SMPD4

Chr 2AR

sphingomyelin phosphodiesterase 4

Also known as: NEDMABA, NEDMEBA, NET13, NSMASE-3, NSMASE3, SKNY

NCBI Gene: 55627 ENSG00000136699 UniProt: Q9NXE4 OMIM: 610457

The protein catalyzes the hydrolysis of membrane sphingomyelin to form phosphorylcholine and ceramide, playing a critical role in membrane sphingolipid homeostasis and endoplasmic reticulum function. Biallelic mutations cause a neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies with autosomal recessive inheritance. The gene shows minimal constraint against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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 downregulated by wild-type p53. The encoded protein localizes to the endoplasmic reticulum and Golgi network. [provided by RefSeq, Mar 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomaliesMIM #618622

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.02

LOEUF

LOF

Mechanism· G2P