CD38

Summary

CD38 (CD38 molecule, HGNC:1667) is a protein-coding gene on chromosome 4p15.32, encoding ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (P28907). Multifunctional transmembrane glycoprotein able to exert enzymatic activities and also to mobilize calcium, to transduce signals, to adhere to hyaluronan and to other ligands.

The protein encoded by this gene is a non-lineage-restricted, type II transmembrane glycoprotein that synthesizes and hydrolyzes cyclic adenosine 5’-diphosphate-ribose, an intracellular calcium ion mobilizing messenger. The release of soluble protein and the ability of membrane-bound protein to become internalized indicate both extracellular and intracellular functions for the protein. This protein has an N-terminal cytoplasmic tail, a single membrane-spanning domain, and a C-terminal extracellular region with four N-glycosylation sites. Crystal structure analysis demonstrates that the functional molecule is a dimer, with the central portion containing the catalytic site. It is used as a prognostic marker for patients with chronic lymphocytic leukemia. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 952 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 57 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001775

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1667
Approved symbol	CD38
Name	CD38 molecule
Location	4p15.32
Locus type	gene with protein product
Status	Approved
Aliases	cADPR1
Ensembl gene	ENSG00000004468
Ensembl biotype	protein_coding
OMIM	107270
Entrez	952

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000226279, ENST00000502843, ENST00000506191, ENST00000510674, ENST00000511430, ENST00000868373

RefSeq mRNA: 1 — MANE Select: NM_001775 NM_001775

CCDS: CCDS3417

Canonical transcript exons

ENST00000226279 — 8 exons

Exon	Start	End
ENSE00000705352	15824881	15825016
ENSE00001131136	15848539	15853232
ENSE00001131145	15778328	15778647
ENSE00003522071	15840452	15840538
ENSE00003548154	15840026	15840118
ENSE00003599703	15816511	15816640
ENSE00003607810	15838092	15838165
ENSE00003661451	15834217	15834302

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 93.71.

FANTOM5 (CAGE): breadth broad, TPM avg 15.4212 / max 646.7317, expressed in 603 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47004	14.4822	596
47005	0.7809	273
47006	0.1580	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
seminal vesicle	UBERON:0000998	93.71	gold quality
bone marrow cell	CL:0002092	91.93	gold quality
lymph node	UBERON:0000029	88.03	gold quality
thymus	UBERON:0002370	87.12	gold quality
vermiform appendix	UBERON:0001154	86.76	gold quality
bone marrow	UBERON:0002371	86.38	gold quality
spleen	UBERON:0002106	85.57	gold quality
bronchial epithelial cell	CL:0002328	85.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.47	gold quality
epithelium of bronchus	UBERON:0002031	84.83	gold quality
bronchus	UBERON:0002185	83.92	gold quality
granulocyte	CL:0000094	83.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.33	gold quality
monocyte	CL:0000576	83.00	gold quality
mononuclear cell	CL:0000842	82.81	gold quality
leukocyte	CL:0000738	82.80	gold quality
vastus lateralis	UBERON:0001379	82.07	silver quality
biceps brachii	UBERON:0001507	82.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.22	gold quality
quadriceps femoris	UBERON:0001377	80.96	silver quality
triceps brachii	UBERON:0001509	80.83	silver quality
caecum	UBERON:0001153	80.64	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	80.46	gold quality
ileal mucosa	UBERON:0000331	79.97	gold quality
muscle organ	UBERON:0001630	79.08	gold quality
skeletal muscle organ	UBERON:0014892	79.08	gold quality
skeletal muscle tissue	UBERON:0001134	78.95	gold quality
epithelium of nasopharynx	UBERON:0001951	78.64	gold quality
nasopharynx	UBERON:0001728	78.63	gold quality
muscle of leg	UBERON:0001383	78.52	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	1316.60
E-CURD-122	yes	335.18
E-MTAB-9467	yes	71.56
E-HCAD-1	yes	61.89
E-HCAD-4	yes	58.02
E-CURD-112	yes	41.55
E-CURD-46	yes	36.25
E-ANND-3	yes	33.42
E-MTAB-8410	yes	27.81
E-MTAB-6678	yes	23.45
E-HCAD-10	yes	16.92
E-HCAD-9	yes	16.60
E-MTAB-9067	yes	16.13
E-CURD-88	yes	13.61
E-MTAB-10553	yes	11.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CUX1, FOXC1, GATA3, IRF1, IRF6, MYC, NCOA2, NFKB1, NFKB, RARA, RELA, TCF3

miRNA regulators (miRDB)

178 targeting CD38, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4803	99.98	71.99	3117
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4789-5P	99.98	70.76	2721

Literature-anchored findings (GeneRIF, showing 40)

• Low CD38 expression parallels a lower propensity to apoptosis. In vivo CD38 crosslinking by its ligand may play a pivotal role in B-CLL apoptosis, and chlorambucil affects CD38 levels. (PMID:11836173)
• CD38 plays a role in the progression of B-chronic lymphocytic leukemia and can be used as a prognostic marker (PMID:12368155)
• expression level does not change in B-cell chronic lymphocytic leukemia (PMID:12382646)
• CD38 expression and the consequential accumulation of cADPR play a causal role in mediating cellular differentiation (PMID:12386160)
• CD38 receptor-mediated signals operate directly suggesting a Fcgamma receptorial surface molecule independent activation pathway. The key element for the receptor mediated signaling is represented by surface density of CD38 on resting monocytes. (PMID:12718937)
• CD38 is not merely a marker in B-CLL, but plays a receptor role with pathogenetic potential ruling the proliferation of the malignant clone. (PMID:12763926)
• results suggest that CD38 is superior to myeloid-associated markers in predicting the prognosis of patients with B-CLL (PMID:12854897)
• CD38 enhances thymocyte death by interacting with CD31 expressed by accessory cells and may play a role in passive immunity. (PMID:12917263)
• CD38 operates in two functionally distinct microdomains of the plasma membrane (PMID:14523017)
• findings indicate a novel negative feedback mechanism between RyR1 channel activity and CD38 abundance acts in cADPr signal transduction in lymphoma b-cells (PMID:14596927)
• CD38 overexpression is associated with B-cell chronic lymphocytic leukemia (PMID:14749705)
• Expression of CD38 on CD8+ T cells is associated with poor prognostic outcome in hiv infected individuals with detectable plasma viremia (PMID:14983032)
• cADPR, in concert with IP(3), operates in airway gland acinar cells to mobilize Ca(2+), resulting in Cl(-) secretion. (PMID:14990397)
• concentrative influx of extracellular cADPR across CNT3 and cs-csg NT could substitute in the absence of CD38 in eliciting cADPR-dependent Ca(2+) increases in granulocyte-differentiated HL-60 cells, as well as in other CD38(-) cells (PMID:15028729)
• CD38 is stimulated by sequential activation of IL8 receptor, IP(3)-mediated Ca(2+) rise, and cGMP/protein kinase G and plays an essential role in IL8-induced migration of LAK cells (PMID:15556942)
• CD38, a negative prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL), plays a role in neoplastic B-cell growth and survival. (PMID:15613544)
• In the current study, ZAP-70 and CD38 expressions were examined in 252 patients with B-CLL. Surface CD38 expression on more than 30% (CD38(+)) of B-CLL cells were associated with an unfavorable clinical course. (PMID:15759031)
• The level of CD38 expression on different T-cell subsets is differentially upregulated in drug-naive HIV-infected patients. (PMID:15764953)
• leukocyte antigen-DR, CD38, and CD9 share a common pathway of tyrosine kinase activation in human monocytes (PMID:15941914)
• CD38 expression is augmented in ex vivo CD3+, CD4+, CD8+, and CD25+ systemic lupus erythematosus T cells, which correlates with its increased insolubility in Brij 98 detergent, and its translocation into lipid rafts. (PMID:15964076)
• The crystal structure of the soluble extracellular domain of human CD38 to 1.9 A resolution was determined. (PMID:16154090)
• localization of CD38 in lipid rafts and its multiple interactions with signaling receptors rule innate and adaptive immune responses by tuning DC migration, survival, and Th1-polarization ability (PMID:16293598)
• Retinoic acid-induced CD38 expression in HL-60 myeloblastic leukemia cells regulates cell differentiation or viability depending on expression levels (PMID:16329108)
• anti-CD38 autoantibodies are more prevalent in long-standing than in new-onset type 1 diabetes, and more prevalent in type 2 than in type 1 diabetes. (review) (PMID:16544364)
• Results showed a simple method of quantitation of CD38 expression to be sufficient to identify patients with an unfavourable prognosis in B cell chronic lymphocytic leukaemia. (PMID:16568475)
• TNF-alpha-induced CD38 expression involves NF-kappaB expression and its activation and dexamethasone inhibits CD38 expression through NF-kappaB-dependent and -independent mechanisms. (PMID:16571778)
• TRPM2 is a potential molecular target for cADPR, which regulates Ca(2+) entry into pancreatic beta-cells at body temperature depending on the production of cADPR-related molecules, thereby regulating insulin secretion. (PMID:16601673)
• B-prolymphocytic leukemia appears biologically heterogeneous regarding IgVH mutations, ZAP-70 and CD38 expression, showing a pattern distinct from that of other lymphoproliferative disorders (PMID:16642047)
• Combined analysis of CD38 in B-chronic lymphocytic leukemia and T cells is superior in predicting outcome of male B-CLL patients. (PMID:16825496)
• results show that, in lymphoma cells, propensity to apoptosis was significantly linked to CD38 expression and that, remarkably, such response was independent of the nature of the trigger used (PMID:16839787)
• These results suggested that the N-linked glycosylation of CD38 plays a crucial role in the structure stability by preventing the formation inter-molecular cross-links. (PMID:16841181)
• active sites of CD38 and ADP-ribosyl cyclase have roles in nicotinic acid adenine dinucleotide phosphate (NAADP) synthesis and hydrolysis activities (PMID:16861223)
• IRTA4/FcRH2 expression as detected by flow cytometry was significantly lower in the poor prognosis subgroup as compared to ZAP-70-CD38- B-chronic lymphocytic leukemia cells (PMID:16932341)
• We found a low incidence of CD38+ CLL patients, and CD38 expression predicted significantly a more advanced stage of the disease, shorter lymphocyte doubling time and shorter therapy- and progression-free time. (PMID:17028452)
• somatic mutation status and CD38 retained prognostic significance on multivariate analysis whereas ZAP-70 did not (PMID:17107912)
• These results indicate that cADPR is an intracellular messenger of Ca(2+) signalling, suggesting that CD38 can contribute to mAChR-cADPR signalling. (PMID:17173996)
• Review. CD38 senses extracellular NAD release in infection/inflammation & produces cADPR. This regulates calcium signaling & chemotaxis in monocytes, neutrophils and dendritic cells. (PMID:17191385)
• results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders (PMID:17287729)
• biological rationale for the poor prognosis of CD38(+) for chronic lymphocytic anemia patients. (PMID:17287849)
• regulation of CD38 expression through p38 and JNK MAPKs involves NF-kappaB and AP-1 activation, and ERK and and p38 MAPKs also regulate expression posttranscriptionally through message stability (PMID:17322278)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000113438
mus_musculus	Cd38	ENSMUSG00000029084
rattus_norvegicus	Cd38	ENSRNOG00000003069

Paralogs (1): BST1 (ENSG00000109743)

Protein

Protein identifiers

ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 — P28907 (reviewed: P28907)

Alternative names: 2’-phospho-ADP-ribosyl cyclase, 2’-phospho-ADP-ribosyl cyclase/2’-phospho-cyclic-ADP-ribose transferase, 2’-phospho-cyclic-ADP-ribose transferase, ADP-ribosyl cyclase 1, Cyclic ADP-ribose hydrolase 1, T10

All UniProt accessions (2): P28907, H0Y950

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional transmembrane glycoprotein able to exert enzymatic activities and also to mobilize calcium, to transduce signals, to adhere to hyaluronan and to other ligands. Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion. Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosphate, NAADP(+), from 2’-phospho-cADPR and nicotinic acid, as well as from NADP(+) and nicotinic acid. At both pH 5.0 and pH 7.4 preferentially transforms 2’-phospho-cADPR into NAADP(+), while preferentially cleaving NADP(+) to cADPR and ADPRP rather than into NADDP(+). Has cADPR hydrolase activity. Functions also as a receptor that binds the ligand CD31 on endothelial cells, promoting lymphocyte activation, proliferation, and migration across the endothelial barrier. Involved in the regulation of crucial dendritic cell functions acquired at the mature stage, such as CCL21-driven migration, survival, and Th1-polarizing activity. In lamina propria T lymphocytes, CD38/CD31 cognate interactions initiate a multistep signaling pathway resulting in activation of LCK anf LAT, followed by cytokine release.

Subunit / interactions. Homodimer.

Subcellular location. Cell surface. Cell membrane.

Tissue specificity. Expressed at high levels in pancreas, liver, kidney, brain, testis, ovary, placenta, malignant lymphoma and neuroblastoma.

Activity regulation. ATP inhibits the cADPR hydrolyzing activity.

Miscellaneous. A cell surface antigen recognized in lymophocytes by multiple mAbs. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the ADP-ribosyl cyclase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P28907-1	1	yes
P28907-2	2

RefSeq proteins (1): NP_001766* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003193	ADP-ribosyl_cyclase	Family

Pfam: PF02267

Enzyme classification (BRENDA):

• EC 2.4.99.20 — 2’-phospho-ADP-ribosyl cyclase/2’-phospho-cyclic-ADP-ribose transferase (BRENDA: 6 organisms, 11 substrates, 6 inhibitors, 2 Km, 0 kcat entries)
• EC 3.2.2.5 — NAD+ glycohydrolase (BRENDA: 41 organisms, 94 substrates, 104 inhibitors, 76 Km, 15 kcat entries)
• EC 3.2.2.6 — ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (BRENDA: 11 organisms, 43 substrates, 66 inhibitors, 36 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

37 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.0046–2.14	35
NAD+	0.0171–1.33	22
NADP+	0.005–0.13	6
3-ACETYLPYRIDINE ADENINE DINUCLEOTIDE	0.006–0.15	4
EPSILON-NAD+	0.009–0.014	3
NADP+	0.065–0.66	3
DNAD+	0.1	2
ETHENO-NAD+	0.0548–0.0883	2
NICOTINAMIDE HYPOXANTHINE DINUCLEOTIDE	0.005–0.02	2
NMN	1.3	2
THIONAD+	0.011–0.057	2
NGDP+	0.0334	1
NICOTINATE	5	1
2-FLUORO-NAD+	0.016	1
3-ACETYLPYRIDINE	20	1

Catalyzed reactions (Rhea), 6 shown:

• NAD(+) + H2O = ADP-D-ribose + nicotinamide + H(+) (RHEA:16301)
• nicotinate + NADP(+) = NAADP(+) + nicotinamide (RHEA:38599)
• NADP(+) = 2’-phospho-cyclic ADP-ribose + nicotinamide (RHEA:38603)
• 2’-phospho-cyclic ADP-ribose + nicotinate = NAADP(+) (RHEA:38607)
• NAD(+) = cyclic ADP-beta-D-ribose + nicotinamide + H(+) (RHEA:38611)
• cyclic ADP-beta-D-ribose + H2O = ADP-D-ribose (RHEA:38615)

UniProt features (59 total): helix 17, strand 14, mutagenesis site 6, disulfide bond 5, glycosylation site 4, turn 3, topological domain 2, splice variant 2, active site 2, chain 1, sequence variant 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

56 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3F6Y	X-RAY DIFFRACTION	1.45
2O3S	X-RAY DIFFRACTION	1.5
6VUA	X-RAY DIFFRACTION	1.5
4CMH	X-RAY DIFFRACTION	1.53
3DZH	X-RAY DIFFRACTION	1.6
3DZG	X-RAY DIFFRACTION	1.65
3ROK	X-RAY DIFFRACTION	1.65
8P8C	X-RAY DIFFRACTION	1.65
2O3T	X-RAY DIFFRACTION	1.68
4F46	X-RAY DIFFRACTION	1.69
2I66	X-RAY DIFFRACTION	1.7
2I67	X-RAY DIFFRACTION	1.71
2PGJ	X-RAY DIFFRACTION	1.71
3DZI	X-RAY DIFFRACTION	1.73
9SXI	X-RAY DIFFRACTION	1.74
2O3R	X-RAY DIFFRACTION	1.75
3I9M	X-RAY DIFFRACTION	1.75
2PGL	X-RAY DIFFRACTION	1.76
3DZK	X-RAY DIFFRACTION	1.81
9GOX	X-RAY DIFFRACTION	1.84
8BYU	X-RAY DIFFRACTION	1.85
3U4H	X-RAY DIFFRACTION	1.88
2I65	X-RAY DIFFRACTION	1.9
3DZJ	X-RAY DIFFRACTION	1.9
5F21	X-RAY DIFFRACTION	1.9
7VKE	X-RAY DIFFRACTION	1.9
1YH3	X-RAY DIFFRACTION	1.91
3ROP	X-RAY DIFFRACTION	1.94
2HCT	X-RAY DIFFRACTION	1.95
2O3Q	X-RAY DIFFRACTION	1.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28907-F1	91.09	0.77

Antibody-complex structures (SAbDab): 13 — 3RAJ, 4CMH, 5F1K, 5F1O, 5F21, 7DHA, 7DUO, 7VKE, 8BYU, 8IL3, 8ZYE, 9GOX, 9GOY

Functional residue map

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

Catalytic / active sites (2): 119; 201

Disulfide bonds (5): 67–82, 99–180, 160–173, 254–275, 287–296

Glycosylation sites (4): 100, 164, 209, 219

Mutagenesis-validated functional residues (6):

Position	Phenotype
119	loss of cadpr hydrolase activity.
119	loss of cadpr hydrolase and adp-ribosyl cyclase activity.
160	loss of cadpr hydrolase and adp-ribosyl cyclase activity.
173	loss of cadpr hydrolase and adp-ribosyl cyclase activity.
201	loss of cadpr hydrolase and adp-ribosyl cyclase activity.
201	loss of cadpr hydrolase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-196807	Nicotinate metabolism
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 581 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_INSULIN_SECRETION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOCC_CELL_SURFACE

GO Biological Process (29): response to hypoxia (GO:0001666), signal transduction (GO:0007165), positive regulation of cytosolic calcium ion concentration (GO:0007204), female pregnancy (GO:0007565), response to xenobiotic stimulus (GO:0009410), negative regulation of neuron projection development (GO:0010977), artery smooth muscle contraction (GO:0014824), positive regulation of cell growth (GO:0030307), positive regulation of B cell proliferation (GO:0030890), positive regulation of insulin secretion (GO:0032024), response to estradiol (GO:0032355), response to retinoic acid (GO:0032526), response to progesterone (GO:0032570), response to hydroperoxide (GO:0033194), B cell proliferation (GO:0042100), negative regulation of apoptotic process (GO:0043066), negative regulation of bone resorption (GO:0045779), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of vasoconstriction (GO:0045907), B cell receptor signaling pathway (GO:0050853), long-term synaptic depression (GO:0060292), response to interleukin-1 (GO:0070555), apoptotic signaling pathway (GO:0097190), nicotinate metabolic process (GO:1901847), positive regulation of cell population proliferation (GO:0008284), response to hormone (GO:0009725), NAD+ metabolic process (GO:0019674), response to cytokine (GO:0034097)

GO Molecular Function (6): transferase activity (GO:0016740), phosphorus-oxygen lyase activity (GO:0016849), identical protein binding (GO:0042802), NAD+ nucleosidase activity, cyclic ADP-ribose generating (GO:0061809), hydrolase activity (GO:0016787), hydrolase activity, acting on glycosyl bonds (GO:0016798)

GO Cellular Component (6): plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), nuclear membrane (GO:0031965), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to oxygen-containing compound	3
response to lipid	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
catalytic activity	2
cellular anatomical structure	2
response to stress	1
response to decreased oxygen levels	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of biological quality	1
multi-organism reproductive process	1
multi-multicellular organism process	1
response to chemical	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
tonic smooth muscle contraction	1
vascular associated smooth muscle contraction	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
response to steroid hormone	1
response to ketone	1
response to oxidative stress	1
B cell activation	1
lymphocyte proliferation	1
apoptotic process	1

Protein interactions and networks

STRING

2692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD38	PECAM1	P16284	992
CD38	CD34	P28906	965
CD38	CD19	P15391	941
CD38	CD4	P01730	930
CD38	CD27	P26842	892
CD38	SDC1	P18827	882
CD38	CD5	P06127	880
CD38	CCR7	P32248	872
CD38	CD8A	P01732	871
CD38	CXCR5	P32302	853
CD38	CD7	P09564	851
CD38	CD86	P42081	843
CD38	PTPRC	P08575	840
CD38	CD28	P10747	838
CD38	MME	P08473	821

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CD38	PECAM1	psi-mi:“MI:0407”(direct interaction)	0.440
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
CD81	CD276	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): CD38 (Affinity Capture-MS), CD38 (Affinity Capture-MS), CD38 (Affinity Capture-MS), CD38 (Affinity Capture-MS), FCGR3A (FRET), CD38 (Affinity Capture-MS), CD38 (Affinity Capture-RNA), CD3E (Affinity Capture-Western), CD247 (Affinity Capture-Western), LCK (Affinity Capture-Western), CD3E (Co-fractionation), CD247 (Co-fractionation), ZAP70 (Co-fractionation), CD38 (FRET), CD38 (Affinity Capture-Western)

ESM2 similar proteins: A0A0A6YXX9, A0A1Z2R986, A2RTF1, C6KI89, E9Q355, F5HFJ7, O36400, P03425, P04853, P09258, P09728, P0DP43, P12554, P12556, P16772, P19758, P21526, P22229, P28907, P35740, P35771, Q04547, Q2TAV2, Q2YDM0, Q3TBN1, Q499E0, Q4R6B2, Q5BKX0, Q5E9L2, Q5RDR5, Q66000, Q66001, Q68FB2, Q6AY76, Q6DFY8, Q6ZRH7, Q76B58, Q77MP7, Q77NN4, Q783Y1

Diamond homologs: P28907, P29241, P56528, Q10588, Q27312, Q5VAN0, Q63072, Q64244, Q64277, Q9MZ03

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CD38	“up-regulates quantity”	“cyclic ADP-ribose”	“chemical modification”
CD38	“up-regulates quantity”	“nicotinic acid-adenine dinucleotide phosphate”	“chemical modification”
CD38	“down-regulates quantity”	NAD(+)	“chemical modification”
CD38	“down-regulates quantity”	NADP(+)	“chemical modification”
CD38	“down-regulates quantity”	NMN(+)	“chemical modification”
CD38	“up-regulates quantity”	nicotinamide	“chemical modification”
PECAM1	“up-regulates activity”	CD38	binding
CD38	down-regulates	Apoptosis
CD38	“up-regulates quantity”	OXT	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1565 predictions. Top by Δscore:

Variant	Effect	Δscore
4:15825017:G:GG	donor_gain	1.0000
4:15838090:A:G	acceptor_gain	1.0000
4:15840447:CCCA:C	acceptor_loss	1.0000
4:15840449:CAGA:C	acceptor_loss	1.0000
4:15840450:A:AG	acceptor_gain	1.0000
4:15840451:G:GA	acceptor_gain	1.0000
4:15840451:GA:G	acceptor_gain	1.0000
4:15840451:GAGA:G	acceptor_gain	1.0000
4:15840451:GAGAC:G	acceptor_gain	1.0000
4:15778617:TC:T	donor_gain	0.9900
4:15778643:A:G	donor_gain	0.9900
4:15778643:ATGAG:A	donor_loss	0.9900
4:15778645:GAGG:G	donor_loss	0.9900
4:15778647:GGTG:G	donor_loss	0.9900
4:15778648:G:A	donor_loss	0.9900
4:15816505:T:G	acceptor_gain	0.9900
4:15816507:TCAG:T	acceptor_loss	0.9900
4:15816508:CA:C	acceptor_loss	0.9900
4:15816509:A:AG	acceptor_gain	0.9900
4:15816510:G:GA	acceptor_loss	0.9900
4:15816510:G:GG	acceptor_gain	0.9900
4:15816510:GA:G	acceptor_gain	0.9900
4:15816510:GAC:G	acceptor_gain	0.9900
4:15816510:GACAT:G	acceptor_gain	0.9900
4:15816636:ACAAG:A	donor_loss	0.9900
4:15816637:CAAGG:C	donor_loss	0.9900
4:15816638:AAGG:A	donor_loss	0.9900
4:15816639:AG:A	donor_loss	0.9900
4:15816640:G:GT	donor_loss	0.9900
4:15816641:GTA:G	donor_loss	0.9900

AlphaMissense

1998 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:15824994:G:C	W159C	0.987
4:15824994:G:T	W159C	0.987
4:15834284:G:C	W189C	0.984
4:15834284:G:T	W189C	0.984
4:15838152:T:C	F216L	0.983
4:15838154:T:A	F216L	0.983
4:15838154:T:G	F216L	0.983
4:15824992:T:A	W159R	0.981
4:15824992:T:C	W159R	0.981
4:15816554:T:C	F93L	0.980
4:15816556:T:A	F93L	0.980
4:15816556:T:G	F93L	0.980
4:15824995:T:A	C160S	0.978
4:15824996:G:C	C160S	0.978
4:15838153:T:G	F216C	0.973
4:15840055:T:C	L230S	0.970
4:15824892:G:C	W125C	0.969
4:15824892:G:T	W125C	0.969
4:15834279:T:C	F188L	0.968
4:15834281:C:A	F188L	0.968
4:15834281:C:G	F188L	0.968
4:15778613:T:A	C67S	0.965
4:15778614:G:C	C67S	0.965
4:15834280:T:G	F188C	0.964
4:15840031:T:G	F222C	0.964
4:15816572:T:A	C99S	0.963
4:15816573:G:C	C99S	0.963
4:15834234:T:A	C173S	0.963
4:15834235:G:C	C173S	0.963
4:15816521:T:A	C82S	0.962

dbSNP variants (sampled 300 via entrez): RS1000004314 (4:15839482 GAC>G,GACAC), RS1000036999 (4:15839191 T>C), RS1000094121 (4:15784394 C>T), RS1000161595 (4:15785322 C>T), RS1000189637 (4:15819704 G>A,C,T), RS1000204924 (4:15787689 G>T), RS1000218539 (4:15832867 G>A), RS1000264456 (4:15795003 C>T), RS1000264810 (4:15819835 A>G), RS1000267299 (4:15801670 T>C), RS1000310651 (4:15832660 A>G), RS10003282 (4:15812723 A>G), RS1000340979 (4:15802417 C>A), RS1000375649 (4:15795798 T>C), RS10004415 (4:15787262 T>C,G)

Disease associations

OMIM: gene MIM:107270 | disease phenotypes: MIM:615873

GenCC curated gene-disease

Mondo (1): ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder (MONDO:0014379)

Orphanet (1): Helsmoortel-Van der Aa syndrome (Orphanet:404448)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003984_11	Parkinson’s disease	8.000000e-11
GCST004902_46	Parkinson’s disease	1.000000e-19
GCST008478_17	Neurological blood protein biomarker levels	1.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4660 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 98,082 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL50	QUERCETIN	3	74,559
CHEMBL151	LUTEOLIN	2	23,523

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1130169	CD38		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Abscisic acid receptor complex

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
isatuximab	Binding	10.0	pKd
mezagitamab	Binding	8.26	pKd
daratumumab	Antagonist	8.22	pKd
MK-0159	Inhibition	7.66	pIC50

Binding affinities (BindingDB)

110 measured of 147 human assays (147 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
ethyl 4-(pyrazolo[1,5-a]pyridine-2-carbonylamino)piperidine-1-carboxylate	IC50	2.4 nM	US-12514858: CD38 inhibitors
2-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]-6-(1-methylpyrazol-4-yl)pyrimidine-4-carboxamide	IC50	4.2 nM	US-12514858: CD38 inhibitors
3-(4-benzylpiperazin-1-yl)sulfonyl-N-[2-(3-fluoroanilino)-2-oxoethyl]-N-methylbenzamide	IC50	4.8 nM	US-12514858: CD38 inhibitors
6-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]-4-(1-methylpyrazol-4-yl)pyridine-2-carboxamide	IC50	5 nM	US-12514858: CD38 inhibitors
4,6-di(imidazol-1-yl)-N-[4-(2-methoxyethoxy)cyclohexyl]pyridine-2-carboxamide	IC50	6.8 nM	US-12514858: CD38 inhibitors
6-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]-4-(1,3-thiazol-5-yl)pyridine-2-carboxamide	IC50	7 nM	US-12514858: CD38 inhibitors
N’-[[4-[bis(2-chloroethyl)amino]phenyl]methyl]-2-(1H-indol-3-yl)acetohydrazide	IC50	7.4 nM	US-12514858: CD38 inhibitors
2-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]pyrimidine-4-carboxamide	IC50	8.8 nM	US-12514858: CD38 inhibitors
6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine	IC50	12 nM	US-12514858: CD38 inhibitors
3-(3,4-difluorophenyl)-N-(thiophen-2-ylmethyl)-1-benzofuran-7-carboxamide	IC50	12 nM	US-12514858: CD38 inhibitors
2-imidazol-1-yl-N-(4-methoxycyclohexyl)pyrimidine-4-carboxamide	IC50	12 nM	US-12514858: CD38 inhibitors
N-(1,3-dimethyl-2,6-dioxopyrimidin-4-yl)-3-phenylpropanamide	IC50	13.4 nM	US-12514858: CD38 inhibitors
2-ethylindeno[1,2-g]quinolin-10-one	IC50	14 nM	US-12514858: CD38 inhibitors
2-(3-chlorophenyl)-3-(thiophen-3-ylmethyl)imidazo[2,1-a]isoquinoline	IC50	15 nM	US-12514858: CD38 inhibitors
5-chloro-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methoxybenzamide	IC50	16 nM	US-12514858: CD38 inhibitors
(7R,9R)-9-acetyl-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-8,10-dihydro-7H-tetracene-5,12-dione	IC50	16 nM	US-12514858: CD38 inhibitors
5-(furan-2-yl)-3-(2-methoxyphenyl)-1,2,4-oxadiazole	IC50	16.5 nM	US-12514858: CD38 inhibitors
6-methyl-2-pyridin-2-yl-1,3-benzoxazole	IC50	16.6 nM	US-12514858: CD38 inhibitors
6-(3,4-dimethoxyphenyl)-N-methylpyrazin-2-amine	IC50	17 nM	US-12514858: CD38 inhibitors
(2S)-1-[(4S)-1,1-dioxo-2-[(1S)-1-phenylethyl]-4-(phenylmethoxymethyl)-3,4-dihydro-5,1lambda6,2-benzoxathiazepin-7-yl]pyrrolidine-2-carboxamide	IC50	17 nM	US-12514858: CD38 inhibitors
N-(3-methoxypropyl)-3-(4-methylphenyl)triazolo[1,5-a]quinazolin-5-amine	IC50	17.9 nM	US-12514858: CD38 inhibitors
3-[(3-fluorophenyl)methyl]-2-(furan-2-yl)imidazo[2,1-a]isoquinoline	IC50	18 nM	US-12514858: CD38 inhibitors
N-(4,5-dihydro-1,3-thiazol-2-yl)-5-methylthiophene-3-carboxamide	IC50	20.9 nM	US-12514858: CD38 inhibitors
US12514858, Example 23	IC50	21 nM	US-12514858: CD38 inhibitors
4-hydroxy-N-(3-hydroxyphenyl)-2-oxo-1H-quinoline-3-carboxamide	IC50	21.5 nM	US-12514858: CD38 inhibitors
2,4-dimethoxy-N-naphthalen-2-ylbenzamide	IC50	24 nM	US-12514858: CD38 inhibitors
2,2,5,5-tetramethyl-1-nitrosoimidazolidine-4-thione	IC50	25.7 nM	US-12514858: CD38 inhibitors
[(2S,6R)-6-[6-[methyl(propan-2-yl)amino]purin-9-yl]-4-(pyridin-3-ylmethyl)morpholin-2-yl]methanol	IC50	28 nM	US-12514858: CD38 inhibitors
N-(1H-indol-3-ylmethyl)-1-methylbenzimidazol-2-amine	IC50	28 nM	US-12514858: CD38 inhibitors
N-(2,3-dihydro-1H-inden-5-yl)-2-methoxy-4-methylsulfanylbenzamide	IC50	31 nM	US-12514858: CD38 inhibitors
3-benzyl-2-(furan-2-yl)imidazo[2,1-a]isoquinoline	IC50	31 nM	US-12514858: CD38 inhibitors
N-[4-(2-methoxyethoxy)cyclohexyl]-2-(1-methylpyrazol-4-yl)-6-(1,3-thiazol-5-yl)pyridine-4-carboxamide	IC50	34 nM	US-12514858: CD38 inhibitors
cyclopropyl-(2,4-dimethylphenyl)methanone	IC50	39 nM	US-12514858: CD38 inhibitors
2-N-(3-chloro-4-methylphenyl)quinazoline-2,4-diamine	IC50	40 nM	US-12514858: CD38 inhibitors
5-(furan-2-yl)-N-(2-phenylethyl)-1,2-oxazole-3-carboxamide	IC50	40 nM	US-12514858: CD38 inhibitors
3-methoxy-N-(4-methoxyphenyl)naphthalene-2-carboxamide	IC50	42 nM	US-12514858: CD38 inhibitors
N-[2-(dimethylamino)ethyl]-5-methyl-9-(methylamino)acridine-4-carboxamide	IC50	42 nM	US-12514858: CD38 inhibitors
4-fluoro-N-[(1-methylbenzimidazol-2-yl)methyl]aniline	IC50	45.9 nM	US-12514858: CD38 inhibitors
(E)-1-(1H-indol-3-yl)-3-phenylprop-2-en-1-one	IC50	49 nM	US-12514858: CD38 inhibitors
ethyl 5-hydroxy-2-methylbenzo[g][1]benzofuran-3-carboxylate	IC50	50 nM	US-12514858: CD38 inhibitors
6-imidazol-1-yl-N-(4-methoxycyclohexyl)pyridine-2-carboxamide	IC50	52 nM	US-12514858: CD38 inhibitors
methyl (1S,3R,3aS,6aR)-1-[[acetyl(methyl)amino]methyl]-5-benzyl-3-methyl-4,6-dioxo-1,2,3a,6a-tetrahydropyrrolo[3,4-c]pyrrole-3-carboxylate	IC50	53 nM	US-12514858: CD38 inhibitors
N-[4-(2-methoxyethoxy)cyclohexyl]-6-(1-methylpyrazol-4-yl)-2-(1,3-thiazol-5-yl)pyrimidine-4-carboxamide	IC50	53 nM	US-12514858: CD38 inhibitors
N-(4-methyl-2-pyridinyl)-2,3-dioxo-1,4-dihydroquinoxaline-6-carboxamide	IC50	54 nM	US-12514858: CD38 inhibitors
2-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]-6-(1,3-thiazol-5-yl)pyridine-4-carboxamide	IC50	60 nM	US-12514858: CD38 inhibitors
6-(1H-Imidazol-1-yl)-4-methyl-N-(1-(methylsulfonyl)piperidin-4-yl)picolinamide	IC50	65 nM	US-20250326739: CD38 MODULATORS AND USES THEREOF
6-(1H-Imidazol-1-yl)-4-methyl-N-(1-(methylsulfonyl)azetidin-3-yl)picolinamide	IC50	65 nM	US-20250326739: CD38 MODULATORS AND USES THEREOF
N-(1-Acetylpiperidin-4-yl)-6-(1H-imidazol-1-yl)-4-methylpicolinamide	IC50	65 nM	US-20250326739: CD38 MODULATORS AND USES THEREOF
N-Cyclobutyl-6-(1H-imidazol-1-yl)-4-methylpicolinamide	IC50	65 nM	US-20250326739: CD38 MODULATORS AND USES THEREOF
N-(1-Butyrylpiperidine-4-yl)-6-(1H-imidazol-1-yl)-4-methylpicolinamide	IC50	65 nM	US-20250326739: CD38 MODULATORS AND USES THEREOF

ChEMBL bioactivities

415 potent at pChembl≥5 of 454 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	Ki	0.3	nM	CHEMBL3426034
9.52	IC50	0.3	nM	CHEMBL5410644
9.35	Ki	0.45	nM	CHEMBL3426039
9.15	Ki	0.7	nM	CHEMBL3426035
8.89	IC50	1.3	nM	CHEMBL5401022
8.89	IC50	1.3	nM	CHEMBL5418653
8.85	IC50	1.4	nM	CHEMBL3426065
8.85	IC50	1.4	nM	CHEMBL5436403
8.85	IC50	1.4	nM	CHEMBL5426011
8.82	IC50	1.5	nM	CHEMBL5398114
8.82	IC50	1.5	nM	CHEMBL5434460
8.82	IC50	1.5	nM	CHEMBL5425216
8.80	IC50	1.6	nM	CHEMBL5440681
8.70	IC50	2	nM	CHEMBL5440312
8.70	IC50	2	nM	CHEMBL5427901
8.62	IC50	2.4	nM	CHEMBL5405079
8.47	IC50	3.4	nM	CHEMBL3426064
8.42	IC50	3.8	nM	CHEMBL3426037
8.42	IC50	3.8	nM	CHEMBL5414411
8.41	IC50	3.9	nM	CHEMBL3426033
8.40	IC50	4	nM	CHEMBL4229241
8.40	IC50	4	nM	CHEMBL5178786
8.38	IC50	4.2	nM	CHEMBL5076763
8.32	IC50	4.8	nM	CHEMBL3426066
8.30	IC50	5	nM	CHEMBL5083478
8.30	IC50	5	nM	CHEMBL5424500
8.30	IC50	5	nM	CHEMBL5396888
8.28	IC50	5.3	nM	CHEMBL3426067
8.22	IC50	6	nM	CHEMBL3426032
8.17	IC50	6.8	nM	CHEMBL5091229
8.15	IC50	7	nM	CHEMBL5076855
8.14	IC50	7.3	nM	CHEMBL3426034
8.11	IC50	7.8	nM	CHEMBL4225752
8.01	IC50	9.8	nM	CHEMBL5420517
8.00	IC50	10	nM	CHEMBL3426035
8.00	IC50	10	nM	CHEMBL5417850
7.96	IC50	11	nM	CHEMBL5403262
7.96	IC50	11	nM	CHEMBL5424631
7.92	IC50	12	nM	CHEMBL5176492
7.92	IC50	12	nM	CHEMBL5430964
7.92	IC50	12	nM	CHEMBL5431367
7.89	IC50	13	nM	CHEMBL3426038
7.89	IC50	13	nM	CHEMBL5172217
7.89	IC50	13	nM	CHEMBL5437449
7.85	IC50	14	nM	CHEMBL3426040
7.85	Ki	14	nM	CHEMBL3426030
7.82	IC50	15	nM	CHEMBL3426039
7.80	IC50	16	nM	CHEMBL5196986
7.77	IC50	17	nM	CHEMBL4224903
7.77	IC50	17	nM	CHEMBL5434181

PubChem BioAssay actives

228 with measured affinity, of 414 total; 50 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
4-[[4-(2-methoxyethoxy)cyclohexyl]amino]-1-methyl-6-(1,3-thiazol-5-yl)quinolin-2-one	1206115: Inhibition of wild type fully glycosylated human recombinant CD38-catalyzed NAD hydrolysis	ki	0.0003	uM
N-(3-fluorophenyl)-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0003	uM
4-[(4-methoxycyclohexyl)amino]-1,8-dimethyl-6-(1,3-thiazol-5-yl)quinolin-2-one	1206115: Inhibition of wild type fully glycosylated human recombinant CD38-catalyzed NAD hydrolysis	ki	0.0004	uM
4-[[4-(2-methoxyethoxy)cyclohexyl]amino]-1,8-dimethyl-6-(1,3-thiazol-5-yl)quinolin-2-one	1206115: Inhibition of wild type fully glycosylated human recombinant CD38-catalyzed NAD hydrolysis	ki	0.0007	uM
N-(3-chlorophenyl)-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0013	uM
N-(4-chloro-3-fluorophenyl)-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0013	uM
N-methyl-4-[[8-methyl-2-oxo-6-(1,3-thiazol-5-yl)-1H-quinolin-4-yl]amino]cyclohexane-1-carboxamide	1206113: Inhibition of human CD38 extracellular domain expressed in Pichia pastoris assessed as NAD hydrolysis by colorimetric-based assay	ic50	0.0014	uM
2-imidazol-1-yl-N-[4-(trifluoromethyl)phenyl]pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0014	uM
N-(3,5-difluorophenyl)-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0014	uM
N-(4-cyanophenyl)-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0015	uM
N-(3,4-difluorophenyl)-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0015	uM
N-(4-fluorophenyl)-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0015	uM
N-(4-chlorophenyl)-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0016	uM
2-imidazol-1-yl-N-pyridin-4-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0020	uM
2-imidazol-1-yl-N-(4-methylphenyl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0020	uM
2-imidazol-1-yl-N-(3-methylphenyl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0024	uM
N-methyl-4-[[2-oxo-6-(1,3-thiazol-5-yl)-1H-quinolin-4-yl]amino]cyclohexane-1-carboxamide	1206113: Inhibition of human CD38 extracellular domain expressed in Pichia pastoris assessed as NAD hydrolysis by colorimetric-based assay	ic50	0.0034	uM
4-[(4-methoxycyclohexyl)amino]-8-methyl-6-(1,3-thiazol-5-yl)-1H-quinolin-2-one	1206113: Inhibition of human CD38 extracellular domain expressed in Pichia pastoris assessed as NAD hydrolysis by colorimetric-based assay	ic50	0.0038	uM
2-imidazol-1-yl-N-pyridin-4-yl-6-(trifluoromethyl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0038	uM
4-[[4-(2-methoxyethoxy)cyclohexyl]amino]-8-methyl-6-(1,3-thiazol-5-yl)-1H-quinolin-2-one	1206113: Inhibition of human CD38 extracellular domain expressed in Pichia pastoris assessed as NAD hydrolysis by colorimetric-based assay	ic50	0.0039	uM
2-(3-aminospiro[1,4-dihydropyrrolo[3,4-d]pyrazole-6,1’-cyclopropane]-5-yl)-4-[[2-fluoro-6-(trifluoromethyl)phenyl]methylamino]-1,4-dihydroquinazoline-8-carboxamide	1391266: Inhibition of recombinant human CD38 extracellular domain expressed in Pichia pastoris using NAD as substrate pretreated for 30 mins followed by substrate addition measured after 15 to 45 mins	ic50	0.0040	uM
5-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]-3-nitro-1H-indole-7-carboxamide	1892757: Inhibition of human his tagged CD38 using N6-etheno-NAD as substrate by fluorescence microplate reader assay	ic50	0.0040	uM
2-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]-6-(1-methylpyrazol-4-yl)pyrimidine-4-carboxamide	1810188: Inhibition of His-tagged human CD38 using etheno-NAD as substrate preincubated for 30 mins followed by substrate addition and further incubated for 10 mins by fluorometry analysis	ic50	0.0042	uM
N-methyl-4-[[1-methyl-2-oxo-6-(1,3-thiazol-5-yl)quinolin-4-yl]amino]cyclohexane-1-carboxamide	1206113: Inhibition of human CD38 extracellular domain expressed in Pichia pastoris assessed as NAD hydrolysis by colorimetric-based assay	ic50	0.0048	uM
6-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]-4-(1-methylpyrazol-4-yl)pyridine-2-carboxamide	1810188: Inhibition of His-tagged human CD38 using etheno-NAD as substrate preincubated for 30 mins followed by substrate addition and further incubated for 10 mins by fluorometry analysis	ic50	0.0050	uM
2-imidazol-1-yl-N-pyridin-3-yl-6-(trifluoromethyl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0050	uM
N-(3-fluorophenyl)-2-imidazol-1-yl-6-(trifluoromethyl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0050	uM
4-[[1,8-dimethyl-2-oxo-6-(1,3-thiazol-5-yl)quinolin-4-yl]amino]-N-methylcyclohexane-1-carboxamide	1206113: Inhibition of human CD38 extracellular domain expressed in Pichia pastoris assessed as NAD hydrolysis by colorimetric-based assay	ic50	0.0053	uM
4-[[4-(2-methoxyethoxy)cyclohexyl]amino]-6-(1,3-thiazol-5-yl)-1H-quinolin-2-one	1206113: Inhibition of human CD38 extracellular domain expressed in Pichia pastoris assessed as NAD hydrolysis by colorimetric-based assay	ic50	0.0060	uM
4,6-di(imidazol-1-yl)-N-[4-(2-methoxyethoxy)cyclohexyl]pyridine-2-carboxamide	1810188: Inhibition of His-tagged human CD38 using etheno-NAD as substrate preincubated for 30 mins followed by substrate addition and further incubated for 10 mins by fluorometry analysis	ic50	0.0068	uM
6-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]-4-(1,3-thiazol-5-yl)pyridine-2-carboxamide	1810188: Inhibition of His-tagged human CD38 using etheno-NAD as substrate preincubated for 30 mins followed by substrate addition and further incubated for 10 mins by fluorometry analysis	ic50	0.0070	uM
2-(3-aminospiro[1,4-dihydropyrrolo[3,4-d]pyrazole-6,1’-cyclobutane]-5-yl)-4-[[2-fluoro-6-(trifluoromethyl)phenyl]methylamino]-1,4-dihydroquinazoline-8-carboxamide	1391266: Inhibition of recombinant human CD38 extracellular domain expressed in Pichia pastoris using NAD as substrate pretreated for 30 mins followed by substrate addition measured after 15 to 45 mins	ic50	0.0078	uM
2-imidazol-1-yl-N-pyridazin-4-yl-6-(trifluoromethyl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0098	uM
N-cycloheptyl-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0100	uM
2-imidazol-1-yl-N-[2-(2-methoxyethoxy)pyrimidin-5-yl]-6-(trifluoromethyl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0110	uM
2-imidazol-1-yl-N-(1,3-thiazol-5-yl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0110	uM
2-imidazol-1-yl-N-(4-methylcyclohexyl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0120	uM
N-[4-(2-methoxyethoxy)cyclohexyl]-2-oxo-6-(1,3-thiazol-5-yl)-1,3,3a,7a-tetrahydrobenzimidazole-4-carboxamide	1892757: Inhibition of human his tagged CD38 using N6-etheno-NAD as substrate by fluorescence microplate reader assay	ic50	0.0120	uM
N-(4,4-difluorocyclohexyl)-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0120	uM
4-[(4-methoxycyclohexyl)amino]-1-methyl-6-(1,3-thiazol-5-yl)quinolin-2-one	1206113: Inhibition of human CD38 extracellular domain expressed in Pichia pastoris assessed as NAD hydrolysis by colorimetric-based assay	ic50	0.0130	uM
N-[4-(2-methoxyethoxy)cyclohexyl]-5-(1,3-thiazol-5-yl)-1H-indole-7-carboxamide	1892757: Inhibition of human his tagged CD38 using N6-etheno-NAD as substrate by fluorescence microplate reader assay	ic50	0.0130	uM
2-imidazol-1-yl-N-pyrimidin-5-yl-6-(trifluoromethyl)pyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0130	uM
1-methyl-4-(oxan-4-ylamino)-6-(1,3-thiazol-5-yl)quinolin-2-one	1206115: Inhibition of wild type fully glycosylated human recombinant CD38-catalyzed NAD hydrolysis	ki	0.0140	uM
4-[(4-hydroxycyclohexyl)amino]-1-methyl-6-(1,3-thiazol-5-yl)quinolin-2-one	1206113: Inhibition of human CD38 extracellular domain expressed in Pichia pastoris assessed as NAD hydrolysis by colorimetric-based assay	ic50	0.0140	uM
3-cyano-N-[4-(2-methoxyethoxy)cyclohexyl]-6-(1,3-thiazol-5-yl)-1H-indole-4-carboxamide	1892757: Inhibition of human his tagged CD38 using N6-etheno-NAD as substrate by fluorescence microplate reader assay	ic50	0.0160	uM
2-(3-aminospiro[1,4-dihydropyrrolo[3,4-d]pyrazole-6,1’-cyclopentane]-5-yl)-4-[[2-fluoro-6-(trifluoromethyl)phenyl]methylamino]-1,4-dihydroquinazoline-8-carboxamide	1391266: Inhibition of recombinant human CD38 extracellular domain expressed in Pichia pastoris using NAD as substrate pretreated for 30 mins followed by substrate addition measured after 15 to 45 mins	ic50	0.0170	uM
N-cyclooctyl-2-imidazol-1-ylpyrimidine-4-carboxamide	2014495: Inhibition of human CD38 using epslon-NAD as substrate and measured for 1 hrs by fluorescence based microplate reader analysis	ic50	0.0170	uM
2-(3-amino-6,6-dimethyl-1,4-dihydropyrrolo[3,4-d]pyrazol-5-yl)-4-[[2-fluoro-6-(trifluoromethyl)phenyl]methylamino]-1,4-dihydroquinazoline-8-carboxamide	1391266: Inhibition of recombinant human CD38 extracellular domain expressed in Pichia pastoris using NAD as substrate pretreated for 30 mins followed by substrate addition measured after 15 to 45 mins	ic50	0.0200	uM
2-[(6R)-3,6-dimethyl-4,6-dihydro-2H-pyrrolo[3,4-c]pyrazol-5-yl]-4-[[2-fluoro-6-(trifluoromethyl)phenyl]methylamino]-1,4-dihydroquinazoline-8-carboxamide	1391266: Inhibition of recombinant human CD38 extracellular domain expressed in Pichia pastoris using NAD as substrate pretreated for 30 mins followed by substrate addition measured after 15 to 45 mins	ic50	0.0210	uM
5-imidazol-1-yl-N-[4-(2-methoxyethoxy)cyclohexyl]-1H-indazole-7-carboxamide	1892757: Inhibition of human his tagged CD38 using N6-etheno-NAD as substrate by fluorescence microplate reader assay	ic50	0.0210	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases reaction, increases expression, affects cotreatment, affects reaction	12
Arsenic Trioxide	affects cotreatment, increases expression, increases response to substance	3
Dacarbazine	affects cotreatment, increases expression, increases reaction	3
tamibarotene	increases expression	2
(+)-JQ1 compound	decreases expression	2
Resveratrol	increases expression	2
Alitretinoin	increases expression, increases reaction, decreases reaction	2
Rotenone	increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, affects methylation	1
quercitrin	decreases expression	1
terbufos	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
periodate-oxidized adenosine	decreases reaction, increases expression, increases reaction	1
ferrous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
Ro 31-8220	decreases reaction, increases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	decreases reaction, increases expression, affects cotreatment	1
rottlerin	decreases reaction, increases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases activity, increases expression	1
CGP 52608	affects binding, increases reaction	1
SB 203580	decreases reaction, increases cleavage	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
Ro 25-6603	affects cotreatment, decreases reaction, increases expression	1
JP8 aviation fuel	decreases expression	1
2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide	decreases reaction, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
gardiquimod	increases expression, decreases reaction	1

ChEMBL screening assays

28 unique, capped per target: 22 binding, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1285540	Binding	Inhibition of human recombinant CD38 expressed in Pichia pastoris by continuous fluorometric method	Identification by high-throughput screening of inhibitors of Schistosoma mansoni NAD(+) catabolizing enzyme. — Bioorg Med Chem
CHEMBL3371551	ADMET	Drug metabolism assessed as human CD38 catalytic domain-mediated compound hydrolysis by measuring 8-NH2-N9-butyl-IDPR level at 1 mM by RP-HPLC method	Cyclic adenosine 5’-diphosphate ribose analogs without a “southern” ribose inhibit ADP-ribosyl cyclase-hydrolase CD38. — J Med Chem

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1MQ	Abcam HeLa CD38 KO	Cancer cell line	Female
CVCL_B8D0	Abcam HCT 116 CD38 KO	Cancer cell line	Male
CVCL_B9F8	Abcam A-549 CD38 KO	Cancer cell line	Male
CVCL_E6PJ	Genomeditech CHO-K1 H_CD38	Spontaneously immortalized cell line	Female
CVCL_KA32	CHO-K1/CD38	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04388774	PHASE1/PHASE2	COMPLETED	Low-Dose Ketamine in Children With ADNP Syndrome
NCT03718936	Not specified	RECRUITING	ADNP Syndrome: The Seaver Autism Center for Research and Treatment is Characterizing ADNP-related Neurodevelopmental Disorders Using Genetic, Medical, and Neuropsychological Measures.