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): 87 total — 2 pathogenic
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005044

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: 14 — 11 protein_coding, 3 protein_coding_CDS_not_defined

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

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.

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

290 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

158 targeting PRKX, 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-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

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)

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), 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 (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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 172 (proton acceptor)

Ligand- & substrate-binding residues (2): 55–63; 78

Post-translational modifications (2): 1, 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

4 pathways

ID	Pathway
R-HSA-111931	PKA-mediated phosphorylation of CREB
R-HSA-442720	CREB1 phosphorylation through the activation of Adenylate Cyclase
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9664323	FCGR3A-mediated IL10 synthesis

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

Rollup of top-3 pathways:

Category	Pathways
Anti-inflammatory response favouring Leishmania parasite infection	2
Calmodulin induced events	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

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
peptidyl-serine modification	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
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

Protein interactions and networks

STRING

1660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKX	AMELX	Q99217	847
PRKX	OSTC	Q9NRP0	841
PRKX	AMELY	Q99218	819
PRKX	VCX3A	Q9NNX9	776
PRKX	PRKAR2B	P31323	775
PRKX	A0A087WUC5	A0A087WUC5	756
PRKX	ARSF	P54793	690
PRKX	TSPY1	P09002	677
PRKX	ARSD	P51689	647
PRKX	GYG2	O15488	643
PRKX	ZFX	P17010	624
PRKX	NLGN4X	Q8N0W4	606
PRKX	TBL1Y	Q9BQ87	602
PRKX	PCDH11X	Q9BZA7	555
PRKX	RPS4X	P12631	553

IntAct

20 interactions, top by confidence:

A	B	Type	Score
HSP90AB1	PRKX	psi-mi:“MI:0915”(physical association)	0.640
PRKX	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.640
PRKX	SMAD6	psi-mi:“MI:0915”(physical association)	0.630
SMAD6	PRKX	psi-mi:“MI:0915”(physical association)	0.630
PRKX	SMAD6	psi-mi:“MI:0217”(phosphorylation reaction)	0.630
PRKAR2B	AMY1A	psi-mi:“MI:0914”(association)	0.530
PRKX	FKBP5	psi-mi:“MI:0914”(association)	0.530
PRKX	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.510
GPKOW	PRKX	psi-mi:“MI:0915”(physical association)	0.510
Prkacb	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
PRKAR2B	PALM2AKAP2	psi-mi:“MI:0914”(association)	0.350
PRKX	AIP	psi-mi:“MI:0914”(association)	0.350
PRKX	IGLL5	psi-mi:“MI:0914”(association)	0.350
PRKAR2B	AKAP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): PRKX (Affinity Capture-MS), PRKX (Affinity Capture-MS), PRKX (Affinity Capture-MS), PRKX (Affinity Capture-MS), PRKX (Affinity Capture-RNA), PRKAR1A (Reconstituted Complex), TUBB8 (Affinity Capture-MS), PRKX (Affinity Capture-MS), HSP90AB4P (Affinity Capture-MS), RAD54L2 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS), CTSG (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), IGLC2 (Affinity Capture-MS), LTF (Affinity Capture-MS)

ESM2 similar proteins: A1CPG7, A8KBH6, A8X6H1, A8XW88, O62846, P00517, P04409, P05126, P05131, P05132, P05383, P05696, P05771, P05772, P0C431, P10102, P12370, P17252, P17612, P20444, P21137, P22612, P22694, P25321, P27791, P36887, P49673, P51817, P54644, P68180, P68181, P68182, P68403, P68404, Q0D0P5, Q13237, Q16974, Q2H332, Q2WGK3, Q52PH6

Diamond homologs: A0A509AKL0, A1A4I4, A5K0N4, A7MBL8, A8XJQ6, A8XNJ6, A8XW88, F4HYG2, G1X456, J9W0G9, O42632, O43930, O77676, P00516, P00517, P04409, P05131, P05132, P05383, P05696, P05986, P06244, P06245, P0C605, P10102, P10665, P10666, P11792, P12370, P12688, P16911, P16912, P17252, P17612, P18652, P18654, P18961, P20444, P21137, P22612

SIGNOR signaling

2 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	27
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
59210	GRCh38/hg38 Xp22.33-22.2(chrX:3057092-13615172)x1	Pathogenic
816249	GRCh37/hg19 Xp22.33-22.32(chrX:168546-5723788)x0	Pathogenic

SpliceAI

2495 predictions. Top by Δscore:

Variant	Effect	Δscore
X:3608862:T:TA	donor_gain	1.0000
X:3608867:ATG:A	donor_gain	1.0000
X:3615888:CCGTT:C	acceptor_gain	1.0000
X:3615889:CGTT:C	acceptor_gain	1.0000
X:3615889:CGTTC:C	acceptor_gain	1.0000
X:3615890:GTT:G	acceptor_gain	1.0000
X:3615890:GTTC:G	acceptor_loss	1.0000
X:3615891:TT:T	acceptor_gain	1.0000
X:3615893:C:CA	acceptor_loss	1.0000
X:3615893:C:CC	acceptor_gain	1.0000
X:3615896:C:CT	acceptor_gain	1.0000
X:3626415:TTACT:T	donor_loss	1.0000
X:3626416:TAC:T	donor_loss	1.0000
X:3626417:A:AC	donor_gain	1.0000
X:3626417:A:T	donor_loss	1.0000
X:3626418:C:A	donor_loss	1.0000
X:3626418:C:CC	donor_gain	1.0000
X:3626418:CTTTA:C	donor_gain	1.0000
X:3626511:AAACC:A	acceptor_loss	1.0000
X:3626512:AACCT:A	acceptor_loss	1.0000
X:3626513:ACCT:A	acceptor_loss	1.0000
X:3626515:C:CC	acceptor_gain	1.0000
X:3626516:T:G	acceptor_loss	1.0000
X:3655145:TTA:T	donor_loss	1.0000
X:3655146:TA:T	donor_loss	1.0000
X:3655147:ACC:A	donor_loss	1.0000
X:3655148:C:CT	donor_loss	1.0000
X:3655410:AAC:A	acceptor_gain	1.0000
X:3655411:AC:A	acceptor_gain	1.0000
X:3655411:ACC:A	acceptor_loss	1.0000

AlphaMissense

2380 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:3641889:A:G	W228R	1.000
X:3641889:A:T	W228R	1.000
X:3641943:A:G	Y210H	1.000
X:3641954:C:T	G206E	1.000
X:3641955:C:G	G206R	1.000
X:3641955:C:T	G206R	1.000
X:3641957:C:T	C205Y	1.000
X:3655169:G:C	F193L	1.000
X:3655169:G:T	F193L	1.000
X:3655170:A:C	F193C	1.000
X:3655170:A:G	F193S	1.000
X:3655171:A:G	F193L	1.000
X:3655173:C:T	G192E	1.000
X:3655178:G:C	D190E	1.000
X:3655178:G:T	D190E	1.000
X:3655179:T:A	D190V	1.000
X:3655179:T:C	D190G	1.000
X:3655179:T:G	D190A	1.000
X:3655180:C:G	D190H	1.000
X:3655217:G:C	N177K	1.000
X:3655217:G:T	N177K	1.000
X:3655218:T:A	N177I	1.000
X:3655218:T:C	N177S	1.000
X:3655219:T:C	N177D	1.000
X:3655219:T:G	N177H	1.000
X:3655226:C:A	K174N	1.000
X:3655226:C:G	K174N	1.000
X:3655228:T:C	K174E	1.000
X:3655232:G:C	D172E	1.000
X:3655232:G:T	D172E	1.000

dbSNP variants (sampled 300 via entrez): RS1000011454 (X:3647295 C>T), RS1000019467 (X:3706573 C>T), RS1000048867 (X:3647704 T>C), RS1000138824 (X:3626656 C>T), RS1000166501 (X:3707416 T>C), RS1000191950 (X:3618750 G>T), RS1000306231 (X:3689845 C>G,T), RS1000424077 (X:3679170 T>C,G), RS1000426417 (X:3608363 C>T), RS1000447803 (X:3646886 G>A), RS1000453920 (X:3678888 A>G), RS1000494636 (X:3639701 TCTC>T), RS1000527273 (X:3691218 T>C), RS1000536676 (X:3709097 T>C), RS1000610581 (X:3638864 CACAT>C)

Disease associations

OMIM: gene MIM:300083 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005997_6	Lymphocyte count	8.000000e-09
GCST006899_22	Thyroid stimulating hormone levels	2.000000e-11

EFO canonical traits (1, from GWAS)

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

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 41,604 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL38380	FASUDIL	3	11,953
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL1967878	CENISERTIB	2	358
CHEMBL1084546	PF-00562271	1	399
CHEMBL1908397	KW-2449	1	622
CHEMBL49120	PD-0166285	1	455
CHEMBL494089	GSK-690693	1	2,061
CHEMBL574738	AST-487	1	451

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

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)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM

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

23 with measured affinity, of 1468 total; 14 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
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	increases expression, decreases 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 cotreatment, affects expression	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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TH08	HAP1 PRKX (-) 1	Cancer cell line	Male
CVCL_TH09	HAP1 PRKX (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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