K	0.759
1:26320297:A:C	S61R	0.755
1:26320299:T:A	S61R	0.755
1:26320299:T:G	S61R	0.755
1:26318040:T:G	L8R	0.752
1:26320288:T:C	F58L	0.746
1:26320290:C:A	F58L	0.746
1:26320290:C:G	F58L	0.746
1:26318052:G:A	S12N	0.725
1:26318058:T:A	L14Q	0.703
1:26320265:T:A	V50E	0.701
1:26320172:T:G	I19R	0.699
1:26320256:T:G	L47R	0.685
1:26318043:T:G	L9R	0.681
1:26320286:T:C	L57P	0.666
1:26320274:C:A	A53D	0.664

dbSNP variants (sampled 300 via entrez): RS1002242524 (1:26316375 G>C), RS1002944347 (1:26317123 C>G), RS1002994005 (1:26317349 G>A,C), RS1003278228 (1:26318487 G>C), RS1004241996 (1:26319818 C>G,T), RS1005275002 (1:26319026 T>G), RS1006274798 (1:26317403 C>T), RS1008898586 (1:26320491 C>A,G), RS1008969366 (1:26317085 C>A), RS1009138392 (1:26316217 C>T), RS1009506057 (1:26319265 A>T), RS1009886647 (1:26319065 T>C), RS1010508694 (1:26317793 C>G), RS1011379474 (1:26316725 A>G), RS1011517218 (1:26316334 C>T)

Disease associations

OMIM: gene MIM:114280 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004609_172	Monocyte percentage of white cells	7.000000e-16
GCST90002381_569	Eosinophil count	7.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0004842	eosinophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1912 (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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects cotreatment, increases expression	5
Arsenic Trioxide	affects cotreatment, decreases expression, increases expression	4
Air Pollutants	increases expression, decreases expression, affects expression, increases abundance	3
perfluorooctanoic acid	decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Fluorouracil	affects expression, affects reaction, decreases expression	2
Nickel	increases expression	2
Valproic Acid	increases expression, increases methylation	2
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
pentanal	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Vorinostat	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects expression	1
Diuron	decreases expression	1
Hydrogen Peroxide	increases expression	1
Ozone	increases abundance, affects expression	1
Silicon Dioxide	increases expression	1
Isotretinoin	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Sodium Selenite	increases expression	1

Clinical trials (associated diseases)

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