CDC5L

Summary

CDC5L (cell division cycle 5 like, HGNC:1743) is a protein-coding gene on chromosome 6p21.1, encoding Cell division cycle 5-like protein (Q99459). DNA-binding protein involved in cell cycle control. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

The protein encoded by this gene shares a significant similarity with Schizosaccharomyces pombe cdc5 gene product, which is a cell cycle regulator important for G2/M transition. This protein has been demonstrated to act as a positive regulator of cell cycle G2/M progression. It was also found to be an essential component of a non-snRNA spliceosome, which contains at least five additional protein factors and is required for the second catalytic step of pre-mRNA splicing.

Source: NCBI Gene 988 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 135 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_001253

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1743
Approved symbol	CDC5L
Name	cell division cycle 5 like
Location	6p21.1
Locus type	gene with protein product
Status	Approved
Aliases	PCDC5RP, hCDC5, CEF1, CDC5
Ensembl gene	ENSG00000096401
Ensembl biotype	protein_coding
OMIM	602868
Entrez	988

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000371477, ENST00000862194, ENST00000862195, ENST00000862196, ENST00000918588, ENST00000918589, ENST00000965044

RefSeq mRNA: 1 — MANE Select: NM_001253 NM_001253

CCDS: CCDS4912

Canonical transcript exons

ENST00000371477 — 16 exons

Exon	Start	End
ENSE00000481284	44424419	44424583
ENSE00000619318	44445655	44445867
ENSE00000754512	44426103	44426183
ENSE00000754513	44426482	44426724
ENSE00000754514	44429713	44429910
ENSE00000850339	44393446	44393573
ENSE00000850341	44403809	44404027
ENSE00000850343	44408444	44408632
ENSE00000850344	44419449	44419597
ENSE00000974545	44422647	44422809
ENSE00001140056	44406323	44406467
ENSE00001140069	44396341	44396440
ENSE00001140084	44392667	44392828
ENSE00001140092	44390268	44390371
ENSE00001911541	44387706	44387868
ENSE00001948716	44446607	44450425

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.2171 / max 1047.8138, expressed in 1811 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68030	37.5628	1808
68028	4.0115	1502
68032	0.7236	252
68029	0.5609	219
68031	0.3584	161

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.79	gold quality
sperm	CL:0000019	99.07	gold quality
male germ cell	CL:0000015	97.71	gold quality
tibia	UBERON:0000979	97.57	gold quality
tendon of biceps brachii	UBERON:0008188	97.29	gold quality
medial globus pallidus	UBERON:0002477	96.33	gold quality
secondary oocyte	CL:0000655	96.17	gold quality
amniotic fluid	UBERON:0000173	96.12	gold quality
gluteal muscle	UBERON:0002000	95.29	gold quality
biceps brachii	UBERON:0001507	95.16	gold quality
globus pallidus	UBERON:0001875	95.16	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.79	gold quality
palpebral conjunctiva	UBERON:0001812	94.75	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.59	gold quality
middle temporal gyrus	UBERON:0002771	94.55	gold quality
visceral pleura	UBERON:0002401	94.38	gold quality
pleura	UBERON:0000977	94.37	gold quality
bronchial epithelial cell	CL:0002328	94.36	gold quality
parietal pleura	UBERON:0002400	94.09	gold quality
esophagus squamous epithelium	UBERON:0006920	94.00	gold quality
corpus epididymis	UBERON:0004359	93.98	gold quality
tendon	UBERON:0000043	93.93	gold quality
endothelial cell	CL:0000115	93.76	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.76	gold quality
germinal epithelium of ovary	UBERON:0001304	93.64	gold quality
epithelium of nasopharynx	UBERON:0001951	93.53	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.48	gold quality
cartilage tissue	UBERON:0002418	93.38	gold quality
squamous epithelium	UBERON:0006914	93.16	gold quality
trabecular bone tissue	UBERON:0002483	93.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.01
E-MTAB-6524	no	158.51

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PLRG1	Unknown

Upstream regulators (CollecTRI, top): GATA5

miRNA regulators (miRDB)

171 targeting CDC5L, 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-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 19)

• CDC5 may function in pre-mRNA processing and cell cycle progression (PMID:14515018)
• the interaction between CDC5L and PLRG1 is essential for pre-mRNA splicing (PMID:14576297)
• Results indicate that CDC5L is the most likely candidate oncogene for the 6p12-p21 amplicon found in osteosarcoma. (PMID:18567798)
• Phosphorylation of CDC5L at threonines 411 and 438 within recognition sequences for CDKs are required for CDC5L-mediated pre-mRNA splicing. (PMID:18583928)
• These findings show a new function for Cdc5L in the regulation of the ATR-mediated cell-cycle checkpoint in response to genotoxic agents. (PMID:19633697)
• Blom7alpha is a novel splicing factor of the K homology domain family that might be implicated in alternative splicing by helping to position the CDC5L-SNEV(Prp19-Pso4) complex at the splice sites (PMID:19641227)
• A central region in hnRNP-M is required for interaction with CDC5L/PLRG1. (PMID:20467437)
• Dbf4 regulates the Cdc5 Polo-like kinase through a distinct non-canonical binding interaction (PMID:21036905)
• CTNNBL1 is a novel nuclear localization sequence-binding protein that recognizes RNA-splicing factors CDC5L and Prp31 (PMID:21385873)
• The N-terminal ARM-repeat domain of CTNNBL1 provides a binding site for CDC5L, a binding partner in the Prp19-CDC5L complex. (PMID:24598747)
• Cdc5L is a key regulator of mitotic progression. (PMID:24675469)
• The results show that CTNNBL1 enhances the association of CWC15 and CDC5L, both core Prp19 complex proteins and identify an overlap in the region of CDC5L that binds either CTNNBL1 or CWC15 suggesting the two proteins might exchange places in the complex. (PMID:26130721)
• CDC5L might play an important role in glioma cell survival and disease progression. (PMID:26490980)
• Cdc5L was highly expressed in hepatocellular carcinoma. Overexpression of Cdc5L favors cell cycle progress of HCC cells, while downregulation of Cdc5L results in cell cycle arrest at G2/M phase and reduced cell proliferation of HCC cells. (PMID:26553251)
• Study demonstrates that the levels of Prp19 and Cdc5L are overexpressed in hepatocellular carcinoma (HCC). Prp19 binds with Cdc5L and its downregulation results in reduction of Cdc5L. Mechanistic insights reveal that silencing Prp19 compromises translation activity of Cdc5L and facilitates lysosome-induced degradation of Cdc5L in HCC cells. (PMID:28387715)
• One target of CDC5L, ARGN, mediated the strong phenotypic consequences of NEAT1 reduction. (PMID:29871935)
• ANXA7 promotes the cell cycle, proliferation and cell adhesion-mediated drug resistance of multiple myeloma cells by up-regulating CDC5L. (PMID:32526706)
• CDC5L promotes early chondrocyte differentiation and proliferation by modulating pre-mRNA splicing of SOX9, COL2A1, and WEE1. (PMID:34298017)
• Downregulation of DEAD-box helicase 21 (DDX21) inhibits proliferation, cell cycle, and tumor growth in colorectal cancer via targeting cell division cycle 5-like (CDC5L). (PMID:34903139)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdc5l	ENSDARG00000043797
mus_musculus	Cdc5l	ENSMUSG00000023932
mus_musculus	Cdc5lrt7	ENSMUSG00000112027
mus_musculus	Cdc5lrt1	ENSMUSG00000112216
mus_musculus	Cdc5lrt4	ENSMUSG00000112252
mus_musculus	Cdc5lrt6	ENSMUSG00000112419
mus_musculus	Cdc5lrt9	ENSMUSG00000112495
mus_musculus	Cdc5lrt8	ENSMUSG00000112781
mus_musculus	Cdc5lrt5	ENSMUSG00000112814
mus_musculus	Cdc5lrt10	ENSMUSG00000112919
rattus_norvegicus	Cdc5l	ENSRNOG00000019975
drosophila_melanogaster	Cdc5	FBGN0265574
caenorhabditis_elegans	cdc-5L	WBGENE00008386

Paralogs (6): MYBL2 (ENSG00000101057), MYB (ENSG00000118513), TTF1 (ENSG00000125482), DMTF1 (ENSG00000135164), SNAPC4 (ENSG00000165684), MYBL1 (ENSG00000185697)

Protein

Protein identifiers

Cell division cycle 5-like protein — Q99459 (reviewed: Q99459)

Alternative names: Pombe cdc5-related protein

All UniProt accessions (1): Q99459

UniProt curated annotations — full annotation on UniProt →

Function. DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays a role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.

Subunit / interactions. Homodimer. Interacts with DAPK3. Component of the precatalytic, catalytic and postcatalytic spliceosome complexes. Part of a spliceosomal ‘core’ complex consisting of CDC5L, PLRG1, SPF27, CCAP1, CCAP3 and CCAP6. Interacts with PLRG1, Lodestar/TTF2, and NIPP1/PPP1R8. Component of the minor spliceosome, which splices U12-type introns. Within this complex, interacts with SCNM1. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. The interaction with CTNNBL1 is direct. Interacts (via its C-terminus) directly in the complex with PRPF19 and BCAS2. Interacts (via its C-terminus) directly with PRGL1 (via its WD40 repeat domain); the interaction is required for mRNA splicing but not for spliceosome assembly. Interacts with PRPF19 (via N-terminus). Interacts with USB1. Interacts with DDX41.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

Tissue specificity. Ubiquitously expressed in both fetal and adult tissues.

Post-translational modifications. Phosphorylated on serine and threonine residues. Phosphorylation on Thr-411 and Thr-438 is required for CDC5L-mediated mRNA splicing. Has no effect on subcellular location nor on homodimerization. Phosphorylated in vitro by CDK2. Phosphorylation enhances interaction with PPP1R8.

Disease relevance. A chromosomal aberration involving CDC5L is found in multicystic renal dysplasia. Translocation t(6;19)(p21;q13.1) with USF2.

Similarity. Belongs to the CEF1 family.

RefSeq proteins (1): NP_001244* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017930	Myb_dom	Domain
IPR021786	Cdc5p/Cef1_C	Domain
IPR047240	SANT_CDC5L_II	Domain
IPR047242	CDC5L/Cef1	Family

Pfam: PF11831, PF13921

UniProt features (81 total): helix 19, modified residue 15, mutagenesis site 11, region of interest 7, strand 6, compositionally biased region 4, turn 4, coiled-coil region 3, cross-link 3, domain 2, DNA-binding region 2, chain 1, short sequence motif 1, site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

37 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8C6J	ELECTRON MICROSCOPY	2.8
6ID1	ELECTRON MICROSCOPY	2.86
7DVQ	ELECTRON MICROSCOPY	2.89
6ID0	ELECTRON MICROSCOPY	2.9
6ICZ	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8I0V	ELECTRON MICROSCOPY	3
7QTT	ELECTRON MICROSCOPY	3.1
6QDV	ELECTRON MICROSCOPY	3.3
8I0U	ELECTRON MICROSCOPY	3.3
9FMD	ELECTRON MICROSCOPY	3.3
6FF4	ELECTRON MICROSCOPY	3.4
6ZYM	ELECTRON MICROSCOPY	3.4
8I0P	ELECTRON MICROSCOPY	3.4
8I0W	ELECTRON MICROSCOPY	3.4
8RO2	ELECTRON MICROSCOPY	3.5
5XJC	ELECTRON MICROSCOPY	3.6
7W59	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6
5YZG	ELECTRON MICROSCOPY	4.1
7AAV	ELECTRON MICROSCOPY	4.2
8I0S	ELECTRON MICROSCOPY	4.2
7W5B	ELECTRON MICROSCOPY	4.3
6FF7	ELECTRON MICROSCOPY	4.5
7ABH	ELECTRON MICROSCOPY	4.5
5Z58	ELECTRON MICROSCOPY	4.9
7A5P	ELECTRON MICROSCOPY	5
5Z56	ELECTRON MICROSCOPY	5.1
5MQF	ELECTRON MICROSCOPY	5.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99459-F1	74.94	0.25

Functional residue map

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

Catalytic / active sites (1): 414 (breakpoint for translocation)

Post-translational modifications (18): 227, 303, 358, 377, 385, 396, 404, 411, 415, 417, 424, 430, 437, 438, 442, 135, 219, 487

Mutagenesis-validated functional residues (11):

Position	Phenotype
31	abolishes dna-binding; when associated with g-53 and g-82.
53	abolishes dna-binding; when associated with g-31 and g-82.
82	abolishes dna-binding; when associated with g-31 and g-53.
227	abolishes phosphorylation. no effect on homodimerization nor on nuclear localization; when associated with a-303; a-358;
303	abolishes phosphorylation. no effect on homodimerization nor on nuclear localization; when associated with a-227; a-358;
358	abolishes phosphorylation. no effect on homodimerization nor on nuclear localization; when associated with a-227; a-303;
404	abolishes phosphorylation. no effect on homodimerization nor on nuclear localization; when associated with a-227; a-303;
411	abolishes phosphorylation. markedly diminished pre-mrna splicing activity; when associated with a-438. no effect on homo
417	abolishes phosphorylation. no effect on homodimerization nor on nuclear localization; when associated with a-227; a-303;
424	abolishes phosphorylation. no effect on homodimerization nor on nuclear localization; when associated with a-227; a-303;
438	abolishes phosphorylation. markedly diminished pre-mrna splicing activity; when associated with a-411. no effect on homo

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 224 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, TGCGCANK_UNKNOWN, E2F4DP1_01, GCM_ZNF198, GOBP_CELL_CYCLE_PHASE_TRANSITION, BROWNE_HCMV_INFECTION_16HR_UP, GOCC_NUCLEAR_REPLICATION_FORK, BROWNE_HCMV_INFECTION_24HR_UP, E2F1DP1_01, E2F1DP2_01, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA

GO Biological Process (9): DNA damage checkpoint signaling (GO:0000077), mRNA splicing, via spliceosome (GO:0000398), DNA repair (GO:0006281), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355), mRNA processing (GO:0006397), DNA damage response (GO:0006974), RNA splicing (GO:0008380)

GO Molecular Function (9): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), RNA binding (GO:0003723), identical protein binding (GO:0042802), WD40-repeat domain binding (GO:0071987), protein binding (GO:0005515), protein domain specific binding (GO:0019904)

GO Cellular Component (10): Prp19 complex (GO:0000974), nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), membrane (GO:0016020), nuclear speck (GO:0016607), U2-type catalytic step 2 spliceosome (GO:0071007), catalytic step 2 spliceosome (GO:0071013), DNA replication factor A complex (GO:0005662)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
mRNA Splicing	1
Dengue Virus Infection	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
RNA processing	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
nucleic acid binding	2
protein binding	2
nuclear protein-containing complex	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
DNA metabolic process	1
DNA damage response	1
regulation of DNA-templated transcription	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
mRNA metabolic process	1
cellular response to stress	1
transcription cis-regulatory region binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
protein domain specific binding	1
binding	1
protein-containing complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
U2-type spliceosomal complex	1
U2 snRNP	1
U6 snRNP	1
catalytic step 2 spliceosome	1
Prp19 complex	1

Protein interactions and networks

STRING

4267 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDC5L	PRPF19	Q9UMS4	998
CDC5L	BCAS2	O75934	996
CDC5L	PLRG1	O43660	996
CDC5L	XAB2	Q9HCS7	981
CDC5L	CTNNBL1	Q8WYA6	966
CDC5L	CWC15	Q9P013	888
CDC5L	PLK3	Q9H4B4	887
CDC5L	SYF2	O95926	883
CDC5L	CDC40	O60508	876
CDC5L	CWC22	Q9HCG8	849
CDC5L	CRNKL1	Q9BZJ0	824
CDC5L	SNW1	Q13573	808
CDC5L	PLK1	P53350	807
CDC5L	RBM22	Q9NW64	796
CDC5L	CWC25	Q9NXE8	789

IntAct

439 interactions, top by confidence:

A	B	Type	Score
BCAS2	CDC5L	psi-mi:“MI:0915”(physical association)	0.930
CSNK2A2	EIF3J	psi-mi:“MI:0914”(association)	0.790
CDC5L	HOOK1	psi-mi:“MI:0915”(physical association)	0.740
PPP1R13B	CDC5L	psi-mi:“MI:0915”(physical association)	0.740
CDC5L	HNRNPC	psi-mi:“MI:0915”(physical association)	0.730
CDC5L	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	CDC5L	psi-mi:“MI:0915”(physical association)	0.720
TTF2	CDC5L	psi-mi:“MI:0915”(physical association)	0.620
PPP1CA	CDC5L	psi-mi:“MI:0203”(dephosphorylation reaction)	0.590
CDC5L	GOLGA8F	psi-mi:“MI:0915”(physical association)	0.560
CDC5L	GOLGA8DP	psi-mi:“MI:0915”(physical association)	0.560
GOLGA8DP	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
GOLGA8F	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
CDC5L	ZRANB1	psi-mi:“MI:0915”(physical association)	0.560
TP53BP2	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
SYNPO	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
VPS52	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
USHBP1	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
KANK2	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
LDOC1	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
TXLNA	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
DVL3	DVL2	psi-mi:“MI:0914”(association)	0.530

BioGRID (1224): CDC5L (Affinity Capture-MS), GOLGA2 (Two-hybrid), GOLGA8EP (Two-hybrid), GOLGA8F (Two-hybrid), CTNNBL1 (Reconstituted Complex), CDC5L (Affinity Capture-MS), CDC5L (Affinity Capture-MS), CDC5L (Affinity Capture-MS), CDC5L (Affinity Capture-MS), CDC5L (Affinity Capture-MS), CDC5L (Affinity Capture-MS), CDC5L (Affinity Capture-MS), CDC5L (Affinity Capture-MS), CDC5L (Affinity Capture-MS), CDC5L (Affinity Capture-MS)

ESM2 similar proteins: A1L243, A4IGY3, A6H767, E1C760, F4ICK8, F7AEX0, O08837, O57476, P26446, P28656, P48724, P55010, P55209, P55876, P59325, Q07205, Q14696, Q16543, Q28EB4, Q2KJC1, Q3T0U1, Q3ZC50, Q4SK88, Q4U0Y4, Q5EAC6, Q5H7N8, Q5R4D4, Q5R4L0, Q5R6F1, Q5U2R7, Q5ZKK4, Q61081, Q63692, Q64267, Q69ZX6, Q6A068, Q6DD06, Q6PFQ2, Q803J8, Q8T9B6

Diamond homologs: A0A1U8QIH0, A0A1U8QVN4, A0A2R6S148, A0A6S6AAU0, A7SD85, B0G0Y5, B4FNX4, C8VBH3, F1B281, F4IRB4, K7UPS5, O04192, O08837, O13493, O15816, O23160, O49608, O49782, O80931, P01103, P01104, P04197, P06876, P0CO94, P10242, P10243, P10244, P20025, P22035, P27900, P34127, P39964, P46200, P48972, P51960, P52550, P52551, P80073, P81394, P81395

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TTF2	“up-regulates quantity by stabilization”	CDC5L	binding
CDC5L	“up-regulates activity”	HNRNPM	binding
CDC5L	“form complex”	PRP19-CDC5L	binding
CDK1	“up-regulates activity”	CDC5L	phosphorylation
CHEK2	“down-regulates activity”	CDC5L	phosphorylation
CDC7	“down-regulates activity”	CDC5L	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 159 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
Activation of BH3-only proteins	5	23.4×	2e-04
Intrinsic Pathway for Apoptosis	5	13.8×	2e-03
Apoptosis	6	9.5×	2e-03
mRNA Splicing - Major Pathway	17	8.8×	4e-09
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	8.7×	3e-03
mRNA Splicing	8	8.3×	5e-04
Programmed Cell Death	6	8.3×	3e-03
Processing of Capped Intron-Containing Pre-mRNA	10	7.8×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal complex assembly	5	22.3×	8e-04
protein targeting	6	16.3×	7e-04
mRNA splicing, via spliceosome	16	10.8×	1e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	14
Benign	29

Top pathogenic / likely-pathogenic (0)

SpliceAI

2348 predictions. Top by Δscore:

Variant	Effect	Δscore
6:44387864:CCGAG:C	donor_gain	1.0000
6:44387865:CGAG:C	donor_gain	1.0000
6:44387866:GAG:G	donor_gain	1.0000
6:44387866:GAGG:G	donor_gain	1.0000
6:44387867:AG:A	donor_gain	1.0000
6:44387868:GG:G	donor_gain	1.0000
6:44387868:GGTA:G	donor_loss	1.0000
6:44387869:G:GG	donor_gain	1.0000
6:44387869:GTAA:G	donor_loss	1.0000
6:44387870:T:A	donor_loss	1.0000
6:44390263:TTTAG:T	acceptor_loss	1.0000
6:44390264:TTA:T	acceptor_loss	1.0000
6:44390265:TAG:T	acceptor_loss	1.0000
6:44390266:A:AG	acceptor_gain	1.0000
6:44390266:A:T	acceptor_loss	1.0000
6:44390267:G:GG	acceptor_gain	1.0000
6:44390267:GGAT:G	acceptor_gain	1.0000
6:44390368:GATG:G	donor_gain	1.0000
6:44392664:TAGGT:T	acceptor_loss	1.0000
6:44392665:AGGT:A	acceptor_loss	1.0000
6:44392666:G:A	acceptor_loss	1.0000
6:44392666:GGT:G	acceptor_gain	1.0000
6:44392666:GGTAT:G	acceptor_gain	1.0000
6:44392786:G:GT	donor_gain	1.0000
6:44392824:CTTCT:C	donor_gain	1.0000
6:44392825:TTCT:T	donor_gain	1.0000
6:44392826:TCT:T	donor_gain	1.0000
6:44392827:CT:C	donor_gain	1.0000
6:44392828:TGTA:T	donor_loss	1.0000
6:44392829:GTAA:G	donor_gain	1.0000

AlphaMissense

5279 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:44387845:G:A	G8R	1.000
6:44387845:G:C	G8R	1.000
6:44387845:G:T	G8W	1.000
6:44387846:G:A	G8E	1.000
6:44387848:G:C	G9R	1.000
6:44387849:G:A	G9D	1.000
6:44387854:T:A	W11R	1.000
6:44387854:T:C	W11R	1.000
6:44387855:G:C	W11S	1.000
6:44387856:G:C	W11C	1.000
6:44387856:G:T	W11C	1.000
6:44387862:T:A	N13K	1.000
6:44387862:T:G	N13K	1.000
6:44387867:A:T	E15V	1.000
6:44387868:G:C	E15D	1.000
6:44387868:G:T	E15D	1.000
6:44390268:G:C	D16H	1.000
6:44390268:G:T	D16Y	1.000
6:44390269:A:C	D16A	1.000
6:44390269:A:T	D16V	1.000
6:44390270:T:A	D16E	1.000
6:44390270:T:G	D16E	1.000
6:44390271:G:A	E17K	1.000
6:44390275:T:A	I18N	1.000
6:44390275:T:G	I18S	1.000
6:44390278:T:A	L19Q	1.000
6:44390278:T:C	L19P	1.000
6:44390282:A:C	K20N	1.000
6:44390282:A:T	K20N	1.000
6:44390286:G:C	A22P	1.000

dbSNP variants (sampled 300 via entrez): RS1000029363 (6:44420486 G>A,T), RS1000140660 (6:44425323 T>C), RS1000166123 (6:44423785 A>G), RS1000255615 (6:44425605 G>A), RS1000279680 (6:44405157 C>T), RS1000295914 (6:44437352 T>C), RS1000344239 (6:44386797 A>C), RS1000407784 (6:44430641 T>C), RS1000458055 (6:44396665 C>T), RS1000461715 (6:44386481 A>G), RS1000467661 (6:44424123 T>C), RS1000708148 (6:44423441 C>G,T), RS1000729772 (6:44437579 T>G), RS1000789628 (6:44388023 G>A,T), RS1000867967 (6:44442375 T>G)

Disease associations

OMIM: gene MIM:602868 | disease phenotypes: MIM:610805

GenCC curated gene-disease

Mondo (1): congenital anomaly of kidney and urinary tract (MONDO:0019719)

Orphanet (1): Renal or urinary tract malformation (Orphanet:93545)

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001592_3	Osteoarthritis	6.000000e-07
GCST001659_1	Stroke (ischemic)	5.000000e-08
GCST002545_6	Ossification of the posterior longitudinal ligament of the spine	9.000000e-09
GCST002988_3	Ischemic stroke	1.000000e-06
GCST003427_44	Alzheimer disease and age of onset	1.000000e-07
GCST003983_34	Male-pattern baldness	3.000000e-09
GCST003989_3	Chin dimples	3.000000e-08
GCST003996_39	Monobrow	6.000000e-16
GCST006110_32	Nose morphology	1.000000e-06
GCST007429_37	Lung function (FVC)	1.000000e-10
GCST007432_72	FEV1	8.000000e-09
GCST008163_617	Height	9.000000e-06
GCST009596_1	Osteoarthritis of the hand	1.000000e-06
GCST010266_6	Femoral neck bone mineral density and trunk fat mass adjusted by trunk lean mass	5.000000e-07
GCST010267_8	Trunk fat mass adjusted for trunk lean mass	7.000000e-06
GCST90011900_186	Serum alkaline phosphatase levels	3.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0007906	synophrys measurement
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume
EFO:0007785	femoral neck bone mineral density
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067407 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs992160	Efficacy	3	gemcitabine	Pancreatic Neoplasms

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs992160	CDC5L	3	2.50	1	gemcitabine

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
7.01	Kd	98.55	nM	CHEMBL5653589
7.01	ED50	98.55	nM	CHEMBL5653589
5.01	Kd	9844	nM	CHEMBL3752910
5.01	ED50	9844	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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	2148039: Binding affinity to human CDC5L incubated for 45 mins by Kinobead based pull down assay	kd	0.0985	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148039: Binding affinity to human CDC5L incubated for 45 mins by Kinobead based pull down assay	kd	9.8441	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	decreases expression	3
Hydrogen Peroxide	affects expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
tetrabromobisphenol A	increases expression	1
coumarin	affects phosphorylation	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
motexafin gadolinium	decreases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	affects response to substance	1
Caffeine	affects phosphorylation	1
Coumestrol	increases expression	1
Dinitrochlorobenzene	affects binding	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Thiram	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651081	Binding	Binding affinity to human CDC5L 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)

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

Trial	Phase	Status	Title
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
NCT04537364	Not specified	COMPLETED	Prediction of Renal Parenchymal Damage of CAKUT
NCT06921733	Not specified	RECRUITING	Ultrasound Localization Microscopy in Patient With Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)