This gene encodes a protein belonging to the spermidine/spermin synthase family and catalyzes the production of spermine from spermidine. Pseudogenes of this gene are located on chromosomes 1, 5, 6 and X. Mutations in this gene cause an X-linked intellectual disability called Snyder-Robinson Syndrome (SRS). Multiple transcript variants encoding different isoforms have been foun... See more...

Aliases for SMS Gene

Aliases for SMS Gene

  • Spermine Synthase 2 3 4 5
  • Spermidine Aminopropyltransferase 3 4
  • SPMSY 3 4
  • Snyder-Robinson X-Linked Mental Retardation Syndrome 2
  • EC 2.5.1.22 4
  • MRSR 3
  • SpS 3
  • SRS 3

External Ids for SMS Gene

Previous HGNC Symbols for SMS Gene

  • SRS

Previous GeneCards Identifiers for SMS Gene

  • GC0XP020700
  • GC0XP020548
  • GC0XP021160
  • GC0XP021320
  • GC0XP021718
  • GC0XP021868
  • GC0XP019699

Summaries for SMS Gene

Entrez Gene Summary for SMS Gene

  • This gene encodes a protein belonging to the spermidine/spermin synthase family and catalyzes the production of spermine from spermidine. Pseudogenes of this gene are located on chromosomes 1, 5, 6 and X. Mutations in this gene cause an X-linked intellectual disability called Snyder-Robinson Syndrome (SRS). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

GeneCards Summary for SMS Gene

SMS (Spermine Synthase) is a Protein Coding gene. Diseases associated with SMS include Mental Retardation, X-Linked, Syndromic, Snyder-Robinson Type and Syndromic X-Linked Intellectual Disability Snyder Type. Among its related pathways are Urea cycle and metabolism of amino groups and Arginine and proline metabolism. Gene Ontology (GO) annotations related to this gene include spermidine synthase activity and spermine synthase activity. An important paralog of this gene is SRM.

UniProtKB/Swiss-Prot Summary for SMS Gene

  • Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM).

Gene Wiki entry for SMS Gene

Additional gene information for SMS Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SMS Gene

Genomics for SMS Gene

GeneHancer (GH) Regulatory Elements for SMS Gene

Promoters and enhancers for SMS Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ021939 Promoter/Enhancer 2.1 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 506.1 +2.0 1977 5.8 HNRNPK CTCF POLR2G JUND TEAD4 FOS ZFX ZIC2 POLR2A ZBTB10 SMS piR-61945-525 YY2 ENSG00000271286 LOC100418871 lnc-SMS-1
GH0XJ021958 Enhancer 0.8 Ensembl ENCODE 21.9 +20.7 20728 7.8 MYC TAL1 SMAD4 ZBTB48 TCF12 ZNF384 EGR1 RARA HDGF POLR2A SMS YY2 MBTPS2 piR-61945-525 piR-55194-429
GH0XJ021989 Enhancer 1.2 FANTOM5 Ensembl ENCODE 9.3 +53.1 53128 11 NCOR1 TCF12 ZNF316 NFIC GABPA TRIM24 ARNT CEBPB SPI1 NR3C1 YY2 SMS MBTPS2 piR-55194-429 piR-61945-525
GH0XJ021971 Enhancer 0.6 ENCODE 13.6 +32.7 32728 4 ZNF217 CUX1 CTBP1 ZNF585B CTCF ESR1 JUND SPI1 ELF1 GATA3 SMS MBTPS2 YY2 piR-55194-429 piR-61945-525
GH0XJ021985 Enhancer 0.9 Ensembl ENCODE 8.1 +45.5 45525 1.8 CTCF REST RAD21 TRIM22 TEAD1 SMC3 DEK TRIM25 MEF2B NBN YY2 SMS piR-55194-429 piR-61945-525
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SMS on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SMS

Top Transcription factor binding sites by QIAGEN in the SMS gene promoter:
  • AP-1
  • ATF-2
  • c-Ets-1
  • c-Jun
  • En-1
  • HNF-4alpha1
  • MAZR
  • Nkx5-1
  • PPAR-gamma1
  • PPAR-gamma2

Genomic Locations for SMS Gene

Genomic Locations for SMS Gene
chrX:21,940,573-21,994,837
(GRCh38/hg38)
Size:
54,265 bases
Orientation:
Plus strand
chrX:21,958,691-22,025,798
(GRCh37/hg19)
Size:
67,108 bases
Orientation:
Plus strand

Genomic View for SMS Gene

Genes around SMS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SMS Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMS Gene

Proteins for SMS Gene

  • Protein details for SMS Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P52788-SPSY_HUMAN
    Recommended name:
    Spermine synthase
    Protein Accession:
    P52788
    Secondary Accessions:
    • A6NHA7
    • A6NI34
    • B2R9M0
    • O00544
    • Q9UQS1

    Protein attributes for SMS Gene

    Size:
    366 amino acids
    Molecular mass:
    41268 Da
    Quaternary structure:
    • Homodimer. Dimerization is mediated through the N-terminal domain and seems to be required for activity as deletion of the N-terminal domain causes complete loss of activity.

    Three dimensional structures from OCA and Proteopedia for SMS Gene

    Alternative splice isoforms for SMS Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SMS Gene

Post-translational modifications for SMS Gene

  • Ubiquitination at Lys151
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for SMS Gene

Domains & Families for SMS Gene

Gene Families for SMS Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • FDA approved drug targets
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for SMS Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ50114, highly similar to Spermine synthase (EC 2.5.1.22) (B4DE40_HUMAN)
  • Spermidine aminopropyltransferase (SPSY_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P52788

UniProtKB/Swiss-Prot:

SPSY_HUMAN :
  • Composed of 3 domains: the N-terminal domain has structural similarity to S-adenosylmethionine decarboxylase, the central domain is made up of four beta strands and the C-terminal domain is similar in structure to spermidine synthase. The N- and C-terminal domains are both required for activity.
  • Belongs to the spermidine/spermine synthase family.
Domain:
  • Composed of 3 domains: the N-terminal domain has structural similarity to S-adenosylmethionine decarboxylase, the central domain is made up of four beta strands and the C-terminal domain is similar in structure to spermidine synthase. The N- and C-terminal domains are both required for activity.
Family:
  • Belongs to the spermidine/spermine synthase family.
genes like me logo Genes that share domains with SMS: view

Function for SMS Gene

Molecular function for SMS Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=S-adenosyl 3-(methylsulfanyl)propylamine + spermidine = H(+) + S-methyl-5'-thioadenosine + spermine; Xref=Rhea:RHEA:19973, ChEBI:CHEBI:15378, ChEBI:CHEBI:17509, ChEBI:CHEBI:45725, ChEBI:CHEBI:57443, ChEBI:CHEBI:57834; EC=2.5.1.22;.
GENATLAS Biochemistry:
spermine synthase,ubiquitously expressed,polyamine blocking the inwardly rectifying K+ channel present in the inner ear,38kb telomeric to PEX,ubiquitous

Enzyme Numbers (IUBMB) for SMS Gene

Gene Ontology (GO) - Molecular Function for SMS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016740 transferase activity IEA --
GO:0016768 spermine synthase activity TAS,IEA --
genes like me logo Genes that share ontologies with SMS: view
genes like me logo Genes that share phenotypes with SMS: view

Human Phenotype Ontology for SMS Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Clone Products

No data available for Phenotypes From GWAS Catalog , Animal Models , Transcription Factor Targets and HOMER Transcription for SMS Gene

Localization for SMS Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SMS gene
Compartment Confidence
cytosol 5
nucleus 3
plasma membrane 1
extracellular 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nuclear bodies (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SMS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0070062 extracellular exosome HDA 23533145
genes like me logo Genes that share ontologies with SMS: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for SMS Gene

Pathways & Interactions for SMS Gene

genes like me logo Genes that share pathways with SMS: view

UniProtKB/Swiss-Prot P52788-SPSY_HUMAN

  • Pathway: Amine and polyamine biosynthesis; spermine biosynthesis; spermine from spermidine: step 1/1.

Gene Ontology (GO) - Biological Process for SMS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006555 methionine metabolic process TAS 7546290
GO:0006595 polyamine metabolic process TAS --
GO:0006596 polyamine biosynthetic process IEA --
GO:0006597 spermine biosynthetic process IEA --
GO:0008215 spermine metabolic process IEA --
genes like me logo Genes that share ontologies with SMS: view

No data available for SIGNOR curated interactions for SMS Gene

Drugs & Compounds for SMS Gene

(4) Drugs for SMS Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
spermine Experimental Nutra Full agonist, Agonist, Antagonist, Pore Blocker, Channel blocker, Target, ligand 0
putrescine Experimental Pharma Antagonist, Pore Blocker 0
spermidine Experimental Pharma Antagonist, Pore Blocker 0

(8) Additional Compounds for SMS Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
1,3-diaminopropane
  • 1,3-Propanediamine
  • 1,3-Propylenediamine
  • Propane-1,3-diamine
  • tn
  • 1,3-diamino-N-Propane
109-76-2
5'-Methylthioadenosine
  • 5'-Deoxy-5'-(methylthio)adenosine
  • 5-Methylthioadenosine
  • 9-(5-S-Methyl-5-thio-beta-D-ribofuranosyl)-9H-purin-6-amine
  • Methylthioadenosine
  • MTA
2457-80-9
N1-acetylspermine
  • N'-acetylspermine
  • N'-monoacetylspermine
  • N(1)-Acetylspermine
  • N-(3-((4-((3-Aminopropyl)amino)butyl)amino)propyl)-acetamide
  • N-Acetylspermine
25593-72-0
Norspermidine
  • 1,7-diamino-4-Azaheptane
  • 3,3'-Iminobis(propylamine)
  • 3,3'-Iminobispropylamine
  • 3,3'-Iminodi(propylamine)
  • 3,3-Diaminodipropylamine
56-18-8
S-Adenosylmethioninamine
  • (5-Deoxy-5-adenosyl)(3-aminopropyl)methylsulfonium
  • (5-Deoxy-5-adenosyl)(3-aminopropyl)methylsulfonium cation
  • (5-Deoxy-5-adenosyl)(3-aminopropyl)methylsulfonium salt
  • [1-(Adenin-9-yl)-1,5-dideoxy-beta-D-ribofuranos-5-yl](3-aminopropyl)(methyl)sulfonium
  • S--Adenosylmethioninamine
22365-13-5
genes like me logo Genes that share compounds with SMS: view

Transcripts for SMS Gene

mRNA/cDNA for SMS Gene

2 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SMS Gene

No ASD Table

Relevant External Links for SMS Gene

GeneLoc Exon Structure for
SMS

Expression for SMS Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SMS Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SMS Gene

This gene is overexpressed in Testis (8.9), Ovary (7.4), and Peripheral blood mononuclear cells (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SMS Gene



Protein tissue co-expression partners for SMS Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SMS

SOURCE GeneReport for Unigene cluster for SMS Gene:

Hs.724874

Evidence on tissue expression from TISSUES for SMS Gene

  • Kidney(4.4)
  • Intestine(4.3)
  • Blood(4.2)
  • Skin(4.1)
  • Nervous system(3.8)
  • Heart(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for SMS Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • face
  • head
  • jaw
  • larynx
  • lip
  • mandible
  • maxilla
  • mouth
  • neck
  • nose
  • outer ear
  • pharynx
  • skull
  • tooth
  • vocal cord
Thorax:
  • breast
  • chest wall
  • clavicle
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Pelvis:
  • pelvis
  • testicle
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • peripheral nerve
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with SMS: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for SMS Gene

Orthologs for SMS Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for SMS Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SMS 30
  • 99.57 (n)
dog
(Canis familiaris)
Mammalia SMS 31 30
  • 93.88 (n)
OneToOne
cow
(Bos Taurus)
Mammalia SMS 31 30
  • 93.7 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Sms 30
  • 91.8 (n)
mouse
(Mus musculus)
Mammalia Sms 31 30
  • 91.26 (n)
OneToOne
Sms-ps 17
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 87 (a)
OneToMany
-- 31
  • 73 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia SMS 31
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves SMS 31 30
  • 81.54 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 90 (a)
OneToMany
-- 31
  • 82 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia sms 30
  • 75.6 (n)
zebrafish
(Danio rerio)
Actinopterygii sms 31 30
  • 68.8 (n)
OneToOne
LOC80872 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005325 30
  • 53.25 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG4300 31 32 30
  • 51.98 (n)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SPE4 31
  • 18 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 51 (a)
OneToMany
-- 31
  • 45 (a)
OneToMany
Cin.4694 30
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4694 30
Species where no ortholog for SMS was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SMS Gene

ENSEMBL:
Gene Tree for SMS (if available)
TreeFam:
Gene Tree for SMS (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SMS: view image

Paralogs for SMS Gene

Paralogs for SMS Gene

genes like me logo Genes that share paralogs with SMS: view

Variants for SMS Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SMS Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
626916 Pathogenic: Snyder Robinson syndrome 21,985,183(+) CAATG/C FRAMESHIFT_VARIANT
728106 Benign: not provided 21,971,897(+) C/T SYNONYMOUS_VARIANT,INTRON_VARIANT
792193 Likely Benign: not provided 21,940,869(+) C/G SYNONYMOUS_VARIANT
792878 Benign: not provided 21,967,209(+) C/T SYNONYMOUS_VARIANT
800832 Uncertain Significance: Snyder Robinson syndrome 21,984,352(+) G/A MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for SMS Gene

Structural Variations from Database of Genomic Variants (DGV) for SMS Gene

Variant ID Type Subtype PubMed ID
esv3573638 CNV loss 25503493
esv3573639 CNV loss 25503493
nsv1139393 CNV deletion 24896259
nsv1145287 CNV deletion 24896259
nsv425472 CNV deletion 16902084
nsv6832 CNV deletion 18451855
nsv819785 CNV loss 19587683

Variation tolerance for SMS Gene

Residual Variation Intolerance Score: 13% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.33; 7.32% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SMS Gene

Human Gene Mutation Database (HGMD)
SMS
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SMS

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMS Gene

Disorders for SMS Gene

MalaCards: The human disease database

(4) MalaCards diseases for SMS Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search SMS in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SPSY_HUMAN
  • X-linked syndromic mental retardation Snyder-Robinson type (MRXSSR) [MIM:309583]: Characterized by moderate intellectual deficit, hypotonia, an unsteady gait, osteoporosis, kyphoscoliosis and facial asymmetry. Transmission is X-linked recessive. {ECO:0000269 PubMed:14508504, ECO:0000269 PubMed:18550699, ECO:0000269 PubMed:19206178, ECO:0000269 PubMed:22612257, ECO:0000269 PubMed:23696453, ECO:0000269 PubMed:23897707}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for SMS

genes like me logo Genes that share disorders with SMS: view

No data available for Genatlas for SMS Gene

Publications for SMS Gene

  1. X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. (PMID: 14508504) Cason AL … Schwartz CE (European journal of human genetics : EJHG 2003) 2 3 4 26 54
  2. Sequence analysis of 139 kb in Xp22.1 containing spermine synthase and the 5' region of PEX. (PMID: 9299240) Grieff M … Mazzarella R (Genomics 1997) 2 3 4 23 54
  3. Molecular cloning of a cDNA encoding human spermine synthase. (PMID: 7546290) Korhonen VP … Jänne J (DNA and cell biology 1995) 2 3 4 23 54
  4. A missense mutation, p.V132G, in the X-linked spermine synthase gene (SMS) causes Snyder-Robinson syndrome. (PMID: 19206178) Becerra-Solano LE … García-Ortiz JE (American journal of medical genetics. Part A 2009) 3 4 23 54
  5. New SMS mutation leads to a striking reduction in spermine synthase protein function and a severe form of Snyder-Robinson X-linked recessive mental retardation syndrome. (PMID: 18550699) de Alencastro G … Sertié AL (Journal of medical genetics 2008) 3 4 23 54

Products for SMS Gene

Sources for SMS Gene