SMPD4 (sphingomyelin phosphodiesterase 4)

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Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases Related genes Diseases linked via similar genes

Gene

• Entrez ID: 55627
• Gene name: Sphingomyelin phosphodiesterase 4
• Gene symbol: SMPD4
• Synonyms (NCBI Gene): NEDMABA, NEDMEBA, NET13, NSMASE-3, NSMASE3, SKNY
• Chromosome: 2
• Chromosome location: 2q21.1
• Summary: The protein encoded by this gene is a sphingomyelinase that catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide. This gene is activated by DNA damage, cellular stress, and tumor necrosis factor, but it is downregulate

SNPs Show/Hide all (6)

SNP ID	Visualize variation	Clinical significance	Consequence
rs747433356	G>A,T	Pathogenic	Missense variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant
rs766318490	C>T	Pathogenic	Genic downstream transcript variant, intron variant
rs780446128	C>A	Pathogenic	Splice donor variant, intron variant
rs1391542283	C>T	Pathogenic	Genic downstream transcript variant, splice donor variant
rs1573664291	GAGCGCG>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant, genic downstream transcript variant
rs1573728266	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, stop gained

miRNA Show/Hide all (160)

miRTarBase ID	miRNA	Experiments	Reference
MIRT022153	hsa-miR-124-3p	Microarray	18668037
MIRT031423	hsa-miR-16-5p	Proteomics	18668040
MIRT043289	hsa-miR-331-3p	CLASH	23622248
MIRT1373853	hsa-miR-1205	CLIP-seq
MIRT1373854	hsa-miR-124	CLIP-seq
MIRT1373855	hsa-miR-1286	CLIP-seq
MIRT1373856	hsa-miR-2467-3p	CLIP-seq
MIRT1373857	hsa-miR-3158-5p	CLIP-seq
MIRT1373858	hsa-miR-3605-5p	CLIP-seq
MIRT1373859	hsa-miR-3613-3p	CLIP-seq
MIRT1373860	hsa-miR-3616-5p	CLIP-seq
MIRT1373861	hsa-miR-3647-5p	CLIP-seq
MIRT1373862	hsa-miR-3663-3p	CLIP-seq
MIRT1373863	hsa-miR-3678-3p	CLIP-seq
MIRT1373864	hsa-miR-3914	CLIP-seq
MIRT1373865	hsa-miR-3942-3p	CLIP-seq
MIRT1373866	hsa-miR-4256	CLIP-seq
MIRT1373867	hsa-miR-4422	CLIP-seq
MIRT1373868	hsa-miR-4504	CLIP-seq
MIRT1373869	hsa-miR-4659a-5p	CLIP-seq
MIRT1373870	hsa-miR-4659b-5p	CLIP-seq
MIRT1373871	hsa-miR-4677-3p	CLIP-seq
MIRT1373872	hsa-miR-4679	CLIP-seq
MIRT1373873	hsa-miR-4691-5p	CLIP-seq
MIRT1373874	hsa-miR-4698	CLIP-seq
MIRT1373875	hsa-miR-4722-5p	CLIP-seq
MIRT1373876	hsa-miR-4724-5p	CLIP-seq
MIRT1373877	hsa-miR-4734	CLIP-seq
MIRT1373878	hsa-miR-4776-3p	CLIP-seq
MIRT1373879	hsa-miR-4795-5p	CLIP-seq
MIRT1373880	hsa-miR-499-3p	CLIP-seq
MIRT1373881	hsa-miR-499a-3p	CLIP-seq
MIRT1373882	hsa-miR-506	CLIP-seq
MIRT1373883	hsa-miR-511	CLIP-seq
MIRT1373884	hsa-miR-520d-5p	CLIP-seq
MIRT1373885	hsa-miR-524-5p	CLIP-seq
MIRT1373886	hsa-miR-542-3p	CLIP-seq
MIRT1373887	hsa-miR-573	CLIP-seq
MIRT1373888	hsa-miR-591	CLIP-seq
MIRT1373889	hsa-miR-604	CLIP-seq
MIRT1373890	hsa-miR-607	CLIP-seq
MIRT1373891	hsa-miR-615-5p	CLIP-seq
MIRT1373892	hsa-miR-647	CLIP-seq
MIRT1373893	hsa-miR-873	CLIP-seq
MIRT1373894	hsa-miR-887	CLIP-seq
MIRT1373895	hsa-miR-9	CLIP-seq
MIRT1373896	hsa-miR-2278	CLIP-seq
MIRT1373897	hsa-miR-4468	CLIP-seq
MIRT1373898	hsa-miR-4738-3p	CLIP-seq
MIRT2111354	hsa-miR-1273f	CLIP-seq
MIRT2111355	hsa-miR-143	CLIP-seq
MIRT2111356	hsa-miR-1470	CLIP-seq
MIRT2111357	hsa-miR-1915	CLIP-seq
MIRT2111358	hsa-miR-3123	CLIP-seq
MIRT2111359	hsa-miR-3137	CLIP-seq
MIRT2111360	hsa-miR-3184	CLIP-seq
MIRT2111361	hsa-miR-3690	CLIP-seq
MIRT2111362	hsa-miR-3919	CLIP-seq
MIRT2111363	hsa-miR-423-5p	CLIP-seq
MIRT2111364	hsa-miR-4254	CLIP-seq
MIRT2111365	hsa-miR-4328	CLIP-seq
MIRT2111366	hsa-miR-4667-3p	CLIP-seq
MIRT1373874	hsa-miR-4698	CLIP-seq
MIRT2111367	hsa-miR-4703-3p	CLIP-seq
MIRT2111368	hsa-miR-4708-5p	CLIP-seq
MIRT2111369	hsa-miR-4726-3p	CLIP-seq
MIRT1373877	hsa-miR-4734	CLIP-seq
MIRT2111370	hsa-miR-4756-3p	CLIP-seq
MIRT2111371	hsa-miR-4770	CLIP-seq
MIRT1373880	hsa-miR-499-3p	CLIP-seq
MIRT1373881	hsa-miR-499a-3p	CLIP-seq
MIRT1373884	hsa-miR-520d-5p	CLIP-seq
MIRT1373885	hsa-miR-524-5p	CLIP-seq
MIRT2111372	hsa-miR-568	CLIP-seq
MIRT2111373	hsa-miR-642a	CLIP-seq
MIRT2111356	hsa-miR-1470	CLIP-seq
MIRT2111357	hsa-miR-1915	CLIP-seq
MIRT2334451	hsa-miR-3151	CLIP-seq
MIRT2111360	hsa-miR-3184	CLIP-seq
MIRT2111361	hsa-miR-3690	CLIP-seq
MIRT2111363	hsa-miR-423-5p	CLIP-seq
MIRT2111364	hsa-miR-4254	CLIP-seq
MIRT2334452	hsa-miR-4662a-5p	CLIP-seq
MIRT2111366	hsa-miR-4667-3p	CLIP-seq
MIRT2111369	hsa-miR-4726-3p	CLIP-seq
MIRT2111373	hsa-miR-642a	CLIP-seq
MIRT2460043	hsa-miR-3194-5p	CLIP-seq
MIRT2460044	hsa-miR-3922-5p	CLIP-seq
MIRT2460045	hsa-miR-4727-5p	CLIP-seq
MIRT2460046	hsa-miR-4753-5p	CLIP-seq
MIRT2460047	hsa-miR-4769-3p	CLIP-seq
MIRT2628477	hsa-miR-1207-3p	CLIP-seq
MIRT2628478	hsa-miR-1229	CLIP-seq
MIRT2628479	hsa-miR-1257	CLIP-seq
MIRT2111354	hsa-miR-1273f	CLIP-seq
MIRT2111355	hsa-miR-143	CLIP-seq
MIRT2628480	hsa-miR-2117	CLIP-seq
MIRT2334451	hsa-miR-3151	CLIP-seq
MIRT2628481	hsa-miR-3185	CLIP-seq
MIRT2628482	hsa-miR-3192	CLIP-seq
MIRT2628483	hsa-miR-326	CLIP-seq
MIRT2628484	hsa-miR-330-5p	CLIP-seq
MIRT2628485	hsa-miR-342-3p	CLIP-seq
MIRT2628486	hsa-miR-342-5p	CLIP-seq
MIRT2628487	hsa-miR-3667-5p	CLIP-seq
MIRT2628488	hsa-miR-4273	CLIP-seq
MIRT2628489	hsa-miR-4287	CLIP-seq
MIRT2628490	hsa-miR-432	CLIP-seq
MIRT2628491	hsa-miR-4447	CLIP-seq
MIRT2628492	hsa-miR-4469	CLIP-seq
MIRT2628493	hsa-miR-4472	CLIP-seq
MIRT2628494	hsa-miR-4639-3p	CLIP-seq
MIRT2628495	hsa-miR-4651	CLIP-seq
MIRT2628496	hsa-miR-4655-3p	CLIP-seq
MIRT2628497	hsa-miR-4664-5p	CLIP-seq
MIRT2628498	hsa-miR-4685-3p	CLIP-seq
MIRT2111368	hsa-miR-4708-5p	CLIP-seq
MIRT2628499	hsa-miR-4713-5p	CLIP-seq
MIRT2628500	hsa-miR-4749-3p	CLIP-seq
MIRT2111371	hsa-miR-4770	CLIP-seq
MIRT2628501	hsa-miR-4802-3p	CLIP-seq
MIRT2628502	hsa-miR-491-5p	CLIP-seq
MIRT2628503	hsa-miR-493	CLIP-seq
MIRT2628504	hsa-miR-494	CLIP-seq
MIRT2628505	hsa-miR-608	CLIP-seq
MIRT2628506	hsa-miR-618	CLIP-seq
MIRT2628477	hsa-miR-1207-3p	CLIP-seq
MIRT2691512	hsa-miR-122	CLIP-seq
MIRT2691513	hsa-miR-1225-3p	CLIP-seq
MIRT2628478	hsa-miR-1229	CLIP-seq
MIRT2691514	hsa-miR-1233	CLIP-seq
MIRT2691515	hsa-miR-1267	CLIP-seq
MIRT2111354	hsa-miR-1273f	CLIP-seq
MIRT2691516	hsa-miR-1343	CLIP-seq
MIRT2111355	hsa-miR-143	CLIP-seq
MIRT2628480	hsa-miR-2117	CLIP-seq
MIRT2691517	hsa-miR-3074-5p	CLIP-seq
MIRT2691518	hsa-miR-3121-5p	CLIP-seq
MIRT2691519	hsa-miR-3124-3p	CLIP-seq
MIRT2628482	hsa-miR-3192	CLIP-seq
MIRT2628483	hsa-miR-326	CLIP-seq
MIRT2628484	hsa-miR-330-5p	CLIP-seq
MIRT2628485	hsa-miR-342-3p	CLIP-seq
MIRT2111361	hsa-miR-3690	CLIP-seq
MIRT2111364	hsa-miR-4254	CLIP-seq
MIRT2628488	hsa-miR-4273	CLIP-seq
MIRT2628489	hsa-miR-4287	CLIP-seq
MIRT2628490	hsa-miR-432	CLIP-seq
MIRT2628492	hsa-miR-4469	CLIP-seq
MIRT2628494	hsa-miR-4639-3p	CLIP-seq
MIRT2628496	hsa-miR-4655-3p	CLIP-seq
MIRT2628498	hsa-miR-4685-3p	CLIP-seq
MIRT2111368	hsa-miR-4708-5p	CLIP-seq
MIRT2628499	hsa-miR-4713-5p	CLIP-seq
MIRT2691520	hsa-miR-4731-5p	CLIP-seq
MIRT2111371	hsa-miR-4770	CLIP-seq
MIRT2628501	hsa-miR-4802-3p	CLIP-seq
MIRT2628504	hsa-miR-494	CLIP-seq
MIRT2628506	hsa-miR-618	CLIP-seq
MIRT2691521	hsa-miR-885-3p	CLIP-seq

Gene ontology (GO) Show/Hide all (31)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	IEA
GO:0004767	Function	Sphingomyelin phosphodiesterase activity	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005635	Component	Nuclear envelope	IEA
GO:0005635	Component	Nuclear envelope	ISS
GO:0005640	Component	Nuclear outer membrane	IDA	31495489
GO:0005783	Component	Endoplasmic reticulum	IDA	16517606, 18505924, 31495489
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005794	Component	Golgi apparatus	IDA	16517606
GO:0005794	Component	Golgi apparatus	IEA
GO:0005802	Component	Trans-Golgi network	IDA	16517606
GO:0005886	Component	Plasma membrane	IEA
GO:0006629	Process	Lipid metabolic process	IEA
GO:0006685	Process	Sphingomyelin catabolic process	IBA
GO:0006685	Process	Sphingomyelin catabolic process	IDA	16517606, 25180167
GO:0007029	Process	Endoplasmic reticulum organization	IMP	31495489
GO:0016020	Component	Membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0042383	Component	Sarcolemma	IEA
GO:0042383	Component	Sarcolemma	ISS
GO:0046475	Process	Glycerophospholipid catabolic process	IBA
GO:0046475	Process	Glycerophospholipid catabolic process	IDA	16517606
GO:0046513	Process	Ceramide biosynthetic process	IBA
GO:0046513	Process	Ceramide biosynthetic process	IDA	16517606, 25180167
GO:0046872	Function	Metal ion binding	IEA
GO:0050290	Function	Sphingomyelin phosphodiesterase D activity	IBA
GO:0050290	Function	Sphingomyelin phosphodiesterase D activity	IDA	16517606, 25180167
GO:0050290	Function	Sphingomyelin phosphodiesterase D activity	IEA
GO:0071356	Process	Cellular response to tumor necrosis factor	IDA	16517606

Other IDs

• MIM: 610457
• HGNC: 32949
• e!Ensembl: ENSG00000136699

Protein

• UniProt ID: Q9NXE4
• Protein name: Sphingomyelin phosphodiesterase 4 (EC 3.1.4.12) (Neutral sphingomyelinase 3) (nSMase-3) (nSMase3) (Neutral sphingomyelinase III)
• Protein function: Catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide (PubMed:16517606, PubMed:25180167). It has a relevant role in the homeostasis of membrane sphingolipids, thereby influencing membrane integrity, and endopl
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF14724	mit_SMPDase	47 → 811	Mitochondrial-associated sphingomyelin phosphodiesterase	Family

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed, with highest levels in heart and skeletal muscle. {ECO:0000269|PubMed:16517606, ECO:0000269|PubMed:18505924, ECO:0000269|PubMed:25180167}.; TISSUE SPECIFICITY: [Isoform 1]: Expressed in skeletal muscle (at protein lev
• Sequence:

  MTTFGAVAEWRLPSLRRATLWIPQWFAKKAIFNSPLEAAMAFPHLQQPSFLLASLKADSI
  NKPFAQQCQDLVKVIEDFPAKELHTIFPWLVESIFGSLDGVLVGWNLRCLQGRVNPVEYS
  IVMEFLDPGGPMMKLVYKLQAEDYKFDFPVSYLPGPVKASIQECILPDSPLYHNKVQFTP
  TGGLGLNLALNPFEYYIFFFALSLITQKPLPVSLHVRTSDCAYFILVDRYLSWFLPTEGS
  VPPPLSSSPGGTSPSPPPRTPAIPFASYGLHHTSLLKRHISHQTSVNADPASHEIWRSET
  LLQVFVEMWLHHYSLEMYQKMQSPHAKLEVLHYRLSVSSALYSPAQPSLQALHAYQESFT
  PTEEHVLVVRLLLKHLHAFANSLKPEQASPSAHSHATSPLEEFKRAAVPRFVQQKLYLFL
  QHCFGHWPLDASFRAVLEMWLSYLQPWRYAPDKQAPGSDSQPRCVSEKWAPFVQENLLMY
  TKLFVGFLNRALRTDLVSPKHALMVFRVAKVFAQPNLAEMIQKGEQLFLEPELVIPHRQH
  RLFTAPTFTGSFLSPWPPAVTDASFKVKSHVYSLEGQDCKYTPMFGPEARTLVLRLAQLI
  TQAKHTAKSISDQCAESPAGHSFLSWLGFSSMDTNGSYTANDLDEMGQDSVRKTDEYLEK
  ALEYLRQIFRLSEAQLRQFTLALGTTQDENGKKQLPDCIVGEDGLILTPLGRYQIINGLR
  RFEIEYQGDPELQPIRSYEIASLVRTLFRLSSAINHRFAGQMAALCSRDDFLGSFCRYHL
  TEPGLASRHLLSPVGRRQVAGHTRGPRLSLRFLGSYRTLVSLLLAFFVASLFCVGPLPCT
  LLLTLGYVLYASAMTLLTERGKLHQP

• Sequence length: 866

Pathways

KEGG Pathway	Reactome Pathway
Sphingolipid metabolism	Glycosphingolipid metabolism
Metabolic pathways

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hepatocellular carcinoma	Pathogenic	rs780446128	RCV005906937	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies	Likely pathogenic; Pathogenic	rs781077687, rs1169024524, rs2104871303, rs773722168, rs2467143206, rs2467146771, rs1302471394, rs2467253753, rs2467139048, rs2467301101, rs2467152962, rs534879577, rs766318490, rs1391542283, rs780446128, rs1573728266, rs1573664291, rs1688560182, rs1688675737	RCV001332215 RCV002245150 RCV002246734 RCV002472159 RCV003132601 RCV003131554 RCV003219186 RCV003333593 RCV003986027 RCV003986028 RCV003989083 RCV003990119 RCV000853213 RCV000853214 RCV000853215 RCV000853216 RCV000853218 RCV001089884 RCV001089883	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Reference	Evidence Score
Abnormal cerebral morphology	Conflicting classifications of pathogenicity	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Conflicting classifications of pathogenicity	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining Show/Hide Text Mining Associations (11)
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthrogryposis	Arthrogryposis multiplex congenita	BEFREE	31495489		★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis	Pubtator	31495489, 33060286, 34621002	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	34621002	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	32813933	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	28349958	Associate	★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	28349958		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	31495489		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	31495489, 34621002	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	31495489		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	31495489, 34621002	Associate	★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	30702345		★☆☆☆☆ Found in Text Mining only

Related Genes

Sort by: Blended Diseases Pathways Evidence source

MED11 3 shared evidence sourcesGWAS catalog (Neurodevelopmental disorder), ClinVar (Neurodevelopmental disorder), HPO (Neurodevelopmental disorder) Related via 3 shared evidence sources. INTS8 3 shared evidence sourcesGWAS catalog (Neurodevelopmental disorder), ClinVar (Neurodevelopmental disorder), HPO (Neurodevelopmental disorder) Related via 3 shared evidence sources. NAE1 3 shared evidence sourcesGWAS catalog (Neurodevelopmental disorder), ClinVar (Neurodevelopmental disorder), HPO (Neurodevelopmental disorder) Related via 3 shared evidence sources. FRA10AC1 3 shared evidence sourcesGWAS catalog (Neurodevelopmental disorder), ClinVar (Neurodevelopmental disorder), HPO (Neurodevelopmental disorder) Related via 3 shared evidence sources. WBP4 3 shared evidence sourcesGWAS catalog (Neurodevelopmental disorder), ClinVar (Neurodevelopmental disorder), HPO (Neurodevelopmental disorder) Related via 3 shared evidence sources.

Related Gene	Shared Diseases	Shared Disease Names	Shared Pathways	Shared Pathway Names	Shared Evidence Sources	Shared Evidence Names
MED11	0	[]	0	[]	3	["GWAS catalog (Neurodevelopmental disorder)","ClinVar (Neurodevelopmental disorder)","HPO (Neurodevelopmental disorder)"]
INTS8	0	[]	0	[]	3	["GWAS catalog (Neurodevelopmental disorder)","ClinVar (Neurodevelopmental disorder)","HPO (Neurodevelopmental disorder)"]
NAE1	0	[]	0	[]	3	["GWAS catalog (Neurodevelopmental disorder)","ClinVar (Neurodevelopmental disorder)","HPO (Neurodevelopmental disorder)"]
FRA10AC1	0	[]	0	[]	3	["GWAS catalog (Neurodevelopmental disorder)","ClinVar (Neurodevelopmental disorder)","HPO (Neurodevelopmental disorder)"]
WBP4	0	[]	0	[]	3	["GWAS catalog (Neurodevelopmental disorder)","ClinVar (Neurodevelopmental disorder)","HPO (Neurodevelopmental disorder)"]

Diseases Linked via Similar Genes

Myocardial infarction Linked via 1 of 5 related genesINTS8 Diabetes mellitus type 2 Linked via 1 of 5 related genesINTS8

Disease	Linked Via (Gene Count)	Linked Via (Gene Names)
Myocardial infarction	1	["INTS8"]
Diabetes mellitus type 2	1	["INTS8"]