SMC2

Summary

SMC2 (structural maintenance of chromosomes 2, HGNC:14011) is a protein-coding gene on chromosome 9q31.1, encoding Structural maintenance of chromosomes protein 2 (O95347). Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Predicted to enable chromatin binding activity. Involved in mitotic chromosome condensation and positive regulation of chromosome condensation. Located in condensed chromosome; cytoplasm; and nuclear lumen. Part of condensin complex. Implicated in colon adenocarcinoma. Biomarker of colorectal cancer.

Source: NCBI Gene 10592 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 191 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_006444

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14011
Approved symbol	SMC2
Name	structural maintenance of chromosomes 2
Location	9q31.1
Locus type	gene with protein product
Status	Approved
Aliases	hCAP-E, CAP-E
Ensembl gene	ENSG00000136824
Ensembl biotype	protein_coding
OMIM	605576
Entrez	10592

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 nonsense_mediated_decay

ENST00000286398, ENST00000374787, ENST00000374793, ENST00000440179, ENST00000493955, ENST00000886042, ENST00000886043, ENST00000926170, ENST00000926171, ENST00000926172, ENST00000926173, ENST00000926174, ENST00000956306, ENST00000956307, ENST00000956308

RefSeq mRNA: 4 — MANE Select: NM_006444 NM_001042550, NM_001042551, NM_001265602, NM_006444

CCDS: CCDS35086

Canonical transcript exons

ENST00000374793 — 25 exons

Exon	Start	End
ENSE00000926624	104132009	104132125
ENSE00000926629	104126641	104126784
ENSE00000926634	104116200	104116319
ENSE00000926638	104111581	104111814
ENSE00000926641	104100389	104100433
ENSE00000926645	104096148	104096297
ENSE00000926646	104095324	104095552
ENSE00001138020	104124912	104125105
ENSE00001138026	104123108	104123232
ENSE00001138038	104114691	104114829
ENSE00001144192	104134415	104134575
ENSE00001304760	104118171	104118375
ENSE00001307115	104099644	104099682
ENSE00001307256	104113316	104113475
ENSE00001310886	104120027	104120162
ENSE00001322979	104100093	104100203
ENSE00001324511	104113964	104114081
ENSE00001330797	104102424	104102573
ENSE00001421187	104094309	104094477
ENSE00001464668	104127286	104127480
ENSE00001897927	104139139	104141419
ENSE00003499790	104098446	104098568
ENSE00003534259	104129645	104129845
ENSE00003583373	104138018	104138165
ENSE00003789764	104101960	104102193

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 95.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0780 / max 354.5567, expressed in 1649 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97779	10.6558	1585
97780	2.3581	909
97781	0.0641	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	95.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.02	gold quality
ganglionic eminence	UBERON:0004023	91.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.34	gold quality
embryo	UBERON:0000922	87.56	gold quality
calcaneal tendon	UBERON:0003701	86.48	gold quality
secondary oocyte	CL:0000655	85.32	gold quality
sperm	CL:0000019	84.27	gold quality
trabecular bone tissue	UBERON:0002483	83.39	gold quality
bone marrow	UBERON:0002371	82.50	gold quality
testis	UBERON:0000473	82.38	gold quality
bone marrow cell	CL:0002092	82.02	gold quality
adrenal tissue	UBERON:0018303	82.00	gold quality
bone element	UBERON:0001474	81.98	gold quality
rectum	UBERON:0001052	81.85	gold quality
vermiform appendix	UBERON:0001154	81.53	gold quality
right testis	UBERON:0004534	81.52	gold quality
male germ cell	CL:0000015	81.38	gold quality
left testis	UBERON:0004533	80.94	gold quality
stromal cell of endometrium	CL:0002255	80.69	gold quality
lymph node	UBERON:0000029	80.05	gold quality
oocyte	CL:0000023	79.41	gold quality
hair follicle	UBERON:0002073	78.92	silver quality
tonsil	UBERON:0002372	78.65	gold quality
caecum	UBERON:0001153	78.33	gold quality
islet of Langerhans	UBERON:0000006	77.93	gold quality
endometrium	UBERON:0001295	77.82	gold quality
esophagus squamous epithelium	UBERON:0006920	77.67	gold quality
gingival epithelium	UBERON:0001949	77.63	gold quality
esophagus mucosa	UBERON:0002469	77.16	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-8559	yes	492.85
E-MTAB-8530	yes	259.77
E-CURD-114	yes	64.31
E-CURD-112	yes	48.36
E-MTAB-9467	yes	30.42
E-HCAD-10	yes	24.01
E-CURD-122	yes	23.61
E-GEOD-125970	yes	23.16
E-HCAD-13	yes	22.82
E-HCAD-5	yes	20.62
E-HCAD-1	yes	18.25
E-MTAB-6678	yes	9.72
E-ANND-3	yes	8.66
E-MTAB-10553	yes	7.56
E-CURD-88	yes	6.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, TCF7L2

miRNA regulators (miRDB)

110 targeting SMC2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-12133	99.92	71.82	2006

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• mutation analysis of hCAP-C & hCAP-E in leukemia-lymphoma cell lines including 8 pyothorax-associated lymphoma (PAL); 3 of 8 PAL cell lines have hCAP-C or hCAP-E heterozygous mutations, indicating condensin mutations are relatively frequent in PAL (PMID:17488335)
• human SMC2 hinge domain with short coiled coils was cloned, expressed, purified and crystallized in the orthorhombic space group C222 in native and SeMet-derivatized forms (PMID:20823528)
• Studies indicate that tagged SMC2 subunit of the condensin complex with the streptavidin-Binding Peptide optimising efficacious use of this tag for protein analysis. (PMID:21194474)
• WNT signaling can directly activate SMC2 transcription as a key player in the mitotic cell division machinery. (PMID:23095742)
• SMC2 gene is altered by both frameshift mutation and loss of expression in gastric and colorectal cancers, suggesting that SMC2 gene alterations might be involved in pathogenesis of these cancers (PMID:24483990)
• SMC2 (or the condensin complex) is a novel molecular target for the treatment of MYCN-amplified neuroblastoma. (PMID:24553121)
• analysis of functional differences of SMC2 and SMC4 hinge domain between condensins and cohesin in DNA recognition (PMID:26491021)
• Rs3818626 and rs9895829 were significantly associated with SMC2 and TP53 messenger RNA expression. (PMID:30794721)
• Structural maintenance of chromosomes 2 is identified as an oncogene in bladder cancer in vitro and in vivo. (PMID:31986889)
• SMC2 knockdown inhibits malignant progression of lung adenocarcinoma by upregulating BTG2 expression. (PMID:38729325)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	smc2	ENSDARG00000017744
mus_musculus	Smc2	ENSMUSG00000028312
rattus_norvegicus	Smc2	ENSRNOG00000022325
drosophila_melanogaster	SMC2	FBGN0027783
caenorhabditis_elegans		WBGENE00003367

Paralogs (7): SMC1A (ENSG00000072501), SMC1B (ENSG00000077935), SMC3 (ENSG00000108055), SMC4 (ENSG00000113810), CKAP4 (ENSG00000136026), CCDC122 (ENSG00000151773), CCDC157 (ENSG00000187860)

Protein

Protein identifiers

Structural maintenance of chromosomes protein 2 — O95347 (reviewed: O95347)

Alternative names: Chromosome-associated protein E, XCAP-E homolog

All UniProt accessions (3): A0A0C4DGE5, O95347, Q5T821

UniProt curated annotations — full annotation on UniProt →

Function. Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases.

Subunit / interactions. Forms a heterodimer with SMC4. Component of the condensin complex, which contains the SMC2 and SMC4 heterodimer, and three non SMC subunits that probably regulate the complex: BRRN1/CAPH, CNAP1/CAPD2 and CAPG. Interacts with BRD4 (isoform B), leading to insulate chromatin from DNA damage response pathway.

Subcellular location. Nucleus. Cytoplasm. Chromosome.

Domain organisation. The SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with SMC4, forming a V-shaped heterodimer.

Similarity. Belongs to the SMC family. SMC2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O95347-1	1	yes
O95347-2	2

RefSeq proteins (4): NP_001036015, NP_001036016, NP_001252531, NP_006435* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003395	RecF/RecN/SMC_N	Domain
IPR010935	SMC_hinge	Domain
IPR024704	SMC	Family
IPR027120	Smc2_ABC	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036277	SMC_hinge_sf	Homologous_superfamily

Pfam: PF02463, PF06470

UniProt features (43 total): helix 14, strand 9, modified residue 5, sequence conflict 3, coiled-coil region 3, turn 3, splice variant 2, chain 1, domain 1, sequence variant 1, binding site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4U4P	X-RAY DIFFRACTION	1.89
9F5W	ELECTRON MICROSCOPY	7.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95347-F1	83.42	0.21

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 (5): 1160, 114, 222, 677, 1158

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2299718	Condensation of Prophase Chromosomes
R-HSA-2514853	Condensation of Prometaphase Chromosomes
R-HSA-1640170	Cell Cycle
R-HSA-68875	Mitotic Prophase
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 376 (showing top): GNF2_CKS1B, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, E2F_Q4_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GNF2_CENPF, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, CROONQUIST_NRAS_SIGNALING_DN, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_CHROMOSOME_SEPARATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, KAUFFMANN_DNA_REPAIR_GENES, KONG_E2F3_TARGETS, GOBP_CHROMOSOME_CONDENSATION

GO Biological Process (12): mitotic chromosome condensation (GO:0007076), meiotic chromosome condensation (GO:0010032), meiotic chromosome segregation (GO:0045132), cell division (GO:0051301), kinetochore organization (GO:0051383), positive regulation of chromosome segregation (GO:0051984), positive regulation of chromosome separation (GO:1905820), positive regulation of chromosome condensation (GO:1905821), nuclear division (GO:0000280), chromosome condensation (GO:0030261), chromosome organization (GO:0051276), nuclear chromosome segregation (GO:0098813)

GO Molecular Function (6): chromatin binding (GO:0003682), single-stranded DNA binding (GO:0003697), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (12): nuclear chromosome (GO:0000228), chromatin (GO:0000785), condensed chromosome (GO:0000793), condensed nuclear chromosome (GO:0000794), condensin complex (GO:0000796), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
M Phase	2
Mitotic Prophase	1
Mitotic Prometaphase	1
Cell Cycle, Mitotic	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromosome	4
cellular anatomical structure	4
chromosome condensation	3
nuclear lumen	3
chromosome organization	2
chromosome segregation	2
positive regulation of cell cycle process	2
binding	2
nucleus	2
intracellular membraneless organelle	2
mitotic sister chromatid segregation	1
mitotic cell cycle	1
mitotic cell cycle process	1
meiotic cell cycle	1
chromosome organization involved in meiotic cell cycle	1
nuclear chromosome segregation	1
meiotic nuclear division	1
meiotic cell cycle process	1
cellular process	1
regulation of chromosome segregation	1
chromosome separation	1
regulation of chromosome separation	1
regulation of chromosome condensation	1
positive regulation of chromosome organization	1
organelle fission	1
organelle organization	1
DNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nuclear chromosome	1
condensed chromosome	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

3351 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMC2	SMC4	Q9NTJ3	978
SMC2	NCAPD2	Q15021	965
SMC2	NCAPH	Q15003	911
SMC2	NCAPG	Q9BPX3	874
SMC2	NCAPG2	Q86XI2	649
SMC2	TOP2A	P11388	643
SMC2	SMC5	Q8IY18	626
SMC2	SMC1A	Q14683	619
SMC2	NCAPD3	P42695	607
SMC2	NCAPH2	Q6IBW4	592
SMC2	SMC3	Q9UQE7	572
SMC2	RAD21	O60216	540
SMC2	SMC6	Q96SB8	536
SMC2	BRD4	O60885	515
SMC2	KIF4A	O95239	449

IntAct

188 interactions, top by confidence:

A	B	Type	Score
NCAPH	SMC2	psi-mi:“MI:0915”(physical association)	0.810
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
NCAPH2	SMC2	psi-mi:“MI:0915”(physical association)	0.720
NCAPH2	SMC2	psi-mi:“MI:0914”(association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HLA-A	TAPBP	psi-mi:“MI:0915”(physical association)	0.690
SMC4	SMC2	psi-mi:“MI:0915”(physical association)	0.690
SMC2	SMC4	psi-mi:“MI:0915”(physical association)	0.690
IFT22	IFT56	psi-mi:“MI:0914”(association)	0.640
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
ARRDC4	WWP2	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
BMP1	TLL1	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
FOXM1	PES1	psi-mi:“MI:0914”(association)	0.500
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
HLA-A	SMC2	psi-mi:“MI:0915”(physical association)	0.400
KIF4B	SMC2	psi-mi:“MI:0915”(physical association)	0.400
MAP7D2	SMC2	psi-mi:“MI:0915”(physical association)	0.400
JMJD1C	SMC2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (465): SMC2 (Affinity Capture-MS), SMC2 (Affinity Capture-MS), SMC2 (Affinity Capture-MS), SMC2 (Affinity Capture-MS), SMC2 (Affinity Capture-MS), SMC2 (Affinity Capture-MS), SMC2 (Affinity Capture-MS), ADAR (Co-fractionation), SMC2 (Co-fractionation), SMC2 (Co-fractionation), SMC2 (Co-fractionation), SMC2 (Co-fractionation), SMC2 (Co-fractionation), SMC2 (Co-fractionation), SMC2 (Co-fractionation)

ESM2 similar proteins: A0A1L8GVF0, A0A1L8GXM0, A0A8M9PQ61, A2ZAC2, G0SHW7, G5EG17, O14777, O44199, O94383, O95347, P12753, P38989, P41003, P48996, P53692, P70388, Q09591, Q10173, Q12267, Q12749, Q196W6, Q336R3, Q4R630, Q503N2, Q54PK4, Q5U4X5, Q6DRJ7, Q6GQ71, Q6P9I7, Q6Q1P4, Q76I89, Q76I90, Q7ZW63, Q802R8, Q8AWF4, Q8AWF5, Q8CG48, Q90988, Q924W5, Q92878

Diamond homologs: A3PMS2, A9II65, B8CW13, B8GZ28, B9E1H0, C4ZJU1, D4GUK1, E1X022, O66878, O95347, P15016, P32908, P41508, P47540, P48996, P50532, P50533, P75361, Q12267, Q1INB1, Q20060, Q24U48, Q54PK4, Q59037, Q5H054, Q5N0D2, Q604U6, Q69GZ5, Q6N1B7, Q6Q1P4, Q7NG51, Q7ZAK1, Q81ZL2, Q8CG47, Q8CG48, Q8KBS6, Q8NDV3, Q8REH4, Q8TZY2, Q90988

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SMC2	“form complex”	“Condensin I”	binding
SMC2	“form complex”	“Condensin II”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 223 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.

GO biological processes:

GO term	Partners	Fold	FDR
mitotic chromosome condensation	5	25.4×	3e-04
cell surface receptor protein tyrosine kinase signaling pathway	9	8.0×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	155
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3200 predictions. Top by Δscore:

Variant	Effect	Δscore
9:104098564:TGCAG:T	donor_loss	1.0000
9:104098565:GCAGG:G	donor_loss	1.0000
9:104098566:CAG:C	donor_loss	1.0000
9:104098567:AGGT:A	donor_loss	1.0000
9:104099681:AG:A	donor_loss	1.0000
9:104099683:G:A	donor_loss	1.0000
9:104100088:TCCA:T	acceptor_loss	1.0000
9:104100089:CCA:C	acceptor_loss	1.0000
9:104100090:CA:C	acceptor_loss	1.0000
9:104100091:A:AG	acceptor_gain	1.0000
9:104100091:A:T	acceptor_loss	1.0000
9:104100092:G:GA	acceptor_gain	1.0000
9:104100092:G:GT	acceptor_loss	1.0000
9:104100092:GA:G	acceptor_gain	1.0000
9:104100092:GAT:G	acceptor_gain	1.0000
9:104100092:GATT:G	acceptor_gain	1.0000
9:104100092:GATTT:G	acceptor_gain	1.0000
9:104100177:G:GT	donor_gain	1.0000
9:104100177:GAGGC:G	donor_loss	1.0000
9:104100180:GC:G	donor_gain	1.0000
9:104100200:GACG:G	donor_gain	1.0000
9:104100203:GGT:G	donor_loss	1.0000
9:104100205:T:C	donor_loss	1.0000
9:104100431:G:GT	donor_gain	1.0000
9:104100431:GAG:G	donor_gain	1.0000
9:104101956:TCA:T	acceptor_loss	1.0000
9:104101958:A:AC	acceptor_loss	1.0000
9:104101958:A:AG	acceptor_gain	1.0000
9:104101958:AG:A	acceptor_gain	1.0000
9:104101959:G:GC	acceptor_loss	1.0000

AlphaMissense

7960 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:104095415:T:C	F11L	1.000
9:104095417:C:A	F11L	1.000
9:104095417:C:G	F11L	1.000
9:104095418:A:G	K12E	1.000
9:104095420:G:C	K12N	1.000
9:104095420:G:T	K12N	1.000
9:104095478:G:C	G32R	1.000
9:104095479:G:A	G32D	1.000
9:104095484:A:G	N34D	1.000
9:104095486:T:A	N34K	1.000
9:104095486:T:G	N34K	1.000
9:104095487:G:C	G35R	1.000
9:104095487:G:T	G35C	1.000
9:104095488:G:A	G35D	1.000
9:104095493:G:A	G37R	1.000
9:104095493:G:C	G37R	1.000
9:104095493:G:T	G37W	1.000
9:104095494:G:A	G37E	1.000
9:104095494:G:T	G37V	1.000
9:104095496:A:C	K38Q	1.000
9:104095497:A:T	K38I	1.000
9:104095499:T:C	S39P	1.000
9:104095500:C:A	S39Y	1.000
9:104095500:C:T	S39F	1.000
9:104095504:C:A	N40K	1.000
9:104095504:C:G	N40K	1.000
9:104098568:G:C	Q147H	1.000
9:104098568:G:T	Q147H	1.000
9:104138083:T:C	L1112P	1.000
9:104138085:G:C	D1113H	1.000

dbSNP variants (sampled 300 via entrez): RS1000090236 (9:104088160 A>C,G), RS1000101023 (9:104086703 C>T), RS1000177297 (9:104102340 G>A), RS1000182516 (9:104093953 G>A,C), RS1000205059 (9:104131694 A>G), RS1000259871 (9:104130674 G>A), RS1000297002 (9:104107844 C>G,T), RS1000347323 (9:104136857 G>A), RS1000356440 (9:104137289 A>G), RS1000399123 (9:104102683 G>A,C), RS1000408055 (9:104099125 A>G), RS1000409269 (9:104102973 G>A,C), RS1000429436 (9:104136936 T>A), RS1000561053 (9:104125802 C>G,T), RS1000608862 (9:104104696 T>C)

Disease associations

OMIM: gene MIM:605576 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001082_2	Orofacial clefts (maternal alcohol consumption interaction)	3.000000e-07
GCST002345_9	Response to cytadine analogues (cytosine arabinoside)	5.000000e-07
GCST004250_21	Alanine aminotransferase (ALT) levels after remission induction therapy in actute lymphoblastic leukemia (ALL)	2.000000e-06
GCST005434_23	Pancreatic cancer	7.000000e-06
GCST005434_28	Pancreatic cancer	6.000000e-07
GCST007235_8	Pancreatic ductal adenocarcinoma	3.000000e-07
GCST008870_35	Keratinocyte cancer (MTAG)	4.000000e-08
GCST008871_30	Basal cell carcinoma	9.000000e-11
GCST009310_28	Sensorimotor dexterity	2.000000e-07
GCST010135_30	Oily fish consumption	4.000000e-09
GCST010140_20	Pork consumption	4.000000e-09
GCST010241_100	Apolipoprotein A1 levels	1.000000e-12
GCST010242_439	HDL cholesterol levels	2.000000e-11
GCST90013410_48	Basal cell carcinoma	2.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0003959	cleft lip
EFO:0007965	response to combination chemotherapy
EFO:0010176	keratinocyte carcinoma
EFO:0008354	cognitive function measurement
EFO:0008111	diet measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105890 (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: 12,282 (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
CHEMBL494089	GSK-690693	1	2,061

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.95	Kd	11.26	nM	CHEMBL5653589
7.95	ED50	11.26	nM	CHEMBL5653589
6.68	Kd	209	nM	SELUMETINIB
5.96	Kd	1106	nM	GSK-690693
5.25	Kd	5620	nM	CHEMBL3752910
5.25	ED50	5620	nM	CHEMBL3752910

PubChem BioAssay actives

4 with measured affinity, of 243 total; 4 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	2149445: Binding affinity to human SMC2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0113	uM
Selumetinib	1425173: 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	0.2090	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	1425173: 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	1.1060	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149445: Binding affinity to human SMC2 incubated for 45 mins by Kinobead based pull down assay	kd	5.6201	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
Estradiol	increases expression	3
Cyclosporine	decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
perfluorooctane sulfonic acid	decreases expression	2
Resveratrol	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
abrine	decreases expression	1
incobotulinumtoxinA	decreases expression	1
Dasatinib	decreases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Azathioprine	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991886	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

Clinical trials (associated diseases)

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