CKAP5

Summary

CKAP5 (cytoskeleton associated protein 5, HGNC:28959) is a protein-coding gene on chromosome 11p11.2, encoding Cytoskeleton-associated protein 5 (Q14008). Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

This gene encodes a cytoskeleton-associated protein which belongs to the TOG/XMAP215 family. The N-terminal half of this protein contains a microtubule-binding domain and the C-terminal half contains a KXGS motif for binding tubulin dimers. This protein has two distinct roles in spindle formation; it protects kinetochore microtubules from depolymerization and plays an essential role in centrosomal microtubule assembly. This protein may be necessary for the proper interaction of microtubules with the cell cortex for directional cell movement. It also plays a role in translation of the myelin basic protein (MBP) mRNA by interacting with heterogeneous nuclear ribonucleoprotein (hnRNP) A2, which associates with MBP. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 9793 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 234 total
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001008938

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28959
Approved symbol	CKAP5
Name	cytoskeleton associated protein 5
Location	11p11.2
Locus type	gene with protein product
Status	Approved
Aliases	ch-TOG, KIAA0097, TOG, TOGp
Ensembl gene	ENSG00000175216
Ensembl biotype	protein_coding
OMIM	611142
Entrez	9793

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 28 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000312055, ENST00000354558, ENST00000525248, ENST00000525896, ENST00000526496, ENST00000526876, ENST00000526943, ENST00000527333, ENST00000528593, ENST00000529230, ENST00000532321, ENST00000533413, ENST00000874207, ENST00000874208, ENST00000874209, ENST00000928119, ENST00000928120, ENST00000928121, ENST00000928122, ENST00000928123, ENST00000928124, ENST00000928125, ENST00000928126, ENST00000928127, ENST00000928128, ENST00000928129, ENST00000928130, ENST00000928131, ENST00000928132, ENST00000928133, ENST00000928134, ENST00000968903, ENST00000968904

RefSeq mRNA: 2 — MANE Select: NM_001008938 NM_001008938, NM_014756

CCDS: CCDS31477, CCDS7924

Canonical transcript exons

ENST00000529230 — 44 exons

Exon	Start	End
ENSE00001181710	46809400	46809500
ENSE00001181715	46809742	46809874
ENSE00001226059	46811007	46811178
ENSE00001226065	46816198	46816404
ENSE00001226071	46818310	46818503
ENSE00001423871	46821175	46821268
ENSE00001613461	46778139	46778313
ENSE00001626567	46770788	46770982
ENSE00001630938	46795594	46795776
ENSE00001641424	46788681	46788773
ENSE00001647325	46797805	46797969
ENSE00001656703	46776255	46776383
ENSE00001657397	46783274	46783368
ENSE00001669205	46778460	46778599
ENSE00001672507	46790470	46790583
ENSE00001697952	46796812	46796940
ENSE00001705916	46784488	46784673
ENSE00001724861	46780428	46780485
ENSE00001755671	46777439	46777552
ENSE00001762771	46780194	46780319
ENSE00001770155	46790076	46790186
ENSE00001773745	46808031	46808144
ENSE00002140420	46846220	46846280
ENSE00002186471	46743048	46744265
ENSE00003458529	46762000	46762193
ENSE00003462248	46750528	46750611
ENSE00003468533	46752635	46752710
ENSE00003475907	46762627	46762762
ENSE00003481721	46751118	46751255
ENSE00003490880	46744426	46744577
ENSE00003495101	46758923	46759043
ENSE00003524976	46753310	46753497
ENSE00003526580	46760612	46760784
ENSE00003550022	46798083	46798172
ENSE00003556648	46765131	46765256
ENSE00003559023	46759269	46759442
ENSE00003568993	46767575	46767663
ENSE00003573381	46763481	46763630
ENSE00003583856	46769963	46770098
ENSE00003622855	46762976	46763179
ENSE00003639928	46750274	46750433
ENSE00003644116	46801200	46801304
ENSE00003649440	46751346	46751534
ENSE00003687997	46754888	46755067

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 99.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.9201 / max 2411.4072, expressed in 1799 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119543	43.4467	1798
119541	0.9324	468
206272	0.4090	211
119540	0.1076	25
119538	0.0095	3
119539	0.0080	3
119537	0.0070	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.33	gold quality
ganglionic eminence	UBERON:0004023	98.44	gold quality
cortical plate	UBERON:0005343	98.03	gold quality
adrenal tissue	UBERON:0018303	97.95	gold quality
oocyte	CL:0000023	97.23	gold quality
right testis	UBERON:0004534	96.03	gold quality
stromal cell of endometrium	CL:0002255	95.98	gold quality
embryo	UBERON:0000922	95.86	gold quality
calcaneal tendon	UBERON:0003701	95.85	gold quality
left testis	UBERON:0004533	95.48	gold quality
secondary oocyte	CL:0000655	95.47	gold quality
prefrontal cortex	UBERON:0000451	95.27	gold quality
cerebellar hemisphere	UBERON:0002245	95.20	gold quality
cerebellar cortex	UBERON:0002129	95.19	gold quality
right adrenal gland	UBERON:0001233	95.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.05	gold quality
right adrenal gland cortex	UBERON:0035827	95.04	gold quality
testis	UBERON:0000473	94.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.62	gold quality
left adrenal gland	UBERON:0001234	94.57	gold quality
colonic epithelium	UBERON:0000397	94.56	gold quality
cerebellum	UBERON:0002037	94.52	gold quality
adrenal gland	UBERON:0002369	94.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.37	gold quality
gastrocnemius	UBERON:0001388	94.24	gold quality
right frontal lobe	UBERON:0002810	94.15	gold quality
muscle of leg	UBERON:0001383	94.11	gold quality
frontal cortex	UBERON:0001870	94.08	gold quality
left adrenal gland cortex	UBERON:0035825	94.07	gold quality
corpus callosum	UBERON:0002336	93.93	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP63

miRNA regulators (miRDB)

34 targeting CKAP5, 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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-4659A-5P	98.03	66.42	819
HSA-MIR-4659B-5P	98.03	66.84	979
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-1227-3P	97.36	66.94	834

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 22)

• Interaction of the transforming acidic coiled-coil 1 (TACC1) protein with ch-TOG and GAS41/NuBI1 suggests multiple TACC1-containing protein complexes in human cells (PMID:11903063)
• TOG has roles during mitosis in focusing MT minus ends at spindle poles, maintaining centrosome integrity, and contributing to spindle bipolarity (PMID:14718566)
• TOG mediates the association of hnRNP A2-positive granules with microtubules during transport and/or localization (PMID:15703215)
• Hsp90 is required to localize ch-TOG to the mitotic spindle. (PMID:17376965)
• A novel function of Aurora-A, the regulation of ch-TOG and MCAK localization, in a common pathway in control of spindle pole integrity. (PMID:18663358)
• ch-Tog has at least two distinct roles in spindle formation: it protects kinetochore microtubules from depolymerization by MCAK, and ch-Tog plays an essential role in centrosomal microtubule assembly, a function independent of MCAK activity. (PMID:18809577)
• Data hypothesize that TOGp is required for chromosome motility as a downstream consequence of reduced microtubule dynamics and/or density. (PMID:19373773)
• Data show that 4-oxo-4-HPR inhibited tubulin polymerization and modulated gene expression of spindle aberration associated genes Kif 1C, Kif 2A, Eg5, Tara, tankyrase-1, centractin, and TOGp. (PMID:19996280)
• the association between aurora A phosphorylation and spindle apparatus; regulation from aurora A is mediated by CHC in recruiting phospho-TACC3 and subsequently ch-TOG to mitotic spindles. (PMID:20566684)
• Data show that ILK performs its centrosome clustering activity in a centrosome-dependent, manner through the microtubule regulating proteins TACC3 and ch-TOG. (PMID:20838383)
• Clathrin promotes centrosome maturation by stabilizing the microtubule-binding protein ch-TOG, defining a novel role for the clathrin-ch-TOG complex. (PMID:22891263)
• These observations indicate that EB1 and ch-TOG regulate microtubule organisation differently via distinct regions in the plus ends of microtubules. (PMID:23251535)
• Data show that five genes CKAP5, KPNB1, RAN, TPX2 and KIF11 were shown to be essential for tumor cell survival in both head and neck squamous cell carcinoma (HNSCC)and non-small cell lung cancer (NSCLC), but most particularly in HNSCC. (PMID:23444224)
• Aurora-A kinase does not regulate TACC3-chTOG complex formation, indicating that Aurora-A solely functions as a recruitment factor for the TACC3-chTOG complex to centrosomes and proximal mitotic spindles. (PMID:24273164)
• Data show that cytoskeleton associated protein 5 (chTOG) only weakly promotes importin-regulated microtubule nucleation, but acts synergistically with microtubule- associated protein TPX2. (PMID:26414402)
• Eribulin binding to the tip of microtubules and subsequent loss of ch-TOG is a priming event leading to alterations in microtubule dynamics and breast cancer cell migration. (PMID:26497677)
• Tyrosine phosphorylation regulates hnRNPA2 granule protein partitioning and reduces neurodegeneration. (PMID:33349959)
• chTOG is a conserved mitotic error correction factor. (PMID:33377866)
• Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity. (PMID:34942120)
• Competing endogenous RNA analysis reveals the regulatory potency of CKAP5 in HPV+ HNSCC. (PMID:35710876)
• TACC3-ch-TOG interaction regulates spindle microtubule assembly by controlling centrosomal recruitment of gamma-TuRC. (PMID:36790370)
• CKAP5 stabilizes CENP-E at kinetochores by regulating microtubule-chromosome attachments. (PMID:38424231)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ckap5	ENSDARG00000102674
mus_musculus	Ckap5	ENSMUSG00000040549
rattus_norvegicus	Ckap5	ENSRNOG00000016067
drosophila_melanogaster	msps	FBGN0027948
caenorhabditis_elegans		WBGENE00011613
caenorhabditis_elegans		WBGENE00018781

Protein

Protein identifiers

Cytoskeleton-associated protein 5 — Q14008 (reviewed: Q14008)

Alternative names: Colonic and hepatic tumor overexpressed gene protein

All UniProt accessions (5): E9PQH5, Q14008, H0YCF6, H0YDX5, H0YEK7

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the plus end of microtubules and regulates microtubule dynamics and microtubule organization. Acts as a processive microtubule polymerase. Promotes cytoplasmic microtubule nucleation and elongation. Plays a major role in organizing spindle poles. In spindle formation protects kinetochore microtubules from depolymerization by KIF2C and has an essential role in centrosomal microtubule assembly independently of KIF2C activity. Contributes to centrosome integrity. Acts as a component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension. Enhances the strength of NDC80 complex-mediated kinetochore-tip microtubule attachments.

Subunit / interactions. Interacts with TACC1. Interacts with SLAIN2 and SLAIN1. Interacts with HNRNPA2B1. Interacts with TACC3 independently of clathrin. Interacts with TACC3 and clathrin forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges. Interacts with NDC80; indicative for an association with the NDC80 complex.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole. Spindle. Chromosome. Centromere. Kinetochore.

Tissue specificity. Overexpressed in hepatomas and colonic tumors. Also expressed in skeletal muscle, brain, heart, placenta, lung, liver, kidney and pancreas. Expression is elevated in the brain; highly expressed in the Purkinje cell bodies of the cerebellum.

Domain organisation. The TOG (tumor overexpressed gene) domains are arranged in a N-terminal pentameric array with each domain composed of six (for the most part non-canonical) HEAT repeats forming a oblong paddle-like structure. Intra-HEAT loops are positioned along a face of the TOG domain and bind to a single alpha/beta-tubulin heterodimer. The TOG domains in the array seem to be structurally and functionally polarized. Differential functions may range from microtubule (MT) lattice binding and/or free tubulin heterodimer binding to potentiating stable incorporation of tubulin into the MT lattice.

Similarity. Belongs to the TOG/XMAP215 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14008-1	1	yes
Q14008-2	2
Q14008-3	3

RefSeq proteins (2): NP_001008938, NP_055571 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021133	HEAT_type_2	Repeat
IPR024395	CLASP_N_dom	Domain
IPR034085	TOG	Domain
IPR045110	XMAP215	Family
IPR048491	XMAP215_CLASP_TOG	Domain

Pfam: PF12348, PF21041

UniProt features (69 total): helix 20, region of interest 12, repeat 10, compositionally biased region 7, modified residue 5, mutagenesis site 4, sequence conflict 3, splice variant 2, strand 2, turn 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4QMI	X-RAY DIFFRACTION	1.9
4QMJ	X-RAY DIFFRACTION	2.5
9F4C	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14008-F1	76.04	0.43

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): 48, 816, 845, 1469, 1861

Mutagenesis-validated functional residues (4):

Position	Phenotype
1939	disrupts interaction with tacc3.
1939	abolishes localization to spindle microtubules, no effect on localization to centrosomes and kinetochores; when associat
1942	disrupts interaction with tacc3.
1942	abolishes localization to spindle microtubules, no effect on localization to centrosomes and kinetochores; when associat

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-68877	Mitotic Prometaphase
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-9648025	EML4 and NUDC in mitotic spindle formation

MSigDB gene sets: 265 (showing top): MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, ROVERSI_GLIOMA_COPY_NUMBER_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MICROTUBULE_NUCLEATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_MICROTUBULE_POLYMERIZATION_OR_DEPOLYMERIZATION, GOBP_REGULATION_OF_MICROTUBULE_POLYMERIZATION

GO Biological Process (11): microtubule depolymerization (GO:0007019), spindle organization (GO:0007051), mitotic spindle organization (GO:0007052), centrosome cycle (GO:0007098), establishment or maintenance of microtubule cytoskeleton polarity (GO:0030951), microtubule polymerization (GO:0046785), RNA transport (GO:0050658), centrosome duplication (GO:0051298), cell division (GO:0051301), positive regulation of microtubule nucleation (GO:0090063), protein-containing complex organization (GO:0043933)

GO Molecular Function (7): microtubule binding (GO:0008017), ribonucleoprotein complex binding (GO:0043021), cadherin binding (GO:0045296), microtubule plus-end binding (GO:0051010), microtubule plus end polymerase activity (GO:0061863), protein binding (GO:0005515), tubulin binding (GO:0015631)

GO Cellular Component (18): kinetochore (GO:0000776), spindle pole (GO:0000922), nucleolus (GO:0005730), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), protein-containing complex (GO:0032991), ciliary basal body (GO:0036064), mitotic spindle (GO:0072686), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), spindle (GO:0005819), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630), microtubule plus-end (GO:0035371)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Mitotic Prometaphase	3
G2/M Transition	2
Centrosome maturation	2
Amplification of signal from the kinetochores	1
Mitotic Anaphase	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Assembly of the 9+0 primary cilium	1
RHO GTPase Effectors	1
M Phase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	5
cellular anatomical structure	4
microtubule cytoskeleton organization	3
cell cycle process	3
microtubule polymerization or depolymerization	2
supramolecular fiber organization	2
microtubule nucleation	2
spindle	2
microtubule organizing center	2
protein depolymerization	1
mitotic cell cycle	1
spindle organization	1
microtubule cytoskeleton organization involved in mitosis	1
microtubule organizing center organization	1
establishment or maintenance of cytoskeleton polarity	1
protein polymerization	1
nucleic acid transport	1
establishment of RNA localization	1
centrosome cycle	1
cellular process	1
regulation of microtubule nucleation	1
positive regulation of microtubule polymerization	1
cellular component organization	1
tubulin binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
microtubule binding	1
transferase activity	1
catalytic activity, acting on a protein	1
binding	1
cytoskeletal protein binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
nuclear lumen	1
intracellular anatomical structure	1
centriole	1
cytoplasm	1
membrane	1
cell periphery	1
intraciliary transport particle	1

Protein interactions and networks

STRING

3232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CKAP5	TACC3	Q9Y6A5	999
CKAP5	AURKA	O14965	959
CKAP5	TACC1	O75410	951
CKAP5	CEP120	Q8N960	851
CKAP5	KIF11	P52732	802
CKAP5	TACC2	O95359	768
CKAP5	NDC80	O14777	765
CKAP5	KIF2C	Q99661	723
CKAP5	CLASRP	Q8N2M8	720
CKAP5	CLIP1	P30622	696
CKAP5	KIFC1	Q9BW19	694
CKAP5	MAPRE3	Q9UPY8	690
CKAP5	MAD2L1	Q13257	677
CKAP5	DLGAP5	Q15398	663
CKAP5	CDK5RAP2	Q96SN8	662

IntAct

202 interactions, top by confidence:

A	B	Type	Score
CTNNB1	AXIN1	psi-mi:“MI:0914”(association)	0.940
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
TACC3	CKAP5	psi-mi:“MI:0915”(physical association)	0.860
CKAP5	TACC3	psi-mi:“MI:0403”(colocalization)	0.860
CKAP5	TACC3	psi-mi:“MI:0915”(physical association)	0.860
TACC1	CKAP5	psi-mi:“MI:0915”(physical association)	0.800
CKAP5	TACC1	psi-mi:“MI:0914”(association)	0.800
CKAP5	TACC1	psi-mi:“MI:0407”(direct interaction)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
SLAIN2	CKAP5	psi-mi:“MI:0915”(physical association)	0.620
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
Zw10	NBAS	psi-mi:“MI:0915”(physical association)	0.560
BTN3A3	BTN3A1	psi-mi:“MI:0914”(association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
KLHL40	CBX4	psi-mi:“MI:0914”(association)	0.530
EPHA1	EXOC5	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
ALOX5	DDHD2	psi-mi:“MI:0914”(association)	0.530
TACC3	HSPA8	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
CHCHD4	ENSA	psi-mi:“MI:0914”(association)	0.530
CLTA	CLTCL1	psi-mi:“MI:0914”(association)	0.530

BioGRID (398): CKAP5 (Affinity Capture-MS), CKAP5 (Affinity Capture-MS), CKAP5 (Affinity Capture-MS), CKAP5 (Affinity Capture-MS), CKAP5 (Affinity Capture-MS), CKAP5 (Affinity Capture-MS), CKAP5 (Affinity Capture-MS), CKAP5 (Affinity Capture-RNA), CKAP5 (Co-fractionation), CKAP5 (Co-fractionation), CKAP5 (Co-fractionation), CKAP5 (Co-fractionation), CKAP5 (Co-fractionation), CKAP5 (Co-fractionation), INTS2 (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: A2AGT5, O94534, Q14008, Q9PT63, Q9VEZ3, G5EEM5, P46675, Q09933, Q1ZXQ8, Q5N749, Q94FN2, A1A5K2, Q4U0G1, Q7Z460, Q80TV8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 215 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
Downstream signal transduction	5	12.8×	3e-03
RHO GTPases activate IQGAPs	5	11.6×	4e-03
RHOU GTPase cycle	6	11.2×	3e-03
Dengue Virus Genome Translation and Replication	5	10.7×	4e-03
Recycling pathway of L1	6	9.0×	4e-03
EPH-ephrin mediated repulsion of cells	6	8.8×	4e-03
Centrosome maturation	5	8.5×	8e-03
Aggrephagy	5	8.3×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitotic spindle organization	8	11.8×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	190
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5912 predictions. Top by Δscore:

Variant	Effect	Δscore
11:46744262:CTTG:C	acceptor_gain	1.0000
11:46744266:C:CC	acceptor_gain	1.0000
11:46744420:CAGTA:C	donor_loss	1.0000
11:46744421:AGTAC:A	donor_loss	1.0000
11:46744422:GTAC:G	donor_loss	1.0000
11:46744423:TAC:T	donor_loss	1.0000
11:46744424:A:AG	donor_loss	1.0000
11:46744425:C:CG	donor_loss	1.0000
11:46744573:GATGC:G	acceptor_gain	1.0000
11:46744574:ATGC:A	acceptor_gain	1.0000
11:46744575:TGC:T	acceptor_gain	1.0000
11:46744576:GC:G	acceptor_gain	1.0000
11:46744577:CC:C	acceptor_gain	1.0000
11:46744578:C:CC	acceptor_gain	1.0000
11:46750268:CCATA:C	donor_loss	1.0000
11:46750269:CATAC:C	donor_loss	1.0000
11:46750271:TACCT:T	donor_loss	1.0000
11:46750272:A:C	donor_loss	1.0000
11:46750273:C:CG	donor_loss	1.0000
11:46750292:G:GT	donor_gain	1.0000
11:46750430:GTCC:G	acceptor_gain	1.0000
11:46750431:TCC:T	acceptor_gain	1.0000
11:46750432:CC:C	acceptor_gain	1.0000
11:46750432:CCC:C	acceptor_gain	1.0000
11:46750433:CC:C	acceptor_gain	1.0000
11:46750434:C:CC	acceptor_gain	1.0000
11:46750434:C:T	acceptor_gain	1.0000
11:46750435:T:A	acceptor_loss	1.0000
11:46750442:C:CT	acceptor_gain	1.0000
11:46750443:A:T	acceptor_gain	1.0000

AlphaMissense

13415 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:46744051:A:G	L2024P	1.000
11:46750327:A:G	L1884P	1.000
11:46750339:A:T	V1880D	1.000
11:46750372:A:G	L1869P	1.000
11:46750420:A:G	L1853S	1.000
11:46750429:A:G	L1850P	1.000
11:46750432:C:T	G1849E	1.000
11:46750433:C:G	G1849R	1.000
11:46750433:C:T	G1849R	1.000
11:46750553:A:T	I1840N	1.000
11:46751470:A:G	L1733P	1.000
11:46751528:A:G	W1714R	1.000
11:46751528:A:T	W1714R	1.000
11:46760749:C:A	R1419S	1.000
11:46760749:C:G	R1419S	1.000
11:46760759:A:G	L1416P	1.000
11:46762061:A:G	L1387P	1.000
11:46762073:C:G	R1383P	1.000
11:46762074:G:T	R1383S	1.000
11:46762086:C:G	D1379H	1.000
11:46762187:A:G	L1345P	1.000
11:46762737:C:G	R1306P	1.000
11:46763125:A:G	W1248R	1.000
11:46763125:A:T	W1248R	1.000
11:46763581:A:G	L1196P	1.000
11:46763619:C:A	W1183C	1.000
11:46763619:C:G	W1183C	1.000
11:46763620:C:G	W1183S	1.000
11:46763621:A:G	W1183R	1.000
11:46763621:A:T	W1183R	1.000

dbSNP variants (sampled 300 via entrez): RS1000040605 (11:46764895 T>A,C), RS1000049092 (11:46818318 T>C), RS1000096481 (11:46826685 A>C,G), RS1000102727 (11:46790920 G>A), RS1000116030 (11:46820150 C>T), RS1000174368 (11:46753738 C>A), RS1000180328 (11:46800287 G>A), RS1000248233 (11:46762840 G>C,T), RS1000270327 (11:46825638 C>CT), RS1000277683 (11:46833375 C>A,T), RS1000352485 (11:46840365 C>G), RS1000354406 (11:46793875 C>T), RS1000383056 (11:46746761 C>G), RS1000420573 (11:46800634 G>A), RS1000422835 (11:46785799 GT>G)

Disease associations

OMIM: gene MIM:611142 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000763_2	Immunoglobulin A	2.000000e-06
GCST004521_122	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_165	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST006803_20	Schizophrenia	3.000000e-13
GCST007269_116	Pulse pressure	3.000000e-09
GCST007511_23	Alzheimer’s disease (late onset)	6.000000e-06
GCST007825_4	Alzheimer’s disease or fasting glucose levels (pleiotropy)	3.000000e-16
GCST012020_177	Serum metabolite levels	2.000000e-11
GCST012021_102	Serum metabolite levels	2.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0005763	pulse pressure measurement
EFO:1001870	late-onset Alzheimers disease

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, increases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
Acetaminophen	increases expression	2
Cisplatin	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
tetrahydropalmatine	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases reaction, affects binding	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
cupric oxide	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer