SGMS1

protein-coding

sphingomyelin synthase 1, the group of Sterile alpha motif domain containing

Gene summary

The protein encoded by this gene is predicted to be a five-pass transmembrane protein. This gene may be predominately expressed in brain. [provided by RefSeq, Jul 2008]

Previous symbols:

TMEM23

MANE transcript

NM_147156.4

Inheritance

ClinVar variants

P:3U:27

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr10:50,305,586-50,625,163

External References & Databases

Ensembl (ENSG00000198964)

Transcript & Mutation Effects

hg38 • Region Span ~319.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SGMS1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 22

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_147156.4. 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						0
missense	2 clinvar	1 clinvar	24 clinvar			27
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	2	1	27	0	0	30

Highest pathogenic variant AF is 0.0000013683878

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 107 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_147156.4	RefSeq	NP_671512.1	5	MANE Select
ENST00000361781.7	Ensembl	ENSP00000354829.2	5	MANE Select
ENST00000361543.3	Ensembl	ENSP00000355235.2	2	Standard
ENST00000429490.5	Ensembl	ENSP00000406795.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Sphingolipid signaling pathway - Homo sapiens (human)
Sphingolipid metabolism - Homo sapiens (human)
Sphingolipid Metabolism
Gaucher Disease
Globoid Cell Leukodystrophy

Biological Process

sphingomyelin biosynthetic process
apoptotic process
inflammatory response
positive regulation of gene expression
phosphorylation

Molecular Function

ceramide phosphoethanolamine synthase activity
kinase activity
sphingomyelin synthase activity
ceramide cholinephosphotransferase activity

Cellular Component

Golgi trans cisterna
Golgi membrane
nucleus
endoplasmic reticulum
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361781
Coding exons: 5
Length: 319564
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125745
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.67	125	242	0.517	0.0000133	2728
Missense (PolyPhen)		35	89.864	0.38948		967
Synonymous	-0.0734	93	92.1	1.01	0.00000549	785
Loss of Function	3.80	3	22.4	0.134	0.00000138	216

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Sphingomyelin synthases synthesize the sphingolipid, sphingomyelin, through transfer of the phosphatidyl head group, phosphatidylcholine, on to the primary hydroxyl of ceramide. The reaction is bidirectional depending on the respective levels of the sphingolipid and ceramide. Golgi apparatus SMS1 directly and specifically recognizes the choline head group on the substrate, requiring two fatty chains on the choline-P donor molecule in order to be recognized efficiently as a substrate. Major form in macrophages. Required for cell growth in certain cell types such as HeLa cells. Suppresses BAX-mediated apoptosis and also prevents cell death in response to stimuli such as hydrogen peroxide, osmotic stress, elevated temperature and exogenously supplied sphingolipids. May protect against cell death by reversing the stress-inducible increase in levels of proapoptotic ceramide. {ECO:0000269|PubMed:14685263, ECO:0000269|PubMed:17449912}.;

Recessive Scores

pRec: 0.388

Intolerance Scores

LoFtool: 0.436
RVIS EVS: -0.45
RVIS percentile EVS: 24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.659

Gene Damage Prediction

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