ALPK1

Summary

ALPK1 (alpha kinase 1, HGNC:20917) is a protein-coding gene on chromosome 4q25, encoding Alpha-protein kinase 1 (Q96QP1). Serine/threonine-protein kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity.

This gene encodes an alpha kinase. Mice which were homozygous for disrupted copies of this gene exhibited coordination defects (PMID: 21208416). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 80216 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (Strong, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 961 total — 2 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 10
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_025144

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20917
Approved symbol	ALPK1
Name	alpha kinase 1
Location	4q25
Locus type	gene with protein product
Status	Approved
Aliases	Lak, FLJ22670, KIAA1527
Ensembl gene	ENSG00000073331
Ensembl biotype	protein_coding
OMIM	607347
Entrez	80216

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 10 protein_coding, 7 protein_coding_CDS_not_defined, 5 retained_intron, 3 nonsense_mediated_decay

ENST00000177648, ENST00000426472, ENST00000458497, ENST00000502366, ENST00000504176, ENST00000504488, ENST00000504745, ENST00000505127, ENST00000505176, ENST00000505912, ENST00000508589, ENST00000509209, ENST00000509688, ENST00000509722, ENST00000512847, ENST00000514594, ENST00000515106, ENST00000515330, ENST00000650871, ENST00000909430, ENST00000909431, ENST00000909432, ENST00000909433, ENST00000909434, ENST00000951187

RefSeq mRNA: 3 — MANE Select: NM_025144 NM_001102406, NM_001253884, NM_025144

CCDS: CCDS3697, CCDS58923

Canonical transcript exons

ENST00000650871 — 16 exons

Exon	Start	End
ENSE00001482792	112315801	112315852
ENSE00002042037	112297369	112297469
ENSE00003463623	112426467	112426543
ENSE00003467293	112430448	112432581
ENSE00003517438	112427570	112427665
ENSE00003540295	112423944	112424003
ENSE00003551265	112411827	112412025
ENSE00003570073	112435148	112435301
ENSE00003611499	112429149	112429253
ENSE00003652287	112438484	112438646
ENSE00003676531	112440917	112441105
ENSE00003688989	112439686	112439872
ENSE00003693508	112425665	112425751
ENSE00003842474	112441203	112442621
ENSE00003891627	112382398	112382552
ENSE00003895233	112377678	112377898

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 97.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.8237 / max 766.6073, expressed in 1544 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49288	9.9969	1519
49286	0.4690	166
49289	0.2602	98
49287	0.0686	25
49290	0.0290	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.99	gold quality
tendon of biceps brachii	UBERON:0008188	94.66	silver quality
blood	UBERON:0000178	91.81	gold quality
tendon	UBERON:0000043	90.00	gold quality
pancreatic ductal cell	CL:0002079	89.94	silver quality
monocyte	CL:0000576	88.32	gold quality
calcaneal tendon	UBERON:0003701	88.25	gold quality
mononuclear cell	CL:0000842	88.17	gold quality
leukocyte	CL:0000738	87.94	gold quality
choroid plexus epithelium	UBERON:0003911	87.08	silver quality
mucosa of stomach	UBERON:0001199	86.91	gold quality
spleen	UBERON:0002106	86.57	gold quality
sural nerve	UBERON:0015488	86.47	gold quality
skin of abdomen	UBERON:0001416	86.36	gold quality
right lung	UBERON:0002167	86.34	gold quality
olfactory bulb	UBERON:0002264	86.28	silver quality
skin of leg	UBERON:0001511	85.86	gold quality
tibial nerve	UBERON:0001323	85.77	gold quality
gluteal muscle	UBERON:0002000	85.69	silver quality
descending thoracic aorta	UBERON:0002345	85.67	gold quality
type B pancreatic cell	CL:0000169	85.58	gold quality
minor salivary gland	UBERON:0001830	85.42	gold quality
lower esophagus mucosa	UBERON:0035834	85.42	gold quality
left ovary	UBERON:0002119	85.31	gold quality
right uterine tube	UBERON:0001302	85.00	gold quality
upper lobe of left lung	UBERON:0008952	84.90	gold quality
right ovary	UBERON:0002118	84.76	gold quality
right coronary artery	UBERON:0001625	84.75	gold quality
bone marrow	UBERON:0002371	84.61	gold quality
lower esophagus	UBERON:0013473	84.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	13.78
E-ANND-3	yes	6.10
E-CURD-112	no	2.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting ALPK1, 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-6798-5P	100.00	65.77	699
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4255	99.72	67.70	1541
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-657	99.48	66.02	848
HSA-MIR-135A-5P	99.36	71.85	1601
HSA-MIR-135B-5P	99.36	71.63	1613
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-4727-5P	99.23	67.55	1154

Literature-anchored findings (GeneRIF, showing 20)

• the phosphorylation of myosin I by ALPK1 is an essential process in the apical trafficking of raft-associated sucrose-isomaltase (PMID:15883161)
• Transposon-inserted Alpk1 homozygous mutant mice display severe defects in motor coordination in a series of behavioral analyses. (PMID:21208416)
• ALPK1 is a gout-susceptible gene involved in Monosodium urate monohydrate-induced inflammatory responses and may contribute to the development of gout by enhancing the inflammatory responses via the MAP kinase pathway (PMID:21822924)
• ALPK1 may be a susceptibility gene for chronic kidney disease in such individuals with diabetes mellitus. (PMID:23539754)
• single nucleotide polymorphisms in the alpha-protein kinase 1 (ALPK1) gene are associated with gout in Han Chinese Taiwanese. (PMID:23569188)
• findings suggest that among genes in a gout-susceptibility locus, not ALPK1 but ABCG2 could be important as a gout-susceptible gene (PMID:25326865)
• ALPK1 is a kinase that participates in the regulation of Golgi-derived TNF-alpha trafficking through myosin IIA phosphorylation in the inflammation of gout. (PMID:27169898)
• In lung and colorectal cancer tissues, the ALPK1 RNA level of the normal part was higher than that of the tumor part. these findings suggested that ALPK1 might play a vital role in cancer development. (PMID:27283888)
• ERN1 and ALPK1 inhibit differentiation of bi-potential tumor-initiating cells in human triple negative breast cancer. (PMID:27829216)
• these results clearly show that ALPK1 is a master regulator of innate immunity against both invasive and extracellular gram-negative bacteria. (PMID:28222186)
• Combined exposure to the four high-risk genotypes of ALPK1 and the uric-acid-related loci of ABCG2, SLC2A9, and SLC22A12 was associated with an increased gout risk and a high PPV for gout. (PMID:29215084)
• ALPK1 serves as a potential biomarker and target for OSCC development in late stages. (PMID:30315765)
• Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder. (PMID:30967659)
• Study reveals alterations of the CYLD gene in 15/15 cylindromas and 5/17 spiradenomas, yet only 2/24 spiradenocarcinomas. Also, a recurrent missense mutation found in the kinase domain of the ALPK1 gene in spiradenomas and spiradenocarcinomas, which is mutually exclusive from mutation of CYLD and can activate the NF-kappaB pathway in reporter assays. (PMID:31101826)
• REVIEW: various mechanisms and pathways involved in H. pylori induction of NF-kappaB-dependent responses in gastric epithelial cells, including a ‘state-of-the-art’ review on the respective roles of NOD1 and ALPK1/TIFA pathways in these responses (PMID:31123889)
• ALPK1 regulates streptozotocin-induced nephropathy through CCL2 and CCL5 expressions. (PMID:31557402)
• Juvenile Onset Splenomegaly and Oculopathy Due to Germline Mutation in ALPK1. (PMID:31939038)
• The ALPK1/TIFA/NF-kappaB axis links a bacterial carcinogen to R-loop-induced replication stress. (PMID:33037203)
• The Role of ALPK1 in Inhibiting Hepatitis B Virus Replication Facilitates the Identification of ALPK1 P660L Variant for Predicting Response to Pegylated Interferon alpha Therapy. (PMID:36932045)
• The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis. (PMID:38494837)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Alpk1	ENSMUSG00000028028
rattus_norvegicus	Alpk1	ENSRNOG00000022636

Paralogs (4): EEF2K (ENSG00000103319), HSPA12B (ENSG00000132622), HSPA12A (ENSG00000165868), ALPK2 (ENSG00000198796)

Protein

Protein identifiers

Alpha-protein kinase 1 — Q96QP1 (reviewed: Q96QP1)

Alternative names: Chromosome 4 kinase, Lymphocyte alpha-protein kinase

All UniProt accessions (4): Q96QP1, B3KUH8, B4E0R2, D6RB29

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity. Specifically recognizes and binds ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria. ADP-Heptose-binding stimulates its kinase activity to phosphorylate and activate TIFA, triggering pro-inflammatory NF-kappa-B signaling. May be involved in monosodium urate monohydrate (MSU)-induced inflammation by mediating phosphorylation of unconventional myosin MYO9A. May also play a role in apical protein transport by mediating phosphorylation of unconventional myosin MYO1A. May play a role in ciliogenesis.

Subcellular location. Cytoplasm. Cytosol. Cytoskeleton. Spindle pole. Microtubule organizing center. Centrosome. Cell projection. Cilium.

Tissue specificity. Highly expressed in liver. Expressed in the optic nerve and retinal pigmented epithelium. Lower expression is observed in the macula and extramacular retina.

Disease relevance. Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (ROSAH) [MIM:614979] An autosomal dominant disorder characterized by decreased vision associated with optic nerve edema, evident in childhood. Low-grade ocular inflammation is common in affected individuals. Later in childhood or the second decade of life, patients have increasing visual impairment, abnormal cone function and loss of rod function. By the third decade of life, visual acuity ranges from counting fingers to no light perception. Patients also show anhidrosis, splenomegaly, mild pancytopenia, and most experience headaches that may be migraine-like in nature. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Serine/threonine-protein kinase activity is stimulated upon ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose)-binding.

Similarity. Belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96QP1-1	1	yes
Q96QP1-2	2

RefSeq proteins (3): NP_001095876, NP_001240813, NP_079420* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004166	a-kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR043529	ALPK1	Family

Pfam: PF02816

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (82 total): sequence variant 24, helix 22, mutagenesis site 10, binding site 8, region of interest 4, compositionally biased region 4, turn 3, sequence conflict 2, strand 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9J4P	X-RAY DIFFRACTION	2.25
8ZD3	X-RAY DIFFRACTION	2.3
5Z2C	X-RAY DIFFRACTION	2.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QP1-F1	66.24	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.

Ligand- & substrate-binding residues (8): 61; 67; 116; 150–153; 231; 233; 236–237; 295

Mutagenesis-validated functional residues (10):

Position	Phenotype
67	impaired adp-d-glycero-beta-d-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity
116	impaired adp-d-glycero-beta-d-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity
150	impaired adp-d-glycero-beta-d-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity
153	impaired adp-d-glycero-beta-d-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity
231	impaired adp-d-glycero-beta-d-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity
233	impaired adp-d-glycero-beta-d-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity
237	impaired adp-d-glycero-beta-d-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity
295	impaired adp-d-glycero-beta-d-manno-heptose-binding and ability to activate the serine/threonine-protein kinase activity
1067	abolishes the serine/threonine-protein kinase and ability to initiate the innate immune response.
1092	the mutant is constitutively active in absence of adp-heptose. activated by udp-alpha-d-mannose and adp-d-ribose.

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-9645460	Alpha-protein kinase 1 signaling pathway
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058	MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-168138	Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168142	Toll Like Receptor 10 (TLR10) Cascade
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168176	Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168179	Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168181	Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168188	Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-181438	Toll Like Receptor 2 (TLR2) Cascade
R-HSA-446652	Interleukin-1 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-9020702	Interleukin-1 signaling
R-HSA-937061	TRIF (TICAM1)-mediated TLR4 signaling
R-HSA-975138	TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975155	MyD88 dependent cascade initiated on endosome
R-HSA-975871	MyD88 cascade initiated on plasma membrane

MSigDB gene sets: 151 (showing top): chr4q25, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, AAGCCAT_MIR135A_MIR135B, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_ORGANELLE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS

GO Biological Process (7): cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), innate immune response (GO:0045087), cilium assembly (GO:0060271), immune system process (GO:0002376), protein phosphorylation (GO:0006468), cell projection organization (GO:0030030)

GO Molecular Function (7): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), monosaccharide binding (GO:0048029), protein serine kinase activity (GO:0106310), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): spindle pole (GO:0000922), centrosome (GO:0005813), cytosol (GO:0005829), cilium (GO:0005929), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Toll-like Receptor Cascades	7
Innate Immune System	2
Immune System	2
Toll Like Receptor 4 (TLR4) Cascade	2
Toll Like Receptor 2 (TLR2) Cascade	2
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
Toll Like Receptor 3 (TLR3) Cascade	1
Interleukin-1 signaling	1
TRIF (TICAM1)-mediated TLR4 signaling	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1
MyD88 cascade initiated on plasma membrane	1
Toll Like Receptor TLR1:TLR2 Cascade	1
Toll Like Receptor TLR6:TLR2 Cascade	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein kinase activity	2
microtubule organizing center	2
positive regulation of cytokine production	1
pattern recognition receptor signaling pathway	1
intracellular receptor signaling pathway	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
immune response	1
defense response to symbiont	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
biological_process	1
phosphorylation	1
protein modification process	1
cellular component organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
carbohydrate binding	1
small molecule binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
spindle	1
centriole	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

423 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALPK1	TIFA	Q96CG3	770
ALPK1	ALPK2	Q86TB3	570
ALPK1	NOD1	Q9Y239	539
ALPK1	MYO1A	Q9UBC5	481
ALPK1	ALPK3	Q96L96	480
ALPK1	TNF	P01375	456
ALPK1	TLR4	O00206	455
ALPK1	MYO1B	O43795	454
ALPK1	EEF2K	O00418	432
ALPK1	TLR2	O60603	427
ALPK1	LARP7	Q4G0J3	412
ALPK1	AGMO	Q6ZNB7	407
ALPK1	CABP5	Q9NP86	384
ALPK1	SGCZ	Q96LD1	379
ALPK1	FAM78B	Q5VT40	370

IntAct

10 interactions, top by confidence:

A	B	Type	Score
ALPK1	SCGB1D2	psi-mi:“MI:0915”(physical association)	0.400
YWHAE	ALPK1	psi-mi:“MI:0915”(physical association)	0.400
SFN	ALPK1	psi-mi:“MI:0915”(physical association)	0.400
ALPK1	ALOXE3	psi-mi:“MI:0915”(physical association)	0.400
ALPK1	CD1B	psi-mi:“MI:0915”(physical association)	0.400
ALPK1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): ALOXE3 (Affinity Capture-MS), ALPK1 (Affinity Capture-MS), SCGB1D2 (Affinity Capture-MS), ALOXE3 (Affinity Capture-MS), ALPK1 (Affinity Capture-MS), CD1B (Affinity Capture-MS), ALPK1 (Biochemical Activity), TIFA (Biochemical Activity), ALPK1 (Affinity Capture-MS), ALPK1 (Affinity Capture-RNA), ALPK1 (Proximity Label-MS), ALPK1 (Dosage Lethality), ALPK1 (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0JMF7, A1L2Y1, A2ALV5, A9JRX0, B2GUZ2, D3ZSP7, F1QB81, O35892, O70608, O75113, P23497, P70347, Q0P5X5, Q13129, Q16533, Q2T9I9, Q3U1D0, Q5CZC0, Q5H9M0, Q5REF4, Q5RHB5, Q5SW75, Q5T4T6, Q5T5J6, Q5XG69, Q5ZLE9, Q60664, Q63HN8, Q7M6U3, Q7Z4H7, Q80VH0, Q8BVK9, Q8C263, Q8CCC3, Q8NA03, Q90WN7, Q92844, Q96QP1

Diamond homologs: O00418, O01991, O08796, P42527, P70531, P90648, Q54DK4, Q54SF9, Q6B9X6, Q6FLI3, Q8CIR4, Q8MY12, Q923J1, Q925B3, Q96QP1, Q96QT4, Q9BX84, Q9CXB8, Q86TB3, Q91ZB0, O95081, P52594, Q2TA45, Q4KLH5, Q80WC7, Q8K2K6, Q9FL69, A2QP30, A7TNS8, P87060, Q924C5, Q96L96, A7T1N0, A8DYE2, J9SQF3, Q2TV84, Q2WEA5, Q7Z4N2, Q93971, Q9HCF6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ALPK1	“up-regulates activity”	TIFA	phosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PAAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	554
Likely benign	259
Benign	58

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2578014	NM_025144.4(ALPK1):c.761A>G (p.Tyr254Cys)	Pathogenic
619031	NM_025144.4(ALPK1):c.710C>T (p.Thr237Met)	Pathogenic
145621	GRCh38/hg38 4q25-26(chr4:111069785-116691879)x1	Likely pathogenic
1527117	GRCh37/hg19 4q25-26(chr4:112849108-115434557)	Likely pathogenic
2500791	NC_000004.12:g.110650730_112833790del	Likely pathogenic
3367191	NM_025144.4(ALPK1):c.830C>T (p.Ser277Phe)	Likely pathogenic

SpliceAI

3360 predictions. Top by Δscore:

Variant	Effect	Δscore
4:112285636:GTACC:G	donor_loss	1.0000
4:112285637:TAC:T	donor_loss	1.0000
4:112285638:ACC:A	donor_loss	1.0000
4:112377895:AGAG:A	donor_loss	1.0000
4:112377897:AGG:A	donor_loss	1.0000
4:112377900:T:A	donor_loss	1.0000
4:112412024:AGGTA:A	donor_loss	1.0000
4:112412026:G:GA	donor_loss	1.0000
4:112412027:T:A	donor_loss	1.0000
4:112425748:C:G	donor_gain	1.0000
4:112435298:G:T	donor_gain	1.0000
4:112435299:G:GT	donor_gain	1.0000
4:112438481:TA:T	acceptor_loss	1.0000
4:112438482:A:AC	acceptor_loss	1.0000
4:112438482:AG:A	acceptor_gain	1.0000
4:112438483:G:GT	acceptor_loss	1.0000
4:112438483:GG:G	acceptor_gain	1.0000
4:112438483:GGT:G	acceptor_gain	1.0000
4:112438483:GGTAT:G	acceptor_gain	1.0000
4:112438643:ACTGG:A	donor_loss	1.0000
4:112438644:CTGG:C	donor_loss	1.0000
4:112438645:TGG:T	donor_loss	1.0000
4:112438647:G:GG	donor_gain	1.0000
4:112438647:G:T	donor_loss	1.0000
4:112438648:T:G	donor_loss	1.0000
4:112439683:CA:C	acceptor_loss	1.0000
4:112439684:A:AG	acceptor_gain	1.0000
4:112439684:A:C	acceptor_loss	1.0000
4:112439685:G:GG	acceptor_gain	1.0000
4:112439870:AAGGT:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000013793 (4:112361341 A>G), RS1000031853 (4:112426836 C>T), RS1000033957 (4:112308419 C>T), RS1000065467 (4:112318428 G>A), RS10000890 (4:112300813 T>G), RS1000104438 (4:112320544 T>C), RS1000149565 (4:112375716 C>A), RS1000151961 (4:112439971 G>A), RS1000155365 (4:112312464 G>A), RS1000189545 (4:112406718 G>A,T), RS1000195591 (4:112405612 G>A), RS10002070 (4:112358310 A>G,T), RS1000220350 (4:112433128 C>A,G), RS1000244243 (4:112339305 C>A), RS1000256802 (4:112398956 A>C,G)

Disease associations

OMIM: gene MIM:607347 | disease phenotypes: MIM:614979, MIM:180500

GenCC curated gene-disease

Disease	Classification	Inheritance
retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome	Strong	Autosomal dominant

Mondo (2): retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome (MONDO:0013999), Axenfeld-Rieger syndrome type 1 (MONDO:0008386)

Orphanet (2): Retinal dystrophy-optic nerve edema-splenomegaly-anhidrosis-migraine headache syndrome (Orphanet:313800), Axenfeld-Rieger syndrome (Orphanet:782)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000548	Cone/cone-rod dystrophy
HP:0000572	Visual loss
HP:0000970	Anhidrosis
HP:0001025	Urticaria
HP:0001744	Splenomegaly
HP:0001876	Pancytopenia
HP:0001954	Recurrent fever
HP:0002076	Migraine
HP:0003621	Juvenile onset

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001175_2	Epirubicin-induced leukopenia	3.000000e-06
GCST001475_4	Obesity	1.000000e-06
GCST004904_258	Body mass index	1.000000e-08
GCST010701_20	Cortical surface area (MOSTest)	1.000000e-242
GCST010702_74	Subcortical volume (MOSTest)	2.000000e-11
GCST010703_129	Brain morphology (MOSTest)	3.000000e-08
GCST010988_76	Adult body size	1.000000e-08
GCST90006993_7	Gut microbiota relative abundance (unclassified genus belonging to the order Clostridiales)	3.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004346	neuroimaging measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Other alpha kinase family kinases

Binding affinities (BindingDB)

475 measured of 475 human assays (475 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(4-(2-(4- chlorophenyl)but-3- yn-2-yl)thiazol-2-yl)- 2,6-difluoro-4- (piperazin-1- yl)benzamide	IC50	3.7 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(S)-1-(4-(2-(4- bromophenyl)but-3-yn- 2-yl)thiazol-2-yl)urea	IC50	4 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(S)-N-(4-(2-(4- chlorophenyl)but-3- yn-2-yl)thiazol-2-yl)- 2,6-difluoro-4- (piperazin-1- yl)benzamide	IC50	5 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-[4-[(2S)-2-(4-chlorophenyl)but-3-yn-2-yl]-1,3-thiazol-2-yl]-3-(2-hydroxyethyl)urea	IC50	5.4 nM	US-20250381196: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING KIDNEY DISEASES AND KIDNEY-RELATED DISEASES
2,6-difluoro-N-(4-(2- (4- fluorophenyl)propan- 2-yl)thiazol-2-yl)-4- (piperazin-1- yl)benzamide	IC50	6 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(S)-N-(4-(2-(4- bromophenyl)but-3-yn- 2-yl)thiazol-2-yl)-3- (hydroxymethyl)azetidine- 1-carboxamide	IC50	7 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-((2-(3- aminopyrrolidin-1- yl)pyrimidin-5- yl)methyl)-3-(4-(2-(4- methoxyphenyl)propan- 2-yl)thiazol-2-yl)urea	IC50	7 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
N-(4-(2-(4- bromophenyl)but-3-yn- 2-yl)thiazol-2-yl)-3-(4- (piperazin-1- yl)phenyl)azetidine-1- carboxamide	IC50	7 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
N-(4-(2-(4- chlorophenyl)but-3- yn-2-yl)thiazol-2-yl)- 2,6-difluoro-4-(4- methylpiperazin-1- yl)benzamide	IC50	7 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
2,6-difluoro-N-[4-[1- methyl-1-(p- tolyl)prop-2- ynyl]thiazol-2-yl]-4- piperazin-1-yl- benzamide	IC50	7 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
4-((3-(4-(2-(4- bromophenyl)propan-2- yl)thiazol-2- yl)ureido)methyl)benz- mide	IC50	8 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
5-((3-(4-(2-(4- methoxyphenyl)propan- 2-yl)thiazol-2- yl)ureido)methyl)-2- (piperazin-1- yl)benzamide	IC50	8 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-((2-(3- aminopyrrolidin-1- yl)pyrimidin-5- yl)methyl)-3-(4-(2-(4- bromophenyl)propan-2- yl)thiazol-2-yl)urea	IC50	8 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(S)-1-(2-hydroxyethyl)- 3-(4-(2-(4- methoxyphenyl)but-3- yn-2-yl)thiazol-2- yl)urea	IC50	8 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(S)-1-(4-(2-(4- methoxyphenyl)but-3- yn-2-yl)thiazol-2- yl)urea	IC50	8 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(S)-N-(4-(2-(4- chlorophenyl)-1- methoxypropan-2- yl)thiazol-2-yl)-2,6- difluoro-4-(piperazin- 1-yl)benzamide	IC50	8 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- bromophenyl)propan-2- yl)thiazol-2-yl)-3-((5- (piperazin-1-yl)pyrazin- 2-yl)methyl)urea	IC50	9 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(4-aminopiperidin- 1-yl)benzyl)-3-(4-(2-(4- bromophenyl)propan-2- yl)thiazol-2-yl)urea	IC50	9 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- bromophenyl)propan-2- yl)thiazol-2-yl)-3-(4- (3,5-dimethylpiperazin- 1-yl)benzyl)urea	IC50	9 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(S)-1-(4-(2-(4- bromophenyl)but-3-yn- 2-yl)thiazol-2-yl)-3-(2- hydroxyethyl)urea	IC50	10 nM	US-20250381196: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING KIDNEY DISEASES AND KIDNEY-RELATED DISEASES
1-[4-[1-(4- chlorophenyl)-1-methyl- prop-2-ynyl]thiazol-2- yl]-3-(2,2-dideuterio-2- hydroxy-ethyl)urea	IC50	10 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(R)-N-(4-(2-(4- chlorophenyl)but-3- yn-2-yl)thiazol-2-yl)- 2,6-difluoro-4- (piperazin-1- yl)benzamide	IC50	10 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
N-(4-(1-(4- chlorophenyl)ethyl)thi- azol-2-yl)-2,6- difluoro-4-(piperazin- 1-yl)benzamide	IC50	11 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
N-(4-(2-(4-chlorophenyl)but- 3-yn-2-yl)thiazol-2-yl)-4- (piperazin-1-yl)benzamide	IC50	12 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- chlorophenyl)but-3-yn- 2-yl)thiazol-2-yl)-3-(2- cyanoethyl)urea	IC50	13 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- bromophenyl)propan-2- yl)thiazol-2-yl)-3-((2- (piperazin-1- yl)pyrimidin-5- yl)methyl)urea compound with methane (1:1)	IC50	13 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-((2-(4-aminopiperidin- 1-yl)pyrimidin-5- yl)methyl)-3-(4-(2-(4- bromophenyl)propan-2- yl)thiazol-2-yl)urea	IC50	13 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
N-(4-(1-(4- bromophenyl)cyclopent- yl)thiazol-2-yl)-3-(3- fluoro-4-(piperazin-1- yl)phenyl)azetidine-1- carboxamide	IC50	13 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- chlorophenyl)but-3-yn- 2-yl)thiazol-2-yl)-3-(3- fluoro-4-(piperazin-1- yl)benzyl)urea	IC50	13 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(4-aminopiperidin- 1-yl)benzyl)-3-(4-(1-(4- bromophenyl)cyclopent- yl)thiazol-2-yl)urea	IC50	15 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
4-((3-(4-(2-(4-methoxy- phenyl)propan-2-yl)thiazol- 2-yl)ureido)methyl)-N- (piperidin-4-yl)benzamide	IC50	15 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- methoxyphenyl)propan- 2-yl)thiazol-2-yl)-3-((2- (piperazin-1- yl)pyrimidin-5- yl)methyl)urea	IC50	16 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- methoxyphenyl)but-3- yn-2-yl)thiazol-2- yl)urea	IC50	16 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
S)-N-(4-(2-(4- chlorophenyl)but-3-yn- 2-yl)thiazol-2-yl)-3-(3- fluoro-4-(piperazin-1- yl)phenyl)azetidine-1- carboxamide	IC50	16 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
N-(4-(2-(4- chlorophenyl)-1- methoxypropan-2- yl)thiazol-2-yl)-2,6- difluoro-4-(piperazin- 1-yl)benzamide	IC50	16 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
2,6-difluoro-N-[4-[(2S)-2-(4-methoxyphenyl)but-3-yn-2-yl]-1,3-thiazol-2-yl]-4-piperazin-1-ylbenzamide	IC50	16 nM	US-20250381196: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING KIDNEY DISEASES AND KIDNEY-RELATED DISEASES
2,6-difluoro-N-(4-(2- (4- methoxyphenyl)but-3- yn-2-yl)thiazol-2-yl)- 4-(piperazin-1- yl)benzamide	IC50	16 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-((2-((2- aminoethyl)amino)pyri- midin-5-yl)methyl)-3- (4-(2-(4- bromophenyl)propan-2- yl)thiazol-2-yl)urea	IC50	17 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(R)-1-(4-(2-(4- bromophenyl)but-3-yn- 2-yl)thiazol-2-yl)urea	IC50	17 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
N-(4-(2-(4-chloro-3- fluorophenyl)but-3- yn-2-yl)thiazol-2-yl)- 2,6-difluoro-4- (piperazin-1- yl)benzamide	IC50	17 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-((2- aminoethyl)amino)-3- fluorobenzyl)-3-(4-(2- (4-bromophenyl)propan- 2-yl)thiazol-2-yl)urea	IC50	18 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
(S)-N-(4-(2-(4- chlorophenyl)but-3- yn-2-yl)thiazol-2-yl)- 2,6-difluoro-4-(4- methylpiperazin-1- yl)benzamide	IC50	18 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
N-(4-(2-(4-chlorophenyl)but- 3-yn-2-yl)thiazol-2- yl)acetamide	IC50	18 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
5-((3-(4-(2-(4- methoxyphenyl)propan- 2-yl)thiazol-2- yl)ureido)methyl)-N-(1- propylpiperidin-4- yl)picolinamide	IC50	19 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-[[6-(3-aminopyrrolidin-1-yl)-3-pyridinyl]methyl]-3-[4-[2-(4-methoxyphenyl)propan-2-yl]-1,3-thiazol-2-yl]urea	IC50	19 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- bromophenyl)but-3-yn- 2-yl)thiazol-2-yl)-3-((4- hydroxypiperidin-4- yl)methyl)urea	IC50	19 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
2,6-difluoro-N-(4-(2- (4-fluorophenyl)but-3- yn-2-yl)thiazol-2-yl)- 4-(piperazin-1- yl)benzamide	IC50	19 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- bromophenyl)propan-2- yl)thiazol-2-yl)-3-((6- (piperazin-1-yl)pyridin- 3-yl)methyl)urea	IC50	20 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
1-(4-(2-(4- bromophenyl)but-3-yn- 2-yl)thiazol-2-yl)-3-(2- (piperazin-1- yl)ethyl)urea	IC50	20 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES
N-[4-[(2S)-2-(4-fluorophenyl)but-3-yn-2-yl]-1,3-thiazol-2-yl]-4-[2-(hydroxymethyl)piperazin-1-yl]benzamide	IC50	20 nM	US-20250241908: ALPHA PROTEIN KINASE 1 INHIBITORS FOR USE IN TREATING ATHEROSCLEROSIS AND RELATED DISEASES

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression, decreases expression	3
sodium arsenite	affects expression, increases abundance, increases expression	3
Air Pollutants	decreases expression, affects cotreatment, increases abundance, affects expression	3
Benzo(a)pyrene	decreases expression, increases methylation, increases mutagenesis	3
Aflatoxin B1	decreases expression, increases methylation	3
Ozone	decreases expression, increases abundance, affects expression, affects cotreatment	2
Silicon Dioxide	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
hydroquinone	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8BU	HEK-Blue KO-ALPK1	Transformed cell line	Female
CVCL_SC40	HAP1 ALPK1 (-) 1	Cancer cell line	Male
CVCL_SC41	HAP1 ALPK1 (-) 2	Cancer cell line	Male
CVCL_SC42	HAP1 ALPK1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06395285	PHASE1	RECRUITING	Evaluating the Safety and Tolerability of Orally Administered DF-003 in ROSAH Syndrome Patients
NCT00001373	Not specified	RECRUITING	Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics