CD72

Summary

CD72 (CD72 molecule, HGNC:1696) is a protein-coding gene on chromosome 9p13.3, encoding B-cell differentiation antigen CD72 (P21854). Co-receptor of B cell receptor (BCR) that plays both positive and negative roles on B-cell functions.

Enables receptor ligand activity and transmembrane signaling receptor activity. Involved in negative regulation of B cell receptor signaling pathway. Is active in plasma membrane.

Source: NCBI Gene 971 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 50 total
• GTEx eGene: eQTL in 28 tissues, sQTL in 15 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.83 (unconstrained)
• MANE Select transcript: NM_001782
• Notable: 50 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1696
Approved symbol	CD72
Name	CD72 molecule
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	LYB2, CD72b
Ensembl gene	ENSG00000137101
Ensembl biotype	protein_coding
OMIM	107272
Entrez	971

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding_CDS_not_defined, 5 protein_coding

MANE Select: ENST00000259633

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 3: 4, TSL 5: 2

ENST00000259633, ENST00000378430, ENST00000378431, ENST00000396757, ENST00000463720, ENST00000465754, ENST00000470387, ENST00000477364, ENST00000482121, ENST00000490239, ENST00001138455

RefSeq mRNA: 1 — MANE Select: NM_001782 NM_001782

CCDS: CCDS6581

Canonical transcript exons

ENST00000259633 — 9 exons

Exon	Start	End
ENSE00001526158	35609982	35610300
ENSE00001526162	35618222	35618413
ENSE00003461777	35612848	35612993
ENSE00003474487	35615943	35616278
ENSE00003497440	35610602	35610753
ENSE00003545291	35618014	35618121
ENSE00003558541	35617176	35617247
ENSE00003633000	35611804	35611919
ENSE00003657273	35616600	35616689

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 96.69.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9198 / max 223.3429, expressed in 800 samples.

Highest expression (Bgee): spleen, lymph node, granulocyte, vermiform appendix, caecum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CD72 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 28 tissues and its splicing (sQTL) in 15 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 43 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Spleen	sqtl	3.2e-37	-1.12	9:35610526:CCCCTGCTCTGAGT:C
Thyroid	eqtl	1.6e-33	-0.61	9:35641216:G:A
Skin Sun Exposed Lower leg	eqtl	1.4e-32	-0.62	9:35646573:G:C
Brain Cerebellar Hemisphere	eqtl	1.4e-29	+0.92	9:35615899:C:G
Skin Not Sun Exposed Suprapubic	eqtl	1.1e-22	-0.54	9:35641216:G:A
Whole Blood	sqtl	5.0e-20	-0.51	9:35610526:CCCCTGCTCTGAGT:C
Adipose Subcutaneous	sqtl	1.1e-17	-0.51	9:35610526:CCCCTGCTCTGAGT:C
Brain Cerebellum	eqtl	3.1e-17	+0.77	9:35615899:C:G
Cells Cultured fibroblasts	eqtl	3.6e-17	-0.32	9:35636307:T:A
Cells EBV-transformed lymphocytes	sqtl	4.4e-17	-0.68	9:35610526:CCCCTGCTCTGAGT:C
Lung	sqtl	4.6e-17	-0.52	9:35610526:CCCCTGCTCTGAGT:C
Nerve Tibial	eqtl	2.0e-16	-0.49	9:35640948:C:T
Thyroid	sqtl	3.7e-15	-0.46	9:35610526:CCCCTGCTCTGAGT:C
Adipose Subcutaneous	eqtl	4.3e-15	-0.44	9:35636307:T:A
Brain Frontal Cortex BA9	eqtl	1.3e-09	-0.71	9:35640948:C:T
Skin Sun Exposed Lower leg	sqtl	2.3e-08	-0.34	9:35610526:CCCCTGCTCTGAGT:C
Adipose Visceral Omentum	sqtl	2.4e-07	-0.39	9:35610526:CCCCTGCTCTGAGT:C
Adrenal Gland	eqtl	3.0e-07	-0.68	9:35636307:T:A
Artery Tibial	eqtl	4.1e-07	-0.34	9:35641216:G:A
Muscle Skeletal	eqtl	1.9e-06	-0.38	9:35646573:G:C

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
100585	1.2476	142
100590	0.9232	551
100589	0.5159	232
100587	0.0998	51
205472	0.0572	24
100591	0.0391	16
100586	0.0370	16

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	96.69	gold quality
lymph node	UBERON:0000029	91.58	gold quality
granulocyte	CL:0000094	91.14	gold quality
vermiform appendix	UBERON:0001154	90.48	gold quality
caecum	UBERON:0001153	83.40	gold quality
blood	UBERON:0000178	82.35	gold quality
bone marrow	UBERON:0002371	79.92	gold quality
tonsil	UBERON:0002372	79.88	gold quality
gall bladder	UBERON:0002110	79.80	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.13	gold quality
superficial temporal artery	UBERON:0001614	77.27	gold quality
right uterine tube	UBERON:0001302	77.08	gold quality
right lung	UBERON:0002167	77.05	gold quality
adenohypophysis	UBERON:0002196	76.94	gold quality
right adrenal gland cortex	UBERON:0035827	75.80	gold quality
Brodmann (1909) area 10	UBERON:0013541	75.69	gold quality
bone marrow cell	CL:0002092	75.68	gold quality
right adrenal gland	UBERON:0001233	75.64	gold quality
leukocyte	CL:0000738	75.52	gold quality
epithelium of nasopharynx	UBERON:0001951	75.32	gold quality
descending thoracic aorta	UBERON:0002345	75.25	gold quality
small intestine	UBERON:0002108	75.22	gold quality
left adrenal gland cortex	UBERON:0035825	75.18	gold quality
islet of Langerhans	UBERON:0000006	74.78	gold quality
left adrenal gland	UBERON:0001234	74.66	gold quality
type B pancreatic cell	CL:0000169	74.56	gold quality
mononuclear cell	CL:0000842	74.40	gold quality
monocyte	CL:0000576	74.39	gold quality
mucosa of stomach	UBERON:0001199	74.28	gold quality
endometrium epithelium	UBERON:0004811	73.94	gold quality
right coronary artery	UBERON:0001625	73.90	gold quality
omental fat pad	UBERON:0010414	73.84	gold quality
peritoneum	UBERON:0002358	73.80	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.77	gold quality
upper lobe of left lung	UBERON:0008952	73.45	gold quality
adipose tissue of abdominal region	UBERON:0007808	73.19	gold quality
left lobe of thyroid gland	UBERON:0001120	73.07	gold quality
ascending aorta	UBERON:0001496	73.07	gold quality
thoracic aorta	UBERON:0001515	72.98	gold quality
adrenal cortex	UBERON:0001235	72.88	gold quality
body of pancreas	UBERON:0001150	72.81	gold quality
pancreas	UBERON:0001264	72.55	gold quality
skin of leg	UBERON:0001511	72.31	gold quality
left coronary artery	UBERON:0001626	72.24	gold quality
sural nerve	UBERON:0015488	72.21	gold quality
upper lobe of lung	UBERON:0008948	71.96	gold quality
adrenal gland	UBERON:0002369	71.92	gold quality
mucosa of transverse colon	UBERON:0004991	71.86	gold quality
thyroid gland	UBERON:0002046	71.63	gold quality
tongue squamous epithelium	UBERON:0006919	71.54	gold quality
frontal pole	UBERON:0002795	71.50	gold quality
right lobe of liver	UBERON:0001114	71.36	gold quality
paraflocculus	UBERON:0005351	71.27	gold quality
middle frontal gyrus	UBERON:0002702	71.03	silver quality
skin of abdomen	UBERON:0001416	70.89	gold quality
tibial nerve	UBERON:0001323	70.64	gold quality
coronary artery	UBERON:0001621	70.64	gold quality
stromal cell of endometrium	CL:0002255	70.56	gold quality
trabecular bone tissue	UBERON:0002483	70.51	gold quality
right lobe of thyroid gland	UBERON:0001119	70.49	gold quality
adipose tissue	UBERON:0001013	70.41	gold quality
metanephros cortex	UBERON:0010533	70.35	gold quality
pituitary gland	UBERON:0000007	70.29	gold quality
decidua	UBERON:0002450	70.10	silver quality
connective tissue	UBERON:0002384	69.81	gold quality
aorta	UBERON:0000947	69.56	gold quality
transverse colon	UBERON:0001157	69.46	gold quality
smooth muscle tissue	UBERON:0001135	69.31	gold quality
zone of skin	UBERON:0000014	69.07	gold quality
left uterine tube	UBERON:0001303	68.94	gold quality
intestine	UBERON:0000160	68.63	gold quality
body of stomach	UBERON:0001161	68.45	gold quality
body of uterus	UBERON:0009853	68.37	gold quality
minor salivary gland	UBERON:0001830	68.27	gold quality
mucosa of urinary bladder	UBERON:0001259	68.22	gold quality
rectum	UBERON:0001052	68.21	gold quality
colonic epithelium	UBERON:0000397	67.93	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	67.65	gold quality
endocervix	UBERON:0000458	67.57	gold quality
liver	UBERON:0002107	67.53	gold quality
tibial artery	UBERON:0007610	67.31	gold quality
popliteal artery	UBERON:0002250	67.30	gold quality
lung	UBERON:0002048	67.29	gold quality
muscle layer of sigmoid colon	UBERON:0035805	67.12	gold quality
colon	UBERON:0001155	67.09	gold quality
large intestine	UBERON:0000059	66.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	66.74	gold quality
right ovary	UBERON:0002118	66.50	gold quality
mouth mucosa	UBERON:0003729	66.18	gold quality
anatomical system	UBERON:0000467	66.12	gold quality
stomach	UBERON:0000945	66.07	gold quality
multicellular organism	UBERON:0000468	65.99	gold quality
material anatomical entity	UBERON:0000465	65.97	gold quality
saliva-secreting gland	UBERON:0001044	65.82	gold quality
ectocervix	UBERON:0012249	65.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	65.46	gold quality
sigmoid colon	UBERON:0001159	65.43	gold quality
lower esophagus	UBERON:0013473	65.17	gold quality
lower esophagus muscularis layer	UBERON:0035833	65.14	gold quality
gastrocnemius	UBERON:0001388	64.94	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	67.72
E-HCAD-4	yes	55.16
E-CURD-112	yes	41.90
E-MTAB-9067	yes	17.11
E-ANND-3	yes	15.07
E-HCAD-10	yes	13.52
E-MTAB-9801	yes	5.43
E-MTAB-6386	no	1605.08

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Lymph node	tissue	60.4	medium
Spleen	tissue	47.3	high
Tonsil	tissue	46.7	high
Appendix	tissue	19.2	high
Bone marrow	tissue	6.2	medium
Thymus	tissue	6.1
Liver	tissue	5.5	not detected
Choroid plexus	tissue	5.1
Adipose tissue	tissue	4.2	not detected
Caudate putamen	tissue	4.1
Urinary bladder	tissue	3.8	not detected
Epididymis	tissue	3.6	not detected
Gallbladder	tissue	3.6	not detected
Placenta	tissue	3.1	not detected
Stomach 1	tissue	2.4	not detected
Lung	tissue	2.4	not detected
Pituitary gland	tissue	2.3
Pancreas	tissue	1.8	not detected
Colon	tissue	1.7	not detected
Skin 1	tissue	1.6	not detected
Small intestine	tissue	1.6	not detected
Salivary gland	tissue	1.5	not detected
Smooth muscle	tissue	1.4	not detected
Cervix	tissue	1.3	not detected
Cerebellum	tissue	1.3	not detected
Rectum	tissue	1.2	not detected
Duodenum	tissue	1.2	not detected
Olfactory bulb	tissue	1.1
Breast	tissue	1.0	not detected
Cerebral cortex	tissue	1.0	not detected
Superior colliculi	tissue	1.0
Locus coeruleus	tissue	1.0
Hippocampal formation	tissue	1.0
Fallopian tube	tissue	1.0	not detected
Somatosensory cortex	tissue	1.0
Occipital cortex	tissue	1.0
Prefrontal cortex	tissue	0.9
Pons	tissue	0.9
Parathyroid gland	tissue	0.9	not detected
Motor cortex	tissue	0.9
Thyroid gland	tissue	0.9	not detected
Spinal cord	tissue	0.9
Retrosplenial cortex	tissue	0.9
Endometrium 1	tissue	0.8	not detected
Basal ganglia	tissue	0.8	not detected
Putamen	tissue	0.8
Midbrain	tissue	0.8
Hypothalamus	tissue	0.8
Substantia nigra	tissue	0.8
Hippocampus	tissue	0.8	not detected
Entorhinal cortex	tissue	0.8
Retrosplenial and cingulate cortex	tissue	0.8
Periaqueductal gray	tissue	0.8
Septum	tissue	0.8
Insular cortex	tissue	0.8
Testis	tissue	0.7	not detected
Ovary	tissue	0.7	not detected
Vagina	tissue	0.7	not detected
Amygdala	tissue	0.7
Nucleus accumbens	tissue	0.7

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Anterior thalamic nucleus, ventral (4.1), Area postrema (3.0), Blood vessel (3.0), Nucleus raphe pallidus (2.7), Frontal operculum (2.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, PAX5, SPI1

miRNA regulators (miRDB)

Targeting CD72 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

15 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813

Functional genomics

gnomAD constraint: pLI 0.000244, LOEUF 0.832, missense Z 0.604 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000259633 — one region, missense o/e 0.96.

Literature-anchored findings (GeneRIF, showing 18)

• results indicated that the presence of CD72-*2 allele decreases risk for human systemic lupus erythematosus conferred by FCGR2B-232Thr, possibly by increasing the AS isoform of CD72 (PMID:15459183)
• CD72 is a key molecule in regulating mature B cell differentiation; CD72 signaling reduces the expression of X-box binding protein 1 in B cells (PMID:16047337)
• increased nucleotide mutation of CD72 mRNA accounts for the decreased expression level of CD72 in B cells, and it might be related to hyperactivity of B cells in patients with SLE (PMID:17121583)
• CD100-CD72 interaction can be the mechanism by which NK cell communicate with B cells. (PMID:17786190)
• CD72 polymorphisms are associated with age of appearing clinical manifestations in idiopathic thrombocytopenic purpura in Chinese patients. (PMID:18071878)
• Data show that ligation of CD72 with the BU40, or with rCD100 negatively regulates KIT-mediated mast cell proliferation, chemotaxis, and chemokine production. (PMID:20100931)
• CD72 mRNA expression level correlates with Sema4D expression in peripheral blood mononuclear cells in immune thrombocytopenia. (PMID:22111667)
• data demonstrated aberrant expression of CD72 exists on B cells of myasthenia gravis and multiple sclerosis patients and expression level of CD72 molecule has a significantly negative correlation with anti-AchR antibody levels in myasthenia gravis (PMID:23184497)
• regulates serum immunoglobulin leveln and disease resistance in systemic lupus erythematosus (PMID:23268649)
• CD72 expression on activated B cells of SLE patients was significantly lower than that of normal controls. sema3A enhanced CD72 expression of B cells, but it was still lower in SLE patients than in normal individuals. (PMID:24461079)
• Increased soluble CD72 in systemic lupus erythematosus is in association with disease activity and lupus nephritis (PMID:26883681)
• Interferon-alpha-induced CD100 expression on naive CD8(+) T cells enhances antiviral responses to hepatitis C infection through CD72 signal transduction. (PMID:28222623)
• A regulatory role for CD72 expression on B cells and increased soluble CD72 in primary Sjogren’s syndrome. (PMID:32306893)
• CD40 and CD72 expression and prognostic values among children with systemic lupus erythematosus: a case-control study. (PMID:32700598)
• Blockage of CD72 reduces B cell proliferation in immune thrombocytopenic purpura, involving interleukin 1 and macrophage migration inhibitory factor secretion. (PMID:36326455)
• CD72-semaphorin3A axis: A new regulatory pathway in systemic lupus erythematosus. (PMID:36470209)
• CD72 is a pan-tumor antigen associated to pediatric acute leukemia. (PMID:37876342)
• CD72, a new immune checkpoint molecule, is a novel prognostic biomarker for kidney renal clear cell carcinoma. (PMID:37980541)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd72	ENSMUSG00000028459
rattus_norvegicus	Cd72	ENSRNOG00000017485

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88345) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 22 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased B cell proliferation	2
lung inflammation	1
abnormal B cell differentiation	1
increased IgM level	1
glomerulonephritis	1
increased pre-B cell number	1
increased anti-double stranded DNA antibody level	1
increased anti-single stranded DNA antibody level	1
increased anti-chromatin antibody level	1
increased spleen weight	1
increased B-1 B cell number	1
decreased B cell number	1
increased B-1a cell number	1
decreased follicular B cell number	1
increased marginal zone B cell number	1
increased pro-B cell number	1
decreased B-2 B cell number	1
decreased mature B cell number	1
increased immature B cell number	1
abnormal B cell activation	1
abnormal B cell calcium ion homeostasis	1
renal glomerular immunoglobulin deposits	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Macaca mulatta	Q8HZR8	94.3%	Diamond
Fowlpox virus strain NVSL	P14370	48.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR4667	ncRNA	100616214
TESK1	protein-coding	7016
CIMIP2B	protein-coding	730112
RUSC2	protein-coding	9853
SIT1	protein-coding	27240
RMRP	ncRNA	6023
CCDC107	protein-coding	203260
ARHGEF39	protein-coding	84904

Protein

Protein identifiers

B-cell differentiation antigen CD72 — P21854 (reviewed: P21854)

Alternative names: Lyb-2

All UniProt accessions (5): A0A6E1WA84, P21854, Q5T4Q7, Q5T4Q8, Q5TLG3

UniProt curated annotations — full annotation on UniProt →

Function. Co-receptor of B cell receptor (BCR) that plays both positive and negative roles on B-cell functions. Recognizes the Sm/ribonucleoprotein (RNP) self-antigen ligand, and coligation of CD72 and BCR inhibits BCR signaling. Mechanistically, ligand binding leads to the recruitment of PTPN6/SHP-1 to the BCR complex which is inhibitory to BCR signaling. Also acts as a ligand for CD5 and thereby plays a critical role in maintaining regulatory T and B-cell homeostasis.

Subunit / interactions. Homodimer; disulfide-linked. Associates with CD5. Interacts (tyrosine phosphorylated) with PTPN6/SHP-1.

Subcellular location. Membrane.

Tissue specificity. Pre-B-cells and B-cells but not terminally differentiated plasma cells.

Post-translational modifications. Phosphorylated upon engagement of the B-cell receptor, probably by LYN or SYK. Phosphorylation at Tyr-7 is important for interaction with PTPN6/SHP-1.

RefSeq proteins (1): NP_001773* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001304	C-type_lectin-like	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR039689	CD72	Family

Pfam: PF00059

UniProt features (12 total): disulfide bond 3, topological domain 2, modified residue 2, chain 1, sequence variant 1, transmembrane region 1, domain 1, glycosylation site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P21854-F1	76.85	0.48

Human Protein Atlas

Protein class: CD markers, Predicted membrane proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF uncertain

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 (2)

Type	Positions
Phosphotyrosine	7, 39

Disulfide bonds (3)

Type	Positions
Disulfide bond	325–342, 233–244, 261–350

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	136

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-416700	Other semaphorin interactions	curated
R-HSA-422475	Axon guidance	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9675108	Nervous system development	—
R-HSA-373755	Semaphorin interactions	—

MSigDB gene sets: 340 (showing top): PID_BCR_5PATHWAY, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, YAGI_AML_WITH_INV_16_TRANSLOCATION, GCANCTGNY_MYOD_Q6, REACTOME_OTHER_SEMAPHORIN_INTERACTIONS, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, MORI_IMMATURE_B_LYMPHOCYTE_UP, CAGCTG_AP4_Q5, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, ODONNELL_TARGETS_OF_MYC_AND_TFRC_UP, chr9p13, MODULE_410

GO Biological Process (3): cell adhesion (GO:0007155), negative regulation of B cell receptor signaling pathway (GO:0050859), signal transduction (GO:0007165)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), signaling receptor binding (GO:0005102), carbohydrate binding (GO:0030246), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Semaphorin interactions	1
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

17 GO namespaces:

Category	Terms
cellular process	2
binding	2
B cell receptor signaling pathway	1
regulation of B cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signaling receptor activity	1
protein binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of B cell receptor signaling pathway	BP	direct assay
plasma membrane	CC	direct assay
receptor ligand activity	MF	direct assay
transmembrane signaling receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,062 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD72	SEMA4D	Q92854	918
CD72	PLXNB1	O43157	838
CD72	CD22	P20273	712
CD72	FCGR2B	P31994	682
CD72	PLXNB2	O15031	602
CD72	PTPN6	P29350	567
CD72	CD79B	P40259	563
CD72	CHIA	Q9BZP6	551
CD72	CD19	P15391	547
CD72	CD5	P06127	540
CD72	BCR	P11274	508
CD72	CR2	P20023	497
CD72	SEMA3B	Q13214	497
CD72	IL13RA2	Q14627	493
CD72	FCRL5	Q96RD9	490

IntAct

Human interaction partners of CD72 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

23 partners by confidence:

Partner	Interaction type	MIscore	Records
CREB3L1	physical association	0.560	5
ATP6AP2	physical association	0.560	3
BIK	physical association	0.560	3
CGRRF1	physical association	0.560	3
CLDN7	physical association	0.560	3
GPR152	physical association	0.560	3
GRAMD1C	physical association	0.560	3
LHFPL5	physical association	0.560	3
LRRC25	physical association	0.560	3
LSMEM2	physical association	0.560	3
MS4A3	physical association	0.560	3
MS4A7	physical association	0.560	3
NRG1	physical association	0.560	3
SPACA1	physical association	0.560	3
SEMA4D	direct interaction	0.440	1
CD5	physical association	0.400	1
FCGR1A	physical association	0.400	1
FCGR2A	physical association	0.400	1
HMGA1	physical association	0.400	1
NCAM2	physical association	0.400	1
TRUB1	physical association	0.400	1
CALML3	association	0.350	1
SIGLEC10	association	0.350	1

BioGRID (33 interactions; top human partners by supporting records): PTPN6 (Affinity Capture-Western; 4 records), KLHL15 (Affinity Capture-MS; 2 records), SEMA4D (Affinity Capture-Western; 2 records), SIGLEC10 (Affinity Capture-MS; 2 records), ATP6AP2 (Two-hybrid), BIK (Two-hybrid), BLNK (Affinity Capture-Western), CALML3 (Affinity Capture-MS), CD5 (Reconstituted Complex), CGRRF1 (Two-hybrid), CLDN7 (Two-hybrid), CREB3L1 (Two-hybrid), GPR152 (Two-hybrid), GRAMD1C (Two-hybrid), HMGA1 (Cross-Linking-MS (XL-MS))

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PTPN6	down-regulates	CD72	dephosphorylation

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
SEMA4D	receptor	Signaling by Semaphorin

Disease & clinical

Genetic variants

Variant evidence for CD72: 50 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 654):

Position(s)	Effect	Δscore	Sites
9:35612915	donor_gain	0.9900
9:35615941–35615942	donor_loss	0.9800	4
9:35618220–35618221	donor_loss	0.9800	6
9:35617248–35617249	acceptor_loss	0.9700	6
9:35616691	acceptor_gain	0.9600
9:35616787	donor_gain	0.9400
9:35618016	donor_gain	0.9400
9:35610301–35610302	acceptor_loss	0.9300	6
9:35614544	donor_gain	0.9300
9:35615941	donor_loss	0.9300

AlphaMissense

319 missense substitutions predicted likely pathogenic (of 2,308 scored), across 110 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F12	8	0.910	0.992
N41	8	0.817	0.920
D9	8	0.795	0.911
C261	7	0.980	0.993
C350	7	0.978	0.991
C244	7	0.975	0.985
W237	7	0.974	0.997
C233	7	0.942	0.967
W298	7	0.930	0.991
C325	7	0.906	0.970
C342	7	0.897	0.937
C232	7	0.896	0.934
S257	7	0.868	0.984
F245	7	0.845	0.944
W254	7	0.839	0.983
E40	7	0.813	0.946
R11	6	0.785	0.883
C226	6	0.674	0.762
T6	6	0.652	0.761
F355	5	0.893	0.935

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:107272 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST002709_10	Electroencephalogram traits	2e-6
GCST006585_1832	Blood protein levels	5e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement
EFO:0006870	alpha wave measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169122 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
titanium dioxide	increases expression	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
ON 01910	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	decreases methylation, increases abundance	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Fonofos	increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, decreases expression	1
Nitrogen Dioxide	decreases methylation, increases abundance	1
Oxygen	increases expression	1
Parathion	increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Permethrin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5136271	Binding	Induction of CD72 degradation in human MINO cells at 100 nM measured after 8 hrs by proteomic analysis	Structural Feature Analyzation Strategies toward Discovery of Orally Bioavailable PROTACs of Bruton’s Tyrosine Kinase for the Treatment of Lymphoma. — *J Med Chem*

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1JS	HyCyte Daudi KO-hCD72	Cancer cell line	Male
CVCL_F4MP	HyCyte HEK293 stable cell line for hCD72 overexpression	Transformed cell line	Female
CVCL_F4NJ	HyCyte Jurkat stable cell line for hCD72 overexpression	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.