PANK3

Summary

PANK3 (pantothenate kinase 3, HGNC:19365) is a protein-coding gene on chromosome 5q34, encoding Pantothenate kinase 3 (Q9H999). Catalyzes the phosphorylation of pantothenate to generate 4’-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.

This gene encodes a protein belonging to the pantothenate kinase family. Pantothenate kinase is a key regulatory enzyme in the biosynthesis of coenzyme A (CoA) in bacteria and mammalian cells. It catalyzes the first committed step in the universal biosynthetic pathway leading to CoA and is itself subject to regulation through feedback inhibition by CoA. This family member is expressed most abundantly in the liver.

Source: NCBI Gene 79646 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 34 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_024594

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19365
Approved symbol	PANK3
Name	pantothenate kinase 3
Location	5q34
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12899
Ensembl gene	ENSG00000120137
Ensembl biotype	protein_coding
OMIM	606161
Entrez	79646

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000239231, ENST00000520504, ENST00000522176, ENST00000908768

RefSeq mRNA: 1 — MANE Select: NM_024594 NM_024594

CCDS: CCDS4368

Canonical transcript exons

ENST00000239231 — 7 exons

Exon	Start	End
ENSE00000812753	168566013	168566266
ENSE00000812754	168563889	168564065
ENSE00001249572	168548495	168557621
ENSE00001370266	168579256	168579368
ENSE00003483262	168568646	168568998
ENSE00003542274	168559032	168559157
ENSE00003557288	168561393	168561516

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7297 / max 170.5182, expressed in 1796 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64714	8.9731	1763
64716	7.4696	1701
64711	0.1182	38
64715	0.0905	20
203787	0.0783	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.22	gold quality
hair follicle	UBERON:0002073	97.54	gold quality
adrenal tissue	UBERON:0018303	97.17	gold quality
upper leg skin	UBERON:0004262	97.09	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.07	gold quality
colonic mucosa	UBERON:0000317	96.89	gold quality
skin of hip	UBERON:0001554	96.57	gold quality
ileal mucosa	UBERON:0000331	96.14	gold quality
choroid plexus epithelium	UBERON:0003911	96.04	gold quality
duodenum	UBERON:0002114	95.78	gold quality
tibia	UBERON:0000979	95.61	gold quality
upper arm skin	UBERON:0004263	95.19	gold quality
jejunum	UBERON:0002115	95.17	gold quality
pigmented layer of retina	UBERON:0001782	95.02	gold quality
cortical plate	UBERON:0005343	95.02	gold quality
retina	UBERON:0000966	94.99	gold quality
mammalian vulva	UBERON:0000997	94.80	gold quality
postcentral gyrus	UBERON:0002581	94.68	gold quality
gingival epithelium	UBERON:0001949	94.61	gold quality
mammary duct	UBERON:0001765	94.54	gold quality
esophagus squamous epithelium	UBERON:0006920	94.44	gold quality
epithelium of mammary gland	UBERON:0003244	94.31	gold quality
gingiva	UBERON:0001828	94.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.10	gold quality
trabecular bone tissue	UBERON:0002483	93.89	gold quality
cranial nerve II	UBERON:0000941	93.83	gold quality
penis	UBERON:0000989	93.77	gold quality
parietal lobe	UBERON:0001872	93.73	gold quality
tongue squamous epithelium	UBERON:0006919	93.40	gold quality
squamous epithelium	UBERON:0006914	93.32	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

171 targeting PANK3, 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-126-5P	100.00	72.71	3180
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 2)

• analysis of the homodimeric structures of the catalytic cores of PanK1alpha and PanK3 in complex with acetyl-CoA and the the structural effects of the PanK2 mutations that have been implicated in neurodegeneration (PMID:17631502)
• Biochemical analyses showed that the transition between the inactive and active conformations, as assessed by the binding of either ATP.Mg(2+) or acyl-CoA to PANK3, is highly cooperative indicating that both protomers move in concert. (PMID:27555321)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pank3	ENSMUSG00000018846
rattus_norvegicus	Pank3	ENSRNOG00000007419
drosophila_melanogaster	fbl	FBGN0011205

Paralogs (3): PANK2 (ENSG00000125779), PANK1 (ENSG00000152782), PANK4 (ENSG00000157881)

Protein

Protein identifiers

Pantothenate kinase 3 — Q9H999 (reviewed: Q9H999)

Alternative names: Pantothenic acid kinase 3

All UniProt accessions (2): E5RHA5, Q9H999

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of pantothenate to generate 4’-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Highly expressed in the liver.

Activity regulation. Subject to allosteric regulation, exists in two distinct conformational states, a catalytically incompetent (or open) conformation stabilized by the binding of acetyl(acyl)-CoA, and a catalytically competent (or closed) conformation stabilized by ATP-binding. Inhibited by acetyl-CoA and its thioesters which act as allosteric inhibitors and compete with the ATP-binding site. Inhibited by sulfonylureas and thiazolidinediones. Activated by oleoylethanolamide, palmitoyl-carnitine and oleoyl-carnitine.

Pathway. Cofactor biosynthesis; coenzyme A biosynthesis; CoA from (R)-pantothenate: step 1/5.

Similarity. Belongs to the type II pantothenate kinase family.

RefSeq proteins (1): NP_078870* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004567	Type_II_PanK	Family
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF03630

Enzyme classification (BRENDA):

• EC 2.7.1.33 — pantothenate kinase (BRENDA: 34 organisms, 95 substrates, 317 inhibitors, 102 Km, 58 kcat entries)

Substrate kinetics (BRENDA)

39 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0031–9.59	31
(R)-PANTOTHENATE	0.0057–0.833	14
PANTOTHENATE	0.009–1.3	13
(2S)-3-ETHYL-2-HYDROXY-3-(HYDROXYMETHYL)-N-[3-OX	0.59–1.2	2
N-HEPTYLPANTOTHENAMIDE	0.008–0.124	2
N-PENTYLPANTOTHENAMIDE	0.003–0.14	2
PANTOTHENOL	0.25–0.28	2
(2R)-2,4-DIHYDROXY-3,3-DIMETHYL-N-(3-OXO-3-[[(PI	1	1
(2R)-2,4-DIHYDROXY-3,3-DIMETHYL-N-(3-OXO-3-[[2-(	1	1
(2R)-2,4-DIHYDROXY-3,3-DIMETHYL-N-(3-OXO-3-[[2-(	0.11	1
(2R)-2,4-DIHYDROXY-3,3-DIMETHYL-N-(3-[[2-OXO-2-(	1.2	1
(2R)-2,4-DIHYDROXY-3,3-DIMETHYL-N-(3-[[3-(MORPHO	0.35	1
(2R)-2,4-DIHYDROXY-3,3-DIMETHYL-N-[(1-PENTYL-1H-	0.19	1
(2R)-2,4-DIHYDROXY-3,3-DIMETHYL-N-[3-(1-PROPYL-1	1	1
(2R)-2,4-DIHYDROXY-3,3-DIMETHYL-N-[3-OXO-3-(PENT	0.036	1

Catalyzed reactions (Rhea), 1 shown:

• (R)-pantothenate + ATP = (R)-4’-phosphopantothenate + ADP + H(+) (RHEA:16373)

UniProt features (57 total): helix 22, strand 16, mutagenesis site 8, turn 5, binding site 3, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7UE7	X-RAY DIFFRACTION	1.55
7UE3	X-RAY DIFFRACTION	1.56
6PE6	X-RAY DIFFRACTION	1.6
6B3V	X-RAY DIFFRACTION	1.6
7UE5	X-RAY DIFFRACTION	1.63
7UEQ	X-RAY DIFFRACTION	1.7
7UER	X-RAY DIFFRACTION	1.7
7UEY	X-RAY DIFFRACTION	1.7
7UE6	X-RAY DIFFRACTION	1.74
7UEO	X-RAY DIFFRACTION	1.8
7UES	X-RAY DIFFRACTION	1.8
7UEV	X-RAY DIFFRACTION	1.8
9D2O	X-RAY DIFFRACTION	1.8
9D2P	X-RAY DIFFRACTION	1.8
5KPR	X-RAY DIFFRACTION	1.83
9CLQ	X-RAY DIFFRACTION	1.85
7UET	X-RAY DIFFRACTION	1.9
7UEX	X-RAY DIFFRACTION	1.9
7UE4	X-RAY DIFFRACTION	1.94
3MK6	X-RAY DIFFRACTION	1.98
6X4L	X-RAY DIFFRACTION	2
7UEP	X-RAY DIFFRACTION	2
7UEU	X-RAY DIFFRACTION	2
5KQ8	X-RAY DIFFRACTION	2
7UE8	X-RAY DIFFRACTION	2.01
9ECH	X-RAY DIFFRACTION	2.04
2I7P	X-RAY DIFFRACTION	2.05
9ECG	X-RAY DIFFRACTION	2.09
6X4K	X-RAY DIFFRACTION	2.1
3SMS	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H999-F1	94.32	0.86

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): 138 (proton acceptor)

Ligand- & substrate-binding residues (3): 192; 195; 207

Mutagenesis-validated functional residues (8):

Position	Phenotype
207	increases affinity for atp and decreases affinity for acetyl-coa. increases acetyl-coa production.
267	loss of catalytic activity but can bind atp normally.
269	loss of catalytic activity but can bind atp normally.
19	loss of catalytic activity.
138	loss of catalytic activity.
138	prevents acetyl-coa production.
195	retains 30% of wild-type activity. refractory to inhibition by acetyl-coa. exhibits a 10-fold increase in the km for pan
207	loss of catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-196783	Coenzyme A biosynthesis

MSigDB gene sets: 194 (showing top): RNGTGGGC_UNKNOWN, RRAGTTGT_UNKNOWN, GOBP_COENZYME_A_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, CEBPB_01, ATGTTAA_MIR302C, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, KOYAMA_SEMA3B_TARGETS_UP, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN

GO Biological Process (2): coenzyme A biosynthetic process (GO:0015937), phosphorylation (GO:0016310)

GO Molecular Function (8): pantothenate kinase activity (GO:0004594), ATP binding (GO:0005524), vitamin binding (GO:0019842), protein homodimerization activity (GO:0042803), acetyl-CoA binding (GO:1905502), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Vitamin B5 (pantothenate) metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
coenzyme A metabolic process	1
sulfur compound biosynthetic process	1
purine-containing compound biosynthetic process	1
nucleoside phosphate biosynthetic process	1
phosphate-containing compound metabolic process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
small molecule binding	1
identical protein binding	1
protein dimerization activity	1
acyl-CoA binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

823 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PANK3	PPCS	Q9HAB8	697
PANK3	PPCDC	Q96CD2	686
PANK3	COASY	Q13057	680
PANK3	FBL	P22087	497
PANK3	SMC4	Q9NTJ3	460
PANK3	PPAN	Q9NQ55	438
PANK3	NUDT7	P0C024	419
PANK3	DCAKD	Q8WVC6	393
PANK3	NUDT19	A8MXV4	391
PANK3	POLM	Q9NP87	387
PANK3	SLC5A6	Q9Y289	382
PANK3	ESRRA	P11474	375
PANK3	A0A0B4J1V8	A0A0B4J1V8	326
PANK3	GALK2	Q01415	326
PANK3	CHD9	Q3L8U1	326

IntAct

8 interactions, top by confidence:

A	B	Type	Score
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
YWHAB	SHTN1	psi-mi:“MI:0914”(association)	0.530
PANK3	PANK2	psi-mi:“MI:0915”(physical association)	0.400
FADS2	PANK3	psi-mi:“MI:0915”(physical association)	0.400
YWHAH	SHTN1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	SHTN1	psi-mi:“MI:0914”(association)	0.350
SCD	PANK1	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): PANK3 (Affinity Capture-RNA), PANK3 (Affinity Capture-RNA), PANK2 (Affinity Capture-MS), PANK3 (Affinity Capture-MS), PANK3 (Affinity Capture-MS), PANK3 (Affinity Capture-MS), PANK3 (Co-fractionation), PANK3 (Affinity Capture-MS), PANK3 (Affinity Capture-MS), PANK3 (Affinity Capture-MS), PANK3 (Affinity Capture-MS), PANK2 (Cross-Linking-MS (XL-MS)), PANK3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1D8PEL1, A0A1D8PLH0, A9RY03, O13935, O13983, O14242, O14353, O42821, O42895, O74742, O74878, O94266, P04385, P07277, P09608, P13045, P24521, P43122, P48445, P50506, P56091, P78875, P78963, Q04409, Q08DA5, Q09780, Q09839, Q54DN6, Q54KI3, Q54NU9, Q6BY07, Q6CUZ3, Q6FWD1, Q8LGM7, Q8R2W9, Q92407, Q9C6T1, Q9FLE2, Q9FZ57, Q9H999

Diamond homologs: B7H5Z8, B7IKP3, B7JSQ5, Q08DA5, Q2FEZ8, Q2FWC7, Q2YUM3, Q49Z76, Q4L811, Q5HE70, Q5HM92, Q63A51, Q6G7I0, Q6GEU5, Q6HHK0, Q736G1, Q7A4D4, Q81C81, Q81PB2, Q8CRM3, Q8EN08, Q8K4K6, Q8NVG0, Q99SC8, Q9H999, O74962, O80765, Q04430, Q0J035, Q4R4U1, Q5R5F8, Q69TF4, Q7M753, Q80YV4, Q8L5Y9, Q8R2W9, Q8TE04, Q923S8, Q9BZ23, Q9NVE7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1417 predictions. Top by Δscore:

Variant	Effect	Δscore
5:168561387:TTTTA:T	donor_loss	1.0000
5:168561388:TTTAC:T	donor_loss	1.0000
5:168561389:TTA:T	donor_loss	1.0000
5:168561390:TAC:T	donor_loss	1.0000
5:168561391:A:C	donor_loss	1.0000
5:168561392:C:A	donor_loss	1.0000
5:168561512:CAAAA:C	acceptor_gain	1.0000
5:168561514:AAA:A	acceptor_gain	1.0000
5:168561517:C:CC	acceptor_gain	1.0000
5:168563882:AACTT:A	donor_loss	1.0000
5:168563883:ACTT:A	donor_loss	1.0000
5:168563884:CTTAC:C	donor_loss	1.0000
5:168563885:TTACC:T	donor_loss	1.0000
5:168563886:TA:T	donor_loss	1.0000
5:168563887:A:AG	donor_loss	1.0000
5:168564066:C:CC	acceptor_gain	1.0000
5:168566067:A:AC	donor_gain	1.0000
5:168566067:ACT:A	donor_gain	1.0000
5:168566068:C:CC	donor_gain	1.0000
5:168566068:CTC:C	donor_gain	1.0000
5:168566263:CAAT:C	acceptor_gain	1.0000
5:168566267:C:CC	acceptor_gain	1.0000
5:168568644:A:AC	donor_gain	1.0000
5:168568645:C:CT	donor_gain	1.0000
5:168568682:T:TA	donor_gain	1.0000
5:168568999:C:CC	acceptor_gain	1.0000
5:168579254:A:AC	donor_gain	1.0000
5:168579255:C:CC	donor_gain	1.0000
5:168579255:CAGG:C	donor_gain	1.0000
5:168579255:CAGGG:C	donor_gain	1.0000

AlphaMissense

2414 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:168559044:A:C	F350L	1.000
5:168559044:A:T	F350L	1.000
5:168559046:A:G	F350L	1.000
5:168559125:A:C	F323L	1.000
5:168559125:A:T	F323L	1.000
5:168559127:A:G	F323L	1.000
5:168559132:C:A	G321V	1.000
5:168559132:C:T	G321E	1.000
5:168559133:C:G	G321R	1.000
5:168559133:C:T	G321R	1.000
5:168561403:G:T	A309D	1.000
5:168561424:C:T	G302D	1.000
5:168561429:G:C	N300K	1.000
5:168561429:G:T	N300K	1.000
5:168561455:C:G	A292P	1.000
5:168561511:C:T	G273E	1.000
5:168563913:A:G	L263S	1.000
5:168563952:A:T	V250D	1.000
5:168564042:C:T	G220D	1.000
5:168564060:C:T	G214E	1.000
5:168564061:C:G	G214R	1.000
5:168564061:C:T	G214R	1.000
5:168566019:C:T	G210E	1.000
5:168566063:A:C	S195R	1.000
5:168566063:A:T	S195R	1.000
5:168566065:T:G	S195R	1.000
5:168566070:C:T	G193E	1.000
5:168568824:A:G	L68P	1.000
5:168557621:C:G	G355R	0.999
5:168559033:T:A	E354V	0.999

dbSNP variants (sampled 300 via entrez): RS1000036735 (5:168558903 G>A,T), RS1000169789 (5:168579573 G>A,C), RS1000254883 (5:168566508 G>A,C), RS1000361902 (5:168548171 G>A), RS1000402195 (5:168579534 C>A,G), RS1000664102 (5:168552828 C>T), RS1000672967 (5:168571507 A>G), RS1000860427 (5:168553022 C>T), RS1001130895 (5:168572396 G>A,C), RS1001308521 (5:168567775 A>G), RS1001411113 (5:168565490 G>A,T), RS1001473861 (5:168573800 GAAT>G), RS1001551392 (5:168567366 C>A), RS1001579704 (5:168558484 A>G), RS1001860238 (5:168578678 G>A)

Disease associations

OMIM: gene MIM:606161 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_581	Metabolite levels	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010501	indole-3-propionate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3407328 (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: 13 (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
CHEMBL5595360	CLAZIPROTAMIDE	2	13

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

ChEMBL bioactivities

82 potent at pChembl≥5 of 90 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.66	IC50	0.22	nM	CHEMBL5082138
9.40	IC50	0.4	nM	CHEMBL5082138
9.22	IC50	0.6	nM	CHEMBL5591518
9.15	IC50	0.7	nM	CHEMBL363699
9.00	IC50	1	nM	CHEMBL5077276
8.99	IC50	1.03	nM	CHEMBL5593149
8.92	IC50	1.2	nM	CHEMBL5579772
8.89	IC50	1.3	nM	CHEMBL5077276
8.86	IC50	1.39	nM	CLAZIPROTAMIDE
8.82	IC50	1.5	nM	CHEMBL5595577
8.80	IC50	1.6	nM	CHEMBL5591881
8.80	IC50	1.6	nM	CHEMBL5583598
8.74	IC50	1.8	nM	CHEMBL5094733
8.66	IC50	2.2	nM	CHEMBL5594834
8.54	IC50	2.9	nM	CHEMBL5593336
8.42	IC50	3.8	nM	CHEMBL5595254
8.40	IC50	4	nM	CHEMBL5078496
8.28	IC50	5.3	nM	CHEMBL5583913
8.28	IC50	5.2	nM	CHEMBL5593309
8.26	IC50	5.5	nM	CHEMBL5595772
8.24	IC50	5.8	nM	CHEMBL5590794
8.19	IC50	6.5	nM	CHEMBL5583858
8.16	IC50	6.9	nM	CHEMBL5592936
8.12	IC50	7.5	nM	CHEMBL5591337
8.05	IC50	8.9	nM	CHEMBL5590407
8.05	IC50	9	nM	CHEMBL5589594
8.05	IC50	8.9	nM	CHEMBL5592363
8.01	IC50	9.7	nM	CHEMBL5595986
8.00	IC50	10	nM	CHEMBL5085732
8.00	IC50	10	nM	CHEMBL5082695
7.90	IC50	12.5	nM	CHEMBL5593608
7.89	IC50	12.9	nM	CHEMBL5592189
7.78	IC50	16.8	nM	CHEMBL5593897
7.75	IC50	17.6	nM	CHEMBL5592747
7.72	IC50	19.2	nM	CHEMBL5593435
7.70	IC50	20	nM	CHEMBL5093027
7.70	IC50	20	nM	CHEMBL5591781
7.60	IC50	25	nM	CHEMBL3410246
7.54	IC50	29	nM	CHEMBL5075383
7.46	IC50	35	nM	CHEMBL5583789
7.30	IC50	50.4	nM	CHEMBL5594484
7.22	IC50	60	nM	CHEMBL5078248
7.22	IC50	60	nM	CHEMBL5092780
7.19	IC50	64	nM	CHEMBL5592445
6.92	IC50	120	nM	CHEMBL3410245
6.85	IC50	140	nM	CHEMBL5088913
6.80	IC50	160	nM	CHEMBL5088098
6.77	IC50	170	nM	CHEMBL5092773
6.75	IC50	180	nM	CHEMBL3410244
6.70	IC50	200	nM	CHEMBL5073319

PubChem BioAssay actives

81 with measured affinity, of 161 total; 50 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
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-(4-propan-2-ylphenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0002	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-(3-fluoro-4-propan-2-ylphenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0006	uM
4-(6-chloropyridazin-3-yl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0007	uM
6-[4-[2-(4-propan-2-ylphenyl)acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0010	uM
6-[4-[2-(4-cyclopropyl-2-fluorophenyl)acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0010	uM
6-[4-[2-(3-fluoro-4-propan-2-ylphenyl)acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0012	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-(4-cyclopropyl-3-fluorophenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0014	uM
6-[4-[2-[4-(1,1,1-trifluoropropan-2-yl)phenyl]acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0015	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-[4-(1,1,1-trifluoropropan-2-yl)phenyl]ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0016	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-(4-cyclopropyl-2-fluorophenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0016	uM
1-[4-(5-chloropyrazin-2-yl)piperazin-1-yl]-2-(4-propan-2-ylphenyl)ethanone	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0018	uM
1-[(2S)-4-(6-chloropyridazin-3-yl)-2-methylpiperazin-1-yl]-2-(4-cyclopropyl-3-fluorophenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0022	uM
1-[(2S)-4-(6-chloropyridazin-3-yl)-2-methylpiperazin-1-yl]-2-(4-cyclopropylphenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0029	uM
1-[(2R)-4-(6-chloropyridazin-3-yl)-2-methylpiperazin-1-yl]-2-(4-cyclopropylphenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0038	uM
4-(6-cyanopyridazin-3-yl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0040	uM
6-[(3S)-4-[2-(4-cyclopropylphenyl)acetyl]-3-methylpiperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0052	uM
6-[4-[2-(4-cyclopropylphenyl)acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0053	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-(4-cyclopropyl-3,5-difluorophenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0055	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-(4-cyclopropylphenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0058	uM
6-[(3S)-4-[2-(4-cyclopropyl-3-fluorophenyl)acetyl]-3-methylpiperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0065	uM
1-[(2R)-4-(6-chloropyridazin-3-yl)-2-methylpiperazin-1-yl]-2-(4-cyclopropyl-3-fluorophenyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0069	uM
6-[4-[2-[4-(1-hydroxypropan-2-yl)phenyl]acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0075	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-[4-(2,2,2-trifluoroethyl)phenyl]ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0089	uM
6-[4-[2-(4-cyclopropyl-3-fluorophenyl)acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0089	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-(6-propan-2-yl-3-pyridinyl)ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0090	uM
6-[4-[2-[4-(1-fluoropropan-2-yl)phenyl]acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0097	uM
(4-propan-2-ylphenyl) 4-(6-cyanopyridazin-3-yl)piperazine-1-carboxylate	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0100	uM
5-[4-[2-(4-propan-2-ylphenyl)acetyl]piperazin-1-yl]pyrimidine-2-carbonitrile	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0100	uM
6-[(3R)-4-[2-(4-cyclopropyl-3-fluorophenyl)acetyl]-3-methylpiperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0125	uM
6-[(3R)-4-[2-(4-cyclopropylphenyl)acetyl]-3-methylpiperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0129	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-[4-(dimethylamino)phenyl]ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0168	uM
6-[4-[2-(6-propan-2-yl-3-pyridinyl)acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0176	uM
6-[4-[2-(4-cyclopropyl-3,5-difluorophenyl)acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0192	uM
4-(5-nitro-2-pyridinyl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0200	uM
6-[4-[2-(5-fluoro-6-propan-2-yl-3-pyridinyl)acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0200	uM
3-(4,6-dimethyl-3,7,8,10-tetrazatricyclo[7.4.0.02,7]trideca-1,3,5,8,10,12-hexaen-5-yl)-N-(3-methylsulfanylphenyl)propanamide	1196665: Inhibition of purified human Pank3 using d-[1-14C]pantothenate as substrate after 10 mins by radiochemical enzyme assay	ic50	0.0250	uM
4-(5-cyanopyrazin-2-yl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0290	uM
6-[4-[2-[4-(2,2,2-trifluoroethyl)phenyl]acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0350	uM
1-[4-(6-chloropyridazin-3-yl)piperazin-1-yl]-2-[4-(trifluoromethoxy)phenyl]ethanone	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0504	uM
6-[4-[2-(4-tert-butylphenyl)acetyl]piperazin-1-yl]pyridine-3-carbonitrile	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0600	uM
6-[4-[2-(4-propan-2-ylphenyl)acetyl]piperazin-1-yl]pyridine-3-carbonitrile	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.0600	uM
6-[4-[2-[4-(dimethylamino)phenyl]acetyl]piperazin-1-yl]pyridazine-3-carbonitrile	2114839: Inhibition of PANK3 (unknown origin) using D-[1-14C]pantothenate as substrate incubated for 10 mins in presence of ATP by scintillation counting analysis	ic50	0.0640	uM
3-(12-oxo-7-thia-9,11-diazatricyclo[6.4.0.02,6]dodeca-1(8),2(6),9-trien-10-yl)-N-(4-propan-2-ylphenyl)propanamide	1196667: Inhibition of Pank3 (unknown origin) by Kinase Glo HTS assay	ic50	0.1200	uM
4-(4-cyanopyrimidin-2-yl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.1400	uM
4-(5-bromopyrimidin-2-yl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.1600	uM
4-(2-cyanopyrimidin-5-yl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.1700	uM
N-(2-bicyclo[2.2.1]heptanyl)-4-(ethylsulfonylamino)benzamide	1196667: Inhibition of Pank3 (unknown origin) by Kinase Glo HTS assay	ic50	0.1800	uM
6-[4-[2-(4-cyclopropylphenyl)acetyl]piperazin-1-yl]pyridine-3-carbonitrile	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.2000	uM
4-(5-chloro-2-pyridinyl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.2200	uM
4-(5-bromo-2-pyridinyl)-N-(4-propan-2-ylphenyl)piperazine-1-carboxamide	1831326: Inhibition of human recombinant N-terminal His6-fusion tagged PanK3 expressed in Escherichia coli BL21 (DE3) measured after 10 mins in presence of ATP and D-[14C]-pantothenate by scintillation counting method	ic50	0.2200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression, decreases expression	3
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases expression	1
pantogab	decreases activity	1
cobaltous chloride	increases expression	1
nickel chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
monomethylarsonous acid	decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	decreases expression, increases abundance, affects cotreatment	1
Azacitidine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Clozapine	affects cotreatment, increases expression	1
Cuprizone	increases expression, affects cotreatment	1
Ethyl Methanesulfonate	decreases expression	1
Fluoxetine	increases expression	1
Formaldehyde	decreases expression	1
Isoflavones	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Nicotine	increases expression	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Rotenone	increases expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3413789	Binding	Inhibition of purified human Pank3 using d-[1-14C]pantothenate as substrate after 10 mins by radiochemical enzyme assay	A high-throughput screen reveals new small-molecule activators and inhibitors of pantothenate kinases. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2G0	HAP1 PANK3 (-) 1	Cancer cell line	Male
CVCL_E2G1	HAP1 PANK3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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