SMS

Summary

SMS (spermine synthase, HGNC:11123) is a protein-coding gene on chromosome Xp22.11, encoding Spermine synthase (P52788). Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM). It is a selective cancer dependency (DepMap: 14.5% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 6611 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic X-linked intellectual disability Snyder type (Definitive, ClinGen)
• Clinical variants (ClinVar): 274 total — 12 pathogenic, 20 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈71% of expected missense variation)
• GTEx eGene: eQTL in 24 tissues, sQTL in 4 (q < 0.05)
• Phenotypes (HPO): 92
• Cancer dependency (DepMap): dependent in 14.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004595

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11123
Approved symbol	SMS
Name	spermine synthase
Location	Xp22.11
Locus type	gene with protein product
Status	Approved
Aliases	SPMSY, SpS, MRSR
Ensembl gene	ENSG00000102172
Ensembl biotype	protein_coding
OMIM	300105
Entrez	6611

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 4 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000404933

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1, TSL 4: 1, TSL 5: 1

ENST00000404933, ENST00000379404, ENST00000457085, ENST00000478094, ENST00000853888, ENST00000853889, ENST00000955899, ENST00001042425, ENST00001069861, ENST00001069862, ENST00001108962, ENST00001124590, ENST00001124591, ENST00001133662

RefSeq mRNA: 2 — MANE Select: NM_004595 NM_001258423, NM_004595

CCDS: CCDS14203, CCDS59161

Canonical transcript exons

ENST00000404933 — 11 exons

Exon	Start	End
ENSE00000666726	21984304	21984418
ENSE00000666728	21985144	21985223
ENSE00000666729	21992597	21992712
ENSE00001434921	21978877	21978966
ENSE00001436366	21977960	21978114
ENSE00001656038	21971897	21971990
ENSE00001899777	21940709	21940873
ENSE00001899895	21994312	21994837
ENSE00003546822	21967196	21967316
ENSE00003665825	21972507	21972571
ENSE00003673242	21977061	21977236

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 112.0783 / max 1817.1032, expressed in 1826 samples.

Highest expression (Bgee): cortical plate, placenta, ganglionic eminence, adrenal tissue, adrenal gland cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SMS is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 24 tissues and its splicing (sQTL) in 4 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adrenal Gland	eqtl	1.1e-29	+0.77	X:21934495:G:C
Whole Blood	eqtl	1.5e-12	-0.20	X:21953359:G:A
Ovary	eqtl	2.7e-12	+0.51	X:21960035:CCG:C
Thyroid	eqtl	8.3e-09	+0.11	X:21756682:A:G
Artery Tibial	eqtl	4.9e-08	+0.18	X:21927297:C:T
Artery Aorta	eqtl	2.4e-07	+0.14	X:21857994:A:G
Cells EBV-transformed lymphocytes	eqtl	2.9e-07	+0.20	X:21989634:A:G
Esophagus Mucosa	eqtl	9.5e-06	-0.18	X:21932786:C:CTT
Spleen	eqtl	1.4e-05	+0.18	X:21967346:C:T
Esophagus Muscularis	eqtl	3.6e-05	-0.12	X:22113225:C:T
Brain Cortex	eqtl	3.3e-04	+1.25	X:22742143:G:A
Skin Not Sun Exposed Suprapubic	eqtl	4.0e-04	-0.19	X:21934495:G:C
Adipose Subcutaneous	eqtl	1.1e-03	-0.12	X:21940733:A:G
Nerve Tibial	eqtl	1.4e-03	+0.16	X:21661377:C:G
Testis	eqtl	1.5e-03	-0.07	X:21992136:G:T
Heart Atrial Appendage	eqtl	2.0e-03	+0.38	X:22238831:A:G
Brain Cerebellum	sqtl	3.9e-03	-0.48	X:21960035:CCG:C
Muscle Skeletal	eqtl	4.0e-03	-0.11	X:21839473:C:A
Brain Cerebellar Hemisphere	sqtl	4.3e-03	-0.56	X:21957368:C:T
Esophagus Muscularis	sqtl	5.9e-03	-0.22	X:22255350:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
195730	106.3363	1826
195728	4.4165	1568
195731	1.1648	672
195729	0.1608	54

Top tissues by expression

showing 100 of 134 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.55	gold quality
placenta	UBERON:0001987	98.38	gold quality
ganglionic eminence	UBERON:0004023	98.26	gold quality
adrenal tissue	UBERON:0018303	97.83	gold quality
right adrenal gland cortex	UBERON:0035827	97.23	gold quality
right adrenal gland	UBERON:0001233	97.18	gold quality
left adrenal gland	UBERON:0001234	97.05	gold quality
adrenal gland	UBERON:0002369	96.80	gold quality
left adrenal gland cortex	UBERON:0035825	96.80	gold quality
adult mammalian kidney	UBERON:0000082	96.76	gold quality
endometrium	UBERON:0001295	96.72	gold quality
ventricular zone	UBERON:0003053	96.58	gold quality
islet of Langerhans	UBERON:0000006	96.47	gold quality
ovary	UBERON:0000992	96.42	gold quality
kidney	UBERON:0002113	96.39	gold quality
left ovary	UBERON:0002119	96.38	gold quality
anterior cingulate cortex	UBERON:0009835	96.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.25	gold quality
superior frontal gyrus	UBERON:0002661	96.06	gold quality
prostate gland	UBERON:0002367	96.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.03	gold quality
cortex of kidney	UBERON:0001225	96.01	gold quality
right ovary	UBERON:0002118	95.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.79	gold quality
monocyte	CL:0000576	95.72	gold quality
cerebellar cortex	UBERON:0002129	95.69	gold quality
cerebellum	UBERON:0002037	95.68	gold quality
cerebellar hemisphere	UBERON:0002245	95.66	gold quality
calcaneal tendon	UBERON:0003701	95.64	gold quality
amygdala	UBERON:0001876	95.59	gold quality
metanephros cortex	UBERON:0010533	95.56	gold quality
leukocyte	CL:0000738	95.55	gold quality
temporal lobe	UBERON:0001871	95.54	gold quality
cerebral cortex	UBERON:0000956	95.47	gold quality
duodenum	UBERON:0002114	95.47	gold quality
rectum	UBERON:0001052	95.40	gold quality
left lobe of thyroid gland	UBERON:0001120	95.31	gold quality
frontal cortex	UBERON:0001870	95.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.24	gold quality
prefrontal cortex	UBERON:0000451	95.18	gold quality
right frontal lobe	UBERON:0002810	95.14	gold quality
stromal cell of endometrium	CL:0002255	95.12	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.10	gold quality
right coronary artery	UBERON:0001625	95.08	gold quality
hypothalamus	UBERON:0001898	95.07	gold quality
primary visual cortex	UBERON:0002436	95.06	gold quality
brain	UBERON:0000955	94.98	gold quality
thyroid gland	UBERON:0002046	94.98	gold quality
ascending aorta	UBERON:0001496	94.93	gold quality
caudate nucleus	UBERON:0001873	94.92	gold quality
thoracic aorta	UBERON:0001515	94.91	gold quality
nucleus accumbens	UBERON:0001882	94.76	gold quality
gall bladder	UBERON:0002110	94.69	gold quality
right lobe of thyroid gland	UBERON:0001119	94.67	gold quality
smooth muscle tissue	UBERON:0001135	94.64	gold quality
descending thoracic aorta	UBERON:0002345	94.63	gold quality
putamen	UBERON:0001874	94.52	gold quality
left coronary artery	UBERON:0001626	94.42	gold quality
mucosa of transverse colon	UBERON:0004991	94.41	gold quality
substantia nigra	UBERON:0002038	94.29	gold quality
mucosa of stomach	UBERON:0001199	94.19	gold quality
right atrium auricular region	UBERON:0006631	94.17	gold quality
colon	UBERON:0001155	94.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.05	gold quality
lymph node	UBERON:0000029	93.99	gold quality
myometrium	UBERON:0001296	93.98	gold quality
body of uterus	UBERON:0009853	93.95	gold quality
heart	UBERON:0000948	93.89	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.86	gold quality
lower esophagus	UBERON:0013473	93.84	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.84	gold quality
popliteal artery	UBERON:0002250	93.69	gold quality
tibial artery	UBERON:0007610	93.69	gold quality
minor salivary gland	UBERON:0001830	93.66	gold quality
intestine	UBERON:0000160	93.63	gold quality
Ammon’s horn	UBERON:0001954	93.60	gold quality
saliva-secreting gland	UBERON:0001044	93.58	gold quality
endocervix	UBERON:0000458	93.43	gold quality
transverse colon	UBERON:0001157	93.40	gold quality
heart left ventricle	UBERON:0002084	93.38	gold quality
vermiform appendix	UBERON:0001154	93.11	gold quality
fundus of stomach	UBERON:0001160	92.91	gold quality
urinary bladder	UBERON:0001255	92.91	gold quality
right lung	UBERON:0002167	92.85	gold quality
ectocervix	UBERON:0012249	92.76	gold quality
vagina	UBERON:0000996	92.59	gold quality
esophagus	UBERON:0001043	92.59	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.58	gold quality
adenohypophysis	UBERON:0002196	92.54	gold quality
multicellular organism	UBERON:0000468	92.50	gold quality
pituitary gland	UBERON:0000007	92.34	gold quality
body of stomach	UBERON:0001161	92.34	gold quality
uterine cervix	UBERON:0000002	92.31	gold quality
left uterine tube	UBERON:0001303	92.29	gold quality
lung	UBERON:0002048	92.27	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.24	gold quality
stomach	UBERON:0000945	92.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.18	gold quality
pancreas	UBERON:0001264	92.05	gold quality
fallopian tube	UBERON:0003889	92.05	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	1465.35
E-GEOD-114530	yes	640.56
E-MTAB-6701	yes	119.47
E-GEOD-134144	yes	26.56
E-HCAD-10	yes	17.65
E-CURD-114	yes	12.41
E-MTAB-7008	no	1298.67
E-MTAB-8271	no	699.25
E-MTAB-7037	no	463.33
E-MTAB-8205	no	421.79
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Prostate	tissue	127.6	medium
Kidney	tissue	111.8	low
Placenta	tissue	107.3	medium
Ovary	tissue	102.9	high
Adrenal gland	tissue	86.6	medium
Cerebellum	tissue	79.9	low
Postcentral gyrus	tissue	62.2
Epididymis	tissue	60.1	low
Frontal cortex	tissue	59.7
Locus coeruleus	tissue	57.3
Caudate putamen	tissue	55.7
Thyroid gland	tissue	51.8	medium
Duodenum	tissue	51.7	low
Urinary bladder	tissue	51.4	low
Heart muscle	tissue	49.6	low
Nucleus accumbens	tissue	48.8
Small intestine	tissue	47.9	low
Bone marrow	tissue	47.9	low
Rectum	tissue	47.3	low
Thymus	tissue	47.2
Putamen	tissue	46.7
Colon	tissue	46.6	low
Breast	tissue	46.5	medium
Cerebral cortex	tissue	46.3	low
Somatosensory cortex	tissue	46.3
Pons	tissue	45.9
Retina	tissue	45.8
Choroid plexus	tissue	45.6
Lymph node	tissue	44.6	not detected
Hippocampus	tissue	44.3	not detected
Tonsil	tissue	44.3	low
Septum	tissue	44.1
Occipital cortex	tissue	43.8
Motor cortex	tissue	43.2
Endometrium 1	tissue	41.8	low
Superior colliculi	tissue	41.6
Liver	tissue	41.4	not detected
Hippocampal formation	tissue	41.3
Prefrontal cortex	tissue	41.2
Basal ganglia	tissue	40.7	not detected
Cervix	tissue	40.1	low
Ventral forebrain	tissue	40.0
Seminal vesicle	tissue	39.7	not detected
Retrosplenial and cingulate cortex	tissue	39.4
Spleen	tissue	38.9	not detected
Temporal cortex	tissue	38.6
Entorhinal cortex	tissue	38.5
Hypothalamus	tissue	38.0
Gallbladder	tissue	37.9	low
Spinal cord	tissue	37.4
Retrosplenial cortex	tissue	37.4
Stomach 1	tissue	37.1	low
Olfactory bulb	tissue	37.1
Medulla oblongata	tissue	37.0
Thalamus	tissue	37.0
Smooth muscle	tissue	36.9	low
Midbrain	tissue	36.1
Substantia nigra	tissue	36.1
Periaqueductal gray	tissue	34.8
Vagina	tissue	34.0	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Cerebellar cortex (70.2), Temporal pole (66.9), Habenula (66.6), Lateral geniculate body (65.8), Perirhinal gyrus (65.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, NR1I2

miRNA regulators (miRDB)

Targeting SMS by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 49 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-130A-5P	99.33	70.26	2623

Functional genomics

Regional missense constraint (gnomAD)

ENST00000404933 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈71% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
X:21,940,825–21,971,955	23 / 60.5	0.38	no
X:21,971,956–21,972,562	25 / 24.4	1.03	no
X:21,972,563–21,994,348	69 / 203.8	0.34	yes (p 3.7e-21)
ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
DepMap (CRISPR cell-line fitness): dependent in 14.5% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): OCI-LY-19 (-1.074), TUHR10TKB (-1.051), HCC38 (-1.019), ES4 (-0.968), HCC-15 (-0.958), RPMI 8226 (-0.943), RL (-0.899), CML-T1 (-0.889), MC116 (-0.847), DOK (-0.842), EBC-1 (-0.83), JVM-3 (-0.826), OCUM-1 (-0.814), UACC-257 (-0.81), COLO-320 (-0.792).

Literature-anchored findings (GeneRIF, showing 17)

• Study reports the identification of a novel mutation at a highly conserved residue within the N-terminal region of spermine synthase (SMS) in a second family with Snyder-Robinson X-linked mental retardation syndrome. (PMID:18550699)
• A missense mutation, p. V132G, in the X-linked SMS gene causes Snyder-Robinson syndrome. (PMID:19206178)
• Data suggest that disruption of spermine synthase function may negatively affect regional brain volumes that subserve cognitive and motor abilities. (PMID:19277733)
• the genetic and epigenetic factors examined in this study show little influence on the expression level of SMS in suicide completers. (PMID:20059804)
• each gene was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). (PMID:21152090)
• Mutations in the spermine synthase have been shown to be responsible for an X-linked intellectual disability condition known as Snyder-Robinson syndrome. (PMID:21318891)
• the mutability of spermine synthase (PMID:21647366)
• spermine synthase activity and the resulting elevation of the spermine:spermidine ratio does not alter susceptibility to tumor development initiated by c-Ha-Ras mutation or Apc loss (PMID:22258329)
• This observation is used to demonstrate, computationally and experimentally, that a particular condition, Snyder-Robinson syndrome caused by the G56S spermine synthase mutation, might be ameliorated by small molecule binding. (PMID:23408511)
• Studied human spermine synthase activity by engineered mutations. (PMID:23468611)
• Results show that p.Y328C, a missense mutation in SMS is responsible for the patients having a mild form of Snyder-Robinson syndrome. (PMID:23696453)
• Missense mutations causing Snyder-Robinson Syndrome resulting in dysfunctional spermine synthase cause the destabilization of the protein. (PMID:26761001)
• Spermine synthase (SMS) localized together with myosin Va (MyoVa) in cytoplasmic vesicles of breast cancer MCF-7 and neuroblastoma SH-SY5Y cell lines, known to produce exosomes, supporting a role for MyoVa in SMS expression and targeting. (PMID:30733278)
• Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression. (PMID:32591507)
• Whole-exome sequencing identifies a novel mutation in spermine synthase gene (SMS) associated with Snyder-Robinson Syndrome. (PMID:32838743)
• Effects of Spermine Synthase Deficiency in Mesenchymal Stromal Cells Are Rescued by Upstream Inhibition of Ornithine Decarboxylase. (PMID:38473716)
• Reduction of spermine synthase enhances autophagy to suppress Tau accumulation. (PMID:38740758)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	sms	ENSDARG00000008155
mus_musculus	Sms	ENSMUSG00000071708
rattus_norvegicus	Sms	ENSRNOG00000007688
rattus_norvegicus	Smsl1	ENSRNOG00000059957
rattus_norvegicus		ENSRNOG00000091204
drosophila_melanogaster	Sms	FBGN0036272

Paralogs (1): SRM (ENSG00000116649)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:109490) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 19 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	3
decreased lean body mass	3
lordosis	2
decreased body length	2
decreased body weight	2
male infertility	2
decreased bone mineral content	2
muscle weakness	1
postnatal growth retardation	1
reduced male fertility	1
abnormal fertility/fecundity	1
oligozoospermia	1
abnormal spine curvature	1
decreased circulating glucose level	1
increased blood urea nitrogen level	1
decreased circulating potassium level	1
increased NK T cell number	1
increased NK cell number	1
testis degeneration	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3SZA5	97.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PHEX-AS1	ncRNA	100873942
YY2	protein-coding	404281
MBTPS2	protein-coding	51360
PHEX	protein-coding	5251
PTCHD1	protein-coding	139411
CBLL2	protein-coding	158506
DDX53	protein-coding	168400
PTCHD1-AS	ncRNA	100873065
SMPX	protein-coding	23676

Protein

Protein identifiers

Spermine synthase — P52788 (reviewed: P52788)

Alternative names: Spermidine aminopropyltransferase

All UniProt accessions (2): P52788, H7C2R7

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. 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.

Disease relevance. Intellectual developmental disorder, X-linked, syndromic, Snyder-Robinson type (MRXSSR) [MIM:309583] An X-linked intellectual disability syndrome characterized by a collection of clinical features including facial asymmetry, marfanoid habitus, hypertonia, osteoporosis and unsteady gait. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. 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.

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

Similarity. Belongs to the spermidine/spermine synthase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P52788-1	1	yes
P52788-2	2

RefSeq proteins (2): NP_001245352, NP_004586* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015576	Spermine_synthase_animal	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR030373	PABS_CS	Conserved_site
IPR030374	PABS	Domain
IPR035246	Spermidine_synt_N	Domain
IPR037163	Spermidine_synt_N_sf	Homologous_superfamily
IPR040900	SpmSyn_N	Domain

Pfam: PF01564, PF17284, PF17950

Enzyme classification (BRENDA)

• EC 2.5.1.22 — spermine synthase (BRENDA: 19 organisms, 27 substrates, 49 inhibitors, 18 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SPERMIDINE	0.006–0.8	6
S-ADENOSYLMETHIONINAMINE	0.0001–0.005	4
S-ADENOSYL 3-(METHYLTHIO)PROPYLAMINE	0.0005–0.0009	2
6,6-DIFLUOROSPERMIDINE	0.458	1
6-MONOFLUOROSPERMIDINE	0.093	1
7,7-DIFLUOROSPERMIDINE	0.0005	1
7-MONOFLUOROSPERMIDINE	0.0011	1

Catalyzed reactions (Rhea)

• S-adenosyl 3-(methylsulfanyl)propylamine + spermidine = spermine + S-methyl-5’-thioadenosine + H(+) (RHEA:19973)

UniProt features (57 total): strand 19, helix 11, binding site 7, sequence variant 6, mutagenesis site 3, turn 3, modified residue 2, initiator methionine 1, chain 1, splice variant 1, domain 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
3C6K	Crystal structure of human spermine synthase in complex with spermidine and …	X-RAY DIFFRACTION	1.95
3C6M	Crystal structure of human spermine synthase in complex with spermine and …	X-RAY DIFFRACTION	2.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52788-F1	95.09	0.89

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear bodies; cytosol

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
276	proton acceptor

Ligand- & substrate-binding residues (7)

Position	Role
353	spermidine
148	S-adenosyl 3-(methylsulfanyl)propylamine
177	spermidine
201	spermidine
220	S-adenosyl 3-(methylsulfanyl)propylamine
255–256	S-adenosyl 3-(methylsulfanyl)propylamine
351	spermidine

Post-translational modifications (2)

Type	Positions
N-acetylalanine	2
Phosphoserine	57

Mutagenesis-validated functional residues (3)

Position	Phenotype
201	100,000-fold decrease in catalytic efficiency.
276	200,000-fold decrease in catalytic efficiency.
353	800-fold decrease in catalytic efficiency.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-351202	Metabolism of polyamines	curated
R-HSA-1430728	Metabolism	—
R-HSA-71291	Metabolism of amino acids and derivatives	—

MSigDB gene sets: 397 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, LEE_NEURAL_CREST_STEM_CELL_DN, GGGNRMNNYCAT_UNKNOWN, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, KEGG_CYSTEINE_AND_METHIONINE_METABOLISM, MODULE_16, GOBP_POLYAMINE_METABOLIC_PROCESS, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, HOWLIN_PUBERTAL_MAMMARY_GLAND, BACH2_01, BROWNE_HCMV_INFECTION_14HR_DN, MARTIN_VIRAL_GPCR_SIGNALING_DN

GO Biological Process (4): L-methionine metabolic process (GO:0006555), polyamine metabolic process (GO:0006595), spermine biosynthetic process (GO:0006597), polyamine biosynthetic process (GO:0006596)

GO Molecular Function (2): spermine synthase activity (GO:0016768), transferase activity (GO:0016740)

GO Cellular Component (2): cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

12 GO namespaces:

Category	Terms
sulfur amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
biogenic amine metabolic process	1
polyamine biosynthetic process	1
spermine metabolic process	1
polyamine metabolic process	1
biogenic amine biosynthetic process	1
transferase activity, transferring alkyl or aryl (other than methyl) groups	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 8 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular exosome	CC	high-throughput assay
spermine synthase activity	MF	experiment

Protein interactions and networks

STRING

showing 15 of 1,456 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMS	ODC1	P11926	968
SMS	PHEX	P78562	816
SMS	PAOX	Q6QHF9	812
SMS	SMOX	Q9NWM0	799
SMS	SAT1	P21673	744
SMS	AZIN2	Q96A70	708
SMS	DHPS	P49366	681
SMS	DOHH	Q9BU89	666
SMS	AGMAT	Q9BSE5	664
SMS	SLC34A1	Q06495	602
SMS	ARG2	P78540	600
SMS	OAT	P04181	577
SMS	ASS1	P00966	565
SMS	ASL	P04424	554
SMS	ARG1	P05089	554

IntAct

Human interaction partners of SMS in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

10 partners by confidence:

Partner	Interaction type	MIscore	Records
MNT	physical association	0.400	1
MAPK6	physical association	0.370	1
MAPK8IP2	physical association	0.370	1
MAPKAPK3	physical association	0.370	1
RPS6KA3	physical association	0.370	1
BAP1	association	0.350	1
TP53RK	association	0.350	1
EZH2	physical association	0.000	1
FTSJ1	physical association	0.000	1
TFE3	physical association	0.000	1

BioGRID (136 interactions; top human partners by supporting records): FASN (Negative Genetic; 2 records), KYNU (Co-fractionation; 2 records), PARK2 (Affinity Capture-MS; 2 records), RPA1 (Co-fractionation; 2 records), TRIM28 (Affinity Capture-MS; 2 records), YWHAB (Co-fractionation; 2 records), ADRM1 (Co-fractionation), AGR2 (Proximity Label-MS), ASF1B (Co-fractionation), ATP6V1C1 (Affinity Capture-MS), BAD (Proximity Label-MS), BAP1 (Affinity Capture-MS), BCCIP (Co-fractionation), BRD4 (Affinity Capture-MS), C11orf58 (Co-fractionation)

Disease & clinical

Genetic variants

Variant evidence for SMS: 274 ClinVar records (32 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

274 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	20
Uncertain significance	97
Likely benign	37
Benign	26

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 32 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
11624	NM_004595.5(SMS):c.166G>A (p.Gly56Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
827761	NM_004595.5(SMS):c.608G>A (p.Gly203Asp)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
981630	NM_004595.5(SMS):c.587T>C (p.Ile196Thr)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
65677	NM_004595.5(SMS):c.200G>A (p.Gly67Glu)	Pathogenic	criteria provided, single submitter	2
626916	NM_004595.5(SMS):c.908_911del (p.Met303fs)	Pathogenic	criteria provided, single submitter	2
816629	NM_004595.5(SMS):c.388C>T (p.Arg130Cys)	Pathogenic	criteria provided, single submitter	2
3366861	NM_004595.5(SMS):c.661-13A>C	Pathogenic	criteria provided, single submitter	1
4813567	NM_004595.5(SMS):c.954T>G (p.Cys318Trp)	Pathogenic	criteria provided, single submitter	1
916028	NM_004595.5(SMS):c.410A>G (p.Asp137Gly)	Likely pathogenic	criteria provided, single submitter	3
1013359	NM_004595.5(SMS):c.350G>T (p.Gly117Val)	Likely pathogenic	criteria provided, single submitter	3
441113	NM_004595.5(SMS):c.665A>T (p.Asp222Val)	Likely pathogenic	criteria provided, single submitter	2
4484781	NM_004595.5(SMS):c.346C>T (p.Arg116Ter)	Likely pathogenic	criteria provided, single submitter	2
421087	NM_004595.5(SMS):c.831G>T (p.Leu277Phe)	Likely pathogenic	criteria provided, single submitter	1
520793	NM_004595.5(SMS):c.638C>A (p.Pro213Gln)	Likely pathogenic	criteria provided, single submitter	1
620039	NM_004595.5(SMS):c.581T>G (p.Val194Gly)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore SMS’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 1,148):

Position(s)	Effect	Δscore	Sites
X:21940874–21940875	donor_loss	1.0000	4
X:21977059–21977060	acceptor_gain	1.0000	2
X:21977059–21977060	acceptor_loss	1.0000	4
X:21977237–21977238	donor_loss	1.0000	5
X:21978873	acceptor_gain	1.0000
X:21984298–21984299	acceptor_gain	1.0000	2
X:21940875	donor_loss	0.9900
X:21966295	donor_gain	0.9900
X:21967186	acceptor_gain	0.9900
X:21969390	acceptor_gain	0.9900

AlphaMissense

984 missense substitutions predicted likely pathogenic (of 2,407 scored), across 232 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M218	9	0.900	0.995
D276	8	0.999	1.000
D201	8	0.998	1.000
D174	8	0.997	0.999
D222	8	0.997	0.999
D255	8	0.989	0.998
F294	8	0.979	0.999
F357	8	0.979	0.999
N169	8	0.966	0.999
D128	8	0.964	0.993
D167	8	0.956	0.984
D135	8	0.945	0.981
F270	8	0.932	0.997
D271	8	0.908	0.987
D10	8	0.802	0.891
D72	8	0.787	0.863
W355	7	0.995	0.999
W292	7	0.989	0.998
E353	7	0.987	0.998
Q148	7	0.982	0.998

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Prostate Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

8 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	5.06e-09
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.86e-05
Lung Adenocarcinoma (TCGA)	unfavorable	5.49e-05
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000374
Bladder Urothelial Carcinoma (TCGA)	unfavorable	0.000422
Breast Invasive Carcinoma (TCGA)	unfavorable	0.000547
Lung Adenocarcinoma (validation)	unfavorable	0.000814
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000847

Disease associations

OMIM: gene MIM:300105 | disease phenotypes: MIM:309583, MIM:182290

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
syndromic X-linked intellectual disability Snyder type	Strong	X-linked	4

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
syndromic X-linked intellectual disability Snyder type	Definitive	XL

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (9 panels, 9 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

9 panels:

Panel	Rating
Clefting	green
DDG2P	green
Early onset or syndromic epilepsy	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (3): syndromic X-linked intellectual disability Snyder type (MONDO:0010664), Smith-Magenis syndrome (MONDO:0008434), intellectual disability (MONDO:0001071)

Orphanet (3): X-linked intellectual disability, Snyder type (Orphanet:3063), Smith-Magenis syndrome (Orphanet:819), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

showing 60 of 92 phenotypes (HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000029	Testicular atrophy
HP:0000047	Hypospadias
HP:0000086	Ectopic kidney
HP:0000098	Tall stature
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000248	Brachycephaly
HP:0000275	Narrow face
HP:0000276	Long face
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000324	Facial asymmetry
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000378	Cupped ear
HP:0000385	Small earlobe
HP:0000391	Thickened helices
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000582	Upslanted palpebral fissure
HP:0000664	Synophrys
HP:0000678	Dental crowding
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000939	Osteoporosis
HP:0000954	Single transverse palmar crease
HP:0001166	Arachnodactyly
HP:0001187	Hyperextensibility of the finger joints
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001336	Myoclonus
HP:0001344	Absent speech
HP:0001355	Megalencephaly
HP:0001419	X-linked recessive inheritance
HP:0001519	Disproportionate tall stature
HP:0001609	Hoarse voice
HP:0001611	Hypernasal speech
HP:0001762	Talipes equinovarus
HP:0001847	Long hallux
HP:0001999	Abnormal facial shape
HP:0002123	Generalized myoclonic seizure
HP:0002136	Broad-based gait

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D058496	Smith-Magenis Syndrome	C10.281.900; C16.131.077.879; C16.131.260.887; C16.320.180.887
C536678	Snyder Robinson syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4934 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
2-[6-Amino-1-(2-amino-ethyl)-hexylsulfanylmethyl]-5-(6-amino-purin-9-yl)-tetrahydro-furan-3,4-diol	IC50	250 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	IC50	20	nM	CHEMBL315995
7.30	IC50	50	nM	CHEMBL330673

PubChem BioAssay actives

2 with measured affinity, of 2 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S,3S,4R,5R)-2-[[1-amino-8-(3-aminopropylamino)octan-3-yl]sulfanylmethyl]-5-(6-aminopurin-9-yl)oxolane-3,4-diol	226564: Inhibitory activity against spermine synthase	ic50	0.0200	uM
(2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-(1,8-diaminooctan-3-ylsulfanylmethyl)oxolane-3,4-diol	226564: Inhibitory activity against spermine synthase	ic50	0.0500	uM

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	6
Tobacco Smoke Pollution	decreases expression, increases expression, increases methylation	3
chloropicrin	affects expression, decreases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Fluorouracil	increases expression, affects reaction, decreases expression	2
Dihydrotestosterone	increases expression	2
aristolochic acid I	increases expression, decreases expression	1
bismuth tripotassium dicitrate	increases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
tetrahydropalmatine	decreases expression	1
sodium arsenite	affects methylation	1
aflatoxin B2	affects methylation	1
CGP 52608	affects binding, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
incobotulinumtoxinA	decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Atrazine	increases expression	1
Azathioprine	decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dichlorodiphenyl Dichloroethylene	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL845254	Binding	Inhibitory activity against spermine synthase	Terminally alkylated polyamine analogues as chemotherapeutic agents. — *J Med Chem*

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1LD	Abcam Jurkat SMS KO	Cancer cell line	Male
CVCL_D1QM	Abcam K-562 SMS KO	Cancer cell line	Female
CVCL_D2M8	Abcam Raji SMS KO	Cancer cell line	Male
CVCL_TP71	HAP1 SMS (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 227 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT06457906	Phase 3	RECRUITING	SRS/SRT/Hypo-RT Versus HA-WBRT for No More Than 10 Brain Metastases in SCLC
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT04180501	Phase 2	UNKNOWN	SRS Sequential Sindilimab in Brain Metastasis of NSLSC
NCT04899908	Phase 2	RECRUITING	Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases
NCT07162246	Phase 2	RECRUITING	Combined Gamma Knife/Linac Radiosurgery for Large Brain Tumors / Metastases
NCT02304302	Phase 2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	Phase 2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	Phase 2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	Phase 2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02776215	Phase 1	COMPLETED	Study of the Pharmacokinetics and Safety of Tasimelteon in Children and Adolescents
NCT05273320	Phase 1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	Phase 1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	Phase 1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	Phase 1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	Phase 1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03915106	Not specified	RECRUITING	Quality of Life (HRQoL) of AIS Patients Who Require Bracing or Surgery Using SRS-22 Questionnaire
NCT06466720	Not specified	ACTIVE_NOT_RECRUITING	Measuring and Mapping Cognitive Decline After Brain Radiosurgery
NCT06852001	Not specified	NOT_YET_RECRUITING	Efficacy of the RayerKnife X Stereotactic Radiotherapy System in the Treatment of Brain Metastases
NCT07405112	Not specified	COMPLETED	Impact of Curve Magnitude on Pain and Body Image in Patients With Adolescents Idiopathic Scoliosis
NCT02231008	Phase 2/3	COMPLETED	Evaluating the Effects of Tasimelteon vs Placebo on Sleep Disturbances in SMS
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00013559	Not specified	COMPLETED	Natural History Study of Smith-Magenis Syndrome
NCT01837121	Not specified	COMPLETED	a Trial of Using SMS Reminder Among Diabetic Retinopathy Patients in Rural China
NCT02180451	Not specified	UNKNOWN	Observational Study to Investigate the Melatonin and Cortisol Circadian Rhythms of Individuals With Smith-Magenis Syndrome (SMS)
NCT02400671	Not specified	COMPLETED	Mobile Strategies for Women’s and Children’s Health: Optimizing Adherence and Efficacy of PMTCT/ART
NCT03346616	Not specified	COMPLETED	Text4Peds: Short Message Service Evaluating Medical Student Education
NCT03379467	Not specified	COMPLETED	Use of SMS and Interactive Reminders to Improve Timely Immunization Coverage
NCT03492970	Not specified	COMPLETED	Melatonin in Adults With SMS
NCT03836300	Not specified	ENROLLING_BY_INVITATION	Parent and Infant Inter(X)Action Intervention (PIXI)
NCT04768803	Not specified	UNKNOWN	Ghrelin in Patients With a Rare Disease Associated With Intellectual Disability, and Hyperphagia, and/or Overweight, and/or Obesity
NCT05116904	Not specified	UNKNOWN	Smith Magenis Syndrome and Autism Spectrum Disorders
NCT06247852	Not specified	COMPLETED	Persistent Pain After Cesarean Delivery - A Danish Multicenter Cohort Study
NCT07510971	Not specified	NOT_YET_RECRUITING	mHealth Intervention for Improving Vaccination Coverage in Bangladesh
NCT03479476	Phase 2/3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	Phase 1/2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	Early Phase 1	TERMINATED	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
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NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SMS across ~30M SureChEMBL compounds — explore on Sugi Predict.