SMS

Chr X

spermine synthase

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

NCBI Gene: 6611 ENSG00000102172 UniProt: P52788

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]

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, X-linked, syndromic, Snyder-Robinson type

135

ClinVar variants

Pathogenic / LP

0.97

pLI score· haploinsufficient

Active trials

Clinical Summary— SMS

🧬

Gene-Disease Validity (ClinGen)

syndromic X-linked intellectual disability Snyder type · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

51 Pathogenic / Likely Pathogenic· 50 VUS of 135 total submissions

💊

Clinical Trials

9 active or recruiting trials — potential therapeutic options may be available

Some data sources returned errors (2)

omim: Error: OMIM fetch failed: 429

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.02–0.30)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.46 (0.37–0.56)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05

0≤1.21.6

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

ClinVar Variant Classifications

135 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41

Likely Pathogenic10

VUS50

Likely Benign3

Benign27

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	3	37	0	41
Likely Pathogenic	0	9	1	0	10
VUS	1	39	10	0	50
Likely Benign	0	0	0	3	3
Benign	0	0	24	3	27
Conflicting	—				4
Total	2	51	72	6	135

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

Gene2Phenotype Curations

SMS-related Snyder-Robinson syndrome

strong

Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product

Dev. DisordersSkeletal

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

External Resources

Links to major genomics databases and tools

📖

GeneReview available — SMS

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Literature

Landmark / reviewRecent case evidence

Recent Gene-Specific Literature

Gene in title · MEDLINE · newest first

Europe PMC

Team-Based Analysis of Large-Scale Qualitative Data: Tutorial Using a Nationwide SMS Text Messaging Poll of Youth.

DeJonckheere M et al.·J Med Internet Res

2026

The AuTOMATIC trial: a multicentre digitally-automated, Bayesian, adaptive, parallel, factorial randomised controlled trial of SMS reminders for childhood vaccination.

Currie G et al.·Lancet Reg Health West Pac

2026🔓 Open Access

Evaluation of a community-based SMS support program for cardiovascular patients from 2020 - 2024: The HeartHealth program.

Sheahen B et al.·JMIR Cardio

2026Cohort

Enhanced patient counselling and SMS reminder messages to improve access to community-based eye care services in Meru, Kenya: an embedded, pragmatic, individual-level, randomised, controlled, adaptive platform trial.

Allen LN et al.·Lancet Glob Health

2026

Interaction with SMS text-reminders correlate with improved medication adherence and readmission rates for congestive heart failure patients: A retrospective cohort study.

Long B et al.·PLOS Digit Health

2025🔓 Open AccessCohort

Top 5 resultsSearch Europe PMC ↗

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

Alzheimer Disease

Does EVOO Induce Gene and Metabolic Changes in Healthy Subjects

ACTIVE NOT RECRUITING

NCT05929924Phase NAAugusta UniversityStarted 2023-08-01

Extra virgin olive oil

Risk FactorsPolypharmacyDrug Interactions

Telecommunication Technology-based Online Survey

RECRUITING

NCT06159699Tomsk National Research Medical Center of the Russian Academy of SciencesStarted 2022-12-02

Online SurveyGenetic Testing

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

EncorafenibCetuximabOxaliplatin

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

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

Somatic Mutation

SMS - Study of Somatic Mutations Using Genome Sequencing

ENROLLING BY INVITATION

NCT06851052The Wellcome Sanger InstituteStarted 2016-10-01