CSDE1

Summary

CSDE1 (cold shock domain containing E1, HGNC:29905) is a protein-coding gene on chromosome 1p13.2, encoding Cold shock domain-containing protein E1 (O75534). RNA-binding protein involved in translationally coupled mRNA turnover. It is a selective cancer dependency (DepMap: 22.0% of cell lines).

Enables RISC complex binding activity; RNA stem-loop binding activity; and lncRNA binding activity. Involved in IRES-dependent viral translational initiation; regulation of gene expression; and stress granule assembly. Located in Golgi apparatus; cytosol; and plasma membrane. Part of CRD-mediated mRNA stability complex and mCRD-mediated mRNA stability complex.

Source: NCBI Gene 7812 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 221 total — 8 pathogenic, 9 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 22.0% of screened cell lines
• MANE Select transcript: NM_001007553

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29905
Approved symbol	CSDE1
Name	cold shock domain containing E1
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	D1S155E, UNR
Ensembl gene	ENSG00000009307
Ensembl biotype	protein_coding
OMIM	191510
Entrez	7812

Gene structure

Transcript identifiers

Ensembl transcripts: 175 — 152 protein_coding, 10 retained_intron, 10 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000261443, ENST00000339438, ENST00000358528, ENST00000369530, ENST00000438362, ENST00000483030, ENST00000483407, ENST00000524652, ENST00000525132, ENST00000525878, ENST00000525970, ENST00000529046, ENST00000530784, ENST00000530886, ENST00000533818, ENST00000534389, ENST00000534699, ENST00000610726, ENST00000684913, ENST00000685676, ENST00000686025, ENST00000686123, ENST00000686235, ENST00000686581, ENST00000686667, ENST00000686781, ENST00000687548, ENST00000687759, ENST00000688211, ENST00000688611, ENST00000689217, ENST00000689510, ENST00000689573, ENST00000689631, ENST00000689727, ENST00000689732, ENST00000689885, ENST00000689989, ENST00000690013, ENST00000690207, ENST00000690420, ENST00000690784, ENST00000691032, ENST00000691377, ENST00000691403, ENST00000692044, ENST00000692629, ENST00000692672, ENST00000692719, ENST00000692950, ENST00000693311, ENST00000693467, ENST00000693644, ENST00000901453, ENST00000901454, ENST00000901455, ENST00000901456, ENST00000901457, ENST00000901458, ENST00000901459, ENST00000901460, ENST00000901461, ENST00000901462, ENST00000901463, ENST00000901464, ENST00000901465, ENST00000901466, ENST00000901467, ENST00000901468, ENST00000901469, ENST00000901470, ENST00000901471, ENST00000901472, ENST00000901473, ENST00000901474, ENST00000901475, ENST00000901476, ENST00000901477, ENST00000901478, ENST00000901479, ENST00000901480, ENST00000901481, ENST00000901482, ENST00000901483, ENST00000901484, ENST00000901485, ENST00000901486, ENST00000901487, ENST00000901488, ENST00000901489, ENST00000901490, ENST00000901491, ENST00000901492, ENST00000901493, ENST00000901494, ENST00000901495, ENST00000901496, ENST00000901497, ENST00000901498, ENST00000901499, ENST00000901500, ENST00000901501, ENST00000901502, ENST00000925899, ENST00000925900, ENST00000925901, ENST00000925902, ENST00000925903, ENST00000925904, ENST00000925905, ENST00000925906, ENST00000925907, ENST00000925908, ENST00000925909, ENST00000925910, ENST00000925911, ENST00000925912, ENST00000925913, ENST00000967151, ENST00000967152, ENST00000967153, ENST00000967154, ENST00000967155, ENST00000967156, ENST00000967157, ENST00000967158, ENST00000967159, ENST00000967160, ENST00000967161, ENST00000967162, ENST00000967163, ENST00000967164, ENST00000967165, ENST00000967166, ENST00000967167, ENST00000967168, ENST00000967169, ENST00000967170, ENST00000967171, ENST00000967172, ENST00000967173, ENST00000967174, ENST00000967175, ENST00000967176, ENST00000967177, ENST00000967178, ENST00000967179, ENST00000967180, ENST00000967181, ENST00000967182, ENST00000967183, ENST00000967184, ENST00000967185, ENST00000967186, ENST00000967187, ENST00000967188, ENST00000967189, ENST00000967190, ENST00000967191, ENST00000967192, ENST00000967193, ENST00000967194, ENST00000967195, ENST00000967196, ENST00000967197, ENST00000967198, ENST00000967199, ENST00000967200, ENST00000967201, ENST00000967202, ENST00000967203, ENST00000967204, ENST00000967205, ENST00000967206, ENST00000967207

RefSeq mRNA: 6 — MANE Select: NM_001007553 NM_001007553, NM_001130523, NM_001242891, NM_001242892, NM_001242893, NM_007158

CCDS: CCDS30811, CCDS30812, CCDS44197, CCDS55626

Canonical transcript exons

ENST00000358528 — 20 exons

Exon	Start	End
ENSE00000784321	114737471	114737563
ENSE00000784325	114733732	114733857
ENSE00000784333	114730258	114730422
ENSE00000784340	114718613	114718745
ENSE00000800117	114726983	114727090
ENSE00000800120	114732604	114732816
ENSE00000800122	114733989	114734117
ENSE00001151196	114720539	114720717
ENSE00001151239	114734442	114734523
ENSE00001196939	114719579	114719742
ENSE00001337441	114749821	114750207
ENSE00001386496	114730508	114730648
ENSE00001450278	114726211	114726386
ENSE00001828752	114757925	114757984
ENSE00002142129	114716916	114718216
ENSE00003468052	114725221	114725333
ENSE00003525642	114737963	114738072
ENSE00003579250	114723883	114724002
ENSE00003759691	114739692	114739890
ENSE00003784800	114736758	114736855

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 386.2257 / max 6359.8614, expressed in 1827 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13968	353.9767	1827
13967	27.0219	1801
13965	1.8444	1030
13966	1.7861	1006
13961	1.5318	795
13969	0.0649	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.78	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.72	gold quality
gluteal muscle	UBERON:0002000	99.68	gold quality
colonic epithelium	UBERON:0000397	99.63	gold quality
gastrocnemius	UBERON:0001388	99.63	gold quality
muscle of leg	UBERON:0001383	99.62	gold quality
biceps brachii	UBERON:0001507	99.59	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.59	gold quality
muscle organ	UBERON:0001630	99.58	gold quality
skeletal muscle organ	UBERON:0014892	99.58	gold quality
cortical plate	UBERON:0005343	99.57	gold quality
skeletal muscle tissue	UBERON:0001134	99.53	gold quality
tendon	UBERON:0000043	99.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.51	gold quality
triceps brachii	UBERON:0001509	99.48	gold quality
deltoid	UBERON:0001476	99.44	gold quality
muscle tissue	UBERON:0002385	99.44	gold quality
vastus lateralis	UBERON:0001379	99.43	gold quality
quadriceps femoris	UBERON:0001377	99.42	gold quality
tibialis anterior	UBERON:0001385	99.40	gold quality
secondary oocyte	CL:0000655	99.39	gold quality
islet of Langerhans	UBERON:0000006	99.38	gold quality
ganglionic eminence	UBERON:0004023	99.38	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.35	gold quality
myocardium	UBERON:0002349	99.34	gold quality
heart right ventricle	UBERON:0002080	99.31	gold quality
monocyte	CL:0000576	99.30	gold quality
choroid plexus epithelium	UBERON:0003911	99.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	99.28	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9543	no	2.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

150 targeting CSDE1, 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-340-5P	100.00	72.50	4437
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-218-5P	99.93	72.22	2103

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 23)

• unr and nPTB act as RNA chaperones by changing the structure of the IRES into one that permits translation initiation (PMID:12667457)
• UNR translation is regulated by an internal ribosome entry site that is downregulated by polypyrimidine tract binding protein. (PMID:15928332)
• regulation of IRES-mediated translation by hnRNP C1/C2 and Unr might be important in mitosis (PMID:17159903)
• The data suggest that Unr acts as an RNA chaperone on rhinovirus RNA 5’ UTR to maintain a complex tertiary internal ribosome entry site structure required for translational competency. (PMID:17947529)
• Study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism (PMID:24189344)
• Hepsin suppressed CDK11p58 internal ribosome entry site activity in prostate cancer cells by modulating UNR expression and eIF-2alpha phosphorylation. (PMID:25576733)
• Studies indicate that Unr (upstream of N-ras) is post-translationally modified by phosphorylation and lysine acetylation. (PMID:26614667)
• Results identify UNR as an oncogenic modulator of melanoma progression, unraveling the underlying molecular mechanisms. UNR seems to regulate translation elongation of Vimentin and RAC1 mRNAs. (PMID:27908735)
• UNR/CDSE1 expression is correlated with outcome in patients with resectable pancreatic ductal adenocarcinoma (PMID:28763470)
• CSDE1 post-transcriptionally modulates core components of multiple regulatory nodes of human embryonic stem cell identity, neuroectoderm commitment and neurogenesis and acts as a negative regulator of neural differentiation and neurogenesis. (PMID:29129916)
• Csde1 is involved in feed-back control in protein homeostasis and that it dampens stochastic changes in mRNA expression (PMID:29422612)
• Strap associates with Csde1 and affects expression of select Csde1-bound transcripts (PMID:30138317)
• CSDE1 binds directly to BC200 RNA.CSDE1 and BC200 expression levels are mutually dependent. (PMID:30247708)
• Our study defines a new autism-related syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission. (PMID:31579823)
• The role of CSDE1 in translational reprogramming and human diseases. (PMID:31987048)
• Cold Shock Domain Containing E1 (CSDE1) Protein is Overexpressed and Can be Targeted to Inhibit Invasiveness in Pancreatic Cancer Cells. (PMID:32170829)
• The CDT of Helicobacter hepaticus induces pro-survival autophagy and nucleoplasmic reticulum formation concentrating the RNA binding proteins UNR/CSDE1 and P62/SQSTM1. (PMID:33662035)
• Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy. (PMID:33772027)
• CSDE1 attenuates microRNA-mediated silencing of PMEPA1 in melanoma. (PMID:33833398)
• Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1. (PMID:35021076)
• Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast cancer. (PMID:35490208)
• Cold shock domain-containing protein E1 is a posttranscriptional regulator of the LDL receptor. (PMID:36103516)
• CSDE1 promotes miR-451 biogenesis. (PMID:37493604)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	csde1	ENSDARG00000074758
danio_rerio	si:dkeyp-121d4.3	ENSDARG00000089355
mus_musculus	Csde1	ENSMUSG00000068823
rattus_norvegicus	Csde1	ENSRNOG00000061058
rattus_norvegicus		ENSRNOG00000072708
drosophila_melanogaster	Unr	FBGN0263352

Protein

Protein identifiers

Cold shock domain-containing protein E1 — O75534 (reviewed: O75534)

Alternative names: N-ras upstream gene protein, Protein UNR

All UniProt accessions (24): O75534, A0A1Y8EMC9, A0A8I5KNL1, A0A8I5KPC0, A0A8I5KPJ6, A0A8I5KPQ8, A0A8I5KS07, A0A8I5KTQ3, A0A8I5KV85, A0A8I5KW29, A0A8I5KW72, A0A8I5KWW0, A0A8I5KXH5, A0A8I5KXL1, A0A8I5KYL4, A0A8I5KYL8, A0A8I5KYY8, A0A8I5QJA6, A0A8I5QKX0, E9PJK7, E9PKN4, E9PLD4, E9PLT0, E9PNG3

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Required for efficient formation of stress granules. (Microbial infection) Required for internal initiation of translation of human rhinovirus RNA.

Subunit / interactions. Component of a multi subunit autoregulatory ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1. Interacts with STRAP. Part of a complex associated with the FOS mCRD domain and consisting of PABPC1, PAIP1, HNRPD and SYNCRIP. The interaction with PABPC1 is direct and RNA-independent. Interacts with EIF4ENIF1/4E-T.

Subcellular location. Cytoplasm. Stress granule. P-body.

Similarity. Belongs to the UNR family.

Isoforms (5)

UniProt ID	Names	Canonical?
O75534-1	1	yes
O75534-2	2
O75534-3	3
O75534-4	4
O75534-5	5

RefSeq proteins (6): NP_001007554, NP_001123995, NP_001229820, NP_001229821, NP_001229822, NP_009089 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002059	CSP_DNA-bd	Domain
IPR011129	CSD	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR019844	CSD_CS	Conserved_site
IPR024642	SUZ-C	Domain
IPR056400	CSDE1	Domain

Pfam: PF00313, PF12901, PF23456

UniProt features (66 total): strand 28, domain 10, sequence conflict 8, modified residue 7, turn 7, splice variant 3, chain 1, cross-link 1, helix 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1WFQ	SOLUTION NMR
1X65	SOLUTION NMR
2YTV	SOLUTION NMR
2YTX	SOLUTION NMR
2YTY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75534-F1	80.05	0.31

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 (8): 81, 123, 276, 514, 584, 761, 91, 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 319 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_CYTOPLASMIC_TRANSLATION, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSLATIONAL_INITIATION, AP4_Q6, KYNG_DNA_DAMAGE_DN, CREBP1_Q2, ACTGCAG_MIR173P

GO Biological Process (10): regulation of translational initiation (GO:0006446), male gonad development (GO:0008584), stress granule assembly (GO:0034063), positive regulation of translation (GO:0045727), CRD-mediated mRNA stabilization (GO:0070934), nuclear-transcribed mRNA catabolic process, no-go decay (GO:0070966), IRES-dependent viral translational initiation (GO:0075522), negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:1900152), positive regulation of cytoplasmic translation (GO:2000767), ERK1 and ERK2 cascade (GO:0070371)

GO Molecular Function (7): RNA binding (GO:0003723), mRNA binding (GO:0003729), RNA stem-loop binding (GO:0035613), lncRNA binding (GO:0106222), RISC complex binding (GO:1905172), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (8): P-body (GO:0000932), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic stress granule (GO:0010494), CRD-mediated mRNA stability complex (GO:0070937), mCRD-mediated mRNA stability complex (GO:0106002), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	3
regulation of translation	2
binding	2
cytoplasmic ribonucleoprotein granule	2
cytoplasm	2
cellular anatomical structure	2
translational initiation	1
gonad development	1
development of primary male sexual characteristics	1
membraneless organelle assembly	1
translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
mRNA stabilization	1
nuclear-transcribed mRNA catabolic process	1
viral process	1
viral translation	1
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
negative regulation of mRNA catabolic process	1
cytoplasmic translation	1
positive regulation of translation	1
regulation of cytoplasmic translation	1
MAPK cascade	1
nucleic acid binding	1
ribonucleoprotein complex binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
intracellular protein-containing complex	1
cytosol	1
protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

3257 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSDE1	PABPC1	P11940	956
CSDE1	STRAP	Q9Y3F4	941
CSDE1	HNRNPD	P07029	841
CSDE1	SYNCRIP	O60506	812
CSDE1	EIF3I	Q13347	795
CSDE1	GEMIN7	Q9H840	782
CSDE1	PAIP1	Q9H074	753
CSDE1	PABPC4	Q13310	679
CSDE1	NRAS	P01111	677
CSDE1	TMEM127	O75204	659
CSDE1	PRRC2C	Q9Y520	625
CSDE1	PCBP2	Q15366	616
CSDE1	MSL2	Q9HCI7	601
CSDE1	UBAP2L	Q14157	600
CSDE1	MAML3	Q96JK9	587

IntAct

143 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CSDE1	HID1	psi-mi:“MI:0915”(physical association)	0.560
CSDE1	FAM9B	psi-mi:“MI:0915”(physical association)	0.560
HID1	CSDE1	psi-mi:“MI:0915”(physical association)	0.560
FAM9B	CSDE1	psi-mi:“MI:0915”(physical association)	0.560
ERBB2	CSDE1	psi-mi:“MI:0915”(physical association)	0.550
	NHERF1	psi-mi:“MI:0914”(association)	0.530
YBX1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
KIF1C	KIF1B	psi-mi:“MI:2364”(proximity)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
NCK1	CSDE1	psi-mi:“MI:0915”(physical association)	0.400
PIK3R1	CSDE1	psi-mi:“MI:0915”(physical association)	0.400
CSDE1		psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
STRAP	RAPH1	psi-mi:“MI:0914”(association)	0.350
ZNFX1	DRC1	psi-mi:“MI:0914”(association)	0.350
CSDE1	PABPC4L	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
	SYNCRIP	psi-mi:“MI:0914”(association)	0.350
PAIP1	SYNCRIP	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (376): CSDE1 (Affinity Capture-MS), FAM9B (Two-hybrid), HID1 (Two-hybrid), CSDE1 (Affinity Capture-RNA), NUP188 (Co-fractionation), CSDE1 (Affinity Capture-MS), CSDE1 (Proximity Label-MS), C11orf68 (Two-hybrid), CSDE1 (Affinity Capture-MS), PPIA (Affinity Capture-MS), CSDE1 (Affinity Capture-MS), CSDE1 (Affinity Capture-MS), STRAP (Affinity Capture-MS), HEATR5A (Affinity Capture-MS), PLEKHA3 (Affinity Capture-MS)

ESM2 similar proteins: A0FKG7, A2AGL3, A4IF63, A6QQZ7, A7MBL8, A8KBF6, B2RYD2, B7Z0E2, D2GXS7, D2XV59, D3ZQG6, O00178, O00560, O08582, O75534, O94806, P18395, P31016, P32298, P34947, P43249, P78352, Q12959, Q15139, Q15413, Q15700, Q16513, Q28C55, Q3US41, Q58DC5, Q5PYH6, Q5PYH7, Q5T2T1, Q5U2Y3, Q5XGS8, Q62101, Q62108, Q62696, Q62833, Q63622

Diamond homologs: B7Z0E2, O75534, P18395, P29174, Q91W50

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FUS	“up-regulates quantity by stabilization”	CSDE1	“post transcriptional regulation”
CSDE1	“down-regulates quantity”	FOS	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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
mRNA stabilization	5	14.3×	6e-03
negative regulation of translation	7	10.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	9
Uncertain significance	131
Likely benign	24
Benign	6

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1302055	NM_001007553.3(CSDE1):c.161C>G (p.Ser54Ter)	Pathogenic
1315179	NM_001007553.3(CSDE1):c.2066_2069del (p.Asn689fs)	Pathogenic
1456687	NM_001007553.3(CSDE1):c.1-1700dup	Pathogenic
1810077	NM_001007553.3(CSDE1):c.500+1G>C	Pathogenic
2150655	NM_001007553.3(CSDE1):c.1-1710del	Pathogenic
3836659	NM_001007553.3(CSDE1):c.775dup (p.Ser259fs)	Pathogenic
4007289	NM_001007553.3(CSDE1):c.422_423insAA (p.Tyr141Ter)	Pathogenic
4074390	NM_001007553.3(CSDE1):c.883A>T (p.Lys295Ter)	Pathogenic
2664623	NM_001007553.3(CSDE1):c.1-1636G>T	Likely pathogenic
3269733	NM_001007553.3(CSDE1):c.598A>T (p.Ile200Phe)	Likely pathogenic
3723881	NM_001007553.3(CSDE1):c.1214A>C (p.Asn405Thr)	Likely pathogenic
3901561	NM_001007553.3(CSDE1):c.1042C>T (p.Arg348Ter)	Likely pathogenic
4072051	NM_001007553.3(CSDE1):c.2153dup (p.Phe719fs)	Likely pathogenic
4081878	NM_001007553.3(CSDE1):c.638A>G (p.Tyr213Cys)	Likely pathogenic
4085093	NM_001007553.3(CSDE1):c.439G>T (p.Glu147Ter)	Likely pathogenic
4293955	NM_001007553.3(CSDE1):c.472_476del (p.Ile158fs)	Likely pathogenic
976762	NM_001007553.3(CSDE1):c.2134C>T (p.Gln712Ter)	Likely pathogenic

SpliceAI

2717 predictions. Top by Δscore:

Variant	Effect	Δscore
1:114718212:AACCC:A	acceptor_gain	1.0000
1:114718214:CCC:C	acceptor_gain	1.0000
1:114718215:CC:C	acceptor_gain	1.0000
1:114718215:CCC:C	acceptor_gain	1.0000
1:114718216:CC:C	acceptor_gain	1.0000
1:114718217:C:CC	acceptor_gain	1.0000
1:114718607:TCATA:T	donor_loss	1.0000
1:114718608:CATAC:C	donor_loss	1.0000
1:114718610:TA:T	donor_loss	1.0000
1:114718611:A:AC	donor_gain	1.0000
1:114718612:C:CA	donor_loss	1.0000
1:114718612:C:CC	donor_gain	1.0000
1:114718612:CCA:C	donor_gain	1.0000
1:114718623:T:C	donor_gain	1.0000
1:114718741:CCTCA:C	acceptor_gain	1.0000
1:114718742:CTCA:C	acceptor_gain	1.0000
1:114718742:CTCAC:C	acceptor_gain	1.0000
1:114718743:TCA:T	acceptor_gain	1.0000
1:114718743:TCACT:T	acceptor_gain	1.0000
1:114718744:CA:C	acceptor_gain	1.0000
1:114718744:CAC:C	acceptor_gain	1.0000
1:114718744:CACTG:C	acceptor_loss	1.0000
1:114718746:C:CC	acceptor_gain	1.0000
1:114718752:T:TC	acceptor_gain	1.0000
1:114718758:C:CT	acceptor_gain	1.0000
1:114718759:A:T	acceptor_gain	1.0000
1:114719578:CCAGA:C	donor_gain	1.0000
1:114719738:CCAAA:C	acceptor_gain	1.0000
1:114719739:CAAA:C	acceptor_gain	1.0000
1:114719739:CAAAC:C	acceptor_gain	1.0000

AlphaMissense

5313 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:114719591:A:T	V735D	1.000
1:114719600:G:T	A732D	1.000
1:114719610:T:C	K729E	1.000
1:114719638:G:C	F719L	1.000
1:114719638:G:T	F719L	1.000
1:114719639:A:G	F719S	1.000
1:114719640:A:G	F719L	1.000
1:114719694:G:C	H701D	1.000
1:114719695:G:C	F700L	1.000
1:114719695:G:T	F700L	1.000
1:114719696:A:G	F700S	1.000
1:114719697:A:G	F700L	1.000
1:114719698:A:C	F699L	1.000
1:114719698:A:T	F699L	1.000
1:114719700:A:G	F699L	1.000
1:114719702:A:G	L698P	1.000
1:114719732:A:C	I688S	1.000
1:114719732:A:T	I688N	1.000
1:114719734:G:C	F687L	1.000
1:114719734:G:T	F687L	1.000
1:114719735:A:G	F687S	1.000
1:114719736:A:G	F687L	1.000
1:114719738:C:T	G686D	1.000
1:114719739:C:G	G686R	1.000
1:114719740:A:C	F685L	1.000
1:114719740:A:T	F685L	1.000
1:114719742:A:G	F685L	1.000
1:114720558:A:T	V678E	1.000
1:114720591:G:T	A667D	1.000
1:114720630:A:G	F654S	1.000

dbSNP variants (sampled 300 via entrez): RS1000018773 (1:114722042 T>C), RS1000034563 (1:114759272 T>C), RS1000055511 (1:114757280 A>C,G), RS1000117180 (1:114722938 T>C), RS1000132414 (1:114744480 G>A), RS1000174655 (1:114730966 A>G), RS1000217722 (1:114753589 T>A), RS1000339592 (1:114747522 G>A,T), RS1000373846 (1:114742189 G>A), RS1000450776 (1:114746946 C>T), RS1000522635 (1:114741300 T>A,C), RS1000545192 (1:114746618 A>C), RS1000586096 (1:114746256 C>T), RS1000781556 (1:114740374 T>G), RS1000800692 (1:114747304 T>A,C)

Disease associations

OMIM: gene MIM:191510 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (2): RASopathy (MONDO:0021060), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (2): RASopathy (Orphanet:536391), Non-specific syndromic intellectual disability (Orphanet:528084)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002268_10	Autism	4.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4742265 (PROTEIN-PROTEIN INTERACTION), CHEMBL6067007 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1065634	CSDE1, NRAS	3	2.75	1	carboplatin;cisplatin;gemcitabine

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.00	Kd	99.05	nM	CHEMBL5653589
7.00	ED50	99.05	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 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	2148154: Binding affinity to human CSDE1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0990	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression, increases expression	2
bisphenol S	affects cotreatment, decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
uranyl acetate	affects expression	1
deoxynivalenol	increases expression	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	increases expression	1
ochratoxin A	increases expression	1
aflatoxin B2	decreases methylation	1
quinoline	increases expression	1
nivalenol	increases expression	1
cyclic 3’,5’-uridine monophosphate	affects binding	1
microcystin RR	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-phenylbutyric acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
tanespimycin	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
VER 155008	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	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
CHEMBL4713760	Binding	Protac activity at CRBN/CSDE1 in human BxPC-3 cells assessed as CSDE1 degradation incubated for 16 hrs by proteomic analysis	Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04888936	Not specified	RECRUITING	Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies
NCT05761314	Not specified	RECRUITING	Solid Tumors in RASopathies
NCT06331117	Not specified	UNKNOWN	Effect of RAS/MAPK Pathway Hyperactivation on Growth’ and Bone’ Profile of the RASopathies
NCT06355622	Not specified	UNKNOWN	Prevalence and Characterization of Pain in RASopathies
NCT06489067	Not specified	RECRUITING	Study of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)
NCT06776380	Not specified	RECRUITING	Pubertal Development in Patients with RASopathies
NCT07005297	Not specified	NOT_YET_RECRUITING	Clinical Genetics Branch Eligibility Screening Survey
NCT07344480	Not specified	RECRUITING	Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)
NCT07464821	Not specified	RECRUITING	National Multicentre Study on Lipid Profile in Noonan Syndrome and Related Disorders: Trends by Age, Gender and Genotype
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder