PRKX

Summary

PRKX (protein kinase cAMP-dependent X-linked catalytic subunit, HGNC:9441) is a protein-coding gene on chromosome Xp22.33, encoding cAMP-dependent protein kinase catalytic subunit PRKX (P51817). Serine/threonine protein kinase regulated by and mediating cAMP signaling in cells.

This gene encodes a serine threonine protein kinase that has similarity to the catalytic subunit of cyclic AMP dependent protein kinases. The encoded protein is developmentally regulated and may be involved in renal epithelial morphogenesis. This protein may also be involved in macrophage and granulocyte maturation. Abnormal recombination between this gene and a related pseudogene on chromosome Y is a frequent cause of sex reversal disorder in XX males and XY females. Pseudogenes of this gene are found on chromosomes X, 15 and Y.

Source: NCBI Gene 5613 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 88 total — 2 pathogenic
• GTEx eGene: eQTL in 32 tissues, sQTL in 10 (q < 0.05)
• ChEMBL bioactivity: 11 clinical-phase molecules tested; no curated mechanism-of-action drug
• MANE Select transcript: NM_005044
• Notable: 88 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9441
Approved symbol	PRKX
Name	protein kinase cAMP-dependent X-linked catalytic subunit
Location	Xp22.33
Locus type	gene with protein product
Status	Approved
Aliases	PKX1
Ensembl gene	ENSG00000183943
Ensembl biotype	protein_coding
OMIM	300083
Entrez	5613

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000262848

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 2, TSL 5: 1

ENST00000262848, ENST00000425240, ENST00000462736, ENST00000496648, ENST00000910396, ENST00000910397, ENST00000910398, ENST00000910399, ENST00000932050, ENST00000932051, ENST00000932052, ENST00000953311, ENST00000953312, ENST00000953313, ENST00001034713, ENST00001076772, ENST00001133069

RefSeq mRNA: 1 — MANE Select: NM_005044 NM_005044

CCDS: CCDS14125

Canonical transcript exons

ENST00000262848 — 9 exons

Exon	Start	End
ENSE00001286771	3612177	3612325
ENSE00001335331	3713088	3713649
ENSE00001401025	3604340	3608945
ENSE00001698438	3674598	3674766
ENSE00003471397	3641852	3641971
ENSE00003495000	3626419	3626514
ENSE00003508942	3655149	3655412
ENSE00003522062	3621259	3621316
ENSE00003647868	3615815	3615892

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 94.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8796 / max 230.0773, expressed in 1556 samples.

Highest expression (Bgee): ganglionic eminence, monocyte, mononuclear cell, leukocyte, lobe of thyroid gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRKX is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 32 tissues and its splicing (sQTL) in 10 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 42 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	4.0e-90	-0.41	X:3697767:C:T
Cells Cultured fibroblasts	eqtl	3.4e-13	-0.21	X:3713581:G:T
Skin Sun Exposed Lower leg	eqtl	4.6e-13	-0.15	X:3712725:C:T
Skin Not Sun Exposed Suprapubic	eqtl	1.9e-11	-0.16	X:3714927:C:T
Skin Sun Exposed Lower leg	sqtl	8.4e-10	-0.38	X:3635040:T:C
Lung	eqtl	4.8e-09	+0.13	X:3744023:C:T
Whole Blood	eqtl	1.1e-08	+0.08	X:3744023:C:T
Cells Cultured fibroblasts	sqtl	2.5e-08	-0.39	X:3635040:T:C
Skin Not Sun Exposed Suprapubic	sqtl	4.9e-08	-0.36	X:3640472:G:A
Brain Putamen basal ganglia	eqtl	5.1e-07	+0.22	X:3728422:G:A
Brain Caudate basal ganglia	eqtl	1.5e-06	+0.16	X:3729773:C:A
Brain Cerebellum	eqtl	2.2e-06	+0.20	X:3728422:G:A
Thyroid	sqtl	2.5e-06	-0.30	X:3640472:G:A
Brain Hippocampus	eqtl	7.5e-06	+0.16	X:3728422:G:A
Esophagus Mucosa	eqtl	8.3e-06	+0.08	X:3771645:G:C
Brain Cortex	eqtl	8.5e-06	+0.16	X:3728444:C:G
Testis	eqtl	1.2e-05	-0.09	X:3714927:C:T
Nerve Tibial	eqtl	2.1e-05	-0.07	X:3614834:T:G
Brain Frontal Cortex BA9	eqtl	4.0e-05	+0.14	X:3728444:C:G
Cells EBV-transformed lymphocytes	eqtl	1.8e-04	+0.15	X:3811336:C:T

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
198336	5.5677	1413
198335	0.8226	348
198330	0.3778	179
198331	0.3734	178
198332	0.3172	116
198333	0.2576	89
198334	0.1633	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	94.30	gold quality
monocyte	CL:0000576	93.06	gold quality
mononuclear cell	CL:0000842	92.67	gold quality
leukocyte	CL:0000738	92.55	gold quality
left lobe of thyroid gland	UBERON:0001120	92.42	gold quality
thyroid gland	UBERON:0002046	91.87	gold quality
right lobe of thyroid gland	UBERON:0001119	91.27	gold quality
right uterine tube	UBERON:0001302	90.93	gold quality
granulocyte	CL:0000094	90.79	gold quality
lower esophagus mucosa	UBERON:0035834	89.11	gold quality
metanephros cortex	UBERON:0010533	88.65	gold quality
esophagus mucosa	UBERON:0002469	88.37	gold quality
skin of abdomen	UBERON:0001416	87.51	gold quality
skin of leg	UBERON:0001511	87.06	gold quality
esophagus squamous epithelium	UBERON:0006920	86.86	gold quality
endometrium	UBERON:0001295	86.73	gold quality
right lung	UBERON:0002167	86.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.93	gold quality
vagina	UBERON:0000996	85.71	gold quality
cortical plate	UBERON:0005343	85.47	gold quality
tibial nerve	UBERON:0001323	85.46	gold quality
lymph node	UBERON:0000029	85.42	gold quality
rectum	UBERON:0001052	85.22	gold quality
vermiform appendix	UBERON:0001154	84.88	gold quality
gall bladder	UBERON:0002110	84.60	gold quality
upper lobe of left lung	UBERON:0008952	83.99	gold quality
zone of skin	UBERON:0000014	83.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.35	gold quality
epithelium of esophagus	UBERON:0001976	83.16	gold quality
minor salivary gland	UBERON:0001830	82.99	gold quality
upper lobe of lung	UBERON:0008948	82.86	gold quality
blood	UBERON:0000178	82.63	gold quality
ectocervix	UBERON:0012249	82.47	gold quality
spleen	UBERON:0002106	82.41	gold quality
peritoneum	UBERON:0002358	82.11	gold quality
omental fat pad	UBERON:0010414	82.10	gold quality
mouth mucosa	UBERON:0003729	82.03	gold quality
esophagus	UBERON:0001043	82.02	gold quality
stromal cell of endometrium	CL:0002255	82.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.84	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	81.53	gold quality
sural nerve	UBERON:0015488	81.16	gold quality
endocervix	UBERON:0000458	81.05	gold quality
embryo	UBERON:0000922	81.02	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.94	gold quality
islet of Langerhans	UBERON:0000006	80.51	gold quality
tonsil	UBERON:0002372	80.42	gold quality
gingival epithelium	UBERON:0001949	80.40	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.00	gold quality
colonic epithelium	UBERON:0000397	79.98	gold quality
caecum	UBERON:0001153	79.74	gold quality
gingiva	UBERON:0001828	79.68	gold quality
spinal cord	UBERON:0002240	79.52	gold quality
calcaneal tendon	UBERON:0003701	79.46	gold quality
left uterine tube	UBERON:0001303	79.42	gold quality
apex of heart	UBERON:0002098	79.11	gold quality
uterus	UBERON:0000995	78.78	gold quality
left coronary artery	UBERON:0001626	78.60	gold quality
transverse colon	UBERON:0001157	78.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.43	gold quality
subcutaneous adipose tissue	UBERON:0002190	78.43	gold quality
squamous epithelium	UBERON:0006914	78.36	gold quality
female reproductive system	UBERON:0000474	78.34	gold quality
left ovary	UBERON:0002119	78.10	gold quality
body of pancreas	UBERON:0001150	77.94	gold quality
pancreas	UBERON:0001264	77.94	gold quality
small intestine	UBERON:0002108	77.54	gold quality
right ovary	UBERON:0002118	77.53	gold quality
mucosa of transverse colon	UBERON:0004991	77.47	gold quality
saliva-secreting gland	UBERON:0001044	77.43	gold quality
ascending aorta	UBERON:0001496	77.41	gold quality
thoracic aorta	UBERON:0001515	77.37	gold quality
fallopian tube	UBERON:0003889	77.35	gold quality
ventricular zone	UBERON:0003053	77.34	gold quality
cranial nerve II	UBERON:0000941	77.27	gold quality
right coronary artery	UBERON:0001625	77.13	gold quality
tibial artery	UBERON:0007610	77.10	gold quality
aorta	UBERON:0000947	77.09	gold quality
popliteal artery	UBERON:0002250	77.09	gold quality
epithelium of nasopharynx	UBERON:0001951	77.03	gold quality
descending thoracic aorta	UBERON:0002345	77.01	gold quality
adult mammalian kidney	UBERON:0000082	76.92	gold quality
coronary artery	UBERON:0001621	76.91	gold quality
renal medulla	UBERON:0000362	76.58	gold quality
body of uterus	UBERON:0009853	76.24	gold quality
mucosa of stomach	UBERON:0001199	76.14	gold quality
body of stomach	UBERON:0001161	75.70	gold quality
hypothalamus	UBERON:0001898	75.57	gold quality
intestine	UBERON:0000160	75.54	gold quality
substantia nigra	UBERON:0002038	75.50	gold quality
anatomical system	UBERON:0000467	75.43	gold quality
right atrium auricular region	UBERON:0006631	75.37	gold quality
pigmented layer of retina	UBERON:0001782	75.32	gold quality
colon	UBERON:0001155	75.29	gold quality
smooth muscle tissue	UBERON:0001135	75.25	gold quality
ovary	UBERON:0000992	75.16	gold quality
multicellular organism	UBERON:0000468	75.14	gold quality
material anatomical entity	UBERON:0000465	75.10	gold quality
left testis	UBERON:0004533	75.06	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.04	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	63.93
E-CURD-119	yes	41.56
E-ANND-3	yes	17.93

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thyroid gland	tissue	31.6	high
Choroid plexus	tissue	21.4
Fallopian tube	tissue	18.2	high
Locus coeruleus	tissue	17.4
Thymus	tissue	14.3
Cerebellum	tissue	12.2	high
Lymph node	tissue	11.9	high
Vagina	tissue	11.7	high
Spleen	tissue	11.7	high
Skin 1	tissue	11.3	high
Spinal cord	tissue	10.6
Hippocampus	tissue	9.9	high
Corpus callosum	tissue	9.8
Kidney	tissue	9.7	high
Nucleus accumbens	tissue	9.3
Tonsil	tissue	9.3	high
Appendix	tissue	9.3	high
Epididymis	tissue	9.1	high
Esophagus	tissue	9.0	high
Substantia nigra	tissue	7.5
Breast	tissue	7.4	high
Cervix	tissue	7.3	high
Medulla oblongata	tissue	7.2
Bone marrow	tissue	7.2	medium
Caudate putamen	tissue	7.0
Testis	tissue	6.4	high
Pons	tissue	6.3
Thalamus	tissue	6.2
Colon	tissue	6.1	high
Amygdala	tissue	5.9
Hippocampal formation	tissue	5.9
Rectum	tissue	5.8	high
Hypothalamus	tissue	5.8
Seminal vesicle	tissue	5.6	low
Frontal cortex	tissue	5.6
Midbrain	tissue	5.6
Lung	tissue	5.6	high
Superior colliculi	tissue	5.4
Adipose tissue	tissue	5.2	high
Periaqueductal gray	tissue	5.1
Placenta	tissue	5.0	high
Postcentral gyrus	tissue	5.0
Ventral forebrain	tissue	5.0
Septum	tissue	5.0
Small intestine	tissue	4.9	high
Duodenum	tissue	4.7	medium
Putamen	tissue	4.6
Cerebral cortex	tissue	4.5	high
Insular cortex	tissue	4.5
Endometrium 1	tissue	4.3	medium
Salivary gland	tissue	4.2	high
Urinary bladder	tissue	4.2	medium
Pancreas	tissue	4.1	high
Basal ganglia	tissue	4.1	high
Gallbladder	tissue	4.1	high
Retrosplenial cortex	tissue	4.1
Prefrontal cortex	tissue	4.0
Retrosplenial and cingulate cortex	tissue	3.8
Stomach 1	tissue	3.7	high
Motor cortex	tissue	3.7

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Inferior olive (32.5), Parieto-temporal junction (white matter) (29.2), Medial olivary nucleus (27.6), Dorsal funiculus (white matter) (27.5), Habenula (27.0).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PRKX by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 158 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000262848 — one region, missense o/e 0.70.

Literature-anchored findings (GeneRIF, showing 7)

• PRKX kinase may regulate epithelial morphogenesis during mammalian kidney development. (PMID:12082174)
• PRKX can restore normal function to PKD1-deficient kidneys and have implications for the development of preventative therapy for autosomal dominant polycystic kidney disease (PMID:17980165)
• The interaction of PRKX with Pin-1, Magi-1 and Bag-3 could contribute to the stimulating role of PRKX in angiogenesis. (PMID:21684272)
• MBD 4–a potential substrate for protein kinase X (PMID:21971312)
• findings reveals a major role of PRKX, TTBK2 and RSK4 in triggering Sunitinib resistance formation; data suggest transcriptional regulation of these kinases together with other proteins might play an important role in formation of Sunitinib resistance by affecting transcription factors (PMID:22020623)
• The characteristics and developmental functions of PRKX. [review] (PMID:26252946)
• PRKX, WNT3 and WNT16 genes, belonging to the WNT signaling pathway, are involved in the tumorigenic process of nodular basal cell carcinoma (PMID:27630294)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkx	ENSDARG00000060716
mus_musculus	Prkx	ENSMUSG00000035725
rattus_norvegicus	Prkx	ENSRNOG00000060168
drosophila_melanogaster	Pka-C3	FBGN0000489
caenorhabditis_elegans		WBGENE00018569

Paralogs (5): PRKACA (ENSG00000072062), PRKG2 (ENSG00000138669), PRKACB (ENSG00000142875), PRKACG (ENSG00000165059), PRKG1 (ENSG00000185532)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1309999) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal startle reflex	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cricetulus griseus	P68180	100.0%	Diamond
Plasmodium falciparum 3D7	Q8I719	100.0%	Diamond
Plasmodium falciparum NF54	W7JX98	100.0%	Diamond
Oryza sativa Indica Group	A2YBX5	99.7%	Diamond
Bos taurus	P00516	99.7%	Diamond
Oryza sativa Japonica Group	Q0DCT8	99.7%	Diamond
Ovis aries	Q9MZD9	99.7%	Diamond
Sus scrofa	P05383	99.4%	Diamond
Canis lupus familiaris	Q8MJ44	99.1%	Diamond
Oryctolagus cuniculus	O77676	99.0%	Diamond
Drosophila pseudoobscura pseudoobscura	Q2LZZ7	97.6%	Diamond
Caenorhabditis briggsae	A8X6H1	94.7%	Diamond
Arabidopsis thaliana	Q683C9	93.9%	Diamond
Plasmodium vivax Sal-1	A5K0N4	92.1%	Diamond
Macaca mulatta	O62846	91.4%	Diamond
Plasmodium berghei ANKA	A0A509AKL0	89.6%	Diamond
Xenopus laevis	Q6NTJ3	87.3%	Diamond
Saccharomyces cerevisiae S288C	P06244	86.8%	Diamond
Toxoplasma gondii	Q8MMZ7	76.3%	Diamond
Eimeria tenella	Q8MMZ8	76.3%	Diamond
Orbilia oligospora ATCC 24927	G1X456	73.5%	Diamond
Mycoplasmoides genitalium G37	P47355	70.8%	Diamond
Mycoplasmoides pneumoniae M129	P75524	70.8%	Diamond
Schizosaccharomyces pombe 972h-	Q09831	70.6%	Diamond
Neurospora crassa OR74A	O42626	69.2%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CWQ4	68.2%	Diamond
Dictyostelium discoideum	Q54XI9	62.8%	Diamond
Eremothecium gossypii ATCC 10895	Q755C4	62.6%	Diamond
Nakaseomyces glabratus CBS 138	Q6FV07	62.1%	Diamond
Cercopithecine herpesvirus 9 (strain DHV)	Q04543	67.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TRI-GAT1-1	tRNA	100189132
PRKX-AS1	ncRNA	100873944
SNORA48B	snoRNA	109616969
MXRA5	protein-coding	25878
TRI-GAT1-2	tRNA	100189050
TRI-GAT1-3	tRNA	100189427

Protein

Protein identifiers

cAMP-dependent protein kinase catalytic subunit PRKX — P51817 (reviewed: P51817)

Alternative names: Protein kinase PKX1

All UniProt accessions (1): P51817

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine protein kinase regulated by and mediating cAMP signaling in cells. Acts through phosphorylation of downstream targets that may include CREB, SMAD6 and PKD1 and has multiple functions in cellular differentiation and epithelial morphogenesis. Regulates myeloid cell differentiation through SMAD6 phosphorylation. Involved in nephrogenesis by stimulating renal epithelial cell migration and tubulogenesis. Also involved in angiogenesis through stimulation of endothelial cell proliferation, migration and vascular-like structure formation.

Subunit / interactions. Like other cAMP-dependent protein kinases, the inactive holoenzyme is probably composed of 2 PRKX catalytic subunits and a dimer of regulatory subunits. Interacts (cAMP-dependent) specifically with the regulatory subunits PRKAR1A and PRKAR1B. Compared to other cAMP-dependent serine/threonine protein kinases, does not interact with the 2 other PKA regulatory subunits PRKAR2A and PRKAR2B. Interacts with cAMP-dependent protein kinase inhibitor/PKI proteins; inhibits PRKX. Interacts with GPKOW. Interacts with SMAD6. Interacts with PKD1; involved in differentiation and controlled morphogenesis of the kidney. Interacts with PIN1 (via WW domain).

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed (at protein level). Specifically expressed in blood by macrophages and granulocytes according to PubMed:9860982.

Post-translational modifications. Phosphorylated; autophosphorylates in vitro.

Disease relevance. A chromosomal aberration involving PRKX is a cause of sex reversal disorder. Translocation t(X;Y)(p22;p11) with PRKY. Chromosomal translocations proximal to PRKY account for about 30% of the cases of sex reversal disorder in XX males and XY females.

Activity regulation. Binding of cAMP to the PRKAR1A or PRKAR1B regulatory subunits induces dissociation of the holoenzyme heterotetramer. The released monomeric PRKX is then active and able to phosphorylate its substrates.

Induction. Up-regulated by phorbol 12-myristate 13-acetate (PMA).

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.

RefSeq proteins (1): NP_005035* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site

Pfam: PF00069

Enzyme classification (BRENDA)

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea)

• 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 (14 total): mutagenesis site 4, domain 2, binding site 2, modified residue 2, chain 1, region of interest 1, active site 1, sequence variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51817-F1	89.71	0.83

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, AGC Ser/Thr protein kinases, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm

Antibody reliability (HPA): IH supported · IF supported

Functional residue map

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

Catalytic / active sites (1)

Position	Role
172	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
55–63	ATP
78	ATP

Post-translational modifications (2)

Type	Positions
N-acetylmethionine	1
Phosphothreonine	203

Mutagenesis-validated functional residues (4)

Position	Phenotype
78	loss of function.
93	constitutive kinase activity; when associated with r-202.
202	constitutive kinase activity; when associated with q-93.
283	increases the affinity for prkar2a and prkar2b.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 27; 8 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

27 pathways:

ID	Pathway	Evidence
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production ⚕	electronic
R-HSA-9662851	Anti-inflammatory response favouring Leishmania parasite infection ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9664323	FCGR3A-mediated IL10 synthesis ⚕	electronic
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9664433	Leishmania parasite growth and survival ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-442755	Activation of NMDA receptors and postsynaptic events	—
R-HSA-442720	CREB1 phosphorylation through the activation of Adenylate Cyclase	electronic
R-HSA-111996	Ca-dependent events	—
R-HSA-111997	CaM pathway	—
R-HSA-111933	Calmodulin induced events	—
R-HSA-1489509	DAG and IP3 signaling	—
R-HSA-418594	G alpha (i) signalling events	—
R-HSA-112040	G-protein mediated events	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-112316	Neuronal System	—
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	—
R-HSA-111885	Opioid Signalling	—
R-HSA-111931	PKA-mediated phosphorylation of CREB	electronic
R-HSA-112043	PLC beta mediated events	—
R-HSA-438064	Post NMDA receptor activation events	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-112315	Transmission across Chemical Synapses	—

MSigDB gene sets: 263 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, MODULE_451, KEGG_HEDGEHOG_SIGNALING_PATHWAY, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_PEPTIDYL_SERINE_MODIFICATION, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION_INVOLVED_IN_KIDNEY_DEVELOPMENT, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_CELL_DIFFERENTIATION_INVOLVED_IN_KIDNEY_DEVELOPMENT, FOSTER_TOLERANT_MACROPHAGE_UP, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (16): angiogenesis (GO:0001525), endothelial cell proliferation (GO:0001935), cell adhesion (GO:0007155), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), peptidyl-serine phosphorylation (GO:0018105), myeloid cell differentiation (GO:0030099), regulation of cell adhesion (GO:0030155), regulation of cell migration (GO:0030334), cell-substrate adhesion (GO:0031589), endothelial cell migration (GO:0043542), protein autophosphorylation (GO:0046777), epithelial tube morphogenesis (GO:0060562), kidney morphogenesis (GO:0060993), regulation of epithelial cell differentiation involved in kidney development (GO:2000696), protein phosphorylation (GO:0006468), cell differentiation (GO:0030154)

GO Molecular Function (9): cAMP-dependent protein kinase activity (GO:0004691), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cAMP-dependent protein kinase complex (GO:0005952)

Reactome top-level categories

17 top-level categories:

Category	Pathways
Anti-inflammatory response favouring Leishmania parasite infection	2
Calmodulin induced events	1
Post NMDA receptor activation events	1
G alpha (i) signalling events	1
CaM pathway	1
PLC beta mediated events	1
Ca-dependent events	1
DAG and IP3 signaling	1
Opioid Signalling	1
G-protein mediated events	1
Transmission across Chemical Synapses	1
Neuronal System	1
Intracellular signaling by second messengers	1
Signal Transduction	1
Signaling by GPCR	1
GPCR downstream signalling	1
Activation of NMDA receptors and postsynaptic events	1

GO top-level categories

43 GO namespaces:

Category	Terms
cellular anatomical structure	3
protein phosphorylation	2
cell adhesion	2
cell migration	2
protein kinase activity	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
epithelial cell proliferation	1
cellular process	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
hemopoiesis	1
cell differentiation	1
regulation of cellular process	1
regulation of cell motility	1
morphogenesis of an epithelium	1
tube morphogenesis	1
kidney development	1
animal organ morphogenesis	1
regulation of epithelial cell differentiation	1
epithelial cell differentiation involved in kidney development	1
phosphorylation	1
protein modification process	1
cellular developmental process	1
cyclic nucleotide-dependent protein kinase activity	1
cAMP binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular protein-containing complex	1
serine/threonine protein kinase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
angiogenesis	BP	mutant phenotype
cell adhesion	BP	mutant phenotype
cell-substrate adhesion	BP	mutant phenotype
endothelial cell migration	BP	mutant phenotype
endothelial cell proliferation	BP	mutant phenotype
epithelial tube morphogenesis	BP	direct assay
kidney morphogenesis	BP	direct assay
myeloid cell differentiation	BP	direct assay
peptidyl-serine phosphorylation	BP	direct assay
protein autophosphorylation	BP	direct assay
regulation of cell adhesion	BP	direct assay
regulation of cell migration	BP	direct assay
regulation of epithelial cell differentiation involved in kidney development	BP	direct assay
cytoplasm	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
cAMP-dependent protein kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,252 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKX	AMELY	Q99218	846
PRKX	AMELX	Q99217	844
PRKX	OSTC	Q9NRP0	840
PRKX	VCX3A	Q9NNX9	757
PRKX	A0A087WUC5	A0A087WUC5	752
PRKX	TSPY1	P09002	685
PRKX	TBL1Y	Q9BQ87	631
PRKX	PRKAR2B	P31323	616
PRKX	GYG2	O15488	592
PRKX	ARSF	P54793	580
PRKX	PCDH11X	Q9BZA7	569
PRKX	ZFX	P17010	561
PRKX	ARSD	P51689	542
PRKX	SRY	Q05066	538
PRKX	PLCXD1	Q9NUJ7	514

IntAct

Human interaction partners of PRKX in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
HSP90AB1	physical association	0.640	2
SMAD6	physical association	0.630	5
FKBP5	association	0.530	1
GPKOW	physical association	0.510	2
PRKAR1A	physical association	0.510	2
AIP	association	0.350	1
IGLL5	association	0.350	1

BioGRID (52 interactions; top human partners by supporting records): PRKAR2B (Affinity Capture-MS; 3 records), FKBP5 (Affinity Capture-MS; 2 records), HSP90AA1 (Affinity Capture-MS; 2 records), HSP90AB4P (Affinity Capture-MS; 2 records), AIP (Affinity Capture-MS), ALB (Affinity Capture-MS), ALOX12B (Affinity Capture-MS), APOD (Affinity Capture-MS), AZGP1 (Affinity Capture-MS), C3 (Affinity Capture-MS), CAD (Affinity Capture-MS), CASP14 (Affinity Capture-MS), CDC37 (Affinity Capture-MS), CTSG (Affinity Capture-MS), DMBT1 (Affinity Capture-MS)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
PRKX	up-regulates	PKD1	phosphorylation
PRKX	“up-regulates activity”	SMAD6	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for PRKX: 88 ClinVar records (2 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	28
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
59210	GRCh38/hg38 Xp22.33-22.2(chrX:3057092-13615172)x1	Pathogenic	criteria provided, single submitter	1
816249	GRCh37/hg19 Xp22.33-22.32(chrX:168546-5723788)x0	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PRKX’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 39 predictions of 1,361):

Position(s)	Effect	Δscore	Sites
X:3615893–3615894	acceptor_loss	1.0000	5
X:3626417–3626418	donor_loss	1.0000	5
X:3626515–3626516	acceptor_loss	1.0000	6
X:3655147–3655148	donor_loss	1.0000	5
X:3655413–3655414	acceptor_loss	1.0000	4
X:3674626	donor_gain	1.0000
X:3674767–3674768	acceptor_loss	1.0000	5
X:3612179	donor_gain	0.9900
X:3612326–3612327	acceptor_loss	0.9900	6
X:3612335	acceptor_gain	0.9900

AlphaMissense

1,212 missense substitutions predicted likely pathogenic (of 2,380 scored), across 256 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N177	8	1.000	1.000
D190	8	1.000	1.000
D172	8	0.999	1.000
D226	8	0.998	0.999
F193	8	0.997	1.000
H93	8	0.989	0.997
F60	8	0.988	1.000
H164	8	0.987	0.995
F135	8	0.986	1.000
F191	8	0.977	0.996
F355	8	0.968	0.994
D329	8	0.965	0.990
H185	8	0.956	0.995
H221	8	0.947	0.997
F244	8	0.943	0.999
F144	8	0.935	0.992
F358	8	0.933	0.995
H300	8	0.916	0.978
F151	8	0.910	0.987
F250	8	0.899	0.981

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.5e-05
Lung Squamous Cell Carcinoma (validation)	favorable	0.000881

Disease associations

OMIM: gene MIM:300083 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST006899_6	Thyroid stimulating hormone levels	2e-11
GCST005997_6	Lymphocyte count	8e-9

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5818 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,297 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

11 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL189963	PALBOCICLIB	4	13,796
CHEMBL522892	DOVITINIB	3	5,162
CHEMBL38380	FASUDIL	3	12,137
CHEMBL603469	LESTAURTINIB	3
CHEMBL1967878	CENISERTIB	2	373
CHEMBL574738	AST-487	1	468
CHEMBL494089	GSK-690693	1	2,164
CHEMBL1908397	KW-2449	1	655
CHEMBL49120	PD-0166285	1	477
CHEMBL1084546	PF-00562271	1	424

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein kinase A (PKA) family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
GSK690693	Inhibition	8.3	pIC50

Binding affinities (BindingDB)

39 measured of 114 human assays (115 total across all organisms); most potent 39 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL6162267	IC50	0.35 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
Staurosporine	KD	1.7 nM
CEP-701	KD	3.4 nM
4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	IC50	5.5 nM
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	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
Staurosporine, 8	IC50	6.5 nM
Momelotinib	IC50	8 nM	US-9469613: (N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
CHEMBL4465866	KD	8 nM
N-[(3-methoxyphenyl)methyl]-6-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carboxamide	IC50	10.2 nM	US-20240246972: AZAINDOLE ROCK INHIBITORS
CHEMBL4872886	IC50	12 nM
CHEMBL2334586	IC50	14 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
N-[1-(3-methoxyphenyl)cyclopropyl]-6-(5-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	IC50	18.5 nM	US-20240246972: AZAINDOLE ROCK INHIBITORS
N-[(3,4-difluorophenyl)methyl]-6-(1H-pyrazol-4-yl)-1H-indole-3-carboxamide	IC50	34 nM	US-20240246972: AZAINDOLE ROCK INHIBITORS
N-[[2-chloro-6-(1-hydroxycyclopropyl)phenyl]methyl]-6-(5-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	IC50	35.6 nM	US-20240246972: AZAINDOLE ROCK INHIBITORS
N-[1-(2-fluorophenyl)cyclopropyl]-1-methyl-6-(1H-pyrazol-4-yl)pyrrolo[2,3-b]pyridine-2-carboxamide	IC50	37.4 nM	US-20240246972: AZAINDOLE ROCK INHIBITORS
N-[[2-(fluoromethyl)phenyl]methyl]-1-methyl-6-pyrazolidin-4-ylpyrrolo[2,3-b]pyridine-2-carboxamide	IC50	45.1 nM	US-20240246972: AZAINDOLE ROCK INHIBITORS
N-[(2-fluorophenyl)methyl]-6-(5-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide	IC50	61 nM	US-20240246972: AZAINDOLE ROCK INHIBITORS
PKC-412	KD	110 nM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	KD	120 nM	US-9145414: 1,2,4-triazine-6-carboxamide derivative
PKC-412	KD	190 nM
N-[1-[3-(1-hydroxycyclopropyl)phenyl]cyclopropyl]-1-methyl-6-pyrazolidin-4-ylpyrrolo[2,3-b]pyridine-2-carboxamide	IC50	357 nM	US-20240246972: AZAINDOLE ROCK INHIBITORS
CHEMBL1908397	KD	650 nM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	KD	740 nM
(9S)-9-[(dimethylamino)methyl]-6,7,10,11-tetrahydro-9H,18H-5,21:12,17-di(metheno)dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecine-18,20(19H)-dione	IC50	743 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
7-chloro-3-oxo-8-[(thiazol-5-ylmethyl)-amino]-11,16-dioxa-2,4,19,21-tetraaza-tricyclo[15.3.1.0*5,10*]henicosa-1(21),5,7,9,17,19-hexaene-18-crbonitrile	KI	1540 nM
3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol	KD	2400 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
SUNITINIB MALATE	KD	3500 nM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide	KD	3900 nM	US-20250129067: PLATELET-DERIVED GROWTH FACTOR RECEPTOR (PDGFR) ALPHA INHIBITORS AND USES THEREOF
(4-chlorophenyl)-[4-(4-pyridylmethyl)phthalazin-1-yl]amine	KD	8800 nM
CHEMBL1667963	IC50	25100 nM
N-[1-(3-methoxyphenyl)cyclopropyl]-1-methyl-6-(1H-pyrazol-4-yl)pyrrolo[2,3-b]pyridine-2-carboxamide	KD	89000 nM	US-20240246972: AZAINDOLE ROCK INHIBITORS

ChEMBL bioactivities

280 potent at pChembl≥5 of 301 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.50	Ki	0.3162	nM	CHEMBL1980995
9.00	Ki	1	nM	CHEMBL1974870
9.00	Ki	1	nM	CHEMBL1998121
8.90	Ki	1.259	nM	CHEMBL1970709
8.90	Ki	1.259	nM	CHEMBL1974288
8.86	IC50	1.39	nM	STAUROSPORINE
8.83	IC50	1.49	nM	STAUROSPORINE
8.80	Ki	1.585	nM	CHEMBL1981782
8.80	Ki	1.585	nM	CHEMBL1969502
8.80	Ki	1.585	nM	CHEMBL1990162
8.70	Ki	1.995	nM	CHEMBL1968930
8.60	Ki	2.512	nM	CHEMBL1972339
8.60	Ki	2.512	nM	CHEMBL1999428
8.50	Ki	3.162	nM	CHEMBL1972290
8.50	Ki	3.162	nM	CHEMBL592030
8.50	Ki	3.162	nM	CHEMBL1973720
8.40	Ki	3.981	nM	CHEMBL1975900
8.40	Ki	3.981	nM	CHEMBL1994438
8.30	IC50	5	nM	GSK-690693
8.30	Ki	5.012	nM	CHEMBL1975128
8.30	Ki	5.012	nM	CHEMBL1965836
8.30	Ki	5.012	nM	CHEMBL1998432
8.20	Ki	6.31	nM	CHEMBL1966628
8.20	Ki	6.31	nM	CHEMBL1990590
8.20	Ki	6.31	nM	CHEMBL1981133
8.20	Ki	6.31	nM	CHEMBL1987073
8.14	Kd	7.2	nM	GSK-690693
8.10	Ki	7.943	nM	CHEMBL1977135
8.10	Ki	7.943	nM	CHEMBL2001751
8.00	Ki	10	nM	CHEMBL1987261
8.00	Ki	10	nM	CHEMBL1995712
8.00	Ki	10	nM	CHEMBL1996111
7.90	Ki	12.59	nM	CHEMBL1969561
7.90	Ki	12.59	nM	CHEMBL1966204
7.90	Ki	12.59	nM	CHEMBL1992363
7.89	Kd	13	nM	STAUROSPORINE
7.80	Ki	15.85	nM	CHEMBL1082440
7.70	Ki	19.95	nM	CHEMBL1993781
7.70	Ki	19.95	nM	CHEMBL1985723
7.70	Ki	19.95	nM	CHEMBL1994669
7.70	Ki	19.95	nM	CHEMBL1870106
7.70	Ki	19.95	nM	CHEMBL1976936
7.70	Ki	19.95	nM	CHEMBL2002726
7.70	Ki	19.95	nM	CHEMBL1994830
7.70	Ki	19.95	nM	CHEMBL1986855
7.60	Ki	25.12	nM	CHEMBL1983589
7.60	Ki	25.12	nM	CHEMBL2005718
7.60	Ki	25.12	nM	CHEMBL2006456
7.60	Ki	25.12	nM	CHEMBL1967544
7.60	Ki	25.12	nM	CHEMBL1969151

PubChem BioAssay actives

24 with measured affinity, of 1470 total; 15 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	1531859: Inhibition of human PRKX using LRRASLG as substrate by [gamma-33P]-ATP assay	ic50	0.0014	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	391392: Inhibition of human PrkX	ic50	0.0050	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508053: Binding affinity to PRKX	kd	0.0420	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-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-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526135: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged PRKX (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0430	uM
6-[(3S)-piperidin-3-yl]oxy-2H-isoquinolin-1-one	568133: Inhibition of human PrkX by RFBA assay	ic50	0.0794	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624976: Binding constant for PRKX kinase domain	kd	0.0970	uM
(2R)-2-amino-N-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide	1769875: Inhibition of wild-type human partial length PRKX (M1 to F358 residues) expressed in bacterial expression system by Kinomescan method	ic50	0.3260	uM
4-(4-amino-3,5,12-triazatetracyclo[9.7.0.02,7.013,18]octadeca-1(11),2,4,6,13(18),14,16-heptaen-16-yl)-2-methylbut-3-yn-2-ol	1856578: Inhibition of human wild type partial length PRKX (M1 to F358 residues) expressed in bacterial expression system by Kinomescan assay	ic50	0.5800	uM
6,9-dichloro-3H-[1]benzothiolo[3,2-d]pyrimidin-4-one	437695: Inhibition of PRKX by HTRF assay	ki	0.5847	uM
Midostaurin	436047: Binding constant for full-length PRKX	kd	0.9600	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624976: Binding constant for PRKX kinase domain	kd	1.2000	uM
4-[5-(3-methylsulfanylprop-1-ynyl)-1H-indol-3-yl]pyrimidin-2-amine	2230261: Inhibition of PRKX (unknown origin) expressed in HEK293 cells using NanoBRET NanoGlo substrate in presence of K5 tracer by NanoBRET assay	ic50	3.2000	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624976: Binding constant for PRKX kinase domain	kd	4.4000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624976: Binding constant for PRKX kinase domain	kd	5.8000	uM
5-(1,4-diazepan-1-ylsulfonyl)isoquinolin-1-amine	568133: Inhibition of human PrkX by RFBA assay	ic50	6.3096	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression, increases expression	4
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	3
Aflatoxin B1	affects expression, affects methylation, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Daunorubicin	increases expression	2
Mitoxantrone	increases expression	2
Nickel	increases expression	2
Valproic Acid	increases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
triphenyl phosphate	affects expression	1
potassium perchlorate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression, decreases expression	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MRK 003	increases expression	1
perfluorobutanesulfonic acid	affects expression, affects cotreatment	1
bisphenol S	affects cotreatment, increases methylation	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1

ChEMBL screening assays

225 unique, capped per target: 224 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011947	Binding	Inhibition of PRKX at 100 nM relative to control	Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases. — *J Med Chem*
CHEMBL1963800	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PRKX	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F5CJ	EDITGENE PRKX Knockout HAP1 Cell Line	Cancer cell line	Male
CVCL_TH08	HAP1 PRKX (-) 1	Cancer cell line	Male
CVCL_TH09	HAP1 PRKX (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRKX across ~30M SureChEMBL compounds — explore on Sugi Predict.