CKAP4

Summary

CKAP4 (cytoskeleton associated protein 4, HGNC:16991) is a protein-coding gene on chromosome 12q23.3, encoding Cytoskeleton-associated protein 4 (Q07065). Mediates the anchoring of the endoplasmic reticulum to microtubules.

Enables RNA binding activity. Located in several cellular components, including lipid droplet; nuclear speck; and rough endoplasmic reticulum. Biomarker of hepatocellular carcinoma.

Source: NCBI Gene 10970 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 89 total
• Druggable target: yes
• MANE Select transcript: NM_006825

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16991
Approved symbol	CKAP4
Name	cytoskeleton associated protein 4
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	P63, CLIMP-63, CLIMP63, ERGIC-63
Ensembl gene	ENSG00000136026
Ensembl biotype	protein_coding
OMIM	618595
Entrez	10970

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000378026, ENST00000552828, ENST00000553039, ENST00000880615

RefSeq mRNA: 1 — MANE Select: NM_006825 NM_006825

CCDS: CCDS9103

Canonical transcript exons

ENST00000378026 — 2 exons

Exon	Start	End
ENSE00001417942	106247369	106248020
ENSE00001475949	106237881	106240349

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 117.4091 / max 1784.9772, expressed in 1745 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133065	106.2114	1743
133067	2.3135	1155
133063	2.2558	978
133062	1.5707	717
133064	1.3677	747
133058	0.9076	412
133069	0.8378	485
133066	0.7859	495
133068	0.5827	322
133059	0.5564	301

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.52	gold quality
gingival epithelium	UBERON:0001949	99.15	gold quality
stromal cell of endometrium	CL:0002255	99.13	gold quality
esophagus squamous epithelium	UBERON:0006920	99.11	gold quality
squamous epithelium	UBERON:0006914	99.03	gold quality
cartilage tissue	UBERON:0002418	98.95	gold quality
buccal mucosa cell	CL:0002336	98.74	gold quality
periodontal ligament	UBERON:0008266	98.69	gold quality
cervix squamous epithelium	UBERON:0006922	98.68	gold quality
gingiva	UBERON:0001828	98.59	gold quality
pancreatic ductal cell	CL:0002079	98.55	gold quality
parietal pleura	UBERON:0002400	98.51	gold quality
epithelium of esophagus	UBERON:0001976	98.45	gold quality
germinal epithelium of ovary	UBERON:0001304	98.30	gold quality
pleura	UBERON:0000977	98.19	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.17	gold quality
visceral pleura	UBERON:0002401	98.12	gold quality
corpus epididymis	UBERON:0004359	97.88	gold quality
penis	UBERON:0000989	97.75	gold quality
pylorus	UBERON:0001166	97.72	gold quality
tongue squamous epithelium	UBERON:0006919	97.55	gold quality
parotid gland	UBERON:0001831	97.52	gold quality
bone marrow cell	CL:0002092	97.48	gold quality
oviduct epithelium	UBERON:0004804	97.38	gold quality
epithelium of nasopharynx	UBERON:0001951	97.27	gold quality
trachea	UBERON:0003126	97.21	gold quality
nipple	UBERON:0002030	97.16	gold quality
type B pancreatic cell	CL:0000169	97.15	gold quality
endometrium epithelium	UBERON:0004811	96.92	gold quality
cervix epithelium	UBERON:0004801	96.86	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	40.75
E-HCAD-13	yes	11.41
E-MTAB-9067	yes	10.46
E-CURD-112	yes	9.65
E-MTAB-6678	no	3.75
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting CKAP4, 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-513A-5P	100.00	69.77	2465
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-12119	99.87	68.35	1653

Literature-anchored findings (GeneRIF, showing 40)

• evidence to support the hypothesis that p63 is the functional tPA binding site on VSMC (PMID:12913003)
• The ectrodactyly, absence of radius side part palm and split foot malformation are caused by the mutation of base pair at number 665 of the exon 5 of P63. (PMID:15476176)
• CLIMP-63-mediated stable anchoring of the endoplasmic reticulum (ER) to microtubules is required to maintain the spatial distribution of the ER during interphase. (PMID:15703217)
• is not responsible for autosomal-dominant amelogenesis imperfecta (PMID:16546853)
• cytoskeleton-associated protein 4/p63 (CKAP4/p63), a type II transmembrane receptor, binds with high affinity to APF (PMID:17030514)
• The p62/p63 protein was first identified because it is palmitoylated during mitosis. (PMID:1730740)
• Olomoucine, a CDK inhibitor, up-regulates CKAP4, a cytoskeleton-linking membrane protein. (PMID:17975794)
• Identification of CKAP4/p63 as a substrate of DHHC2, a putative tumor suppressor. (PMID:18296695)
• CK MNF116 and p63 were useful in identifying squamous cell carcinomas with single cell infiltration. (PMID:18333895)
• Results substantiate the role of P63 as a lung surfactant protein-A receptor protein localized on the surface of lung type II cells. (PMID:18708633)
• DHHC2-mediated palmitoylation of CKAP4 has a role in opposing cancer-related cellular behaviors. (PMID:19144824)
• p73 and p63, but not p53, are modulated during the cell cycle (PMID:19861536)
• I510T mutation of p63 was detected in both RHS and AEC syndrome patients and mutation of S541 residue can lead to either RHS (S541Y) or AEC syndrome (S541F). (PMID:20156774)
• p63 was not found to be highly sensitive for squamous cell carcinoma (PMID:20184665)
• p63 binds to an enhancer element in the SHFM1 locus and this element controls expression of DLX6 and DLX5 which are important for limb development. (PMID:20808887)
• Data demonstrate an important role for the PI3-kinase-Akt pathway in intracellular transport of surfactant protein A receptor P63. (PMID:20870746)
• CLIMP63 regulates the luminal diameter within the endoplasmic reticulum and may play a role in regulating the formation of endoplasmic reticulum sheets. (PMID:21111237)
• Synthetic as-antiproliferative factor inhibits cell proliferation in T24 bladder carcinoma cells via the CKAP4 receptor (PMID:21143984)
• Telomere length in Sjogren syndrome is shorter and associated with lower levels of expression of p63 and nucleostemin than in non-Sjogren syndrome. (PMID:21655359)
• This study found a consistent expression profile and localization analysis of p63 and GM1 in primary keratinocytes and in human epidermal biopsies. (PMID:21820419)
• These findings strongly support the routine use of p40 in place of p63 for the diagnosis of pulmonary squamous cell carcinoma. (PMID:22056955)
• This study identifies specific changes in skin structural biology and signalling pathways that result from mutant p63 and provides new molecular insight into the AEC syndrome phenotype (PMID:22329826)
• Tumor markers, p63 and high molecular weight cytokeratin, may be utilised in the distinction between urothelial carcinoma with prostatic stromal invasion and urothelial carcinoma with colonisation of prostatic ducts and acini. (PMID:22406481)
• CCN2 regulation by antiproliferative factor involves CKAP4 nuclear translocation and binding to the CCN2 promoter. (PMID:22438586)
• Treatment of airway epitheial cells (AEC) with SP-A, monoclonal antibodies to CKAP4/P63, or CKAP4/P63-specific small interfering RNA decreased the binding of purified alginate exopolysaccharide to AEC. (PMID:22966120)
• The results define CLIMP-63 as a novel protein interactor and regulator of Dicer function, involved in maintaining Dicer protein levels in human cells. (PMID:23047949)
• p63 positively regulates desmosome adhesion by directly controlling the expression of several desmosome genes, including Dsp, Dsc3 and Dsg1. (PMID:23108156)
• CKAP4 was correlated with favorable clinical outcome and was an independent predictor for overall survival in hepatic cholangiocarcinoma patients. (PMID:23665508)
• Single nucleotide polymorphisms in p63 are implicated in the etiology of nonsyndromic bladder-exstrophy-epispadias complex. (PMID:23913486)
• Here we report that the combination of p63, a master regulator of epidermal development and differentiation, and KLF4, a regulator of epidermal differentiation, is sufficient to convert dermal fibroblasts to a keratinocyte phenotype. (PMID:23921950)
• revealed that CKAP4 could associate with EGFR at basal status and the complex was reduced upon EGF stimulation, leading to release EGFR into cytoplasm (PMID:24838946)
• Although VIMP can interact with CLIMP-63 and Syn5L, it does not interact with MT-binding ER proteins (such as Reep1) that shape the tubular smooth ER (PMID:25008318)
• The still rudimentary information of how CLIMP-63 fulfills these different roles, what these are exactly and how post-translational modifications control them, will be discussed. (PMID:25849921)
• CKAP4 has a role as a Dickkopf1 receptor and in pancreatic and lung tumor progression (PMID:27322059)
• CLIMP-63 (also known as CKAP4), is the partner of triadin, is responsible for this association of triads and microtubules. (PMID:27562070)
• Both DKK1 and CKAP4 are frequently expressed in pancreatic and lung tumours, and their simultaneous expression is negatively correlated with prognosis. (PMID:28514532)
• Human Prostate Basal cell hyperplasia is an expansion of p63. (PMID:28795417)
• APF binds specifically to sites within the cytoskeleton-associated protein 4 (CKAP4) extracellular domain (PMID:28893174)
• The findings suggest that the DKK1-CKAP4 pathway promotes esophageal squamous cell carcinoma cell proliferation and that CKAP4 might represent a novel therapeutic target for esophageal squamous cell carcinomas expressing both DKK1 and CKAP4. (PMID:29563607)
• High CKAP4 expression is associated with Lung Cancer. (PMID:29751934)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ckap4	ENSMUSG00000046841
rattus_norvegicus	Ckap4	ENSRNOG00000008016
drosophila_melanogaster	SMC3	FBGN0015615
caenorhabditis_elegans		WBGENE00004873
caenorhabditis_elegans		WBGENE00012198
caenorhabditis_elegans		WBGENE00019087

Paralogs (7): SMC1A (ENSG00000072501), SMC1B (ENSG00000077935), SMC3 (ENSG00000108055), SMC4 (ENSG00000113810), SMC2 (ENSG00000136824), CCDC122 (ENSG00000151773), CCDC157 (ENSG00000187860)

Protein

Protein identifiers

Cytoskeleton-associated protein 4 — Q07065 (reviewed: Q07065)

Alternative names: 63-kDa cytoskeleton-linking membrane protein

All UniProt accessions (2): Q07065, F8VVU0

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the anchoring of the endoplasmic reticulum to microtubules. High-affinity epithelial cell surface receptor for the FZD8-related low molecular weight sialoglycopeptide APF/antiproliferative factor. Mediates the APF antiproliferative signaling within cells.

Subunit / interactions. Interacts with REEP5.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane. Cytoplasm. Cytoskeleton. Perinuclear region.

Post-translational modifications. Reversibly palmitoylated. Palmitoylation at Cys-100 by ZDHHC2 is required for its trafficking from the ER to the plasma membrane and for its perinuclear localization. Palmitoylation by ZDHHC2 is also required for its function in APF-mediated antiproliferative signaling. Increased phosphorylation during mitosis prevents binding to microtubules.

RefSeq proteins (1): NP_006816* (*=MANE)

Domains & families (InterPro)

UniProt features (20 total): modified residue 6, coiled-coil region 3, topological domain 2, sequence conflict 2, compositionally biased region 2, chain 1, lipid moiety-binding region 1, sequence variant 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07065-F1	76.61	0.36

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 (7): 3, 17, 19, 21, 232, 312, 100

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-5683826	Surfactant metabolism
R-HSA-6798695	Neutrophil degranulation
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696270	RND2 GTPase cycle

MSigDB gene sets: 297 (showing top): RNGTGGGC_UNKNOWN, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOZGIT_ESR1_TARGETS_DN, HALMOS_CEBPA_TARGETS_UP, CTATGCA_MIR153, TTGCWCAAY_CEBPB_02, FOXD3_01, WEI_MYCN_TARGETS_WITH_E_BOX, BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, BLALOCK_ALZHEIMERS_DISEASE_UP, HNF4_DR1_Q3, LIAO_METASTASIS

GO Biological Process (0):

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (16): mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), rough endoplasmic reticulum (GO:0005791), lipid droplet (GO:0005811), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), nuclear speck (GO:0016607), azurophil granule membrane (GO:0035577), specific granule membrane (GO:0035579), lamellar body (GO:0042599), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of proteins	2
RHO GTPase cycle	2
Innate Immune System	1
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
cellular anatomical structure	3
intracellular membrane-bounded organelle	2
endoplasmic reticulum	2
intracellular membraneless organelle	2
secretory granule membrane	2
nucleic acid binding	1
binding	1
endomembrane system	1
intracellular organelle lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
nuclear ribonucleoprotein granule	1
lysosomal membrane	1
azurophil granule	1
specific granule	1
secretory granule	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1678 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CKAP4	DKK1	O94907	977
CKAP4	ZDHHC2	Q9UIJ5	718
CKAP4	VDAC2	P45880	667
CKAP4	KTN1	Q86UP2	643
CKAP4	ATL3	Q6DD88	641
CKAP4	ATL2	Q8NHH9	621
CKAP4	ATL1	Q8WXF7	588
CKAP4	REEP5	Q00765	583
CKAP4	REEP1	Q9H902	547
CKAP4	STX5	Q13190	532
CKAP4	TMEM214	Q6NUQ4	528
CKAP4	RTN4	Q9NQC3	506
CKAP4	CDH5	P33151	490
CKAP4	TRDN	Q13061	486
CKAP4	STIM1	Q13586	480
CKAP4	DICER1	Q9UPY3	480

IntAct

316 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
FBXO28	TRAF5	psi-mi:“MI:0914”(association)	0.740
CKAP4	FBXO28	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
RNF144A	CKAP4	psi-mi:“MI:0915”(physical association)	0.590
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
SLC7A1	TMEM223	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SEMA7A	SGPL1	psi-mi:“MI:0914”(association)	0.530
KCNA10	GAPDHS	psi-mi:“MI:0914”(association)	0.530
LYPD6	PLXNB2	psi-mi:“MI:0914”(association)	0.530
SSMEM1	NDUFA7	psi-mi:“MI:0914”(association)	0.530
STS	GJA1	psi-mi:“MI:0914”(association)	0.530
PRELP	AMD1	psi-mi:“MI:0914”(association)	0.530
RTN4R	SOAT1	psi-mi:“MI:0914”(association)	0.530
COL1A1	GOLIM4	psi-mi:“MI:0914”(association)	0.500
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
EIF2AK2	ZC3H11A	psi-mi:“MI:0914”(association)	0.480
TGOLN2	PGRMC1	psi-mi:“MI:0914”(association)	0.420
NEURL1	CKAP4	psi-mi:“MI:0915”(physical association)	0.400
DNAH7	CKAP4	psi-mi:“MI:0915”(physical association)	0.400
TRHDE	CKAP4	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (846): CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-RNA), CKAP4 (Affinity Capture-RNA), CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-Western), CKAP4 (Co-fractionation), CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS), CKAP4 (Affinity Capture-MS)

ESM2 similar proteins: A2VE00, A2VE53, A2XW69, A5PMY6, A6QP79, B2RPV6, F1QC17, F7DP49, O75071, Q07065, Q0II90, Q13201, Q2LK54, Q32L59, Q3UIJ9, Q4V7C8, Q4V885, Q53EZ4, Q5BIX7, Q5EAJ6, Q5EB94, Q5KU26, Q5R6R3, Q5R923, Q5RI56, Q5ZM60, Q61595, Q640L3, Q6AZY7, Q6NRC9, Q6P6L0, Q70UQ0, Q7XU27, Q7Z7B0, Q84VY2, Q8BGQ6, Q8BIS8, Q8BMK4, Q8BT07, Q8BVC4

Diamond homologs: Q07065, Q8BMK4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 253 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	6	13.5×	8e-04
Signaling by high-kinase activity BRAF mutants	5	9.4×	1e-02
RHOQ GTPase cycle	7	7.5×	4e-03
RHOJ GTPase cycle	6	7.1×	1e-02
RAC3 GTPase cycle	8	5.6×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	9	7.5×	2e-03
protein autophosphorylation	11	7.3×	5e-04
cell surface receptor protein tyrosine kinase signaling pathway	9	7.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

439 predictions. Top by Δscore:

Variant	Effect	Δscore
12:106247364:CCCA:C	donor_loss	1.0000
12:106247365:CCA:C	donor_loss	1.0000
12:106247366:CA:C	donor_loss	1.0000
12:106247367:ACC:A	donor_loss	1.0000
12:106247368:C:G	donor_loss	1.0000
12:106247368:CCTT:C	donor_gain	1.0000
12:106240348:ACC:A	acceptor_loss	0.9900
12:106240349:CCT:C	acceptor_loss	0.9900
12:106240351:T:C	acceptor_loss	0.9900
12:106240350:C:CC	acceptor_gain	0.9800
12:106240352:G:C	acceptor_loss	0.9800
12:106247367:A:AC	donor_gain	0.9800
12:106247368:C:CC	donor_gain	0.9800
12:106247407:C:CA	donor_gain	0.9800
12:106240347:CAC:C	acceptor_gain	0.9700
12:106240357:CAAAA:C	acceptor_loss	0.9700
12:106240345:TGCAC:T	acceptor_gain	0.9600
12:106304175:G:GT	donor_gain	0.9600
12:106244439:C:CT	acceptor_gain	0.9500
12:106303059:G:T	donor_gain	0.9500
12:106247365:CCACC:C	donor_gain	0.9400
12:106302942:G:GG	donor_gain	0.9300
12:106302940:CGGTG:C	donor_loss	0.9200
12:106302942:GTG:G	donor_loss	0.9200
12:106302943:TG:T	donor_loss	0.9200
12:106302944:GCG:G	donor_loss	0.9200
12:106302945:CG:C	donor_loss	0.9200
12:106303059:G:GT	donor_gain	0.9200
12:106304204:GT:G	donor_gain	0.9200
12:106304205:TT:T	donor_gain	0.9200

AlphaMissense

3928 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:106240102:A:G	L244P	0.999
12:106240111:A:G	L241P	0.999
12:106240189:A:G	L215P	0.999
12:106240213:A:G	L207P	0.998
12:106239154:A:G	L560S	0.997
12:106239154:A:C	L560W	0.996
12:106239166:G:T	A556D	0.996
12:106239167:C:G	A556P	0.996
12:106240114:C:G	R240P	0.996
12:106239151:A:T	V561D	0.995
12:106240222:A:G	L204P	0.995
12:106240189:A:T	L215H	0.994
12:106240198:A:G	L212P	0.994
12:106240201:A:G	I211T	0.994
12:106247481:C:T	G124D	0.994
12:106239156:A:C	S559R	0.993
12:106239156:A:T	S559R	0.993
12:106239158:T:G	S559R	0.993
12:106239175:A:G	L553P	0.993
12:106240090:A:C	I248S	0.993
12:106240090:A:T	I248N	0.993
12:106240160:C:G	A225P	0.993
12:106240201:A:C	I211S	0.993
12:106239187:T:A	D549V	0.992
12:106240094:A:G	S247P	0.992
12:106240102:A:T	L244H	0.992
12:106240111:A:T	L241Q	0.992
12:106240156:C:G	R226P	0.992
12:106239175:A:T	L553H	0.991
12:106247482:C:G	G124R	0.991

dbSNP variants (sampled 300 via entrez): RS1000086109 (12:106247594 G>A,C,T), RS1000541191 (12:106247950 G>A,C,T), RS1001082951 (12:106248839 TC>T,TCC), RS1001350396 (12:106242856 C>G,T), RS1001586950 (12:106248181 A>C,G), RS1002030045 (12:106249280 G>A), RS1002127783 (12:106241622 C>A,T), RS1002269966 (12:106237500 C>CT), RS1002460226 (12:106243655 T>C), RS1002531843 (12:106245408 G>A,C), RS1002589820 (12:106249498 CACCATTTGAT>C), RS1002863843 (12:106243358 T>C), RS1002976804 (12:106238759 C>A), RS1003274884 (12:106238648 TCCC>T,TCC,TCCCC), RS1003543588 (12:106243834 T>C,G)

Disease associations

OMIM: gene MIM:618595 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST009391_1577	Metabolite levels	3.000000e-06
GCST010002_222	Refractive error	1.000000e-12
GCST90002379_54	Basophil count	2.000000e-10
GCST90002380_109	Basophil percentage of white cells	5.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010349	cholesteryl ester 20:5 measurement
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296025 (SINGLE PROTEIN)

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

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
8.26	Kd	5.468	nM	CHEMBL3752910
8.26	ED50	5.468	nM	CHEMBL3752910
6.76	Kd	173.6	nM	CHEMBL5653589
6.76	ED50	173.6	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 11 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148075: Binding affinity to human CKAP4 incubated for 45 mins by Kinobead based pull down assay	kd	0.0055	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148075: Binding affinity to human CKAP4 incubated for 45 mins by Kinobead based pull down assay	kd	0.1736	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases expression	4
bisphenol S	increases expression, affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4232642	Binding	Binding affinity to CKAP4 cysteine residue in human 786-O cell soluble proteomic lysate at 5 uM incubated for 1 hr followed by cell lysis by IA-alkyne probe based isoTOP-ABPP analysis	Covalent inhibitors of nicotinamide N-methyltransferase (NNMT) provide evidence for target engagement challenges in situ. — Bioorg Med Chem Lett

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1VU	Abcam A-549 CKAP4 KO	Cancer cell line	Male
CVCL_D2AB	Abcam HCT 116 CKAP4 KO	Cancer cell line	Male
CVCL_D8J3	Ubigene HCT 116 CKAP4 KO	Cancer cell line	Male
CVCL_E6PY	Genomeditech CHO-K1 H_CKAP4	Spontaneously immortalized cell line	Female
CVCL_F1LM	HyCyte 5637 KO-hCKAP4	Cancer cell line	Male
CVCL_SJ11	HAP1 CKAP4 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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