CD38

Chr 4

CD38 molecule

Also known as: ADPRC 1, ADPRC1, cADPR1

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. [provided by RefSeq, Sep 2015]

GeneReviewsOMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.13
Clinical SummaryCD38
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 VUS of 55 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — CD38
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.13LOEUF
pLI 0.000
Z-score 1.19
OE 0.68 (0.431.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.06Z-score
OE missense 1.01 (0.891.15)
167 obs / 164.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.68 (0.431.13)
00.351.4
Missense OE?1.01 (0.891.15)
00.61.4
Synonymous OE?0.84
01.21.6
LoF obs/exp: 11 / 16.2Missense obs/exp: 167 / 164.7Syn Z: 0.96

This gene — mechanism propensity

DN
0.6649th %ile
GOF
0.72top 25%
LOF
0.2386th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

55 submitted variants in ClinVar

Classification Summary

VUS34
Likely Benign3
Benign2
34
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
1
33
0
0
34
Likely Benign
0
3
0
0
3
Benign
0
0
1
1
2
Total1361139

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

52 pathogenic / likely-pathogenic (of 57) ClinVar copy-number / structural variants overlap CD38 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CD38 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

AutophagyGalectinsHIV Infections

Study of Autophagy and the Effects of GALIG Gene Products in HIV-1 Infected Patients Who Are Under Antiretroviral Therapy Since Primary-infection, Chronic Phase, or Never Treated.

RECRUITING
NCT04160455Centre Hospitalier Régional d'OrléansStarted 2019-11-07
expression of a panel
Recurrent Plasma Cell MyelomaRefractory Plasma Cell Myeloma

Selinexor, Daratumumab, Carfilzomib and Dexamethasone for the Treatment of High-Risk, Recurrent or Refractory Multiple Myeloma

ACTIVE NOT RECRUITING
NCT04756401Phase PHASE2Academic and Community Cancer Research UnitedStarted 2022-12-08
CarfilzomibDaratumumabDexamethasone
HivHIV I Infection

Multi Interventional Approaches to Mitigate HIV Reservoirs Aiming the Sustained HIV Remission Without Antiretrovirals

NOT YET RECRUITING
NCT06805656Phase PHASE2Federal University of São PauloStarted 2026-07-01
MaravirocDolutegravirDendritic Cell Vaccine
Cavernous Malformation, Cerebral

Daratumumab for Familial Cerebral Cavernous Malformations: A Single-Arm Safety and Efficacy Study

NOT YET RECRUITING
NCT07026604Phase EARLY_PHASE1Beijing Tiantan HospitalStarted 2025-07-01
Daratumumab
AstrocytomaGlioblastomaProgressive Disease

First-in Cancer-Type Phase I Study of FT536 for Recurrent WHO Grade 4 Astrocytoma

RECRUITING
NCT07560865Phase PHASE1Masonic Cancer Center, University of MinnesotaStarted 2026-04-23
FT536Biopsy/ Intratumoral Injection/ Gross Tumor ResectionBlood/ Cerebrospinal Fluid/ Tumor Pathology
SepsisSeptic Shock

Myeloid Bias in the Bone Marrow of Septic Patients and Its Correlation With Disease Severity and Prognosis: A Single-Center, Prospective Cohort Study

NOT YET RECRUITING
NCT07667153Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyStarted 2026-07-15
Bone marrow aspirate collection
Acute Myeloid Leukemia

A Clinical Study to Evaluate the Safety and Efficacy of CLL1 and CD38 Dual-Target CAR-T Cell Injection in the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

RECRUITING
NCT06880354Phase PHASE1Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2025-05-22
CLL1 and CD38 Dual-Target CAR-T Cell Injection
Artemis (DCLRE1C ) Deficient Severe Combined Immunodeficiency

Safety and Efficacy Study of Transplantation of Autologous CD34+ Cells Transduced With the G2ARTE Lentiviral Vector Expressing the DCLRE1C cDNA in Artemis (DCLRE1C) Deficient Severe Combined Immunodeficiency Patients (ARTEGENE)

RECRUITING
NCT05071222Phase PHASE1, PHASE2Assistance Publique - Hôpitaux de ParisStarted 2023-07-19
ARTEGENE drug product
Multiple Myeloma in Relapse

Study of Elranatamab for Relapsed or Refractory Myeloma in Patients Previously Exposed to Three-drug Classes

ACTIVE NOT RECRUITING
NCT06282978Phase PHASE2PETHEMA FoundationStarted 2023-11-23
Elranatamab (PF-06863135)
Acute Myeloid Leukemia

Role of Adrenomedullin in Leukemic Endosteal/Vascular Niches

ACTIVE NOT RECRUITING
NCT04460963Phase NAGruppo Italiano Malattie EMatologiche dell'AdultoStarted 2021-06-09
Adrenomedullin
Plasma Cell Myeloma

Comparing Combinations of Drugs to Treat Newly Diagnosed Multiple Myeloma (NDMM) When a Stem Cell Transplant is Not a Medically Suitable Treatment

RECRUITING
NCT05561387Phase PHASE3SWOG Cancer Research NetworkStarted 2023-10-12
BortezomibDaratumumab and Hyaluronidase-fihjDexamethasone
Maternal ObesityObesity

The Developmental Origins of Obesity

RECRUITING
NCT06981676Phase NAPontificia Universidad Catolica de ChileStarted 2023-07-25
DHA and EPA