SGMS2

Chr 4q25

sphingomyelin synthase 2

Aliases:: MGC26963, SMS2
MANE:: ENST00000690982.1

OMIM: 611574 ↗NCBI: 166929 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

SGMS2 · Q8NHU3

v62025-08-01

Predicted Aligned Error matrix for SGMS2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

76.8/ 100

Confident

365 residues

Confidence breakdown

Very high(≥ 90)45%
Confident(70–90)27%
Low(50–70)5%
Very low(< 50)23%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Skeletal dysplasia
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Osteogenesis imperfecta
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

calvarial doughnut lesions-bone fragility syndrome
0.64
Calvarial doughnut lesions - bone fragility
0.63
calvarial doughnut lesions with bone fragility and spondylometaphyseal dysplasia
0.48
hereditary disease
0.34
neurodegenerative disease
0.28
glomerulonephritis
0.24
poisoning
0.22
response to antihypertensive drug
0.22
age-related macular degeneration
0.12
breast carcinoma
0.10

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Phosphatidylcholine:ceramide cholinephosphotransferase 2

Sphingomyelin synthase that primarily contributes to sphingomyelin synthesis and homeostasis at the plasma membrane. Catalyzes the reversible transfer of phosphocholine moiety in sphingomyelin biosynthesis: in the forward reaction transfers phosphocholine head group of phosphatidylcholine (PC) on to ceramide (CER) to form ceramide phosphocholine (sphingomyelin, SM) and diacylglycerol (DAG) as by-product, and in the reverse reaction transfers phosphocholine from SM to DAG to form PC and CER (PubMed:14685263, PubMed:17449912, PubMed:17982138, PubMed:18370930, PubMed:38388831). The direction of the reaction appears to depend on the levels of CER and DAG in the plasma membrane (PubMed:14685263, PubMed:17449912, PubMed:17982138, PubMed:18370930). Does not use free phosphorylcholine or CDP-choline as donors (PubMed:14685263). Can also transfer phosphoethanolamine head group of phosphatidylethanolamine (PE) on to ceramide (CER) to form ceramide phosphoethanolamine (CPE) (PubMed:19454763). Regulates receptor-mediated signal transduction via mitogenic DAG and proapoptotic CER, as well as via SM, a structural component of membrane rafts that serve as platforms for signal transduction and protein sorting (PubMed:17449912, PubMed:17982138). To a lesser extent, plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1 (PubMed:18370930, PubMed:21980337). Required for normal bone matrix mineralization (PubMed:30779713)