SMS

Chr XADIsolated casesXLR

spermine synthase

Also known as: MRSR, MRXSSR, SPMSY, SRS, SpS

NCBI Gene: 6611 ENSG00000102172 UniProt: P52788 OMIM: 182290

This gene encodes spermidine/spermine synthase, which catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine. Mutations cause X-linked recessive Snyder-Robinson syndrome (intellectual developmental disorder) and autosomal dominant Smith-Magenis syndrome, both presenting with intellectual disability and syndromic features. The gene is highly constrained against loss-of-function variants (pLI 0.97, LOEUF 0.31), indicating critical cellular function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Smith-Magenis syndromeMIM #182290

ADIsolated cases

Intellectual developmental disorder, X-linked syndromic, Snyder-Robinson typeMIM #309583

XLR

Clinical highlights

Gene-disease validity (ClinGen)

syndromic X-linked intellectual disability Snyder type · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

1434

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

GeneReview available — SMS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.30LOEUF

pLI 0.973

Z-score 3.42

OE 0.06 (0.02–0.30)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.32Z-score

OE missense 0.46 (0.37–0.56)

66 obs / 144.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.30)

0≤0.351.4

Missense OE?0.46 (0.37–0.56)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 15.5Missense obs/exp: 66 / 144.3Syn Z: -0.29

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SMS · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — SMS

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Advanced Solid Tumor

Dose Escalation Study of Immunomodulatory Nanoparticles

ACTIVE NOT RECRUITING

NCT04751786Phase PHASE1Radboud University Medical CenterStarted 2021-01-11

PRECIOUS-01

Influenza, HumanSARS-CoV-2 Infection

Does Repeat Influenza Vaccination Constrain Influenza Immune Responses and Protection

ACTIVE NOT RECRUITING

NCT05110911University of MelbourneStarted 2020-04-02

Influenza vaccination: Fluarix Tetra, Vaxigrip Tetra, Fluquadri, Fluad Quad, Afluia Quad, Flucelvax QuadSARS-CoV-2 vaccination: Comirnaty or Vaxzevria

RAI1 Gene 17P11.2 Deletion+Duplication

Clinical and Molecular Biomarker Studies in RAI1 (Retinoic Acid-Induced 1) -Related Disorders

RECRUITING

NCT06274164Baylor College of MedicineStarted 2024-03-13

Electroencephalography/Polysomnography (EEG/PSG)Skin BiopsyBlood draw

Colorectal Neuroendocrine Tumor G1Gastric Neuroendocrine Tumor G1Neuroendocrine Neoplasm

Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor

ACTIVE NOT RECRUITING

NCT00569127Phase PHASE3National Cancer Institute (NCI)Started 2007-12-01

BevacizumabLaboratory Biomarker AnalysisOctreotide Acetate

Somatic Mutation

SMS - Study of Somatic Mutations Using Genome Sequencing

ENROLLING BY INVITATION

NCT06851052The Wellcome Sanger InstituteStarted 2016-10-01

sample collectionSeeking consentSample Collection: Surgical

Neoplasms

A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer

ACTIVE NOT RECRUITING

NCT04607421Phase PHASE3PfizerStarted 2020-12-21