SMPD3

protein-coding

sphingomyelin phosphodiesterase 3

Gene summary

Enables sphingomyelin phosphodiesterase activity. Involved in sphingomyelin catabolic process. Located in endoplasmic reticulum. Biomarker of pulmonary emphysema. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_018667.4

Inheritance

—

ClinVar variants

U:102B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr16:68,358,327-68,448,508

External References & Databases

Ensembl (ENSG00000103056)

Transcript & Mutation Effects

hg38 • Region Span ~90.2 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 SMPD3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 103

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018667.4. 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			101 clinvar	2 clinvar		103
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	102	2	0	104

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018667.4	RefSeq	NP_061137.1	7	MANE Select
ENST00000219334.10	Ensembl	ENSP00000219334.5	7	MANE Select
ENST00000561749.1	Ensembl	ENSP00000457236.1	1	Standard
ENST00000563226.1	Ensembl	ENSP00000455955.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Sphingolipid metabolism - Homo sapiens (human)
Signal Transduction
Metabolism of lipids
sphingomyelin metabolism/ceramide salvage
Metabolism

Biological Process

hematopoietic progenitor cell differentiation
sphingomyelin metabolic process
sphingomyelin catabolic process
cell cycle
peptide hormone secretion

Molecular Function

sphingomyelin phosphodiesterase activity
protein binding
metal ion binding

Cellular Component

Golgi cis cisterna
Golgi membrane
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000219334
Coding exons: 7
Length: 90361
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125735
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.11	356	420	0.848	0.0000282	4181
Missense (PolyPhen)		96	156.71	0.61261		1588
Synonymous	-1.34	228	204	1.12	0.0000156	1368
Loss of Function	3.66	5	24.6	0.203	0.00000140	254

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Regulates the cell cycle by acting as a growth suppressor in confluent cells. Probably acts as a regulator of postnatal development and participates in bone and dentin mineralization. {ECO:0000269|PubMed:10823942, ECO:0000269|PubMed:14741383, ECO:0000269|PubMed:15051724}.;

Recessive Scores

pRec: 0.183

Intolerance Scores

LoFtool: 0.152
RVIS EVS: -0.91
RVIS percentile EVS: 10.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.984

Gene Damage Prediction

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