SMC3

Summary

SMC3 (structural maintenance of chromosomes 3, HGNC:2468) is a protein-coding gene on chromosome 10q25.2, encoding Structural maintenance of chromosomes protein 3 (Q9UQE7). Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. It is a common-essential gene (DepMap: required in 98.4% of cancer cell lines).

This gene belongs to the SMC3 subfamily of SMC proteins. The encoded protein occurs in certain cell types as either an intracellular, nuclear protein or a secreted protein. The nuclear form, known as structural maintenance of chromosomes 3, is a component of the multimeric cohesin complex that holds together sister chromatids during mitosis, enabling proper chromosome segregation. Post-translational modification of the encoded protein by the addition of chondroitin sulfate chains gives rise to the secreted proteoglycan bamacan, an abundant basement membrane protein.

Source: NCBI Gene 9126 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Cornelia de Lange syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 788 total — 26 pathogenic, 52 likely-pathogenic
• Phenotypes (HPO): 147
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.4% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005445

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2468
Approved symbol	SMC3
Name	structural maintenance of chromosomes 3
Location	10q25.2
Locus type	gene with protein product
Status	Approved
Aliases	HCAP, BAM, SMC3L1, bamacan
Ensembl gene	ENSG00000108055
Ensembl biotype	protein_coding
OMIM	606062
Entrez	9126

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 retained_intron, 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000361804, ENST00000462899, ENST00000684797, ENST00000684988, ENST00000685743, ENST00000686057, ENST00000687823, ENST00000689321, ENST00000689932, ENST00000689986, ENST00000691297, ENST00000691527, ENST00000692792, ENST00000901787, ENST00000918255, ENST00000918256, ENST00000918257, ENST00000918258, ENST00000966376, ENST00000966377

RefSeq mRNA: 1 — MANE Select: NM_005445 NM_005445

CCDS: CCDS31285

Canonical transcript exons

ENST00000361804 — 29 exons

Exon	Start	End
ENSE00000723810	110603184	110603290
ENSE00000723821	110602825	110603002
ENSE00000723835	110602474	110602665
ENSE00000723845	110601966	110602178
ENSE00000723856	110601637	110601884
ENSE00000723866	110601022	110601130
ENSE00000723879	110600439	110600546
ENSE00000723890	110599654	110599812
ENSE00000723964	110584183	110584396
ENSE00000723973	110583841	110583962
ENSE00000723979	110583384	110583548
ENSE00000723987	110582562	110582642
ENSE00000723995	110581923	110582098
ENSE00000811837	110589605	110589708
ENSE00000811838	110589892	110589991
ENSE00000811839	110590412	110590572
ENSE00000811840	110590991	110591132
ENSE00000811841	110593073	110593223
ENSE00001383247	110598139	110598290
ENSE00001432730	110604231	110606048
ENSE00001434774	110567695	110567831
ENSE00001450299	110596398	110596550
ENSE00003561538	110573707	110573745
ENSE00003564319	110575336	110575403
ENSE00003570259	110578628	110578706
ENSE00003607121	110580904	110581021
ENSE00003611418	110568938	110569013
ENSE00003633274	110577835	110577914
ENSE00003674243	110577421	110577492

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 99.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8401 / max 387.5476, expressed in 1776 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106976	21.1748	1774
106977	0.6653	384

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.11	gold quality
ventricular zone	UBERON:0003053	97.89	gold quality
oocyte	CL:0000023	97.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.04	gold quality
ganglionic eminence	UBERON:0004023	96.87	gold quality
tendon	UBERON:0000043	96.38	gold quality
medial globus pallidus	UBERON:0002477	95.31	gold quality
calcaneal tendon	UBERON:0003701	95.14	gold quality
cortical plate	UBERON:0005343	94.70	gold quality
secondary oocyte	CL:0000655	94.03	gold quality
superior surface of tongue	UBERON:0007371	93.92	gold quality
embryo	UBERON:0000922	93.89	gold quality
mammary duct	UBERON:0001765	93.30	gold quality
globus pallidus	UBERON:0001875	93.29	gold quality
buccal mucosa cell	CL:0002336	92.20	gold quality
pylorus	UBERON:0001166	92.08	gold quality
epithelium of mammary gland	UBERON:0003244	91.81	gold quality
pericardium	UBERON:0002407	91.68	gold quality
cranial nerve II	UBERON:0000941	90.81	gold quality
testis	UBERON:0000473	90.74	gold quality
saphenous vein	UBERON:0007318	90.55	gold quality
right testis	UBERON:0004534	90.50	gold quality
islet of Langerhans	UBERON:0000006	90.31	gold quality
cervix squamous epithelium	UBERON:0006922	89.68	gold quality
renal medulla	UBERON:0000362	89.33	gold quality
left testis	UBERON:0004533	89.32	gold quality
colonic epithelium	UBERON:0000397	89.17	gold quality
inferior vagus X ganglion	UBERON:0005363	88.97	gold quality
hair follicle	UBERON:0002073	88.83	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	3357.19
E-CURD-112	yes	39.38
E-GEOD-134144	yes	29.87
E-CURD-122	yes	23.39
E-MTAB-6678	yes	8.56
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CTCF, CTNNB1, IRF2, SFPQ, TBX15, TCF7L2

miRNA regulators (miRDB)

44 targeting SMC3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4496	99.88	68.89	2236
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-374B-3P	98.63	68.24	1360

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 98.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 33)

• identification as target for beta-catenin/T-cell factor 4 transactivation pathway (PMID:12651860)
• Hinderin is a novel binding partner of SMC3. Based on its ability to modulate SMC1/SMC3 interaction we postulate that Hinderin affects the availability of SMC3 to engage in the formation of multimeric protein complexes (PMID:15656913)
• RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC3. (PMID:16043481)
• RhoB and cAMP cis-acting response elements -BPa two known oncogenic mediators whose expression is significantly increased following SMC3 overexpression play a significant role in mediating SMC3 tumorigenesis (PMID:16156898)
• SMC3 deficiency affects chromosomal stability leading to the activation of p53-dependent mitotic checkpoint. (PMID:17081288)
• Mutations in SMC3 cause a mild variant of cornelia de Lange syndrome with predominant mental retardation (PMID:17273969)
• identified as one of five genes containing 11 somatic mutations in a panel that included 132 colorectal cancers, then demonstrated that down-regulation of such homologs resulted in chromosomal instability and chromatid cohesion defects in human cells (PMID:18299561)
• phosphorylation of a core cohesin subunit SMC3 by ATM plays an important role in DNA damage (PMID:18442975)
• This study identified a molecular target for the acetyltransferase Eco1 and revealed that Smc3 acetylation is a conserved mechanism in regulating sister chromatid cohesion. (PMID:18614053)
• There were greater levels of chondroitin sulphate WF6 epitope in gingival crevicular fluid from destructive sites of patients with chronic periodontitis compared with non-destructive sites of patients with gingivitis or chronic periodontitis. (PMID:18727658)
• Cornelia de Lange syndrome mutations in SMC1A or SMC3 bind to DNA with higher affinity and display genomic instability. (PMID:18996922)
• Data describe alterations of myocardial intercellular and cell-matrix contacts in hypertrophic tissue, and show intracellular translocation of beta-catenin, alpha-actinin and chondroitin sulfate proteoglycan 6 in both an animal model and in LVH patients. (PMID:19094982)
• these studies clearly suggest that bamacan interacts with the vaccinia virus-N1L and such interactions seem to play a positive role in promoting the viral growth and perhaps contribute to the virulence of VV in neural cells. (PMID:19444697)
• The identification of 14 additional mutations of the cohesin complex genes NIPBL and SMC1A in a cohort of 30 unrelated patients with Cornelia de Lange syndrome, is reported. (PMID:20358602)
• SMC3 and separase are upregulated and securin is downregulated in malignant transformation of BEAS-2B cells induced by coal tar pitch smoke extracts. (PMID:21126432)
• NIPBL, SMC1A, and SMC3 mutation-positive patients were equally likely to have congenital heart diseases in Cornelia de lange syndrome. (PMID:22965847)
• c-MYC down-regulation caused by cohesin mutations in SMC1A and SMC3 genes may be an early/primary event in the pathogenesis of Cornelia de Lange syndrome. (PMID:23106691)
• Upon knock-down of human SMC1, much of SMC3 remains stable, accumulates in the cytoplasm and does not associate with other cohesin proteins. (PMID:23776448)
• Mutations in SMC3 is associated with acute myeloid leukemia. (PMID:24335498)
• Cross-sectional deep-sequencing analysis for clonal hierarchy demonstrated STAG2, SMC3, and RAD21 mutations to be ancestral in 18%, 18%, and 47% of cases, respectively, and each expanded to clonal dominance concordant with disease transformation (PMID:25006131)
• cohesin’s proposed DNA exit gate is formed by interactions between Scc1 and the coiled-coil region of Smc3. (PMID:25414306)
• Results show that SMC3 is upregulated in asthma patients and suggest that it may play an important role in atopic asthma development, especially in asthma epithelial-mesenchymal transition. (PMID:25515564)
• De novo heterozygous mutations in SMC3 cause a range of Cornelia de Lange syndrome-overlapping phenotypes (PMID:25655089)
• Data show that histone deacetylase 8 (HDAC8) inhibition led to accumulation of acetylated-SMC3 protein but had no influence on the transcription of estrogen-responsive genes. (PMID:27072133)
• We identified a large number of mutations in the CC region of both Smc1 and Smc3… we introduced them to the yeast Smc1 and Smc3 CC domains and characterized the effect of these mutant alleles on cohesin’s function. We identified a missense mutation in the region of the kink domain of Smc3, which was previously identified in kidney carcinoma (PMID:27307603)
• Both the SMC1A and SMC3 gene mutation tests were negative in all Chinese patients with Cornelia de Lange syndrome. (PMID:29452578)
• H2 inhibited lung cancer progression through down-regulating SMC3. (PMID:29852353)
• SMC3 protein levels impact on karyotype. (PMID:30323357)
• Cohesin Core Complex Gene Dosage Contributes to Germinal Center Derived Lymphoma Phenotypes and Outcomes. (PMID:34621263)
• Stepwise GATA1 and SMC3 mutations alter megakaryocyte differentiation in a Down syndrome leukemia model. (PMID:35587378)
• SMC3 epigenetic silencing regulates Rab27a expression and drives pancreatic cancer progression. (PMID:37641131)
• RIT1 regulates mitosis and promotes proliferation by interacting with SMC3 and PDS5 in hepatocellular carcinoma. (PMID:38017479)
• Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features. (PMID:38297832)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	smc3	ENSDARG00000019000
mus_musculus	Smc3	ENSMUSG00000024974
rattus_norvegicus	Smc3	ENSRNOG00000014173
drosophila_melanogaster	SMC3	FBGN0015615
caenorhabditis_elegans		WBGENE00004873
caenorhabditis_elegans		WBGENE00012198
caenorhabditis_elegans		WBGENE00019087

Paralogs (7): SMC1A (ENSG00000072501), SMC1B (ENSG00000077935), SMC4 (ENSG00000113810), CKAP4 (ENSG00000136026), SMC2 (ENSG00000136824), CCDC122 (ENSG00000151773), CCDC157 (ENSG00000187860)

Protein

Protein identifiers

Structural maintenance of chromosomes protein 3 — Q9UQE7 (reviewed: Q9UQE7)

Alternative names: Basement membrane-associated chondroitin proteoglycan, Chondroitin sulfate proteoglycan 6, Chromosome-associated polypeptide

All UniProt accessions (1): Q9UQE7

UniProt curated annotations — full annotation on UniProt →

Function. Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement.

Subunit / interactions. Forms a heterodimer with SMC1A or SMC1B in cohesin complexes. Cohesin complexes are composed of the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer attached via their SMC hinge domain, RAD21 which link them, and one STAG protein (STAG1, STAG2 or STAG3), which interacts with RAD21. Also found in meiosis-specific cohesin complexes. Found in a complex with SMC1A, CDCA5 and RAD21, PDS5A/SCC-112 and PDS5B/APRIN. Interacts with NUMA1, and forms a ternary complex with KIF3B and KIFAP3, suggesting a function in tethering the chromosomes to the spindle pole and in chromosome movement. Interacts with PDS5A and WAPL; regulated by SMC3 acetylation. Interacts (via SMC hinge domain) with KIAA1328 (via N- and C-terminal domains). Interacts with DDX11. Found in a cohesin complex with SMC1A, STAG1 and RAD21. The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1. Interacts with MXI1, MXD3, MXD4, SYCP2, RPGR and STAG3. Interacts with the NuRD complex component HDAC2; the interaction is direct.

Subcellular location. Nucleus. Chromosome. Centromere.

Post-translational modifications. Ubiquitinated by the DCX(DCAF15) complex, leading to its degradation. Phosphorylated at Ser-1083 in a SPO11-dependent manner. Acetylation at Lys-105 and Lys-106 by ESCO1 is important for genome stability and S phase sister chromatid cohesion. Regulated by DSCC1, it is required for processive DNA synthesis, coupling sister chromatid cohesion establishment during S phase to DNA replication. Deacetylation by HDAC8, regulates release of the cohesin complex from chromatin.

Disease relevance. Cornelia de Lange syndrome 3 with or without midline brain defects (CDLS3) [MIM:610759] A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. Characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. Cornelia de Lange syndrome type 3 is a mild form with absence of major structural anomalies. The phenotype in some instances approaches that of apparently non-syndromic intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterotypic interaction with the corresponding domain of SMC1A or SMC1B, forming a V-shaped heterodimer. The two heads of the heterodimer are then connected by different ends of the cleavable RAD21 protein, forming a ring structure.

Miscellaneous. Mutated Cornelia de Lange cell lines display genomic instability and sensitivity to ionizing radiation and interstrand cross-linking agents.

Similarity. Belongs to the SMC family. SMC3 subfamily.

RefSeq proteins (1): NP_005436* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003395	RecF/RecN/SMC_N	Domain
IPR010935	SMC_hinge	Domain
IPR024704	SMC	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036277	SMC_hinge_sf	Homologous_superfamily
IPR041741	SMC3_ABC_euk	Domain

Pfam: PF02463, PF06470

UniProt features (103 total): helix 34, strand 33, modified residue 12, mutagenesis site 6, coiled-coil region 4, turn 4, sequence conflict 3, region of interest 2, sequence variant 2, chain 1, domain 1, binding site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
8ROK	X-RAY DIFFRACTION	2.25
6WG4	X-RAY DIFFRACTION	2.31
8ROI	X-RAY DIFFRACTION	2.45
8ROH	X-RAY DIFFRACTION	2.6
8ROJ	X-RAY DIFFRACTION	3
8ROL	X-RAY DIFFRACTION	3.11
6WG6	X-RAY DIFFRACTION	3.54
8P0A	ELECTRON MICROSCOPY	3.67
6WGE	ELECTRON MICROSCOPY	3.9
8PQ5	ELECTRON MICROSCOPY	4.4
6WG3	ELECTRON MICROSCOPY	5.3
7W1M	ELECTRON MICROSCOPY	6.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UQE7-F1	82.37	0.14

Functional residue map

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

Ligand- & substrate-binding residues (1): 32–39

Post-translational modifications (12): 106, 140, 783, 787, 886, 1013, 1065, 1067, 1074, 1083, 1190, 105

Mutagenesis-validated functional residues (6):

Position	Phenotype
105	20% loss of sister chromatid cohesion, no effect on cohesin complex assembly; when associated with a-106.
105	no effect on sister chromatid cohesion, nor on cohesin complex assembly; when associated with q-106.
105	stabilizes interaction with pds5a and wapl; when associated with r-106.
106	20% loss of sister chromatid cohesion, no effect on cohesin complex assembly; when associated with a-105.
106	no effect on sister chromatid cohesion, nor on cohesin complex assembly; when associated with q-105.
106	stabilizes interaction with pds5a and wapl; when associated with r-105.

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-1221632	Meiotic synapsis
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2468052	Establishment of Sister Chromatid Cohesion
R-HSA-2470946	Cohesin Loading onto Chromatin
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-1474165	Reproduction
R-HSA-1500620	Meiosis
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-68877	Mitotic Prometaphase
R-HSA-68882	Mitotic Anaphase
R-HSA-68884	Mitotic Telophase/Cytokinesis
R-HSA-68886	M Phase
R-HSA-69242	S Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 673 (showing top): E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, MORF_DNMT1, E2F_Q4_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, REACTOME_MEIOTIC_SYNAPSIS, GCM_ZNF198, MORF_RRM1, MORF_UBE2N, GCM_PPM1D, MITSIADES_RESPONSE_TO_APLIDIN_DN, KAUFFMANN_DNA_REPAIR_GENES, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (13): mitotic cell cycle (GO:0000278), regulation of DNA replication (GO:0006275), DNA repair (GO:0006281), sister chromatid cohesion (GO:0007062), mitotic sister chromatid cohesion (GO:0007064), stem cell population maintenance (GO:0019827), establishment of mitotic sister chromatid cohesion (GO:0034087), establishment of meiotic sister chromatid cohesion (GO:0034089), cell division (GO:0051301), meiotic cell cycle (GO:0051321), mitotic spindle assembly (GO:0090307), DNA damage response (GO:0006974), chromosome organization (GO:0051276)

GO Molecular Function (12): cis-regulatory region sequence-specific DNA binding (GO:0000987), chromatin binding (GO:0003682), double-stranded DNA binding (GO:0003690), microtubule motor activity (GO:0003777), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), mediator complex binding (GO:0036033), protein heterodimerization activity (GO:0046982), beta-tubulin binding (GO:0048487), dynein complex binding (GO:0070840), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (13): chromosome, centromeric region (GO:0000775), chromatin (GO:0000785), lateral element (GO:0000800), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829), cohesin complex (GO:0008278), nuclear matrix (GO:0016363), mitotic cohesin complex (GO:0030892), meiotic cohesin complex (GO:0030893), mitotic spindle pole (GO:0097431), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
M Phase	3
Meiosis	1
Mitotic Anaphase	1
S Phase	1
Mitotic Telophase/Cytokinesis	1
Mitotic Prometaphase	1
SUMO E3 ligases SUMOylate target proteins	1
ESR-mediated signaling	1
Reproduction	1
Cell Cycle	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell cycle	2
mitotic nuclear division	2
establishment of sister chromatid cohesion	2
binding	2
ATP-dependent activity	2
protein-containing complex binding	2
chromosome	2
nuclear lumen	2
cohesin complex	2
DNA replication	1
regulation of DNA metabolic process	1
DNA metabolic process	1
DNA damage response	1
cell cycle process	1
chromosome organization	1
sister chromatid cohesion	1
multicellular organismal process	1
maintenance of cell number	1
mitotic cell cycle	1
mitotic sister chromatid cohesion	1
mitotic cell cycle process	1
meiotic sister chromatid cohesion	1
cellular process	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
cellular response to stress	1
organelle organization	1
transcription cis-regulatory region binding	1
DNA binding	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
protein dimerization activity	1

Protein interactions and networks

STRING

4092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMC3	STAG2	Q8N3U4	999
SMC3	RAD21	O60216	999
SMC3	PDS5A	Q29RF7	999
SMC3	STAG1	Q8WVM7	999
SMC3	NIPBL	Q6KC79	998
SMC3	REC8	O95072	996
SMC3	STAG3	Q9UJ98	996
SMC3	SMC1A	Q14683	993
SMC3	SMC1B	Q8NDV3	993
SMC3	WAPL	Q7Z5K2	991
SMC3	CTCF	P49711	984
SMC3	ESCO1	Q5FWF5	976
SMC3	RAD21L1	Q9H4I0	974
SMC3	ESCO2	Q56NI9	973
SMC3	MDC1	Q14676	961

IntAct

267 interactions, top by confidence:

A	B	Type	Score
STAG2	RAD21	psi-mi:“MI:0914”(association)	0.970
RAD21	SMC3	psi-mi:“MI:0915”(physical association)	0.960
SMC3	RAD21	psi-mi:“MI:0914”(association)	0.960
SMC3	RAD21	psi-mi:“MI:0915”(physical association)	0.960
STAG2	SMC3	psi-mi:“MI:0915”(physical association)	0.950
SMC3	STAG2	psi-mi:“MI:0915”(physical association)	0.950
PSMA1	PSMA7	psi-mi:“MI:2364”(proximity)	0.950
STAG1	SMC3	psi-mi:“MI:0915”(physical association)	0.940
SMC1A	SMC3	psi-mi:“MI:0915”(physical association)	0.940
SMC3	SMC1A	psi-mi:“MI:0915”(physical association)	0.940
SMC3	SMC1A	psi-mi:“MI:0914”(association)	0.940
STAG1	RAD21	psi-mi:“MI:0914”(association)	0.930
RAE1	NUP98	psi-mi:“MI:0914”(association)	0.930
SMC1A	RAD21	psi-mi:“MI:0914”(association)	0.930

BioGRID (697): SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Reconstituted Complex), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-MS), SMC3 (Affinity Capture-Western), SMC3 (Affinity Capture-Western)

ESM2 similar proteins: B2FDA8, G0SHW7, G5EG17, J9VL63, O01789, O13710, O42649, O93309, O94383, O95347, O97594, P32908, P38989, P41003, P41004, P47037, P48996, P50533, P53692, P92199, P97690, Q00737, Q08204, Q09591, Q12267, Q12749, Q18237, Q20060, Q54I56, Q54LV0, Q54PK4, Q552D9, Q5R4K5, Q6C3V4, Q6DRJ7, Q6P9I7, Q6Q1P4, Q802R8, Q8CG48, Q8NDV3

Diamond homologs: A9BZW2, A9II65, B8CW13, B8GZ28, B9E1H0, C4ZJU1, O42649, O66878, O93309, O94383, O97594, P15016, P32908, P38989, P47540, P48996, P50532, P75361, P97690, Q09591, Q12267, Q12749, Q1D2R5, Q20060, Q24U48, Q3JR19, Q59037, Q5H054, Q5N0D2, Q5R4K5, Q604U6, Q69GZ5, Q7NG51, Q81ZL2, Q8KBS6, Q8REH4, Q8TZY2, Q920F6, Q9CW03, Q9FJL0

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
ATM	unknown	SMC3	phosphorylation
CSNK2A1	unknown	SMC3	phosphorylation
CSNK2A2	unknown	SMC3	phosphorylation
SMC3	“form complex”	“RAD21L Cohesin complex”	binding
SMC3	“down-regulates activity”	MXI1	binding
SMC3	“down-regulates activity”	MXD1	binding
SMC3	“down-regulates activity”	MXD3	binding
SMC3	“down-regulates activity”	MXD4	binding
SMC3	“form complex”	“Cohesin complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 179 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
S Phase	9	13.5×	2e-06
Degradation of DVL	6	11.8×	8e-04
SPOP-mediated proteasomal degradation of PD-L1(CD274)	6	11.3×	9e-04
Ubiquitin-dependent degradation of Cyclin D	5	11.0×	4e-03
Orc1 removal from chromatin	7	10.3×	4e-04
GSK3B-mediated proteasomal degradation of PD-L1(CD274)	5	9.8×	5e-03
G1/S Transition	5	9.6×	5e-03
Regulation of RUNX3 expression and activity	5	9.6×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitotic sister chromatid cohesion	5	37.2×	4e-05
sister chromatid cohesion	5	25.4×	2e-04
mitotic spindle assembly	8	18.2×	5e-06
intrinsic apoptotic signaling pathway	5	11.9×	7e-03
cell surface receptor protein tyrosine kinase signaling pathway	7	8.1×	4e-03
cell division	19	5.8×	8e-07
transcription by RNA polymerase II	11	5.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	52
Uncertain significance	284
Likely benign	261
Benign	92

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1335863	NM_005445.4(SMC3):c.717TGA[1] (p.Asp240del)	Pathogenic
1686220	NM_005445.4(SMC3):c.2044G>A (p.Val682Ile)	Pathogenic
180199	NM_005445.4(SMC3):c.2536-5_2541del	Pathogenic
208656	NM_005445.4(SMC3):c.2750A>C (p.His917Pro)	Pathogenic
217799	NM_005445.4(SMC3):c.139T>C (p.Phe47Leu)	Pathogenic
217800	NM_005445.4(SMC3):c.703_705del (p.Thr235del)	Pathogenic
217802	NM_005445.4(SMC3):c.1462G>A (p.Glu488Lys)	Pathogenic
217804	NM_005445.4(SMC3):c.1997G>C (p.Gly666Ala)	Pathogenic
2633290	NM_005445.4(SMC3):c.778C>T (p.Gln260Ter)	Pathogenic
2695095	NM_005445.4(SMC3):c.2530G>T (p.Glu844Ter)	Pathogenic
2735489	NM_005445.4(SMC3):c.1892T>C (p.Leu631Pro)	Pathogenic
2784079	NM_005445.4(SMC3):c.2899C>T (p.Arg967Ter)	Pathogenic
3252587	NM_005445.4(SMC3):c.3349G>A (p.Gly1117Ser)	Pathogenic
3341123	NM_005445.4(SMC3):c.3104A>G (p.Gln1035Arg)	Pathogenic
3632582	NM_005445.4(SMC3):c.3454C>T (p.Gln1152Ter)	Pathogenic
3720422	NM_005445.4(SMC3):c.1127A>G (p.Tyr376Cys)	Pathogenic
3764216	NM_005445.4(SMC3):c.1339C>T (p.Arg447Ter)	Pathogenic
3958639	NM_005445.4(SMC3):c.2242C>T (p.Gln748Ter)	Pathogenic
4086482	NM_005445.4(SMC3):c.2087T>C (p.Leu696Pro)	Pathogenic
419035	NM_005445.4(SMC3):c.1539del (p.Asn513fs)	Pathogenic
4631	NM_005445.4(SMC3):c.1461AGA[1] (p.Glu488del)	Pathogenic
546269	NM_005445.4(SMC3):c.965A>C (p.Gln322Pro)	Pathogenic
581922	NM_005445.4(SMC3):c.661C>T (p.Arg221Ter)	Pathogenic
626275	NM_005445.4(SMC3):c.1071_1074del (p.Glu358fs)	Pathogenic
864833	NM_005445.4(SMC3):c.1138_1152del (p.Gly380_Gln384del)	Pathogenic
985132	NM_005445.4(SMC3):c.3439C>G (p.Gln1147Glu)	Pathogenic
1067573	NM_005445.4(SMC3):c.1901G>A (p.Arg634His)	Likely pathogenic
1098399	NM_005445.4(SMC3):c.2002TAT[1] (p.Tyr669del)	Likely pathogenic
1304271	NM_005445.4(SMC3):c.1417T>G (p.Trp473Gly)	Likely pathogenic
1319924	NM_005445.4(SMC3):c.3442G>T (p.Ala1148Ser)	Likely pathogenic

SpliceAI

3342 predictions. Top by Δscore:

Variant	Effect	Δscore
10:110567828:GCAG:G	donor_gain	1.0000
10:110567829:CAG:C	donor_loss	1.0000
10:110567831:GGTAA:G	donor_loss	1.0000
10:110575331:TCCA:T	acceptor_loss	1.0000
10:110575334:A:AG	acceptor_gain	1.0000
10:110575335:G:GG	acceptor_gain	1.0000
10:110575335:GC:G	acceptor_gain	1.0000
10:110575335:GCA:G	acceptor_gain	1.0000
10:110575404:G:GG	donor_gain	1.0000
10:110575408:G:GG	donor_gain	1.0000
10:110577413:A:AG	acceptor_gain	1.0000
10:110577414:T:G	acceptor_gain	1.0000
10:110577419:A:AG	acceptor_gain	1.0000
10:110577419:AG:A	acceptor_gain	1.0000
10:110577420:G:GG	acceptor_gain	1.0000
10:110577420:GG:G	acceptor_gain	1.0000
10:110577420:GGAA:G	acceptor_gain	1.0000
10:110577488:TACCA:T	donor_gain	1.0000
10:110577490:CCA:C	donor_gain	1.0000
10:110577491:CA:C	donor_gain	1.0000
10:110577492:AG:A	donor_loss	1.0000
10:110577493:GT:G	donor_loss	1.0000
10:110577493:GTAA:G	donor_gain	1.0000
10:110577494:TAA:T	donor_loss	1.0000
10:110577495:AA:A	donor_loss	1.0000
10:110577497:G:GG	donor_gain	1.0000
10:110577823:A:AG	acceptor_gain	1.0000
10:110577824:T:G	acceptor_gain	1.0000
10:110577831:TTAG:T	acceptor_loss	1.0000
10:110577833:A:AG	acceptor_gain	1.0000

AlphaMissense

8128 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:110568950:G:C	G10R	1.000
10:110568951:G:A	G10D	1.000
10:110568951:G:T	G10V	1.000
10:110568953:T:C	F11L	1.000
10:110568953:T:G	F11V	1.000
10:110568954:T:C	F11S	1.000
10:110568955:T:A	F11L	1.000
10:110568955:T:G	F11L	1.000
10:110568957:G:C	R12P	1.000
10:110568959:A:C	S13R	1.000
10:110568961:T:A	S13R	1.000
10:110568961:T:G	S13R	1.000
10:110568962:T:C	Y14H	1.000
10:110568962:T:G	Y14D	1.000
10:110569006:T:A	N28K	1.000
10:110569006:T:G	N28K	1.000
10:110573709:G:A	G32S	1.000
10:110573709:G:C	G32R	1.000
10:110573709:G:T	G32C	1.000
10:110573710:G:A	G32D	1.000
10:110573710:G:T	G32V	1.000
10:110573715:A:C	N34H	1.000
10:110573715:A:G	N34D	1.000
10:110573715:A:T	N34Y	1.000
10:110573716:A:C	N34T	1.000
10:110573716:A:T	N34I	1.000
10:110573717:T:A	N34K	1.000
10:110573717:T:G	N34K	1.000
10:110573718:G:A	G35R	1.000
10:110573718:G:C	G35R	1.000

dbSNP variants (sampled 300 via entrez): RS1000002273 (10:110598016 T>A,G), RS1000111212 (10:110580472 G>A,T), RS1000269651 (10:110592179 C>T), RS1000350027 (10:110574879 G>A,T), RS1000352167 (10:110586432 A>G), RS1000402969 (10:110586663 A>G), RS1000507234 (10:110604358 C>A,T), RS1000576882 (10:110604581 T>C), RS1000632720 (10:110580936 G>A), RS1000650656 (10:110580234 T>A), RS1000655651 (10:110586437 C>G), RS1000672822 (10:110569437 A>C,G), RS1000704141 (10:110587669 G>C), RS1000922773 (10:110581770 T>A), RS1000953419 (10:110576341 A>T)

Disease associations

OMIM: gene MIM:606062 | disease phenotypes: MIM:610759, MIM:605130, MIM:122470

GenCC curated gene-disease

Disease	Classification	Inheritance
Cornelia de Lange syndrome	Definitive	Autosomal dominant
Cornelia de Lange syndrome 3	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Cornelia de Lange syndrome	Definitive	AD

Mondo (10): Cornelia de Lange syndrome 3 (MONDO:0012555), Wiedemann-Steiner syndrome (MONDO:0011518), Cornelia de Lange syndrome (MONDO:0016033), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), congenital heart disease (MONDO:0005453), neuromuscular disease (MONDO:0019056), multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042), autism spectrum disorder (MONDO:0005258), Cornelia de Lange syndrome 1 (MONDO:0007387)

Orphanet (6): Cornelia de Lange syndrome (Orphanet:199), Wiedemann-Steiner syndrome (Orphanet:319182), Neuromuscular disease (Orphanet:68381), Multiple congenital anomalies/dysmorphic syndrome (Orphanet:68341), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

147 total (30 of 147 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000059	Hypoplastic labia majora
HP:0000072	Hydroureter
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000130	Abnormality of the uterus
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000319	Smooth philtrum
HP:0000324	Facial asymmetry
HP:0000331	Short chin
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007015_3	Lumbar spine bone mineral density (integral)	7.000000e-07
GCST009391_1273	Metabolite levels	1.000000e-06
GCST010680_2	Acute respiratory distress syndrome in sepsis	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007620	volumetric bone mineral density
EFO:0010546	uridine measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D009468	Neuromuscular Diseases	C10.668
C536704	Wiedemann Grosse Dibbern syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725110 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.36	Kd	43.39	nM	CHEMBL3752910
7.36	ED50	43.39	nM	CHEMBL3752910
6.37	Kd	430.9	nM	CHEMBL5653589
6.37	ED50	430.9	nM	CHEMBL5653589
5.88	IC50	1310	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 10 total; 3 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149446: Binding affinity to human SMC3 incubated for 45 mins by Kinobead based pull down assay	kd	0.0434	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149446: Binding affinity to human SMC3 incubated for 45 mins by Kinobead based pull down assay	kd	0.4309	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178682: Inhibition of SMC3 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.3100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, affects cotreatment, decreases expression	3
Tretinoin	affects cotreatment, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
perfluorooctane sulfonic acid	decreases expression	2
Quercetin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	affects sumoylation	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
lasiocarpine	decreases expression, increases metabolic processing	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression, affects cotreatment	1
riddelliine	decreases expression, increases metabolic processing	1
afimoxifene	affects response to substance	1
fludarabine	increases phosphorylation, affects cotreatment	1
coumarin	increases phosphorylation	1
cadmium sulfate	increases expression	1
deguelin	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
picoxystrobin	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652488	Binding	Binding affinity to human SMC3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 1 cancer cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_7917	MOLM-7	Cancer cell line	Male
CVCL_A6J3	SEES3-1V human SMC3, clone1	Embryonic stem cell	Male
CVCL_A6J4	SEES3-1V human SMC3, clone2	Embryonic stem cell	Male
CVCL_A6J5	SEES3-1V human SMC3, clone3	Embryonic stem cell	Male
CVCL_YU40	PSADFN489	Finite cell line	Female

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	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
NCT04381897	PHASE2	NOT_YET_RECRUITING	Use of N-Acetylcysteine in the Treatment of Repetitive and Self-Injurious Behaviors in Cornelia de Lange Syndrome
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT06789783	PHASE2/PHASE3	RECRUITING	Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03113877	Not specified	TERMINATED	Evaluation of Autonomic Function in Individuals With Cornelia de Lange Syndrome (CdLS)
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT05829668	Not specified	RECRUITING	Behavioral Assessment and Treatment of Problem Behavior in Children With Cornelia de Lange Syndrome
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