CSE1L

Summary

CSE1L (chromosome segregation 1 like, HGNC:2431) is a protein-coding gene on chromosome 20q13.13, encoding Exportin-2 (P55060). Export receptor for importin-alpha. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

Proteins that carry a nuclear localization signal (NLS) are transported into the nucleus by the importin-alpha/beta heterodimer. Importin-alpha binds the NLS, while importin-beta mediates translocation through the nuclear pore complex. After translocation, RanGTP binds importin-beta and displaces importin-alpha. Importin-alpha must then be returned to the cytoplasm, leaving the NLS protein behind. The protein encoded by this gene binds strongly to NLS-free importin-alpha, and this binding is released in the cytoplasm by the combined action of RANBP1 and RANGAP1. In addition, the encoded protein may play a role both in apoptosis and in cell proliferation. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 1434 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 105 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_001316

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2431
Approved symbol	CSE1L
Name	chromosome segregation 1 like
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Aliases	CAS, XPO2, CSE1
Ensembl gene	ENSG00000124207
Ensembl biotype	protein_coding
OMIM	601342
Entrez	1434

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 23 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000262982, ENST00000396192, ENST00000469700, ENST00000889062, ENST00000889063, ENST00000889064, ENST00000889065, ENST00000889066, ENST00000889067, ENST00000889068, ENST00000889069, ENST00000889070, ENST00000933031, ENST00000933032, ENST00000933033, ENST00000933034, ENST00000933035, ENST00000933036, ENST00000933037, ENST00000933038, ENST00000933039, ENST00000933040, ENST00000966734, ENST00000966735

RefSeq mRNA: 3 — MANE Select: NM_001316 NM_001256135, NM_001316, NM_001362762

CCDS: CCDS13412, CCDS58773

Canonical transcript exons

ENST00000262982 — 25 exons

Exon	Start	End
ENSE00000845498	49072286	49072453
ENSE00000845499	49072568	49072697
ENSE00000845500	49074785	49074850
ENSE00000845501	49075318	49075520
ENSE00000845502	49076980	49077064
ENSE00000845503	49078561	49078622
ENSE00000845504	49084026	49084162
ENSE00000845505	49085283	49085386
ENSE00000845506	49088009	49088106
ENSE00000845507	49089247	49089397
ENSE00000845508	49089538	49089746
ENSE00000845509	49090742	49090839
ENSE00001651849	49070205	49070297
ENSE00001712711	49068715	49068822
ENSE00001730140	49067190	49067280
ENSE00001854414	49046312	49046423
ENSE00001862273	49096349	49096949
ENSE00003067279	49066365	49066510
ENSE00003164952	49066192	49066293
ENSE00003200156	49063202	49063344
ENSE00003484807	49094732	49094963
ENSE00003511431	49092046	49092127
ENSE00003650138	49094140	49094286
ENSE00003659614	49090937	49091022
ENSE00003673128	49058453	49058548

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.6231 / max 442.4410, expressed in 1817 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185146	53.6231	1817

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.98	gold quality
endothelial cell	CL:0000115	98.78	gold quality
embryo	UBERON:0000922	98.04	gold quality
ganglionic eminence	UBERON:0004023	97.61	gold quality
ventricular zone	UBERON:0003053	97.59	gold quality
adult organism	UBERON:0007023	97.23	gold quality
gingiva	UBERON:0001828	97.16	gold quality
cortical plate	UBERON:0005343	97.09	gold quality
gingival epithelium	UBERON:0001949	97.08	gold quality
sperm	CL:0000019	96.96	gold quality
male germ cell	CL:0000015	96.93	gold quality
oral cavity	UBERON:0000167	96.85	gold quality
esophagus squamous epithelium	UBERON:0006920	96.79	gold quality
right testis	UBERON:0004534	96.61	gold quality
cartilage tissue	UBERON:0002418	96.57	gold quality
skin of hip	UBERON:0001554	96.46	gold quality
cauda epididymis	UBERON:0004360	96.44	gold quality
squamous epithelium	UBERON:0006914	96.43	gold quality
testis	UBERON:0000473	96.29	gold quality
medial globus pallidus	UBERON:0002477	96.29	gold quality
trabecular bone tissue	UBERON:0002483	96.28	gold quality
left testis	UBERON:0004533	96.22	gold quality
corpus epididymis	UBERON:0004359	96.05	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.02	gold quality
upper leg skin	UBERON:0004262	95.95	gold quality
mammalian vulva	UBERON:0000997	95.94	gold quality
epithelium of esophagus	UBERON:0001976	95.89	gold quality
globus pallidus	UBERON:0001875	95.86	gold quality
biceps brachii	UBERON:0001507	95.73	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.70	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.49
E-MTAB-7249	no	776.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, GLI3

miRNA regulators (miRDB)

32 targeting CSE1L, 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-8075	99.97	67.20	962
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-4539	98.78	67.18	888
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-4662B	98.33	66.37	1163
HSA-MIR-4647	98.30	66.41	1139
HSA-MIR-4684-3P	98.24	69.91	1075
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-5571-3P	97.80	66.07	640

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon epithelial cells. (PMID:12061792)
• CSE1L/CAS has a role in proliferation and apoptosis [review] (PMID:12510150)
• a single phosphorylation site on CAS can effectively separate cell migration from other transformed growth characteristics (PMID:12972425)
• Results suggested that CAS may be associated with cell proliferation rather than apoptosis, and further, CAS might play an important role in the development of human hepatocellular carcinoma. (PMID:16786158)
• hCAS/CSE1L associates with chromatin and regulates expression of select p53 target genes. (PMID:17719542)
• These results indicate that CAS may play an important role in regulating the cytotoxicities of chemotherapeutic drugs. (PMID:18377724)
• Results show that heat upregulates the initial docking of importin-alpha at the nuclear envelope and stimulates the translocation of cellular apoptosis susceptibility protein into the nuclear interior. (PMID:18425415)
• PHAPI, CAS, and Hsp70 function together to accelerate nucleotide exchange on Apaf-1 and prevent inactive Apaf-1/cytochrome c aggregation. (PMID:18439902)
• Herein, we report that cellular apoptosis susceptibility (CAS) (or CSE1L) protein regulates the secretion of HT-29 human colorectal cells. (PMID:19224336)
• Serum cellular apoptosis susceptibility protein may have a role in progression of metastatic colorectal cancer (PMID:20150437)
• These results indicate that examination of CSE1L and E-cadherin distribution in colorectal epithelium glands may be valuable for evaluating the malignance of colorectal disease. (PMID:20734115)
• Increased immunoexpression of CAS protein in serous ovarian tumors may be useful in identifying the patients with more aggressive disease. (PMID:21290345)
• the requirement for and the regulation of CAS in the functioning of the Vpr-Impalpha complex (PMID:22110766)
• These results indicate that CSE1L is associated with viability and apoptosis, cellular adhesion and invasion, thus implicating CSE1L in the progression of colorectal cancer. (PMID:22450763)
• Nuclear CSE1L may play an oncogenic role in bladder tumor progression and that immunohistochemical staining of nuclear CSE1L may be useful for the prognosis of bladder urothelial carcinomas. (PMID:22476051)
• Our results suggest that urinary CSE1L deserves further evaluation for the screening of bladder cancer. (PMID:22653741)
• Data show that CSE1L, DIDO1 and RBM39 mRNA expression levels correlated with chromosome 20q DNA copy number status. (PMID:22711543)
• CSE1L may be involved in the “early” and “late” metastasis of tumor cells in tumorigenesis. (PMID:22952058)
• CSE1L- and inhibitor of DNA binding-3 (ID3)-overexpression was associated with the diagnosis of BL and signal transduction and transcription-3 (STAT3) with DLBCL (P<0.001 for all markers). All three markers were associated with patient outcome in DLBCL (PMID:22967991)
• CAS protein expression is related closely to tumor differentiation in hepatocellular carcinoma tissues. (PMID:23189846)
• CSE1L expression was significantly inhibited in RKO cells, causing cell cycle arrest in the G2/M and S phases and a delay in cell proliferation, as well as induction of apoptosis and an inhibition of colony growth capacity. (PMID:23621178)
• Most colorectal tumors were positive for CSE1L staining (98.4%). CRT’s with K-Ras mutation or high cytoplasmic CSE1L expression were correlated with T status (depth of tumor penetration; P = .004), stage (P = .004), and lymph node metastasis (P = .019). (PMID:23806821)
• The cellular apoptosis susceptibility/importin-alpha1 transport cycle is linked to X-linked inhibitor (XIAP) and is required to maintain tumor cell survival in hepatocellular carcinoma. (PMID:24799195)
• nuclear CSE1L is mainly non-phosphorylated CSE1L and is involved in gene regulation and cytoplasmic CSE1L is mainly phosphorylated CSE1L and is involved in cytoplasmic signaling regulation in melanocytic tumorigenesis. (PMID:25973023)
• hCAS/CSE1L is responsible for controlling the homologous recombinational repair activity by directly interacting with RAD51. (PMID:26123175)
• There is a relationship between nuclear CSE1L overexpression and distant metastasis in breast cancer. (PMID:26278417)
• CAS plays contrasting roles in proliferation and apoptosis (PMID:26668314)
• Data suggest that CAS overexpression in thyroid carcinoma depends on the subtype and the disease stage. Our findings also indicate that CAS maintains papillary thyroid cell proliferation and survival. (PMID:26892809)
• Our data suggest a previously unanticipated link between CAS and integrin beta1 signaling which correlates with an aggressive hepatocellular carcinoma phenotype. (PMID:27015362)
• CSE1L knockdown by shRNA inhibited protein, resulting in decreased cell proliferation, reduced colony formation in soft agar, and induction of apoptosis. CSE1L protein is expressed early and across all stages of colorectal carcinoma (CRC) development. shRNA knockdown of CSE1L was associated with inhibition of tumorigenesis in CRC cells. CSE1L may represent a potential target for treatment of CRC. (PMID:27521996)
• These findings show changes in CAS/CSE1L during Barrett’s esophagus progression. CAS/CSE1L may represent a potential marker for dysplasia/carcinoma. (PMID:27941559)
• CSE1L expression was correlated with MSH6 expression in tumor samples and was associated with poor prognosis in patients with osteosarcoma. Taken together, our results demonstrate that the CSE1L-MSH6 axis has an important role in osteosarcoma progression. (PMID:28387323)
• The combination of CTNB1, XPO2, and CAPG achieved 95% sensitivity and 96% specificity for the discrimination of these subtypes. We developed two uterine aspirate-based signatures to diagnose Endometrial cancer and classify tumors in the most prevalent histologic subtypes. This will improve diagnosis and assist in the prediction of the optimal surgical treatment (PMID:28790116)
• CSE1L appears to be critical for the nuclear import of certain key repressive proteins. Indeed, NOVA1, HDAC1, HDAC2, and HDAC8, genes known as silencing factors, became delocalized into cytosol upon CSE1L depletion. (PMID:29636421)
• CSE1L was significantly enriched in the seminoma tissue compared with the non-tumour normal testis tissue. CSE1L also co-localized with alpha-tubulin in the cells with a potential to divide. In the seminoma cell line TCam-2, CSE1L was associated with the spindles and the centrosomes during cell division. (PMID:30485574)
• Functional regulation of human trophoblast cells by CSE1L. (PMID:31394954)
• Cellular apoptosis susceptibility protein (CAS) suppresses the proliferation of breast cancer cells by upregulated cyp24a1. (PMID:32270348)
• CSE1L promotes proliferation and migration in oral cancer through positively regulating MITF. (PMID:32495878)
• CSE1L promotes nuclear accumulation of transcriptional coactivator TAZ and enhances invasiveness of human cancer cells. (PMID:34022224)
• The microRNA-451a/chromosome segregation 1-like axis suppresses cell proliferation, migration, and invasion and induces apoptosis in nasopharyngeal carcinoma. (PMID:34516344)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cse1l	ENSDARG00000006963
mus_musculus	Cse1l	ENSMUSG00000002718
rattus_norvegicus	Cse1l	ENSRNOG00000007665
drosophila_melanogaster	Cse1	FBGN0022213
caenorhabditis_elegans	xpo-2	WBGENE00002079

Paralogs (4): IPO11 (ENSG00000086200), IPO8 (ENSG00000133704), IPO9 (ENSG00000198700), IPO7 (ENSG00000205339)

Protein

Protein identifiers

Exportin-2 — P55060 (reviewed: P55060)

Alternative names: Cellular apoptosis susceptibility protein, Chromosome segregation 1-like protein, Importin-alpha re-exporter

All UniProt accessions (2): A0A384NKW7, P55060

UniProt curated annotations — full annotation on UniProt →

Function. Export receptor for importin-alpha. Mediates importin-alpha re-export from the nucleus to the cytoplasm after import substrates (cargos) have been released into the nucleoplasm. In the nucleus binds cooperatively to importin-alpha and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the importin-alpha from the export receptor. CSE1L/XPO2 then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.

Subunit / interactions. Found in a complex with CSE1L/XPO2, Ran and KPNA2. Binds with high affinity to importin-alpha only in the presence of RanGTP. The complex is dissociated by the combined action of RanBP1 and RanGAP1. Interacts with CFTR.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Detected in brain, placenta, ovary, testis and trachea (at protein level). Widely expressed. Highly expressed in testis and in proliferating cells.

Similarity. Belongs to the XPO2/CSE1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
P55060-1	1, A	yes
P55060-2	2
P55060-3	3
P55060-4	4

RefSeq proteins (3): NP_001243064, NP_001307, NP_001349691 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001494	Importin-beta_N	Domain
IPR005043	XPO2_C	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR013713	XPO2_central	Domain
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF03378, PF03810, PF08506

UniProt features (20 total): splice variant 5, sequence conflict 5, modified residue 5, sequence variant 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55060-F1	91.22	0.74

Functional residue map

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

Post-translational modifications (5): 1, 112, 574, 824, 931

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 247 (showing top): MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, BASSO_B_LYMPHOCYTE_NETWORK, CROONQUIST_NRAS_SIGNALING_DN, KENNY_CTNNB1_TARGETS_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, MODULE_352, GOMF_GTPASE_BINDING, CACCAGC_MIR138, PUJANA_CHEK2_PCC_NETWORK, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, GOBP_NUCLEAR_TRANSPORT, MODULE_118

GO Biological Process (4): protein import into nucleus (GO:0006606), protein export from nucleus (GO:0006611), intracellular protein transport (GO:0006886), protein transport (GO:0015031)

GO Molecular Function (3): nuclear export signal receptor activity (GO:0005049), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular protein transport	2
nuclear export	2
intracellular protein localization	2
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
protein transport	1
intracellular transport	1
transport	1
establishment of protein localization	1
nucleocytoplasmic carrier activity	1
GTPase binding	1
binding	1
intracellular membrane-bounded organelle	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

2352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSE1L	XPO1	O14980	939
CSE1L	XPO4	Q9C0E2	906
CSE1L	RANGAP1	P46060	875
CSE1L	XPOT	O43592	836
CSE1L	KPNA1	P52294	834
CSE1L	TNPO1	Q92973	794
CSE1L	KPNB1	Q14974	790
CSE1L	XPO6	Q96QU8	770
CSE1L	EFS	O43281	769
CSE1L	XPO7	Q9UIA9	759
CSE1L	TXN2	Q99757	756
CSE1L	KPNA2	P52292	741
CSE1L	KPNA4	O00629	727
CSE1L	IPO4	Q8TEX9	715
CSE1L	RANBP1	P43487	690

IntAct

199 interactions, top by confidence:

A	B	Type	Score
EIF4ENIF1	EIF4E	psi-mi:“MI:0914”(association)	0.940
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MMS19	ERCC2	psi-mi:“MI:0914”(association)	0.690
PRPF8	PRPF4	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
LRRK2	PSMD11	psi-mi:“MI:0914”(association)	0.600
CSE1L	rep	psi-mi:“MI:0915”(physical association)	0.550
	CSE1L	psi-mi:“MI:0407”(direct interaction)	0.540
	CSE1L	psi-mi:“MI:0915”(physical association)	0.540
CSE1L	TP53	psi-mi:“MI:0407”(direct interaction)	0.540
TP53	CSE1L	psi-mi:“MI:0915”(physical association)	0.540
CSE1L	TP53	psi-mi:“MI:0915”(physical association)	0.540
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
EGFR	NDUFA4	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
CD40	EXOC5	psi-mi:“MI:0914”(association)	0.530
EGFR	XPOT	psi-mi:“MI:0914”(association)	0.530
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
URM1	CSE1L	psi-mi:“MI:0915”(physical association)	0.500
CSE1L	MS4A4A	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (432): CSE1L (Affinity Capture-MS), CSE1L (Affinity Capture-MS), CSE1L (Affinity Capture-MS), CSE1L (Affinity Capture-MS), CSE1L (Affinity Capture-MS), CSE1L (Affinity Capture-MS), CSE1L (Affinity Capture-MS), CDH1 (Reconstituted Complex), CDH1 (Affinity Capture-Western), CSE1L (Affinity Capture-MS), CSE1L (Affinity Capture-MS), CSE1L (Affinity Capture-MS), CSE1L (Affinity Capture-RNA), CSE1L (Co-fractionation), CSE1L (Co-fractionation)

ESM2 similar proteins: A1A5G0, A1A5K2, A2AGT5, A2VE21, A7MBJ5, D4ABY2, G5EEM5, O35643, O81742, P22892, P52303, P53620, P55060, P62944, P63009, P63010, P97536, Q08DS7, Q0WW26, Q10567, Q14008, Q1ZXQ8, Q29AE5, Q32PG1, Q4AEF8, Q4U0G1, Q5N749, Q5R6L5, Q5RHR0, Q66JI9, Q6DDM4, Q6DKD7, Q6GM65, Q6Z382, Q6ZQ38, Q7Z460, Q80TV8, Q86VP6, Q8H852, Q94FN2

Diamond homologs: A5D785, O13671, P33307, P55060, Q54E36, Q5R9J2, Q6GMY9, Q7SZC2, Q8AY73, Q9ERK4, Q9PTU3, Q9XZU1, Q9ZPY7, Q8K2V6, Q9UI26, O59809

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
BIRC2	“down-regulates quantity by destabilization”	CSE1L	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 208 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
FCERI mediated MAPK activation	5	13.3×	4e-03
Transport of vitamins, nucleosides, and related molecules	5	10.5×	6e-03
Negative regulation of MAPK pathway	5	10.2×	6e-03
Antimicrobial mechanism of IFN-stimulated genes	6	9.1×	4e-03
Defective CFTR causes cystic fibrosis	5	8.4×	9e-03
TNFR2 non-canonical NF-kB pathway	6	8.4×	5e-03
Maturation of DENV proteins	5	8.1×	9e-03
MAPK6/MAPK4 signaling	7	7.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
NLS-bearing protein import into nucleus	6	28.0×	4e-05
protein import into nucleus	11	9.2×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	71
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3495 predictions. Top by Δscore:

Variant	Effect	Δscore
20:49058451:A:AG	acceptor_gain	1.0000
20:49058452:G:GA	acceptor_gain	1.0000
20:49058452:GATC:G	acceptor_gain	1.0000
20:49063200:A:AG	acceptor_gain	1.0000
20:49063201:G:GG	acceptor_gain	1.0000
20:49063201:GCT:G	acceptor_gain	1.0000
20:49063201:GCTGA:G	acceptor_gain	1.0000
20:49063294:G:GG	donor_gain	1.0000
20:49063340:GAATT:G	donor_gain	1.0000
20:49066190:A:AG	acceptor_gain	1.0000
20:49066190:AGGTT:A	acceptor_loss	1.0000
20:49066191:G:GG	acceptor_gain	1.0000
20:49066289:AGCAG:A	donor_loss	1.0000
20:49066290:GCAG:G	donor_gain	1.0000
20:49066291:CAG:C	donor_loss	1.0000
20:49066292:AGG:A	donor_loss	1.0000
20:49066293:GG:G	donor_loss	1.0000
20:49066294:GTAAT:G	donor_loss	1.0000
20:49066295:T:A	donor_loss	1.0000
20:49066363:A:AG	acceptor_gain	1.0000
20:49066364:G:GG	acceptor_gain	1.0000
20:49066364:GTTA:G	acceptor_gain	1.0000
20:49066364:GTTAA:G	acceptor_gain	1.0000
20:49066506:AAAAG:A	donor_loss	1.0000
20:49066507:AAAGG:A	donor_loss	1.0000
20:49066509:AGGTA:A	donor_loss	1.0000
20:49066510:GGTAT:G	donor_loss	1.0000
20:49066511:G:T	donor_loss	1.0000
20:49066512:T:G	donor_loss	1.0000
20:49072560:T:TA	acceptor_gain	1.0000

AlphaMissense

6439 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:49063315:A:G	K67E	1.000
20:49063316:A:T	K67I	1.000
20:49063317:A:C	K67N	1.000
20:49063317:A:T	K67N	1.000
20:49063336:T:A	W74R	1.000
20:49063336:T:C	W74R	1.000
20:49063338:G:C	W74C	1.000
20:49063338:G:T	W74C	1.000
20:49066229:G:C	R89P	1.000
20:49066374:G:C	A114P	1.000
20:49066413:T:A	W127R	1.000
20:49066413:T:C	W127R	1.000
20:49066483:T:C	L150P	1.000
20:49066491:G:C	A153P	1.000
20:49070241:T:A	W238R	1.000
20:49070241:T:C	W238R	1.000
20:49072580:G:C	A317P	1.000
20:49075327:C:T	T381I	1.000
20:49075330:G:C	R382T	1.000
20:49075330:G:T	R382I	1.000
20:49075331:A:C	R382S	1.000
20:49075331:A:T	R382S	1.000
20:49075332:C:A	R383S	1.000
20:49075338:G:C	A385P	1.000
20:49075342:C:A	A386D	1.000
20:49075351:T:C	L389P	1.000
20:49075455:T:A	W424R	1.000
20:49075455:T:C	W424R	1.000
20:49075457:G:C	W424C	1.000
20:49075457:G:T	W424C	1.000

dbSNP variants (sampled 300 via entrez): RS1000019775 (20:49059473 A>G), RS1000073282 (20:49074961 G>A,C,T), RS1000092651 (20:49063461 C>T), RS1000122289 (20:49080466 T>C,G), RS1000220918 (20:49077977 C>G), RS1000274619 (20:49051657 A>G), RS1000278661 (20:49070413 A>G), RS1000457311 (20:49071555 C>T), RS1000481934 (20:49077177 T>A), RS1000497005 (20:49089502 T>C), RS1000506066 (20:49082958 T>TAA), RS1000560740 (20:49059080 G>A), RS1000584746 (20:49054985 G>A), RS1000692988 (20:49047245 G>A), RS1000748773 (20:49097091 TTTTTTATA>T)

Disease associations

OMIM: gene MIM:601342 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002324_11	Anger	7.000000e-06
GCST003766_49	Subjective well-being	2.000000e-08
GCST003810_2	Non-response to citalopram or escitalopram and depression	7.000000e-07
GCST004364_12	Intelligence	1.000000e-08
GCST004364_26	Intelligence	1.000000e-08
GCST005316_242	Intelligence (MTAG)	3.000000e-19
GCST006269_520	General cognitive ability	1.000000e-14
GCST006269_621	General cognitive ability	3.000000e-14
GCST006923_15	Loneliness	3.000000e-08
GCST006924_7	Loneliness (MTAG)	3.000000e-09
GCST007044_24	Extremely high intelligence	7.000000e-10
GCST008294_1	Response to fluticasone propionate/salmeterol in chronic obstructive pulmonary disease	1.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003015	aggressive behavior
EFO:0007869	wellbeing measurement
EFO:0004337	intelligence
EFO:0007865	loneliness measurement
EFO:0007939	respiratory symptom measurement
EFO:0010062	response to salmeterol

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725048 (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
6.31	Kd	486.8	nM	CHEMBL5653589
6.31	ED50	486.8	nM	CHEMBL5653589
5.71	Kd	1938	nM	CHEMBL3752910
5.71	ED50	1938	nM	CHEMBL3752910
5.00	IC50	1e+04	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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148155: Binding affinity to human CSE1L incubated for 45 mins by Kinobead based pull down assay	kd	0.4868	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148155: Binding affinity to human CSE1L incubated for 45 mins by Kinobead based pull down assay	kd	1.9378	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	2178600: Inhibition of CSE1L (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression, affects binding, decreases reaction	5
bisphenol A	affects expression, decreases expression, increases expression	4
Air Pollutants	affects expression, increases abundance, decreases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Calcitriol	decreases expression, affects cotreatment	2
Copper	decreases expression, increases expression, affects binding	2
Doxorubicin	increases expression, increases reaction, affects expression	2
Tretinoin	decreases expression, increases reaction	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
kojic acid	decreases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
2,3,5,6-tetrachlorohydroquinone	decreases expression	1
epigallocatechin gallate	increases expression	1
K 7174	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
jinfukang	decreases 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
CHEMBL5651197	Binding	Binding affinity to human CSE1L 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

Clinical trials (associated diseases)

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