PEAK1

Summary

PEAK1 (pseudopodium enriched atypical kinase 1, HGNC:29431) is a protein-coding gene on chromosome 15q24.3, encoding Inactive tyrosine-protein kinase PEAK1 (Q9H792). Probable catalytically inactive kinase.

This gene encodes a non-receptor tyrosine kinase that is a member of the new kinase family three (NFK3) family. In migrating cells, the encoded protein is associated with the actin cytoskeleton and focal adhesions and promotes developing focal adhesion elongation. This protein may play a role in the regulation of cell migration, proliferation and cancer metastasis.

Source: NCBI Gene 79834 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 287 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001385026

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29431
Approved symbol	PEAK1
Name	pseudopodium enriched atypical kinase 1
Location	15q24.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA2002, sgk269
Ensembl gene	ENSG00000173517
Ensembl biotype	protein_coding
OMIM	614248
Entrez	79834

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000312493, ENST00000558305, ENST00000559791, ENST00000560626, ENST00000560854, ENST00000564328, ENST00000565820, ENST00000567337, ENST00000567808, ENST00000569159, ENST00000569692, ENST00000569819, ENST00000682557, ENST00000859358, ENST00000923571, ENST00000923572, ENST00000923573, ENST00000923574, ENST00000968026, ENST00000968027, ENST00000968028

RefSeq mRNA: 5 — MANE Select: NM_001385026 NM_001385026, NM_001385027, NM_001387085, NM_001387086, NM_024776

CCDS: CCDS42062

Canonical transcript exons

ENST00000682557 — 10 exons

Exon	Start	End
ENSE00001207555	77158503	77158696
ENSE00001207561	77178790	77182040
ENSE00001232978	77133005	77133750
ENSE00002539439	77252367	77252526
ENSE00002561611	77286423	77286504
ENSE00002564119	77365163	77365225
ENSE00002575896	77420006	77420104
ENSE00002578947	77283883	77284030
ENSE00002592570	77284958	77285055
ENSE00003917487	77108158	77115319

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 96.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.7902 / max 536.9256, expressed in 1802 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151041	16.6311	1747
151042	1.7814	1077
151044	1.4867	827
151043	1.1215	745
151046	0.3854	170
151045	0.3842	180

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of hip	UBERON:0001554	96.31	gold quality
visceral pleura	UBERON:0002401	96.31	gold quality
calcaneal tendon	UBERON:0003701	95.95	gold quality
sural nerve	UBERON:0015488	95.63	gold quality
parietal pleura	UBERON:0002400	95.55	gold quality
colonic epithelium	UBERON:0000397	94.59	gold quality
pleura	UBERON:0000977	93.99	gold quality
heart right ventricle	UBERON:0002080	93.98	gold quality
lower lobe of lung	UBERON:0008949	93.79	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.95	gold quality
tendon	UBERON:0000043	92.65	gold quality
trabecular bone tissue	UBERON:0002483	92.29	gold quality
corpus callosum	UBERON:0002336	92.20	gold quality
caput epididymis	UBERON:0004358	92.09	gold quality
germinal epithelium of ovary	UBERON:0001304	91.89	gold quality
postcentral gyrus	UBERON:0002581	91.63	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.62	gold quality
superficial temporal artery	UBERON:0001614	91.52	gold quality
medial globus pallidus	UBERON:0002477	91.47	gold quality
bronchial epithelial cell	CL:0002328	91.35	gold quality
secondary oocyte	CL:0000655	91.00	gold quality
globus pallidus	UBERON:0001875	90.87	gold quality
jejunal mucosa	UBERON:0000399	90.85	gold quality
nipple	UBERON:0002030	90.75	gold quality
colonic mucosa	UBERON:0000317	90.63	gold quality
stromal cell of endometrium	CL:0002255	90.61	gold quality
cauda epididymis	UBERON:0004360	90.56	gold quality
entorhinal cortex	UBERON:0002728	90.48	gold quality
parietal lobe	UBERON:0001872	90.34	gold quality
cartilage tissue	UBERON:0002418	90.29	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	25.16
E-ANND-3	yes	8.67
E-GEOD-110499	no	1500.41

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 23)

• Also known as SgK269. Contains a divergent and possibly inactive eukaryotic protein kinase domain. Has one human paralog, known as SgK223 or pragmin. These two constitute the NKF3 subfamily of protein kinases, found in vertebrates and echinoderms (PMID:12471243)
• Here, we report that the novel tyrosine kinase PEAK1 is upregulated in human malignancies, including human PDACs and pancreatic intraepithelial neoplasia (PanIN). (PMID:22589274)
• phosphorylation of tyrosine 665 in pseudopodium-enriched atypical kinase 1 (PEAK1) is essential for the regulation of cell migration and focal adhesion turnover (PMID:23105102)
• results define a novel signaling pathway in basal breast cancer involving Lyn and SgK269 that offers clinical opportunities for therapeutic intervention (PMID:23378338)
• eIF5A proteins utilize PEAK1 as a downstream effector to drive pancreatic ductal adenocarcinoma (PDAC) pathogenesis. (PMID:25261239)
• Suggest that loss of PEAK1/E-cadherin may play an important role in carcinogenesis and development of gastric cancer through activating epithelial to mesenchymal transition. (PMID:25445115)
• report is the first to provide evidence that PEAK1 mediates signaling cross talk between TGFbeta receptors and integrin/Src/MAPK pathways and that PEAK1 is an important molecular regulator of TGFbeta-induced tumor progression and metastasis in breast cancer (PMID:26267863)
• this regard, we have demonstrated that PEAK1 is necessary for TGFbeta to induce ZEB1-mediated EMT in the context of fibronectin/ITGB3 activation. (PMID:26297948)
• the critical role of the CH region in SgK269/SgK223 association. Importantly, although SgK269 bridged SgK223 to Grb2, it was unable to activate Stat3 or efficiently enhance migration in SgK223 knock-out cells generated by CRISPR/Cas9. (PMID:27531744)
• Findings indicate that eIF5A-PEAK1-YAP signaling contributes to PDAC development by regulating an STF program associated with increased tumorigenicity. (PMID:28381547)
• PEAK1’s kinase cleft is occluded, and its newly identified SHED region may promote an unexpected dimerization mode. Similarities of PEAK1 with the active kinase PINK1 may reclassify the latter as a member of the new kinase family 3 group. (PMID:29212708)
• PEAK1 protein level is increased during pancreatic ductal adenocarcinoma progression with the highest levels of expression observed in metastatic cell populations.Kras protein expression is controlled by a self-regulating feedforward mechanism mediated by eIF5A-PEAK1. (PMID:29321164)
• PEAK1 functions as a tumor promoter in colorectal cancer cells, and its expression is regulated by the EGFR/KRas signaling axis and miR-181d. (PMID:29449544)
• PEAK1 overexpression could induce epithelial-to-mesenchymal transition (EMT) and the expression of matrix metalloproteinase-2 (MMP2) and MMP9 both in vitro and in vivo, whereas PEAK1 knockout had the opposite effects. (PMID:30038287)
• PEAK1-PPP1R12B axis inhibits colorectal tumorigenesis and metastasis through deactivation of the Grb2/PI3K/Akt pathway. (PMID:30472186)
• AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion protein network. (PMID:32681075)
• LncRNA NORAD, sponging miR-363-3p, promotes invasion and EMT by upregulating PEAK1 and activating the ERK signaling pathway in NSCLC cells. (PMID:33742335)
• BioID-Screening Identifies PEAK1 and SHP2 as Components of the ALK Proximitome in Neuroblastoma Cells. (PMID:34273398)
• Pseudopodium enriched atypical kinase 1(PEAK1) promotes invasion and of melanoma cells by activating JAK/STAT3 signals. (PMID:34365903)
• PEAK1 promotes invasion and metastasis and confers drug resistance in breast cancer. (PMID:34554318)
• PEAK1 Y635 phosphorylation regulates cell migration through association with Tensin3 and integrins. (PMID:35687021)
• Clinical Significance of PEAK1 Expression and BRAF V600E Mutation in Papillary Thyroid Cancer. (PMID:35996515)
• Exosome-delivered circSATB2 targets the miR-330-5p/PEAK1 axis to regulate proliferation, migration and invasion of lung cancer cells. (PMID:36148757)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	peak1	ENSDARG00000079756
mus_musculus	Peak1	ENSMUSG00000074305
rattus_norvegicus	Peak1	ENSRNOG00000042519

Paralogs (3): PINK1 (ENSG00000158828), PEAK3 (ENSG00000188305), PRAG1 (ENSG00000275342)

Protein

Protein identifiers

Inactive tyrosine-protein kinase PEAK1 — Q9H792 (reviewed: Q9H792)

Alternative names: Pseudopodium-enriched atypical kinase 1, Sugen kinase 269, Tyrosine-protein kinase SgK269

All UniProt accessions (4): Q9H792, H0YN99, H3BUE6, H3BUZ5

UniProt curated annotations — full annotation on UniProt →

Function. Probable catalytically inactive kinase. Scaffolding protein that regulates the cytoskeleton to control cell spreading and migration by modulating focal adhesion dynamics. Acts as a scaffold for mediating EGFR signaling.

Subunit / interactions. Homodimer. Interacts with BCAR1 and CRK. Interacts with PRAG1. Interacts (when phosphorylated at Tyr-1188) with SHC1 (via PID domain). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1. Interacts (when phosphorylated at Tyr-635) with tensin TNS3 (when phosphorylated on the SH2 domain); TNS3 also interacts with integrins ITGB1, ITGB3 and ITGB5 and mediates their association with PEAK1. Interacts with RASAL2 and GRB2.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Focal adhesion.

Post-translational modifications. Phosphorylated on tyrosine in a CSK-dependent manner in response to adhesion to fibronectin and to EGF stimulation. Phosphorylation at Tyr-665 by a Src family kinase controls subcellular localization to focal adhesion and focal adhesion dynamics. Phosphorylation at Tyr-1188 is essential for binding to SHC1. Phosphorylation at Tyr-635 promotes interaction with tensin TNS3.

Domain organisation. The dimerization region encompasses helices both from the N- and C-terminal of the protein kinase domain.

Similarity. Belongs to the protein kinase superfamily.

RefSeq proteins (5): NP_001371955, NP_001371956, NP_001374014, NP_001374015, NP_079052 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR051511	MitoQC_Scaffold_Kinases	Family

Pfam: PF00069

UniProt features (97 total): helix 19, compositionally biased region 15, modified residue 14, sequence variant 13, region of interest 12, strand 8, mutagenesis site 7, sequence conflict 4, turn 3, chain 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6BHC	X-RAY DIFFRACTION	2.3
8DGM	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H792-F1	48.60	0.14

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 (14): 281, 540, 572, 587, 635, 641, 648, 665, 826, 854, 898, 1151, 1188, 1374

Mutagenesis-validated functional residues (7):

Position	Phenotype
635	50% reduction in interaction with grb2. no effect on interaction with shc1.
635	impairs interaction with tensin tns3 and association with integrin itgb1. 50% reduction in interaction with grb2. no eff
665	no effect on localization with actin. decreases localization in focal adhesion. fails to regulate focal adhesion dynamic
665	no effect on focal adhesion subcellular localization. does not affect colocalization with f-actin.
1188	fails to bind shc1. reduced recruitment of shc1 to focal adhesions. slightly reduces interaction with grb2. does not aff
1609	no effect on interaction with prag1.
1707	disrupts homodimerization.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013424	RHOV GTPase cycle

MSigDB gene sets: 263 (showing top): GCM_MAP4K4, GOBP_FOCAL_ADHESION_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, STARK_HYPPOCAMPUS_22Q11_DELETION_UP, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_REGULATION_OF_CELL_SUBSTRATE_ADHESION, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELL_MATRIX_ADHESION, GOBP_CELL_SUBSTRATE_ADHESION, GOBP_CELL_MATRIX_ADHESION, GOBP_PROTEIN_AUTOPHOSPHORYLATION

GO Biological Process (7): cell migration (GO:0016477), substrate adhesion-dependent cell spreading (GO:0034446), protein autophosphorylation (GO:0046777), focal adhesion assembly (GO:0048041), regulation of focal adhesion assembly (GO:0051893), regulation of cell motility (GO:2000145), protein phosphorylation (GO:0006468)

GO Molecular Function (5): protein kinase activity (GO:0004672), non-membrane spanning protein tyrosine kinase activity (GO:0004715), identical protein binding (GO:0042802), protein binding (GO:0005515), ATP binding (GO:0005524)

GO Cellular Component (6): cytosol (GO:0005829), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell motility	2
cellular anatomical structure	2
cell-substrate adhesion	1
protein phosphorylation	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of cell-substrate junction assembly	1
regulation of locomotion	1
regulation of cellular process	1
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein tyrosine kinase activity	1
protein binding	1
binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cytoplasm	1
cell-substrate junction	1
cytoskeleton	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cell junction	1

Protein interactions and networks

STRING

636 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEAK1	EIF5A	P10159	727
PEAK1	SHC1	P29353	727
PEAK1	DOHH	Q9BU89	540
PEAK1	DHPS	P49366	506
PEAK1	STRADA	Q7RTN6	497
PEAK1	STKLD1	Q8NE28	497
PEAK1	EIF5AL1	Q6IS14	477
PEAK1	EPHA10	Q5JZY3	460
PEAK1	ULK4	Q96C45	456
PEAK1	MLKL	Q8NB16	444
PEAK1	EPHB6	O15197	438
PEAK1	FAM20A	Q96MK3	418
PEAK1	PAN3	Q58A45	410
PEAK1	PRKCA	P17252	408
PEAK1	EIF5A2	Q9GZV4	395

IntAct

141 interactions, top by confidence:

A	B	Type	Score
S100B	S100A4	psi-mi:“MI:0914”(association)	0.870
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
SHC1	AP2A1	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
ZMYND19	TNFAIP1	psi-mi:“MI:0914”(association)	0.670
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
CSK	TNS3	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
CARNMT1	NUP42	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CRK	ARHGAP42	psi-mi:“MI:0914”(association)	0.530

BioGRID (202): PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Proximity Label-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Affinity Capture-MS), PEAK1 (Proximity Label-MS)

ESM2 similar proteins: A0A140LFM6, A0A1B0GVH6, A0A1L8H8C0, A0A2K1JJ00, A0JMD2, A2ARZ3, A2AWL7, A4IGV6, A6H5Y1, D3ZJ47, E9Q309, F1QPR4, F5H4B4, H0WFA5, O14513, O35413, O94875, P0CAX8, P48437, Q12912, Q15468, Q1LXZ9, Q1X8D7, Q28FG2, Q3UTJ2, Q3ZBS1, Q499E5, Q49A88, Q4V7H1, Q5T5U3, Q5VT06, Q62417, Q62770, Q69Z38, Q6DFB0, Q80TY4, Q8BLN6, Q8CB14, Q8IWI9, Q8K0T7

Diamond homologs: D3ZMK9, Q571I4, Q69Z38, Q86YV5, Q9BXM7, Q9H792, D6WMX4, Q4V7Q6, E0W1I1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 151 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 BAD and translocation to mitochondria	7	45.5×	6e-09
Erythropoietin activates RAS	7	45.5×	6e-09
SHC1 events in EGFR signaling	7	42.7×	8e-09
Constitutive Signaling by EGFRvIII	7	42.7×	8e-09
Signalling to RAS	7	40.2×	9e-09
Insulin receptor signalling cascade	7	40.2×	9e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	40.2×	9e-09
Signaling by ERBB2 ECD mutants	7	40.2×	9e-09

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of Rac protein signal transduction	6	28.8×	1e-05
peptidyl-tyrosine phosphorylation	7	21.9×	1e-05
ephrin receptor signaling pathway	7	17.8×	3e-05
protein targeting	5	13.6×	2e-03
substantia nigra development	5	13.6×	2e-03
insulin receptor signaling pathway	8	13.1×	3e-05
protein autophosphorylation	12	12.9×	2e-07
epidermal growth factor receptor signaling pathway	6	11.0×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	238
Likely benign	24
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
369835	GRCh37/hg19 15q22.1-26.3(chr15:59297293-102480888)x3	Likely pathogenic

SpliceAI

4106 predictions. Top by Δscore:

Variant	Effect	Δscore
15:77133747:TGCC:T	acceptor_gain	1.0000
15:77158498:CTTA:C	donor_loss	1.0000
15:77158499:TTAC:T	donor_loss	1.0000
15:77158500:TA:T	donor_loss	1.0000
15:77158501:A:AC	donor_gain	1.0000
15:77158501:A:C	donor_loss	1.0000
15:77158502:C:CC	donor_gain	1.0000
15:77158502:CCTAA:C	donor_gain	1.0000
15:77158658:C:CT	acceptor_gain	1.0000
15:77158658:C:T	acceptor_gain	1.0000
15:77158659:G:T	acceptor_gain	1.0000
15:77158692:TGTGA:T	acceptor_gain	1.0000
15:77158693:GTGA:G	acceptor_gain	1.0000
15:77158694:TGA:T	acceptor_gain	1.0000
15:77158695:GA:G	acceptor_gain	1.0000
15:77158697:C:CC	acceptor_gain	1.0000
15:77219583:T:TA	donor_gain	1.0000
15:77252365:A:AC	donor_gain	1.0000
15:77252366:C:CC	donor_gain	1.0000
15:77252366:CT:C	donor_gain	1.0000
15:77252366:CTA:C	donor_gain	1.0000
15:77252386:T:TA	donor_gain	1.0000
15:77252432:T:A	donor_gain	1.0000
15:77252522:GTTTA:G	acceptor_gain	1.0000
15:77252523:TTTA:T	acceptor_gain	1.0000
15:77252524:TTA:T	acceptor_gain	1.0000
15:77252525:TA:T	acceptor_gain	1.0000
15:77252527:C:CC	acceptor_gain	1.0000
15:77255310:A:AC	donor_gain	1.0000
15:77255319:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000013848 (15:77187434 A>G), RS1000020921 (15:77194829 C>G), RS1000076746 (15:77387652 G>A), RS1000086462 (15:77279559 G>A,T), RS1000090955 (15:77324929 C>T), RS1000098810 (15:77132643 C>T), RS1000099445 (15:77245516 T>G), RS1000104968 (15:77130391 C>T), RS1000122909 (15:77407845 T>C), RS1000127538 (15:77412708 T>C,G), RS1000138683 (15:77158776 C>T), RS1000139034 (15:77155045 G>C), RS1000173437 (15:77392119 T>C,G), RS1000177299 (15:77106558 G>A), RS1000189564 (15:77153269 A>G)

Disease associations

OMIM: gene MIM:614248 | 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
GCST010002_100	Refractive error	1.000000e-09
GCST012227_519	Hip circumference adjusted for BMI	2.000000e-08
GCST012490_52	Femur bone mineral density x serum urate levels interaction	2.000000e-11
GCST90020028_1751	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3627585 (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
8.69	IC50	2.03	nM	STAUROSPORINE
8.57	IC50	2.69	nM	STAUROSPORINE
8.52	IC50	3.04	nM	STAUROSPORINE
6.21	IC50	620	nM	CHEMBL5279425

PubChem BioAssay actives

4 with measured affinity, of 24 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
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715222: Inhibition of human PEAK1 using MBP as substrate by [gamma-33P]-ATP assay	ic50	0.0020	uM
2,3-dihydro-1,4-benzodioxin-6-yl-(1-thieno[2,3-d]pyrimidin-4-ylpiperidin-4-yl)methanone	1944346: Inhibition of PEAK1 (unknown origin)	ic50	0.6200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
Cisplatin	affects cotreatment, decreases expression	3
Aflatoxin B1	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	affects phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	increases expression, affects cotreatment, 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
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	increases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3631912	Binding	Inhibition of PEAK1 (unknown origin) at 10 uM after 120 mins P33 radiolabeled kinase activity assay	Crystal structures of human RIP2 kinase catalytic domain complexed with ATP-competitive inhibitors: Foundations for understanding inhibitor selectivity. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TC89	HAP1 PEAK1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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