CD38

protein-coding

CD38 molecule, the group of CD molecules

Gene summary

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]

MANE transcript

NM_001775.4

Inheritance

—

ClinVar variants

U:41B:4

Top phenotype

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr4:15,778,275-15,853,232

External References & Databases

Ensembl (ENSG00000004468)

Transcript & Mutation Effects

hg38 • Region Span ~75.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CD38 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 35

not providedTotal: 3

ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001775.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			34 clinvar	3 clinvar		37
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	41	3	1	45

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001775.4	RefSeq	NP_001766.2	8	MANE Select
ENST00000226279.8	Ensembl	ENSP00000226279.2	8	MANE Select
ENST00000502843.5	Ensembl	ENSP00000427277.1	3	Standard
ENST00000510674.1	Ensembl	ENSP00000423047.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxytocin signaling pathway - Homo sapiens (human)
Nicotinate and nicotinamide metabolism - Homo sapiens (human)
Calcium signaling pathway - Homo sapiens (human)
Salivary secretion - Homo sapiens (human)
Pancreatic secretion - Homo sapiens (human)

Biological Process

response to hypoxia
signal transduction
positive regulation of cytosolic calcium ion concentration
female pregnancy
negative regulation of neuron projection development

Molecular Function

NAD+ nucleosidase activity
transferase activity
phosphorus-oxygen lyase activity
identical protein binding
NAD(P)+ nucleosidase activity

Cellular Component

nucleus
plasma membrane
cell surface
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000226279
Coding exons: 8
Length: 74956
Individuals with no LoFs: 125539
Homozygous LoFs: 1
Heterozygous LoFs: 208
Defined: 125748
p: 0.000831

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0647	167	165	1.01	0.00000800	1982
Missense (PolyPhen)		49	51.685	0.94805		668
Synonymous	0.961	52	61.6	0.844	0.00000306	548
Loss of Function	1.19	11	16.2	0.680	6.88e-7	180

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0088	0.0083	notable
Latino/Admixed American	0.00081	0.00078	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.000066	0.000065	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Synthesizes the second messagers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system.;

Recessive Scores

pRec: 0.355

Intolerance Scores

LoFtool: 0.890
RVIS EVS: -0.6
RVIS percentile EVS: 17.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium