SMPD4

Chr 2AR

sphingomyelin phosphodiesterase 4

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.021 OMIM phenotype
Clinical SummarySMPD4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.000
Z-score 1.43
OE 0.77 (0.591.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.86Z-score
OE missense 0.90 (0.830.97)
474 obs / 529.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.77 (0.591.02)
00.351.4
Missense OE0.90 (0.830.97)
00.61.4
Synonymous OE1.12
01.21.6
LoF obs/exp: 35 / 45.4Missense obs/exp: 474 / 529.5Syn Z: -1.42

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SMPD4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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