PASK

Summary

PASK (PAS domain containing serine/threonine kinase, HGNC:17270) is a protein-coding gene on chromosome 2q37.3, encoding PAS domain-containing serine/threonine-protein kinase (Q96RG2). Serine/threonine-protein kinase involved in energy homeostasis and protein translation.

This gene encodes a member of the serine/threonine kinase family that contains two PAS domains. Expression of this gene is regulated by glucose, and the encoded protein plays a role in the regulation of insulin gene expression. Downregulation of this gene may play a role in type 2 diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 23178 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 267 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015148

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17270
Approved symbol	PASK
Name	PAS domain containing serine/threonine kinase
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	PASKIN, KIAA0135, STK37
Ensembl gene	ENSG00000115687
Ensembl biotype	protein_coding
OMIM	607505
Entrez	23178

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 25 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000234040, ENST00000358649, ENST00000403638, ENST00000405260, ENST00000415234, ENST00000433589, ENST00000437780, ENST00000452907, ENST00000459710, ENST00000472072, ENST00000475666, ENST00000485940, ENST00000489256, ENST00000493544, ENST00000544142, ENST00000629419, ENST00000872361, ENST00000872362, ENST00000930256, ENST00000930257, ENST00000930258, ENST00000930259, ENST00000930260, ENST00000930261, ENST00000930262, ENST00000930263, ENST00000930264, ENST00000930265, ENST00000930266, ENST00000930267, ENST00000930268, ENST00000930269

RefSeq mRNA: 5 — MANE Select: NM_015148 NM_001252119, NM_001252120, NM_001252122, NM_001252124, NM_015148

CCDS: CCDS2545, CCDS58758, CCDS58759

Canonical transcript exons

ENST00000234040 — 18 exons

Exon	Start	End
ENSE00000827778	241112240	241112439
ENSE00000827780	241115043	241115177
ENSE00000827785	241132874	241133030
ENSE00000827787	241135871	241136039
ENSE00000827792	241140521	241140753
ENSE00001038616	241142837	241143074
ENSE00001038619	241106099	241106723
ENSE00001951272	241149414	241149472
ENSE00003459118	241139885	241140055
ENSE00003463083	241123949	241124133
ENSE00003476388	241138654	241138794
ENSE00003532600	241126196	241127451
ENSE00003549057	241137004	241137264
ENSE00003559238	241137953	241138087
ENSE00003583349	241107353	241107499
ENSE00003641334	241108167	241108300
ENSE00003643048	241115288	241115413
ENSE00003643282	241122732	241122899

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 93.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5425 / max 336.6363, expressed in 1273 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34891	4.0095	1201
34882	1.0542	100
34892	0.4385	151
34890	0.2969	186
34883	0.1565	47
34893	0.1522	71
34888	0.0967	37
34885	0.0903	36
34884	0.0778	34
34881	0.0589	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	93.36	gold quality
oocyte	CL:0000023	91.48	gold quality
right testis	UBERON:0004534	91.26	gold quality
left testis	UBERON:0004533	90.98	gold quality
secondary oocyte	CL:0000655	90.36	gold quality
lymph node	UBERON:0000029	89.75	gold quality
vermiform appendix	UBERON:0001154	89.16	gold quality
testis	UBERON:0000473	88.67	gold quality
caudate nucleus	UBERON:0001873	88.55	gold quality
putamen	UBERON:0001874	87.61	gold quality
nucleus accumbens	UBERON:0001882	87.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.46	gold quality
cerebellar hemisphere	UBERON:0002245	85.89	gold quality
cerebellar cortex	UBERON:0002129	85.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.26	gold quality
left lobe of thyroid gland	UBERON:0001120	85.20	gold quality
granulocyte	CL:0000094	85.07	gold quality
blood	UBERON:0000178	85.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.99	gold quality
cortical plate	UBERON:0005343	84.96	gold quality
metanephros cortex	UBERON:0010533	84.66	gold quality
right lobe of thyroid gland	UBERON:0001119	84.43	gold quality
caecum	UBERON:0001153	84.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.26	gold quality
thyroid gland	UBERON:0002046	84.10	gold quality
spleen	UBERON:0002106	83.87	gold quality
epithelium of nasopharynx	UBERON:0001951	83.86	gold quality
nasopharynx	UBERON:0001728	83.85	silver quality
prostate gland	UBERON:0002367	83.35	gold quality
tonsil	UBERON:0002372	82.98	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	566.12
E-GEOD-139324	yes	367.49
E-HCAD-4	yes	99.33
E-CURD-122	yes	42.16
E-ANND-3	yes	10.83
E-MTAB-5061	yes	6.78
E-MTAB-7606	no	970.74
E-CURD-95	no	708.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting PASK, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626

Literature-anchored findings (GeneRIF, showing 12)

• molecular cloning, gene expression, and comparison with mouse protein (PMID:11688972)
• Results suggest that elevated glucose concentrations rapidly increase Per-Arnt-Sim kinase activity in pancreatic islet beta cells, followed by up-regulation by glucose of preproinsulin and pancreatic duodenum homeobox 1 gene expression. (PMID:15148392)
• identified the multifunctional eukaryotic translation elongation factor eEF1A1 as a novel interaction partner of PASKIN in the nuclei of testis germ cells and in the midpiece of sperm tails (PMID:17595531)
• Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation. (PMID:20943661)
• PASK is involved in the regulation of glucagon secretion by glucose and may be a useful target for the treatment of type 2 diabetes. (PMID:21181396)
• Per-Arnt-Sim (PAS) domain-containing protein kinase (PASK) has a role in insulin hypersecretion (PMID:22065581)
• The role of PAS kinase in PASsing the glucose signal. (PMID:22219681)
• Mutations that affect PAS domain cause a severe protein trafficking defect and change the interactions with Kv11.1 channels. (PMID:23721480)
• PASK phosphorylates and inactivates GSK3beta, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3beta-mediated PDX-1 protein degradation in pancreatic beta-cells. (PMID:23853095)
• we provide the first evidence for a role of USF1 in respiration since it appeared to complement Cbf1 in vivo as determined by respiration phenotypes. In addition, we confirmed USF1 as a substrate of human PAS kinase (hPASK) in vitro Combined, our data supports a model in which Cbf1/USF1 functions to partition glucose toward respiration and away from lipid biogenesis (PMID:30381292)
• MTORC1-PASK signaling is required for the rise of myogenin-positive committed myoblasts. (PMID:31072927)
• we show that the nuclear PASK associates with the mammalian H3K4 MLL2 methyltransferase complex and enhances H3K4 di- and tri-methylation. We also show that PASK is a histone kinase that phosphorylates H3 at T3, T6, S10 and T11. (PMID:31529049)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pask	ENSDARG00000075008
mus_musculus	Pask	ENSMUSG00000026274
rattus_norvegicus	Pask	ENSRNOG00000016888
drosophila_melanogaster	Pask	FBGN0034950

Protein

Protein identifiers

PAS domain-containing serine/threonine-protein kinase — Q96RG2 (reviewed: Q96RG2)

All UniProt accessions (5): C9J1Z3, C9J4R3, Q96RG2, F8WEB4, H7C0L7

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate in respiratory regulation.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed, with slightly higher expression in brain, prostate and testis. Reduced expression was found in placenta. Present in germ cells of testis and in the midpiece of sperm tails (at protein level).

Post-translational modifications. Autophosphorylated on Thr-1161 and Thr-1165. Autophosphorylation is activated by phospholipids.

Activity regulation. Protein kinase activity is inhibited by the first PAS domain: binding of an unidentified ligand desinhibits the protein kinase activity. May be activated by autophosphorylation on Thr-1161 and Thr-1165. The activating role of autophosphorylation at Thr-1161 is unclear: according to a report, autophosphorylation at Thr-1161 does not play a major role in activation. Autophosphorylation is enhanced upon phosphatidylinositol monophosphate (phosphatidylinositol 4-phosphate) binding and inhibited upon phosphatidylinositol bi- and tri-phosphate binding. In contrast, phosphorylation of target proteins is inhibited upon all phosphatidylinositol-binding (phosphatidylinositol mono- bi- and tri-phosphate).

Domain organisation. The protein kinase domain mediates binding to phosphatidylinositol.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96RG2-1	1	yes
Q96RG2-2	2
Q96RG2-4	3

RefSeq proteins (5): NP_001239048, NP_001239049, NP_001239051, NP_001239053, NP_055963* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000014	PAS	Domain
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR035965	PAS-like_dom_sf	Homologous_superfamily

Pfam: PF00069, PF13426

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 (97 total): strand 19, helix 18, sequence variant 14, sequence conflict 9, modified residue 7, mutagenesis site 7, turn 7, binding site 4, domain 3, splice variant 3, region of interest 3, chain 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3DLS	X-RAY DIFFRACTION	2.3
1LL8	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RG2-F1	54.14	0.17

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): 1128 (proton acceptor)

Ligand- & substrate-binding residues (4): 1028; 1082–1089; 1146; 1005–1013

Post-translational modifications (7): 1, 19, 34, 582, 939, 1161, 1165

Mutagenesis-validated functional residues (7):

Position	Phenotype
1028	loss of autophosphorylating activity.
1058	induces lower protein kinase activity.
1058	does not affect protein kinase activity.
1151	induces lower protein kinase activity and ability to autophosphorylate.
1152	induces lower protein kinase activity.
1161	loss of catalytic activity (pubmed:11459942). according to another report, does not affect the protein kinase activity (
1165	loss of catalytic activity. does not affect protein translation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 223 (showing top): GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, FISCHER_G1_S_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, GOBP_TRANSLATION, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MUELLER_PLURINET, LEE_NAIVE_T_LYMPHOCYTE, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, TGIF_01

GO Biological Process (8): protein phosphorylation (GO:0006468), intracellular signal transduction (GO:0035556), regulation of respiratory gaseous exchange (GO:0043576), negative regulation of glycogen biosynthetic process (GO:0045719), positive regulation of translation (GO:0045727), protein autophosphorylation (GO:0046777), regulation of glucagon secretion (GO:0070092), energy homeostasis (GO:0097009)

GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), phosphatidylinositol binding (GO:0035091), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), lipid binding (GO:0008289), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
protein kinase activity	2
binding	2
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
signal transduction	1
respiratory gaseous exchange by respiratory system	1
regulation of multicellular organismal process	1
glycogen biosynthetic process	1
regulation of glycogen biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of glycogen metabolic process	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
protein phosphorylation	1
glucagon secretion	1
regulation of peptide hormone secretion	1
multicellular organismal-level homeostasis	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
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1

Protein interactions and networks

STRING

1170 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PASK	PPP1R7	Q15435	936
PASK	UCK2	Q9BZX2	891
PASK	GYS1	P13807	722
PASK	UGP2	Q16851	611
PASK	SNAPC5	O75971	471
PASK	SLC12A9	Q9BXP2	468
PASK	C10orf62	Q5T681	450
PASK	CMYA5	Q8N3K9	431
PASK	ARMCX6	Q7L4S7	411
PASK	DRG1	Q9Y295	402
PASK	A0A1W2PRG6	A0A1W2PRG6	399
PASK	CFAP141	Q5VU69	396
PASK	PTPRJ	Q12913	381
PASK	PTPRZ1	P23471	372
PASK	TRAPPC6B	Q86SZ2	365

IntAct

169 interactions, top by confidence:

A	B	Type	Score
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
PRG2	YPEL5	psi-mi:“MI:0914”(association)	0.640
PASK	CREB1	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
RPS6	PASK	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
PHKB	PASK	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
PASK	RPS6	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
PASK	PHKB	psi-mi:“MI:0217”(phosphorylation reaction)	0.560
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
EMILIN3	ZZEF1	psi-mi:“MI:0914”(association)	0.530
AURKA	WDR62	psi-mi:“MI:0914”(association)	0.530
RASL10B	AHCYL1	psi-mi:“MI:0914”(association)	0.530
WNT7A	LDLR	psi-mi:“MI:0914”(association)	0.530
DNASE2B	ARSA	psi-mi:“MI:0914”(association)	0.530
CTSG	MANBA	psi-mi:“MI:0914”(association)	0.530
TIMP3	ZZEF1	psi-mi:“MI:0914”(association)	0.530
RPUSD3	HSPD1	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
WNT4	TOMM40	psi-mi:“MI:0914”(association)	0.530
PASK	GYS1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PDX1	PASK	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PIAS1	PASK	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RAB11FIP1	PASK	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PASK	FXN	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PASK	KCNH2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
NFATC4	PASK	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (175): PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Proximity Label-MS), PASK (Proximity Label-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS), PASK (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8I316, A7XW16, A9YTQ3, B2RQL2, F1Q4R9, I7HJS4, O14901, O43638, O75593, O88621, P0C1T1, P0C6A0, P20428, P27792, P43688, P48985, P70061, P78412, Q00175, Q12950, Q15583, Q3B7M4, Q3B8N5, Q3U133, Q3U1U7, Q5IS58, Q5NCP0, Q5SSZ7, Q5VV16, Q60688, Q61574, Q63449, Q66HH3, Q68DV7, Q6NUN9, Q6U8D7, Q6ZNG2, Q75NT5, Q7TSH3, Q8BG36

Diamond homologs: A0AUV4, A1A5Q6, B2DD29, B7XHR6, C0HKC8, C0HKC9, D3ZML2, F1QGZ6, O08679, O22932, O22971, O54863, O59697, O60285, O70444, O94168, P06803, P11309, P26794, P31374, P52497, P54645, P57059, P58750, P92958, Q00372, Q00771, Q05512, Q08217, Q0JI49, Q13131, Q14680, Q19469, Q1PFH8, Q20443, Q28GW8, Q38997, Q54DF2, Q54MV2, Q54WX4

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PASK	unknown	EEF1A1	phosphorylation
PASK	“up-regulates activity”	WDR5	phosphorylation
PASK	“down-regulates activity”	GSK3B	phosphorylation
PASK	“up-regulates activity”	PASK	phosphorylation
PASK	“down-regulates activity”	GYS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 204 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Negative regulation of TCF-dependent signaling by WNT ligand antagonists	5	28.3×	2e-04
WNT ligand biogenesis and trafficking	7	23.5×	1e-05
Transcriptional Regulation by MECP2	5	12.6×	9e-03
Class B/2 (Secretin family receptors)	8	12.1×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
cell fate commitment	7	11.4×	2e-03
canonical Wnt signaling pathway	11	9.3×	4e-05
neuron differentiation	10	5.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	188
Likely benign	30
Benign	15

Top pathogenic / likely-pathogenic (0)

SpliceAI

3914 predictions. Top by Δscore:

Variant	Effect	Δscore
2:241107347:CCTCA:C	donor_loss	1.0000
2:241107348:CTCA:C	donor_loss	1.0000
2:241107349:TCA:T	donor_loss	1.0000
2:241107350:CACC:C	donor_loss	1.0000
2:241107352:CCTGG:C	donor_gain	1.0000
2:241107495:GAGTT:G	acceptor_gain	1.0000
2:241107496:AGTT:A	acceptor_gain	1.0000
2:241107497:GTT:G	acceptor_gain	1.0000
2:241107498:TT:T	acceptor_gain	1.0000
2:241107500:C:CA	acceptor_loss	1.0000
2:241107500:C:CC	acceptor_gain	1.0000
2:241107501:T:A	acceptor_loss	1.0000
2:241107507:C:CT	acceptor_gain	1.0000
2:241107509:C:CT	acceptor_gain	1.0000
2:241108162:CTCA:C	donor_loss	1.0000
2:241108165:A:C	donor_loss	1.0000
2:241108166:C:CT	donor_loss	1.0000
2:241108301:C:CC	acceptor_gain	1.0000
2:241108603:T:TA	donor_gain	1.0000
2:241112238:A:AC	donor_gain	1.0000
2:241112239:C:CC	donor_gain	1.0000
2:241112258:T:TA	donor_gain	1.0000
2:241112312:T:A	donor_gain	1.0000
2:241114974:T:C	donor_gain	1.0000
2:241115002:AGG:A	donor_gain	1.0000
2:241115041:A:AC	donor_gain	1.0000
2:241115042:C:CC	donor_gain	1.0000
2:241115042:CTTGT:C	donor_gain	1.0000
2:241115344:T:A	donor_gain	1.0000
2:241122730:ACCT:A	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000010692 (2:241149177 G>A,C), RS1000041848 (2:241148985 C>A), RS1000063982 (2:241114594 T>C), RS1000098260 (2:241119520 A>G), RS1000107832 (2:241125328 C>G,T), RS1000139265 (2:241120981 T>C), RS1000141063 (2:241109511 C>A,T), RS1000184674 (2:241133994 A>G), RS1000192034 (2:241120832 T>A), RS1000359631 (2:241142811 G>A,C), RS1000371526 (2:241138225 T>C), RS1000563685 (2:241118724 T>A,G), RS1000610923 (2:241130837 G>A), RS1000622124 (2:241130666 T>C), RS1000795761 (2:241125914 A>G,T)

Disease associations

OMIM: gene MIM:607505 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): chronic kidney disease (MONDO:0005300)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001885_2	Height	3.000000e-07
GCST008839_29	Height	1.000000e-23
GCST90000025_717	Appendicular lean mass	3.000000e-12
GCST90020026_152	Hip index	1.000000e-08
GCST90020026_153	Hip index	1.000000e-08
GCST90020028_712	Hip circumference adjusted for BMI	6.000000e-09
GCST90020028_713	Hip circumference adjusted for BMI	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007676	Kidney Failure, Chronic	C12.050.351.968.419.780.750.500; C12.200.777.419.780.750.500; C12.950.419.780.750.500; C23.550.291.500.906.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6054 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,061 (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
CHEMBL494089	GSK-690693	1	2,061

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — PASK subfamily

ChEMBL bioactivities

33 potent at pChembl≥5 of 36 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.26	IC50	5.54	nM	STAUROSPORINE
7.80	IC50	15.8	nM	STAUROSPORINE
6.90	Ki	125.9	nM	CHEMBL1967116
6.90	Ki	125.9	nM	CHEMBL2000832
6.60	Ki	251.2	nM	CHEMBL1970104
6.60	Ki	251.2	nM	CHEMBL1993722
6.60	Ki	251.2	nM	CHEMBL225519
6.58	IC50	260	nM	CHEMBL3775576
6.50	Ki	316.2	nM	CHEMBL2005936
6.40	Ki	398.1	nM	CHEMBL1979577
6.40	Ki	398.1	nM	CHEMBL2000354
6.40	Ki	398.1	nM	ALSTERPAULLONE
6.30	Ki	501.2	nM	CHEMBL1965988
6.20	Ki	631	nM	CHEMBL1983025
6.10	Ki	794.3	nM	CHEMBL1974310
6.10	Ki	794.3	nM	CHEMBL1964777
6.10	Ki	794.3	nM	CHEMBL497151
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
6.00	Ki	1000	nM	CHEMBL1992922
6.00	Ki	1000	nM	CHEMBL210032
5.97	Kd	1067	nM	GSK-690693
5.90	Ki	1259	nM	CHEMBL1975138
5.90	Ki	1259	nM	CHEMBL1989708
5.90	Ki	1259	nM	CHEMBL1989029
5.85	IC50	1400	nM	CHEMBL4552628
5.82	IC50	1500	nM	CHEMBL4568087
5.36	IC50	4340	nM	CHEMBL466397
5.00	IC50	1e+04	nM	CHEMBL3884319

PubChem BioAssay actives

9 with measured affinity, of 634 total; 7 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	1715225: Inhibition of human PASK using KKLNRTLSFAEPG as substrate by [gamma-33P]-ATP assay	ic50	0.0055	uM
N-methyl-3-[(1-methylindazol-5-yl)methyl]-2H-indazole-5-carboxamide	1283693: Inhibition of PASK (unknown origin)	ic50	0.2600	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	1425102: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.0670	uM
N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-4-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-5-methylthiophene-2-carboxamide	1637118: Inhibition of recombinant human GST-tagged PASK catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	1.4000	uM
N-[(1R,2S)-2-aminocyclohexyl]-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide	1637118: Inhibition of recombinant human GST-tagged PASK catalytic domain expressed in baculovirus expression system by Z’-LYTE assay	ic50	1.5000	uM
N-(2,6-difluorophenyl)-5-[3-[2-[5-ethyl-2-methoxy-4-[4-(4-methylsulfonylpiperazin-1-yl)piperidin-1-yl]anilino]pyrimidin-4-yl]imidazo[1,2-a]pyridin-2-yl]-2-methoxybenzamide	2167083: Inhibition of human PASK by filter binding assay	ic50	4.3400	uM
2-anilino-7-[(1S)-4-hydroxy-2,3-dihydro-1H-inden-1-yl]-5,5-dimethylpyrrolo[2,3-d]pyrimidin-6-one	1336082: Inhibition of human recombinant GST-tagged PASK catalytic domain (879 to 1323 residues) expressed in baculovirus expression system	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Cyclosporine	decreases expression	3
Acetaminophen	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol A	affects methylation	1
nuciferine	decreases reaction, increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases methylation	1
jinfukang	increases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Arsenic	increases abundance, decreases expression	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Manganese	decreases expression, increases abundance	1
Nickel	increases expression	1
Oxygen	decreases expression	1
Quercetin	decreases expression	1

ChEMBL screening assays

199 unique, capped per target: 198 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1041172	Binding	Residual activity of PASK at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL1963700	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PASK	PubChem BioAssay data set

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_D9MC	Ubigene HEK293 PASK KO	Transformed cell line	Female
CVCL_TC28	HAP1 PASK (-) 1	Cancer cell line	Male
CVCL_TC29	HAP1 PASK (-) 2	Cancer cell line	Male
CVCL_TC30	HAP1 PASK (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00073710	PHASE4	COMPLETED	Study to Evaluate the Effects of Zemplar Injection and Calcijex on Intestinal Absorption of Calcium
NCT00125593	PHASE4	COMPLETED	Study of Heart and Renal Protection
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00155246	PHASE4	COMPLETED	Efficacy of Pentoxifylline on Chronic Kidney Disease
NCT00175149	PHASE4	TERMINATED	Active Vitamin D Effect on Left Ventricular Hypertrophy
NCT00184769	PHASE4	COMPLETED	Growth Hormone Treatment in Infants Aged 1 to 2 Years With Chronic Renal Insufficiency (CRI) and Growth Retardation.
NCT00190580	PHASE4	COMPLETED	Kanagawa Valsartan Trial (KVT): Effects of Valsartan on Renal and Cardiovascular Disease
NCT00194961	PHASE4	TERMINATED	Effect of Growth Hormone on Leptin, Cytokines and Body Composition of Children With Growth Failure Due to Chronic Kidney Disease
NCT00239642	PHASE4	COMPLETED	Safety and Efficacy of Iron Sucrose in Children
NCT00324571	PHASE4	COMPLETED	Dialysis Clinical Outcomes Revisited (DCOR) Trial
NCT00364884	PHASE4	UNKNOWN	Keto-/Amino Acid Supplemented Low Protein Diet in Patients With Chronic Kidney Disease
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00384618	PHASE4	TERMINATED	Anti-Oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study
NCT00478543	PHASE4	COMPLETED	Loop Diuretics in Chronic Kidney Disease
NCT00632125	PHASE4	COMPLETED	Post-authorization Safety Study in CKD Subjects Receiving HX575 i.v.
NCT00644046	PHASE4	COMPLETED	Chronic Kidney Disease Prevention of An-Lo District, Keelung
NCT00719316	PHASE4	UNKNOWN	Aliskiren and Muscle Sympathetic Nerve Activity
NCT00725517	PHASE4	COMPLETED	Efficacy and Safety of a 7.5% Icodextrin Peritoneal Dialysis Solution in Once-Daily Long Dwell Exchange
NCT00741585	PHASE4	COMPLETED	Prognostic Value of the Circadian Pattern of Ambulatory Blood Pressure for Multiple Risk Assessment
NCT00749736	PHASE4	COMPLETED	The Role of Vitamin D in Immune Function in Patients With Chronic Kidney Disease (CKD) Stages 3 and 4.
NCT00752102	PHASE4	COMPLETED	Vitamin D and Coronary Calcification Study
NCT00756145	PHASE4	COMPLETED	The Use of Low Molecular Weight Heparin in Hemodiafiltration
NCT00768638	PHASE4	COMPLETED	Study of Atorvastatin Dose Dependent Reduction of Proteinuria
NCT00786136	PHASE4	COMPLETED	Rosuvastatin Prevent Contrast Induced Acute Kidney Injury in Patients With Diabetes
NCT00803712	PHASE4	COMPLETED	20070360 Incident Dialysis
NCT00812123	PHASE4	COMPLETED	Calcineurin Free Immunosuppression in Renal Transplant Recipients
NCT00823303	PHASE4	COMPLETED	Paricalcitol Versus Calcitriol for Efficacy and Safety in Stage 3/4 Chronic Kidney Disease (CKD) With Secondary Hyperparathyroidism (SHPT)
NCT00830037	PHASE4	TERMINATED	A Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease
NCT00852969	PHASE4	COMPLETED	Niacin and Endothelial Function in Early CKD
NCT00858299	PHASE4	UNKNOWN	The Change of Urinary Angiotensinogen Excretion After Valsartan Treatment in Patients With Persistent Proteinuria
NCT00860431	PHASE4	COMPLETED	Kremezin Study Against Renal Disease Progression in Korea
NCT00882401	PHASE4	COMPLETED	Vitamin D, Chronic Kidney Disease (CKD) and the Microcirculation
NCT00889629	PHASE4	COMPLETED	Pilot Study Evaluating Doxercalciferol Replacement Therapy in Kidney Transplant Recipients
NCT00892892	PHASE4	WITHDRAWN	Sympathetic Nerve Activity in Renal Failure
NCT00893425	PHASE4	COMPLETED	Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria
NCT00908310	PHASE4	COMPLETED	Post-marketing Safety Study in Patients With Moderate Renal Insufficiency Who Receive Omniscan for Contrast-enhanced Magnetic Resonance Imaging (MRI)
NCT00958451	PHASE4	COMPLETED	Vitamin D Deficiency in Chronic Kidney Disease (CKD) Patients