SMC1A

Summary

SMC1A (structural maintenance of chromosomes 1A, HGNC:11111) is a protein-coding gene on chromosome Xp11.22, encoding Structural maintenance of chromosomes protein 1A (Q14683). Involved in chromosome cohesion during cell cycle and in DNA repair. It is a common-essential gene (DepMap: required in 98.9% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores. In addition, this protein interacts with BRCA1 and is phosphorylated by ATM, indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an area of the X-chromosome that escapes X inactivation. Mutations in this gene result in Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 8243 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked complex neurodevelopmental disorder (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,210 total — 130 pathogenic, 77 likely-pathogenic
• Phenotypes (HPO): 248
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 98.9% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_006306

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11111
Approved symbol	SMC1A
Name	structural maintenance of chromosomes 1A
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	DXS423E, KIAA0178, SB1.8, Smcb
Ensembl gene	ENSG00000072501
Ensembl biotype	protein_coding
OMIM	300040
Entrez	8243

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000322213, ENST00000375340, ENST00000463684, ENST00000469129, ENST00000470241, ENST00000674590, ENST00000675065, ENST00000675504, ENST00000947776, ENST00000947777

RefSeq mRNA: 2 — MANE Select: NM_006306 NM_001281463, NM_006306

CCDS: CCDS14352, CCDS75985

Canonical transcript exons

ENST00000322213 — 25 exons

Exon	Start	End
ENSE00000671349	53414981	53415169
ENSE00000671350	53414758	53414870
ENSE00001095076	53374149	53380186
ENSE00001632840	53396472	53396617
ENSE00001642196	53405771	53405956
ENSE00001655824	53411761	53411901
ENSE00001683252	53409062	53409269
ENSE00001710159	53405245	53405391
ENSE00001720507	53380620	53380730
ENSE00001729089	53381018	53381087
ENSE00001736172	53399589	53399730
ENSE00001753597	53396227	53396380
ENSE00001780772	53403777	53403893
ENSE00001781699	53409421	53409503
ENSE00001798824	53403566	53403672
ENSE00001799334	53405493	53405672
ENSE00001800349	53405012	53405149
ENSE00001914377	53422492	53422654
ENSE00003491335	53413232	53413435
ENSE00003657098	53411995	53412253
ENSE00003706023	53382232	53382383
ENSE00003708392	53382506	53382660
ENSE00003709779	53383097	53383253
ENSE00003711269	53394778	53394888
ENSE00003791370	53412900	53413138

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.3607 / max 459.3157, expressed in 1815 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199346	39.5577	1814
199345	0.4767	304
199344	0.3263	183

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.13	gold quality
trabecular bone tissue	UBERON:0002483	95.43	gold quality
embryo	UBERON:0000922	95.20	gold quality
tendon of biceps brachii	UBERON:0008188	95.19	gold quality
jejunal mucosa	UBERON:0000399	94.94	gold quality
germinal epithelium of ovary	UBERON:0001304	94.92	gold quality
ventricular zone	UBERON:0003053	94.86	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.78	gold quality
tibia	UBERON:0000979	94.53	gold quality
calcaneal tendon	UBERON:0003701	94.32	gold quality
vermiform appendix	UBERON:0001154	94.27	gold quality
tendon	UBERON:0000043	94.19	gold quality
thymus	UBERON:0002370	94.18	gold quality
ganglionic eminence	UBERON:0004023	94.17	gold quality
caecum	UBERON:0001153	94.04	gold quality
pigmented layer of retina	UBERON:0001782	94.00	gold quality
bone marrow cell	CL:0002092	93.76	gold quality
stromal cell of endometrium	CL:0002255	93.75	gold quality
colonic mucosa	UBERON:0000317	93.71	gold quality
endometrium epithelium	UBERON:0004811	93.69	gold quality
gingiva	UBERON:0001828	93.48	gold quality
bronchial epithelial cell	CL:0002328	93.44	gold quality
gingival epithelium	UBERON:0001949	93.43	gold quality
mammary duct	UBERON:0001765	93.34	gold quality
parietal pleura	UBERON:0002400	93.13	gold quality
oral cavity	UBERON:0000167	93.12	gold quality
skin of hip	UBERON:0001554	93.03	gold quality
superficial temporal artery	UBERON:0001614	92.98	gold quality
epithelium of mammary gland	UBERON:0003244	92.95	gold quality
choroid plexus epithelium	UBERON:0003911	92.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6, EZH2

miRNA regulators (miRDB)

136 targeting SMC1A, 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-513A-5P	100.00	69.77	2465
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-507	99.97	70.11	1915
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 98.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• This protein is localized at the kinetochores and is involved in cell division. (PMID:12199140)
• Inhibition of SMC1 is associated with chromosomal aberrations (PMID:15640246)
• RPGR-ORF15, which is mutated in retinitis pigmentosa, associates with SMC1. (PMID:16043481)
• Replication timing of FRA3B in G2 was studied by bromodeoxyuridine (BrdU) labeling by a fluorescence in situ hybridization (FISH)-based approach through the analysis of clones spanning the FRA3B region. (PMID:16242161)
• mutations in SMC1L1 (also known as SMC1), which encodes a different subunit of the cohesin complex, are responsible for Cornelia de Lange syndrome in three male members of an affected family and in one sporadic case (PMID:16604071)
• SMC1 binding represses OARE [OA (okadaic acid) response element] activity and its dissociation allows the recruitment of CAR(constitutive active/androstane receptor) to the OARE, synergizing the expression of the CYP2B6 gene. (PMID:16623664)
• nuclear exclusion is important to prevent cohesin cleavage during interphase in the absence of securin and the phosphorylation inhibition (PMID:17102637)
• So far, two genes (NIPBL and SMC1L1) have been identified causing Cornelia de Lange syndrome (CdLS) or CdLS-like phenotypes. (PMID:17106445)
• Mutations in SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation (PMID:17273969)
• The S-phase checkpoint, regulated by the ATM-p95/NBS1-SMC1 pathway, was also triggered in hypoxia/reoxygenation-exposed lymphocytes. (PMID:17544403)
• 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)
• ATM plays a fundamental role in promoting the radiation-induced interaction of NBS1 with SMC1 in the presence of BRCA1, leading to the maintenance of chromosomal integrity. (PMID:18763866)
• SMC1 is recruited to microtubule-bound RNA export factor 1 (Rae1) at the mitotic spindle pole. (PMID:18832153)
• Cornelia de Lange syndrome mutations in SMC1A or SMC3 bind to DNA with higher affinity and display genomic instability. (PMID:18996922)
• This study identified duplications Cornelia de Lange syndrome (CdLS) on chromosomes 5 or X using genome wide array comparative genomic hybridisation (aCGH). The duplicated regions contain either the NIPBL or the SMC1A genes. (PMID:19052029)
• SMC1, a substrate of ATM, could not be phosphorylated at the DNA damage sites in the absence of PTIP (PMID:19414588)
• Transcription in severely affected Cornelia de Lange Syndrome probands has identified a unique profile of dysregulated gene expression that correlates with phenotypic severity and SMC1A binding analysis demonstrates a preference for intergenic regions. (PMID:19468298)
• results suggest that mechanistically SMC1A-related Cornelia de Lange Syndrome is not due to altered levels of the SMC1A transcript, but rather that the mutant proteins maintain a residual function in males and enact a dominant negative effect in females. (PMID:19701948)
• Interaction between Rae1 and cohesin subunit SMC1 is required for proper spindle formation. (PMID:20016259)
• 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)
• Low SMC1A expression predicts poor survival in acute myeloid leukemia. (PMID:20514443)
• SMC1A missense mutation is associated with Cornelia de Lange syndrome. (PMID:20635401)
• phosphorylation of SMC1 is required for an increased mobility after DNA damage in G2-phase cells, suggesting that ATM-dependent phosphorylation facilitates mobilization of the cohesin complex after DNA damage (PMID:21056556)
• phosphorylation of Rad50 plays a key regulatory role as an adaptor for specific ATM-dependent downstream signaling through SMC1 for DNA repair and cell cycle checkpoint control in the maintenance of genome integrity. (PMID:21757780)
• 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)
• These results suggest that SMC1A upregulation is involved in the pathogenesis of glioma. (PMID:23638217)
• Clinical comparison between our patient with a previously reported individual with a SMC1A duplication and four male carriers of similar sSMC reported in databases, suggest that they all share clinical features related to cohesinopathies (PMID:23683030)
• studies report for the first time that SMC1 is overexpressed in TNBC cells where it plays a role in cell migration and drug sensitivity, and thus provides a potential therapeutic target for this highly invasive breast cancer subtype (PMID:23717600)
• Inhibiting SMC1A expression efficiently (P < 0.001) resulted in inhibiting the proliferation and colony formation of U251 and U87MG glioblastoma cells. (PMID:23754617)
• Human SMC3 knock-down rendered SMC1 instable without cytoplasmic accumulation. (PMID:23776448)
• The mutation c.1731G>A/p.E577E in our patient expands the mutational spectrum of SMC1A to splice site mutations and also represents the first exonic synonymous splice site mutation observed in any human cohesinopathy (PMID:23863341)
• Our clinical and molecular findings expand the total number of characterized SMC1A-mutated patients (from 44 to 52) and the restricted repertoire of SMC1A mutations (from 29 to 34), contributing to the molecular and clinical signature of SMC1A-based CdLS. (PMID:24124034)
• A dominant negative effect is considered the pathogenic mechanism in SMC1A-defective female patients, the level of allelic preferential expression might be one of the factors contributing to the wide phenotypic variability observed in these patients. (PMID:24756084)
• The SMC1a mutation leads to chromosomal instability and tumorigenesis in early colorectal adenomas. (PMID:25080505)
• Our findings identify both SMC1 and CTCF as critical regulators of the differentiation-dependent life cycle of high-risk human papillomaviruses (PMID:25875106)
• Results show that SMC1A is overexpressed in colorectal cancer tissues and correlated with poor prognosis for late stage disease. (PMID:25884313)
• same down-regulation of cohesin targets is observed in SMC1A-mutated patient fibroblasts (PMID:26206533)
• Loss-of-function mutations of SMC1A may be associated with early-onset encephalopathy with epilepsy. (PMID:26358754)
• two novel de novo heterozygous frameshift mutations in the SMC1A gene were identified in two patients with developmental delay and epilepsy. (PMID:26386245)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	smc1a	ENSDARG00000055754
danio_rerio	smc1al	ENSDARG00000058203
mus_musculus	Smc1a	ENSMUSG00000041133
rattus_norvegicus	Smc1a	ENSRNOG00000003139
caenorhabditis_elegans		WBGENE00012198
caenorhabditis_elegans		WBGENE00019087

Paralogs (7): SMC1B (ENSG00000077935), SMC3 (ENSG00000108055), SMC4 (ENSG00000113810), CKAP4 (ENSG00000136026), SMC2 (ENSG00000136824), CCDC122 (ENSG00000151773), CCDC157 (ENSG00000187860)

Protein

Protein identifiers

Structural maintenance of chromosomes protein 1A — Q14683 (reviewed: Q14683)

Alternative names: Sb1.8

All UniProt accessions (6): Q14683, A0A384MR33, A0A6Q8PHC3, G8JLG1, V9GY57, V9GYN9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in chromosome cohesion during cell cycle and in DNA repair. Central component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms 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. The cohesin complex may also play a role in spindle pole assembly during mitosis. Involved in DNA repair via its interaction with BRCA1 and its related phosphorylation by ATM, or via its phosphorylation by ATR. Works as a downstream effector both in the ATM/NBS1 branch and in the ATR/MSH2 branch of S-phase checkpoint.

Subunit / interactions. Forms a heterodimer with SMC3 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. In germ cell cohesin complexes, SMC1A is mutually exclusive with SMC1B. Interacts with BRCA1. Found in a complex with CDCA5, SMC3 and RAD21, PDS5A/SCC-112 and PDS5B/APRIN. Interacts with NDC80. Interacts with BRAT1. Found in a complex containing POLE and SMC3. Interacts with RPGR, STAG3 and SYCP2. 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.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Post-translational modifications. Ubiquitinated by the DCX(DCAF15) complex, leading to its degradation. Phosphorylated by ATM upon ionizing radiation in a NBS1-dependent manner. Phosphorylated by ATR upon DNA methylation in a MSH2/MSH6-dependent manner. Phosphorylation of Ser-957 and Ser-966 activates it and is required for S-phase checkpoint activation.

Disease relevance. Cornelia de Lange syndrome 2 (CDLS2) [MIM:300590] 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. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 85 with or without midline brain defects (DEE85) [MIM:301044] An X-linked form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE85 is characterized by onset of severe refractory seizures in the first year of life, global developmental delay with impaired intellectual development and poor or absent speech, and dysmorphic facial features. Many patients have midline brain defects on brain imaging. 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 SMC3, 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. SMC1 subfamily.

RefSeq proteins (2): NP_001268392, NP_006297* (*=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
IPR028468	Smc1_ABC	Domain
IPR036277	SMC_hinge_sf	Homologous_superfamily

Pfam: PF02463, PF06470

UniProt features (128 total): sequence variant 37, helix 34, strand 28, modified residue 9, turn 5, coiled-coil region 4, region of interest 3, compositionally biased region 2, mutagenesis site 2, chain 1, domain 1, binding site 1, sequence conflict 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
8ROE	X-RAY DIFFRACTION	1.36
8ROD	X-RAY DIFFRACTION	1.5
8ROF	X-RAY DIFFRACTION	1.65
8RO9	X-RAY DIFFRACTION	1.77
8ROC	X-RAY DIFFRACTION	1.85
8RO8	X-RAY DIFFRACTION	1.9
8ROG	X-RAY DIFFRACTION	1.94
8RO7	X-RAY DIFFRACTION	2.09
8RO6	X-RAY DIFFRACTION	2.2
6WG4	X-RAY DIFFRACTION	2.31
8ROA	X-RAY DIFFRACTION	2.44
8ROB	X-RAY DIFFRACTION	2.5
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-Q14683-F1	83.02	0.23

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 (9): 358, 360, 648, 713, 957, 962, 966, 970, 1037

Mutagenesis-validated functional residues (2):

Position	Phenotype
957	reduces phosphorylation and the s-phase checkpoint activation. abolishes s-phase activation; when associated with a-966.
966	reduces phosphorylation and the s-phase checkpoint activation. increases sensitivity to dna methylation. abolishes s-pha

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: 779 (showing top): E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, E2F_Q4_01, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, AAGCAAT_MIR137, MORF_SMC1L1, E2F4DP1_01, REACTOME_MEIOTIC_SYNAPSIS, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MATTIOLI_MGUS_VS_PCL, AAGCCAT_MIR135A_MIR135B, MORF_RRM1, MORF_HDAC1, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GNF2_MCM5

GO Biological Process (14): mitotic sister chromatid segregation (GO:0000070), DNA repair (GO:0006281), sister chromatid cohesion (GO:0007062), mitotic sister chromatid cohesion (GO:0007064), response to radiation (GO:0009314), establishment of mitotic sister chromatid cohesion (GO:0034087), establishment of meiotic sister chromatid cohesion (GO:0034089), somatic stem cell population maintenance (GO:0035019), cell division (GO:0051301), meiotic cell cycle (GO:0051321), response to DNA damage checkpoint signaling (GO:0072423), mitotic spindle assembly (GO:0090307), DNA damage response (GO:0006974), chromosome organization (GO:0051276)

GO Molecular Function (9): DNA binding (GO:0003677), chromatin binding (GO:0003682), RNA binding (GO:0003723), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), mediator complex binding (GO:0036033), protein heterodimerization activity (GO:0046982), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (13): chromosome, centromeric region (GO:0000775), kinetochore (GO:0000776), condensed nuclear chromosome (GO:0000794), 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	3
mitotic nuclear division	2
mitotic cell cycle process	2
establishment of sister chromatid cohesion	2
nucleic acid binding	2
binding	2
intracellular membraneless organelle	2
nucleus	2
nuclear lumen	2
cohesin complex	2
sister chromatid segregation	1
DNA metabolic process	1
DNA damage response	1
cell cycle process	1
chromosome organization	1
sister chromatid cohesion	1
response to abiotic stimulus	1
mitotic cell cycle	1
mitotic sister chromatid cohesion	1
meiotic sister chromatid cohesion	1
stem cell population maintenance	1
cellular process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
response to DNA integrity checkpoint signaling	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
cellular response to stress	1
organelle organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
protein-containing complex binding	1
protein dimerization activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

4260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMC1A	RAD21	O60216	999
SMC1A	NIPBL	Q6KC79	998
SMC1A	STAG2	Q8N3U4	997
SMC1A	STAG1	Q8WVM7	996
SMC1A	SMC3	Q9UQE7	993
SMC1A	STAG3	Q9UJ98	991
SMC1A	REC8	O95072	955
SMC1A	PDS5A	Q29RF7	953
SMC1A	RAD21L1	Q9H4I0	937
SMC1A	CTCF	P49711	914
SMC1A	WAPL	Q7Z5K2	892
SMC1A	PDS5B	Q9NTI5	852
SMC1A	MDC1	Q14676	816
SMC1A	HDAC8	Q9BY41	797
SMC1A	MRE11	P49959	775

IntAct

310 interactions, top by confidence:

A	B	Type	Score
STAG2	RAD21	psi-mi:“MI:0914”(association)	0.970
SMC3	RAD21	psi-mi:“MI:0914”(association)	0.960
SMC3	RAD21	psi-mi:“MI:0915”(physical association)	0.960
SMC1A	SMC3	psi-mi:“MI:0915”(physical association)	0.940
SMC3	SMC1A	psi-mi:“MI:0915”(physical association)	0.940
STAG1	RAD21	psi-mi:“MI:0914”(association)	0.930
RAD21	SMC1A	psi-mi:“MI:0915”(physical association)	0.930
RAE1	NUP98	psi-mi:“MI:0914”(association)	0.930
SMC1A	RAD21	psi-mi:“MI:0914”(association)	0.930
SMC1A	RAD21	psi-mi:“MI:0915”(physical association)	0.930
RAD21	SMC1A	psi-mi:“MI:0914”(association)	0.930
STAG1	RAD21	psi-mi:“MI:0915”(physical association)	0.930
SMC1A	STAG2	psi-mi:“MI:0915”(physical association)	0.920
WAPL	RAD21	psi-mi:“MI:0914”(association)	0.910
WAPL	RAD21	psi-mi:“MI:0915”(physical association)	0.910

BioGRID (676): SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC1A (Reconstituted Complex), SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), SMC1A (Affinity Capture-MS), NDC80 (Co-fractionation), PDS5A (Co-fractionation)

ESM2 similar proteins: A2VDP1, A5D7M3, A8HUA1, B2RW38, D3Z8K2, E1BM70, E2R1I5, F1QNW4, O75150, O93308, O95995, O97593, P02562, P04462, P0CK98, P11778, P29616, P46824, P46825, Q0V9R4, Q14683, Q3U319, Q499U4, Q4R7K7, Q5DTM8, Q5R9B3, Q5RAU7, Q5T655, Q5VTR2, Q5ZLS3, Q60779, Q68CZ1, Q6DGZ3, Q7XJ96, Q7Z3E2, Q8BKE9, Q8BR07, Q8C9S4, Q8CG73, Q8CJB9

Diamond homologs: A3PMS2, B2FDA8, B8CW13, B8GZ28, B9E1H0, E1X022, O01789, O66878, O93308, O93309, O94383, O95347, O97593, O97594, P15016, P50533, P73340, P75361, P97690, P9WGF2, P9WGF3, Q09591, Q14683, Q1INB1, Q20060, Q24U48, Q3JR19, Q54LV0, Q552D9, Q59037, Q5H054, Q5R4K5, Q69GZ5, Q73VM3, Q8I1U7, Q8IED2, Q8NDV3, Q8TZY2, Q90988, Q920F6

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ATM	up-regulates	SMC1A	phosphorylation
ATM	“up-regulates activity”	SMC1A	phosphorylation
SMC1A	“form complex”	“RAD21L Cohesin complex”	binding
SMC1A	“form complex”	“Cohesin complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 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	10	14.1×	2e-07
Meiosis	6	13.3×	2e-04
Activation of the pre-replicative complex	5	12.7×	1e-03
G1/S Transition	6	10.8×	7e-04
Resolution of Sister Chromatid Cohesion	16	10.7×	4e-10
G2/M Checkpoints	9	9.4×	4e-05
SUMOylation of DNA damage response and repair proteins	8	9.1×	1e-04
Reproduction	6	8.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitotic sister chromatid cohesion	5	36.2×	3e-05
sister chromatid cohesion	6	29.6×	1e-05
mitotic spindle assembly	7	15.5×	5e-05
cellular response to xenobiotic stimulus	8	12.4×	4e-05
centrosome cycle	5	10.9×	7e-03
double-strand break repair	8	10.5×	1e-04
protein autophosphorylation	8	7.5×	1e-03
DNA replication	7	7.5×	3e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — AML.

Clinical variants and AI predictions

ClinVar

1210 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	130
Likely pathogenic	77
Uncertain significance	375
Likely benign	366
Benign	57

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068642	NM_006306.4(SMC1A):c.3145C>T (p.Arg1049Ter)	Pathogenic
1068693	NM_006306.4(SMC1A):c.2842_2845dup (p.Asp949delinsGlyTer)	Pathogenic
1069931	NM_006306.4(SMC1A):c.10del (p.Phe3_Leu4insTer)	Pathogenic
1069969	NM_006306.4(SMC1A):c.2398C>T (p.Gln800Ter)	Pathogenic
1072544	NC_000023.10:g.(?53449431)(53449549_?)del	Pathogenic
1074295	NM_006306.4(SMC1A):c.2923C>T (p.Arg975Ter)	Pathogenic
1075881	NM_006306.4(SMC1A):c.481del (p.Ser161fs)	Pathogenic
1076178	NM_006306.4(SMC1A):c.586C>G (p.Arg196Gly)	Pathogenic
1164033	NM_006306.4(SMC1A):c.2341T>C (p.Cys781Arg)	Pathogenic
1164034	NM_006306.4(SMC1A):c.1171C>T (p.Gln391Ter)	Pathogenic
11672	NM_006306.4(SMC1A):c.2493_2495del (p.Asp831_Gln832delinsGlu)	Pathogenic
11673	NM_006306.4(SMC1A):c.1478A>C (p.Glu493Ala)	Pathogenic
11674	NM_006306.4(SMC1A):c.173_187del (p.Val58_Arg62del)	Pathogenic
11675	NM_006306.4(SMC1A):c.1487G>A (p.Arg496His)	Pathogenic
1184942	NM_006306.4(SMC1A):c.1813_1814del (p.Ile605fs)	Pathogenic
1199214	NM_006306.4(SMC1A):c.2039_2040del (p.Arg680fs)	Pathogenic
1320145	NM_006306.4(SMC1A):c.109+575dup	Pathogenic
1323620	NM_006306.4(SMC1A):c.2069del (p.Lys690fs)	Pathogenic
1346682	NM_006306.4(SMC1A):c.1607A>G (p.Lys536Arg)	Pathogenic
1351039	NM_006306.4(SMC1A):c.2437C>T (p.Gln813Ter)	Pathogenic
1351269	NM_006306.4(SMC1A):c.2173C>T (p.Arg725Ter)	Pathogenic
1378122	NM_006306.4(SMC1A):c.302del (p.Gly101fs)	Pathogenic
1398517	NM_006306.4(SMC1A):c.628C>T (p.Gln210Ter)	Pathogenic
1418836	NM_006306.4(SMC1A):c.2899C>T (p.Gln967Ter)	Pathogenic
1419270	NM_006306.4(SMC1A):c.286C>T (p.Arg96Cys)	Pathogenic
1446827	NM_006306.4(SMC1A):c.761del (p.Lys254fs)	Pathogenic
1453732	NM_006306.4(SMC1A):c.547_548del (p.Gln183fs)	Pathogenic
1455114	NM_006306.4(SMC1A):c.733_734del (p.Lys245fs)	Pathogenic
1455891	NM_006306.4(SMC1A):c.2132_2139del (p.Arg711fs)	Pathogenic
1459972	NC_000023.10:g.(?53430478)(53442138_?)del	Pathogenic

SpliceAI

3196 predictions. Top by Δscore:

Variant	Effect	Δscore
X:53380099:A:AC	donor_gain	1.0000
X:53380100:C:CC	donor_gain	1.0000
X:53380614:CCCTA:C	donor_loss	1.0000
X:53380615:CCTA:C	donor_loss	1.0000
X:53380616:CTA:C	donor_loss	1.0000
X:53380617:TACC:T	donor_loss	1.0000
X:53380618:ACCTC:A	donor_loss	1.0000
X:53380619:C:CA	donor_loss	1.0000
X:53380619:CCT:C	donor_gain	1.0000
X:53380726:GCCAC:G	acceptor_gain	1.0000
X:53380727:CCAC:C	acceptor_gain	1.0000
X:53380727:CCACC:C	acceptor_gain	1.0000
X:53380728:CAC:C	acceptor_gain	1.0000
X:53380728:CACC:C	acceptor_gain	1.0000
X:53380729:AC:A	acceptor_gain	1.0000
X:53380730:CC:C	acceptor_gain	1.0000
X:53380731:C:CC	acceptor_gain	1.0000
X:53381014:CCAC:C	donor_loss	1.0000
X:53381015:CAC:C	donor_loss	1.0000
X:53381085:TAG:T	acceptor_gain	1.0000
X:53381088:C:CC	acceptor_gain	1.0000
X:53382226:CCTTA:C	donor_loss	1.0000
X:53382227:CTTAC:C	donor_loss	1.0000
X:53382228:TTA:T	donor_loss	1.0000
X:53382229:TAC:T	donor_loss	1.0000
X:53382230:A:AC	donor_gain	1.0000
X:53382230:A:AT	donor_loss	1.0000
X:53382231:C:A	donor_loss	1.0000
X:53382231:C:CC	donor_gain	1.0000
X:53382379:AATGC:A	acceptor_gain	1.0000

AlphaMissense

8247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:53380166:G:C	S1213R	1.000
X:53380166:G:T	S1213R	1.000
X:53380167:C:A	S1213I	1.000
X:53380168:T:G	S1213R	1.000
X:53380630:A:T	V1203D	1.000
X:53380633:C:T	G1202E	1.000
X:53380634:C:G	G1202R	1.000
X:53380634:C:T	G1202R	1.000
X:53380639:A:G	L1200P	1.000
X:53380668:C:A	K1190N	1.000
X:53380668:C:G	K1190N	1.000
X:53380672:A:G	L1189P	1.000
X:53380675:G:A	S1188F	1.000
X:53380675:G:T	S1188Y	1.000
X:53380676:A:G	S1188P	1.000
X:53380681:A:T	V1186D	1.000
X:53380727:C:G	A1171P	1.000
X:53381027:G:C	N1166K	1.000
X:53381027:G:T	N1166K	1.000
X:53381029:T:C	N1166D	1.000
X:53381036:A:C	D1163E	1.000
X:53381036:A:T	D1163E	1.000
X:53381037:T:A	D1163V	1.000
X:53381037:T:C	D1163G	1.000
X:53381037:T:G	D1163A	1.000
X:53381038:C:A	D1163Y	1.000
X:53381038:C:G	D1163H	1.000
X:53381038:C:T	D1163N	1.000
X:53381039:C:A	L1162F	1.000
X:53381039:C:G	L1162F	1.000

dbSNP variants (sampled 300 via entrez): RS1000320526 (X:53419200 C>T), RS1000522033 (X:53378456 A>G), RS1001022445 (X:53408353 A>T), RS1001082215 (X:53419407 G>A), RS1001164920 (X:53377995 T>C), RS1001178868 (X:53383544 C>A,T), RS1001271237 (X:53397379 G>A), RS1001440015 (X:53392437 T>A), RS1001652226 (X:53402432 A>C), RS1001684337 (X:53413113 T>C), RS1001748769 (X:53423352 C>A), RS1001839274 (X:53382895 G>C), RS1001936226 (X:53401691 G>A,C), RS1002252438 (X:53421662 T>C), RS1002384123 (X:53399745 G>A,C,T)

Disease associations

OMIM: gene MIM:300040 | disease phenotypes: MIM:300590, MIM:301044, MIM:605130, MIM:122470, MIM:169300, MIM:309530

GenCC curated gene-disease

Disease	Classification	Inheritance
Cornelia de Lange syndrome 2	Definitive	X-linked
developmental and epileptic encephalopathy, 85, with or without midline brain defects	Definitive	X-linked
Cornelia de Lange syndrome	Supportive	Autosomal dominant
atypical Rett syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
X-linked complex neurodevelopmental disorder	Definitive	XL

Mondo (14): Cornelia de Lange syndrome 2 (MONDO:0010370), developmental and epileptic encephalopathy, 85, with or without midline brain defects (MONDO:0026771), congenital nervous system disorder (MONDO:0002320), microcephaly (MONDO:0001149), Wiedemann-Steiner syndrome (MONDO:0011518), intellectual disability (MONDO:0001071), atypical Rett syndrome (MONDO:0017746), Cornelia de Lange syndrome (MONDO:0016033), polyneuropathy (MONDO:0001824), pectus excavatum (MONDO:0008213), Cornelia de Lange syndrome 1 (MONDO:0007387), congenital heart disease (MONDO:0005453), X-linked complex neurodevelopmental disorder (MONDO:0100148), intellectual disability, X-linked 1 (MONDO:0010656)

Orphanet (6): Cornelia de Lange syndrome (Orphanet:199), Wiedemann-Steiner syndrome (Orphanet:319182), Atypical Rett syndrome (Orphanet:3095), X-linked non-syndromic intellectual disability (Orphanet:777), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), Severe intellectual disability-progressive postnatal microcephaly-midline stereotypic hand movements syndrome (Orphanet:397933)

HPO phenotypes

248 total (30 of 248 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000059	Hypoplastic labia majora
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000119	Abnormality of the genitourinary system
HP:0000130	Abnormality of the uterus
HP:0000161	Median cleft upper lip
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000233	Thin vermilion border
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000294	Low anterior hairline
HP:0000311	Round face
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000324	Facial asymmetry
HP:0000325	Triangular face
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000396	Overfolded helix

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008103_88	Bipolar disorder	1.000000e-06
GCST90002392_235	Mean corpuscular volume	2.000000e-10

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D005660	Funnel Chest	C05.116.099.386; C05.660.386; C16.131.621.386
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
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D011115	Polyneuropathies	C10.668.829.800
C567906	Mental Retardation, X-Linked 1 (supp.)
C564489	Mental Retardation, X-Linked 78 (supp.)
C536704	Wiedemann Grosse Dibbern syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105747 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 11,759 (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
CHEMBL1614701	SELUMETINIB	4	10,221
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.91	Kd	1.243	nM	CHEMBL5653589
8.91	ED50	1.243	nM	CHEMBL5653589
6.44	Kd	365	nM	SELUMETINIB
5.78	IC50	1660	nM	MOLIBRESIB

PubChem BioAssay actives

3 with measured affinity, of 229 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149444: Binding affinity to human SMC1A incubated for 45 mins by Kinobead based pull down assay	kd	0.0012	uM
Selumetinib	1425172: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3650	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	2178702: Inhibition of SMC1A (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.6600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
Resveratrol	increases reaction, affects cotreatment, increases expression, decreases reaction, increases phosphorylation	2
Acetaminophen	decreases expression, increases expression	2
Acetylcysteine	decreases reaction, increases phosphorylation, increases reaction	2
Benzo(a)pyrene	increases expression	2
Doxorubicin	decreases reaction, increases phosphorylation, increases reaction, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
pradimicin-IRD	affects response to substance, affects expression	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
lasiocarpine	increases metabolic processing, decreases expression	1
myristicin	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
fludarabine	affects cotreatment, increases phosphorylation	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	decreases expression	1
coumarin	increases phosphorylation	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991885	Binding	Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A6J0	SEES3-1V human SMC1A, clone1	Embryonic stem cell	Male
CVCL_A6J1	SEES3-1V human SMC1A, clone2	Embryonic stem cell	Male
CVCL_A6J2	SEES3-1V human SMC1A, clone3	Embryonic stem cell	Male
CVCL_D3AL	GM29122	Finite cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00162968	PHASE4	COMPLETED	Escitalopram as a Treatment for Pain in Polyneuropathy
NCT00832572	PHASE4	TERMINATED	Study of Ranexa in Patients With Coronary Artery Disease and Painful Polyneuropathy
NCT01047488	PHASE4	UNKNOWN	Imipramine and Pregabalin Combination in Painful Polyneuropathy
NCT01076478	PHASE4	COMPLETED	Asian Study on Cilostazol Effectivity in Neuropathies of Diabetes Mellitus Type 2-A Pilot Study in the Philippines
NCT01302275	PHASE4	COMPLETED	Oxcarbazepine for the Treatment of Chronic Peripheral Neuropathic Pain
NCT02033057	PHASE4	UNKNOWN	Muscular Electrostimulation of the Sedated and Mechanically Ventilated Critically Ill Patient. Analysis of the Effect on Acquired Muscular Weakness and Its Clinical Consequences.
NCT01486953	PHASE4	UNKNOWN	Pulmonary Mechanics During Minimally Invasive Repair of Pectus Excavatum
NCT02056301	PHASE4	TERMINATED	A Comparison Trial Between PCA and Epidural Analgesia for Pectus Excavatum Repair
NCT02169297	PHASE4	COMPLETED	Sub-Paraspinal Block in Nuss Patients. A Pilot Project
NCT02721017	PHASE4	COMPLETED	Cryoanalgesia vs. Epidural in the Nuss Procedure
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
NCT00259974	PHASE3	COMPLETED	RIMAG Study: Trial of Rituximab Versus Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy
NCT01263132	PHASE3	COMPLETED	Neuropathic Pain Management
NCT01450163	PHASE3	COMPLETED	Evaluate The Efficacy and Safety Of Pregabalin In Prevention, Reduction of Oxaliplatin-Induced Painful Neuropathy
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT04381897	PHASE2	NOT_YET_RECRUITING	Use of N-Acetylcysteine in the Treatment of Repetitive and Self-Injurious Behaviors in Cornelia de Lange Syndrome
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
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