PCK2

Summary

PCK2 (phosphoenolpyruvate carboxykinase 2, mitochondrial, HGNC:8725) is a protein-coding gene on chromosome 14q11.2-q12, encoding Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (Q16822). Mitochondrial phosphoenolpyruvate carboxykinase that catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.

This gene encodes a mitochondrial enzyme that catalyzes the conversion of oxaloacetate to phosphoenolpyruvate in the presence of guanosine triphosphate (GTP). A cytosolic form of this protein is encoded by a different gene and is the key enzyme of gluconeogenesis in the liver. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 5106 — RefSeq curated summary.

At a glance

• Gene–disease (curated): peripheral neuropathy (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 33 total
• GTEx eGene: eQTL in 35 tissues, sQTL in 19 (q < 0.05)
• Phenotypes (HPO): 27
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.06 (unconstrained)
• MANE Select transcript: NM_004563
• Interaction hub: 2,020 STRING partners (top 7% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8725
Approved symbol	PCK2
Name	phosphoenolpyruvate carboxykinase 2, mitochondrial
Location	14q11.2-q12
Locus type	gene with protein product
Status	Approved
Aliases	PEPCK, PEPCK2
Ensembl gene	ENSG00000100889
Ensembl biotype	protein_coding
OMIM	614095
Entrez	5106

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 30 protein_coding, 10 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000216780

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 6, TSL 3: 4, TSL 5: 4

ENST00000216780, ENST00000396973, ENST00000545054, ENST00000557969, ENST00000558096, ENST00000558674, ENST00000559171, ENST00000559250, ENST00000559503, ENST00000559584, ENST00000559837, ENST00000560106, ENST00000560657, ENST00000560736, ENST00000561050, ENST00000561286, ENST00000905563, ENST00000905564, ENST00000905565, ENST00000905566, ENST00000905567, ENST00000905568, ENST00000905569, ENST00000905570, ENST00000905571, ENST00000934106, ENST00000958076, ENST00000997810, ENST00000997811, ENST00000997813, ENST00000997814, ENST00000997816, ENST00000997817, ENST00000997820, ENST00000997823, ENST00000997824, ENST00001027054, ENST00001063885, ENST00001063886, ENST00001063888, ENST00001117645, ENST00001117646, ENST00001125883, ENST00001136324

RefSeq mRNA: 4 — MANE Select: NM_004563 NM_001018073, NM_001291556, NM_001308054, NM_004563

CCDS: CCDS41928, CCDS76660, CCDS9609

Canonical transcript exons

ENST00000216780 — 10 exons

Exon	Start	End
ENSE00000654200	24102753	24102890
ENSE00002541482	24094311	24094434
ENSE00003489581	24099995	24100213
ENSE00003546979	24098203	24098387
ENSE00003554857	24096892	24097137
ENSE00003567725	24103160	24103255
ENSE00003595695	24099049	24099236
ENSE00003625222	24099558	24099720
ENSE00003640250	24098475	24098678
ENSE00003894179	24103510	24104125

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 98.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.6443 / max 918.2773, expressed in 1790 samples.

Highest expression (Bgee): lobe of liver, mucosa of transverse colon, small intestine Peyer’s patch, rectum, transverse colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PCK2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 35 tissues and its splicing (sQTL) in 19 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 54 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	4.3e-49	+0.49	14:24058463:G:A
Skin Sun Exposed Lower leg	eqtl	1.4e-33	+0.42	14:24058463:G:A
Cells EBV-transformed lymphocytes	sqtl	1.8e-31	+3.43	14:24100209:A:G
Cells Cultured fibroblasts	sqtl	1.6e-27	+2.81	14:24100209:A:G
Artery Tibial	eqtl	6.4e-19	+0.20	14:24058463:G:A
Nerve Tibial	sqtl	1.6e-14	+2.17	14:24100209:A:G
Adipose Subcutaneous	sqtl	2.0e-14	+2.02	14:24100209:A:G
Brain Anterior cingulate cortex BA24	eqtl	4.0e-13	-0.42	14:24094003:T:C
Colon Sigmoid	eqtl	4.8e-13	+0.23	14:24058463:G:A
Artery Tibial	sqtl	5.2e-12	+2.15	14:24098299:T:C
Adipose Subcutaneous	eqtl	2.5e-11	+0.19	14:24089025:C:T
Brain Frontal Cortex BA9	eqtl	2.8e-11	-0.39	14:24089025:C:T
Brain Cortex	eqtl	8.4e-10	-0.39	14:24094003:T:C
Esophagus Muscularis	eqtl	1.7e-09	+0.20	14:24058463:G:A
Colon Transverse	sqtl	4.6e-09	+2.23	14:24088398:G:A
Esophagus Mucosa	eqtl	5.6e-09	+0.22	14:24058463:G:A
Artery Aorta	eqtl	2.0e-08	+0.22	14:24056065:G:A
Skin Sun Exposed Lower leg	sqtl	3.0e-08	+1.65	14:24100209:A:G
Muscle Skeletal	eqtl	3.7e-08	+0.18	14:24056065:G:A
Nerve Tibial	eqtl	3.8e-08	+0.14	14:24094003:T:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
138974	45.0347	1785
138973	0.5671	262
138975	0.0425	21

Top tissues by expression

showing 100 of 256 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.84	gold quality
mucosa of transverse colon	UBERON:0004991	96.78	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.89	gold quality
rectum	UBERON:0001052	94.01	gold quality
transverse colon	UBERON:0001157	93.02	gold quality
small intestine	UBERON:0002108	92.82	gold quality
mucosa of stomach	UBERON:0001199	92.67	gold quality
body of pancreas	UBERON:0001150	91.50	gold quality
granulocyte	CL:0000094	90.82	gold quality
right lobe of thyroid gland	UBERON:0001119	89.86	gold quality
left lobe of thyroid gland	UBERON:0001120	89.61	gold quality
liver	UBERON:0002107	89.10	gold quality
leukocyte	CL:0000738	88.59	gold quality
monocyte	CL:0000576	88.52	gold quality
vermiform appendix	UBERON:0001154	88.16	gold quality
spleen	UBERON:0002106	87.98	gold quality
pancreas	UBERON:0001264	87.97	gold quality
minor salivary gland	UBERON:0001830	87.79	gold quality
upper lobe of left lung	UBERON:0008952	87.67	gold quality
stromal cell of endometrium	CL:0002255	87.56	gold quality
metanephros cortex	UBERON:0010533	87.39	gold quality
omental fat pad	UBERON:0010414	87.37	gold quality
peritoneum	UBERON:0002358	87.24	gold quality
adult mammalian kidney	UBERON:0000082	87.23	gold quality
thyroid gland	UBERON:0002046	86.93	gold quality
duodenum	UBERON:0002114	86.79	gold quality
body of stomach	UBERON:0001161	86.50	gold quality
islet of Langerhans	UBERON:0000006	85.69	gold quality
left coronary artery	UBERON:0001626	85.39	gold quality
jejunal mucosa	UBERON:0000399	85.38	gold quality
tibial artery	UBERON:0007610	85.38	gold quality
popliteal artery	UBERON:0002250	85.37	gold quality
cortex of kidney	UBERON:0001225	85.26	gold quality
right lung	UBERON:0002167	85.12	gold quality
upper lobe of lung	UBERON:0008948	85.08	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.82	gold quality
skin of leg	UBERON:0001511	84.36	gold quality
left testis	UBERON:0004533	84.21	gold quality
aorta	UBERON:0000947	84.15	gold quality
right testis	UBERON:0004534	84.10	gold quality
right adrenal gland	UBERON:0001233	84.02	gold quality
intestine	UBERON:0000160	83.92	gold quality
esophagus mucosa	UBERON:0002469	83.84	gold quality
ileal mucosa	UBERON:0000331	83.82	gold quality
tibial nerve	UBERON:0001323	83.79	gold quality
right adrenal gland cortex	UBERON:0035827	83.74	gold quality
gall bladder	UBERON:0002110	83.57	gold quality
skin of abdomen	UBERON:0001416	83.39	gold quality
descending thoracic aorta	UBERON:0002345	83.31	gold quality
right coronary artery	UBERON:0001625	83.12	gold quality
stomach	UBERON:0000945	83.07	gold quality
left adrenal gland	UBERON:0001234	83.06	gold quality
thoracic aorta	UBERON:0001515	82.98	gold quality
ascending aorta	UBERON:0001496	82.97	gold quality
subcutaneous adipose tissue	UBERON:0002190	82.97	gold quality
left adrenal gland cortex	UBERON:0035825	82.93	gold quality
bone marrow cell	CL:0002092	82.91	gold quality
coronary artery	UBERON:0001621	82.78	gold quality
esophagus	UBERON:0001043	82.77	gold quality
lymph node	UBERON:0000029	82.74	gold quality
colonic epithelium	UBERON:0000397	82.72	gold quality
lower esophagus mucosa	UBERON:0035834	82.40	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.21	gold quality
colon	UBERON:0001155	82.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.05	gold quality
lower esophagus	UBERON:0013473	82.04	gold quality
mouth mucosa	UBERON:0003729	81.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.47	silver quality
saliva-secreting gland	UBERON:0001044	81.42	gold quality
adenohypophysis	UBERON:0002196	81.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.05	gold quality
large intestine	UBERON:0000059	80.96	gold quality
testis	UBERON:0000473	80.86	gold quality
ectocervix	UBERON:0012249	80.48	gold quality
adrenal cortex	UBERON:0001235	80.13	gold quality
adrenal gland	UBERON:0002369	80.05	gold quality
smooth muscle tissue	UBERON:0001135	79.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.58	gold quality
zone of skin	UBERON:0000014	78.93	gold quality
kidney	UBERON:0002113	78.80	gold quality
right atrium auricular region	UBERON:0006631	78.66	gold quality
left uterine tube	UBERON:0001303	78.58	gold quality
endocervix	UBERON:0000458	78.43	gold quality
body of uterus	UBERON:0009853	78.12	gold quality
calcaneal tendon	UBERON:0003701	78.00	gold quality
caecum	UBERON:0001153	77.95	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.29	gold quality
pituitary gland	UBERON:0000007	77.24	gold quality
cerebellar hemisphere	UBERON:0002245	77.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.96	gold quality
cerebellar cortex	UBERON:0002129	76.95	gold quality
apex of heart	UBERON:0002098	76.78	gold quality
cardiac atrium	UBERON:0002081	76.69	gold quality
vagina	UBERON:0000996	76.28	gold quality
right ovary	UBERON:0002118	76.27	gold quality
uterine cervix	UBERON:0000002	75.89	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.76	gold quality
buccal mucosa cell	CL:0002336	75.44	gold quality
anatomical system	UBERON:0000467	75.26	gold quality
prefrontal cortex	UBERON:0000451	75.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.82

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	246.0	medium
Duodenum	tissue	184.6	high
Small intestine	tissue	128.4	high
Kidney	tissue	92.5	high
Pancreas	tissue	30.4	medium
Colon	tissue	23.5	high
Rectum	tissue	18.0	high
Parathyroid gland	tissue	16.4	not detected
Adipose tissue	tissue	13.2	not detected
Thyroid gland	tissue	11.6	low
Vagina	tissue	10.0	not detected
Stomach 1	tissue	9.1	not detected
Lung	tissue	8.7	high
Spleen	tissue	8.2	not detected
Lymph node	tissue	8.1	not detected
Frontal cortex	tissue	7.8
Pituitary gland	tissue	7.7
Appendix	tissue	7.5	high
Salivary gland	tissue	7.4	not detected
Tonsil	tissue	7.0	not detected
Skin 1	tissue	6.6	low
Testis	tissue	6.6	not detected
Seminal vesicle	tissue	6.6	low
Urinary bladder	tissue	6.4	low
Breast	tissue	5.5	not detected
Locus coeruleus	tissue	5.5
Esophagus	tissue	5.4	not detected
Choroid plexus	tissue	5.3
Hippocampus	tissue	4.6	not detected
Caudate putamen	tissue	4.4
Nucleus accumbens	tissue	4.3
Gallbladder	tissue	4.2	medium
Bone marrow	tissue	4.2	not detected
Prostate	tissue	3.9	not detected
Adrenal gland	tissue	3.6	not detected
Postcentral gyrus	tissue	3.5
Smooth muscle	tissue	3.4	not detected
Thymus	tissue	3.4
Cervix	tissue	3.2	not detected
Epididymis	tissue	2.9	not detected
Placenta	tissue	2.6	not detected
Fallopian tube	tissue	2.5	not detected
Retina	tissue	2.4
Hippocampal formation	tissue	2.2
Pons	tissue	2.1
Thalamus	tissue	2.0
Hypothalamus	tissue	1.9
Endometrium 1	tissue	1.8	not detected
Superior colliculi	tissue	1.7
Substantia nigra	tissue	1.7
Olfactory bulb	tissue	1.7
Midbrain	tissue	1.6
Heart muscle	tissue	1.5	not detected
Septum	tissue	1.5
Cerebral cortex	tissue	1.4	low
Ovary	tissue	1.4	not detected
Motor cortex	tissue	1.4
Cerebellum	tissue	1.4	not detected
Somatosensory cortex	tissue	1.4
Retrosplenial cortex	tissue	1.4

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Blood vessel (13.7), Area postrema (7.8), Nucleus gracilis (7.5), Nucleus cuneatus (7.1), Inferior olive (7.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, ATF3, ATF6, BHLHE40, CEBPA, CEBPB, CREB1, CREB3L3, CREBBP, ESRRA, FOS, FOXO1, FOXO4, HDAC3, HNF4A, JUN, KLF15, NCOA1, NCOR2, NFIA, NFIC, NR0B2, NR1H2, NR1H3, NR1H4, NR2F2, PPARGC1A, PROX1, RELA, SMAD6, SRCAP, USF1

miRNA regulators (miRDB)

Targeting PCK2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

24 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-4724-3P	97.57	67.31	785
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4693-5P	97.35	67.02	1234
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-571	95.38	66.54	671

Functional genomics

gnomAD constraint: pLI 1.27e-16, LOEUF 1.06, missense Z 0.578 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000216780 — one region, missense o/e 0.98.

Literature-anchored findings (GeneRIF, showing 33)

• Results suggest that pepck2 gene expression is regulated by its 5’ flanking region up to 822 bp, and 317 bp upstream of transcriptional start point. (PMID:15315819)
• Wild-type AREBP, but not Ser(470) to Ala(470) substituted non-phosphorylating mutant, represses gene expression of the phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme of gluconeogenesis. (PMID:17097062)
• skeletal muscle PEPCK has a role in determining physical activity levels (PMID:19521512)
• Increased transcriptional expression of PEPCK1 and G6Pc does not account for increased gluconeogenesis and fasting hyperglycemia in patients with type 2 diabetes mellitus. (PMID:19587243)
• Endoplasmic reticulum stress triggers suppression of AMPK while increasing C/EBPbeta and pCREB expression which activates PEPCK gene transcription. (PMID:20797423)
• results reveal a novel link between glucose metabolism and the DNA damage signaling pathway and suggest a possible role for PEPCK and G6P in the DNA damage response (PMID:21733854)
• expression of HCV nonstructural component NS5A in Huh7 or primary hepatocytes stimulated PEPCK gene expression and glucose output in HepG2 cells. (PMID:22955269)
• Expression of phosphoenolpyruvate carboxykinase linked to chemoradiation susceptibility of human colon cancer cells. (PMID:24602180)
• PEPCK activity was elevated threefold in lung cancer samples over normal lungs and its activation mediates an adaptive response to glucose depletion in lung cancer. (PMID:24632615)
• Amino acid limitation and ER stress inducers, conditions that activate the amino acid response (AAR) and the unfolded protein response (UPR), stimulate PCK2 gene transcription in tumor cell lines. (PMID:24973213)
• When autophagy was blocked, the level of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) was reduced in HepG2 cells and not in Hep3B cells. (PMID:26036577)
• Mitochondrial PCK2 regulates metabolic adaptation and enables glucose-independent tumor growth in various neoplasms. (PMID:26474064)
• Results indicate that PEPCK promotes tumor growth by increasing glucose and glutamine metabolism, increases anabolic metabolism and promotes mTORC1 activity. (PMID:26481663)
• ApoA-IV colocalizes with NR4A1, which suppresses G6Pase and PEPCK gene expression at the transcriptional level, reducing hepatic glucose output and lowering blood glucose. (PMID:26556724)
• Downregulation of PCK2 remodels tricarboxylic acid cycle in tumor-repopulating cells of melanoma (PMID:28166201)
• Our study indicates that the T allele of the rs4982856 single-nucleotide polymorphisms in the PCK2 gene may be a risk factor for glucose intolerance after kidney transplantation (PMID:29731064)
• This study unveiled a novel role for PCK2 in integrating autophagy and bone formation, providing a potential target for stem cell-based bone tissue engineering that may lead to improved therapies for metabolic bone diseases. (PMID:31574189)
• The relationship between PEPCK metabolism in the urinary tract and insulin resistance and diabetes is reported. (PMID:32036699)
• Hypoxia increases the rate of renal gluconeogenesis via hypoxia-inducible factor-1-dependent activation of phosphoenolpyruvate carboxykinase expression. (PMID:32045650)
• Restoring the epigenetically silenced PCK2 suppresses renal cell carcinoma progression and increases sensitivity to sunitinib by promoting endoplasmic reticulum stress. (PMID:33052225)
• PURalpha Promotes the Transcriptional Activation of PCK2 in Oesophageal Squamous Cell Carcinoma Cells. (PMID:33142842)
• Proteomic Analysis of Hepatocellular Carcinoma Tissues With Encapsulation Shows Up-regulation of Leucine Aminopeptidase 3 and Phosphoenolpyruvate Carboxykinase 2. (PMID:33893083)
• Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis. (PMID:34020084)
• PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells. (PMID:34520823)
• A novel mutation in PCK2 gene causes primary angle-closure glaucoma. (PMID:34650006)
• Low expression of PCK2 in breast tumors contributes to better prognosis by inducing senescence of cancer cells. (PMID:35580079)
• Mitochondrial phosphoenolpyruvate carboxykinase promotes tumor growth in estrogen receptor-positive breast cancer via regulation of the mTOR pathway. (PMID:35757841)
• Role of PCK2 in the proliferation of vascular smooth muscle cells in neointimal hyperplasia. (PMID:35982907)
• Glycosylation defects, offset by PEPCK-M, drive entosis in breast carcinoma cells. (PMID:36002449)
• AF9 sustains glycolysis in colorectal cancer via H3K9ac-mediated PCK2 and FBP1 transcription. (PMID:37565737)
• Dysregulation of phosphoenolpyruvate carboxykinase in cancers: A comprehensive analysis. (PMID:38697449)
• Association of mitochondrial phosphoenolpyruvate carboxykinase with prognosis and immune regulation in hepatocellular carcinoma. (PMID:38890507)
• Targeting SOX4/PCK2 signaling suppresses neuroendocrine trans-differentiation of castration-resistant prostate cancer. (PMID:39014441)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	pck2	ENSDARG00000020956
mus_musculus	Pck2	ENSMUSG00000040618
rattus_norvegicus	Pck2	ENSRNOG00000018536
drosophila_melanogaster	Pepck1	FBGN0003067
drosophila_melanogaster	Pepck2	FBGN0034356
caenorhabditis_elegans	pck-2	WBGENE00011232
caenorhabditis_elegans		WBGENE00019151
caenorhabditis_elegans		WBGENE00021043

Paralogs (1): PCK1 (ENSG00000124253)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1860456) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal stomach morphology	1
enlarged lymph nodes	1
abnormal skin morphology	1
decreased circulating triglyceride level	1
small epididymis	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Mycobacterium tuberculosis variant bovis BCG str. Pasteur 1173P2	A1KF31	100.0%	Diamond
Mycobacterium sp. KMS	A1U995	100.0%	Diamond
Mycobacterium sp. JLS	A3PSV1	100.0%	Diamond
Mycobacterium tuberculosis H37Ra	A5TYT6	100.0%	Diamond
Acinetobacter baumannii AYE	B0VDR1	100.0%	Diamond
Acinetobacter baumannii SDF	B0VSN6	100.0%	Diamond
Acinetobacter baumannii ACICU	B2HXC1	100.0%	Diamond
Treponema pallidum subsp. pallidum SS14	B2S270	100.0%	Diamond
Acinetobacter baumannii AB307-0294	B7GY31	100.0%	Diamond
Acinetobacter baumannii AB0057	B7I624	100.0%	Diamond
Mycobacterium leprae Br4923	B8ZTI5	100.0%	Diamond
Mycobacterium tuberculosis variant bovis BCG str. Tokyo 172	C1AJN6	100.0%	Diamond
Mycobacterium leprae TN	O06084	100.0%	Diamond
Treponema pallidum subsp. pallidum str. Nichols	O83159	100.0%	Diamond
Mycobacterium tuberculosis variant bovis AF2122/97	P65687	100.0%	Diamond
Mycobacterium tuberculosis CDC1551	P9WIH2	100.0%	Diamond
Mycobacterium tuberculosis H37Rv	P9WIH3	100.0%	Diamond
Mycobacterium sp. MCS	Q1BFN7	100.0%	Diamond
Burkholderia mallei ATCC 23344	Q62FI7	100.0%	Diamond
Burkholderia pseudomallei K96243	Q63VB7	100.0%	Diamond
Mycobacterium ulcerans Agy99	A0PMX1	99.8%	Diamond
Mycolicibacterium smegmatis MC2 155	A0QP32	99.8%	Diamond
Acinetobacter baumannii ATCC 17978	A3M840	99.8%	Diamond
Mycobacterium marinum M	B2HMX9	99.8%	Diamond
Bordetella parapertussis 12822	Q7WAK8	99.8%	Diamond
Bordetella bronchiseptica RB50	Q7WJQ9	99.8%	Diamond
Mycolicibacterium smegmatis	Q9AGJ6	99.8%	Diamond
Anaeromyxobacter sp. K	B4UDY7	99.5%	Diamond
Anaeromyxobacter dehalogenans 2CP-1	B8J7G1	99.5%	Diamond
Corynebacterium glutamicum R	A4QHQ4	99.3%	Diamond
Corynebacterium glutamicum ATCC 13032	Q9AEM1	99.3%	Diamond
Anaeromyxobacter dehalogenans 2CP-C	Q2IFT1	98.8%	Diamond
Pongo abelii	Q5R5J1	98.7%	Diamond
Salinispora tropica CNB-440	A4X388	96.1%	Diamond
Salinispora arenicola CNS-205	A8M2V8	96.1%	Diamond
Mycolicibacterium vanbaalenii PYR-1	A1T1K1	94.9%	Diamond
Mycolicibacterium gilvum PYR-GCK	A4T3S1	94.9%	Diamond
Ralstonia pickettii 12J	B2U804	93.7%	Diamond
Ralstonia pseudosolanacearum GMI1000	Q8Y3G3	93.7%	Diamond
Acinetobacter baylyi ADP1	Q6F8P2	93.6%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
DHRS4L2	protein-coding	317749
NRL	protein-coding	4901
CARMIL3	protein-coding	90668
CPNE6	protein-coding	9362
FITM1	protein-coding	161247
DCAF11	protein-coding	80344
PSME1	protein-coding	5720
EMC9	protein-coding	51016

Protein

Protein identifiers

Phosphoenolpyruvate carboxykinase [GTP], mitochondrial — Q16822 (reviewed: Q16822)

Alternative names: Phosphoenolpyruvate carboxykinase 2, mitochondrial, Serine/threonine-protein kinase PCK2

All UniProt accessions (10): A0A384MTT2, Q16822, H0YKC4, H0YM31, H0YMA5, H0YML5, H0YMU6, H0YMY3, H0YNG4, H0YNH9

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial phosphoenolpyruvate carboxykinase that catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. Can play an active role in glyceroneogenesis and gluconeogenesis. Also acts as a serine/threonine-protein kinase: phosphorylates and activates ACSL4, thereby promoting ferroptosis.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion.

Tissue specificity. Widely expressed.

Disease relevance. Mitochondrial phosphoenolpyruvate carboxykinase deficiency (M-PEPCKD) [MIM:261650] Metabolic disorder resulting from impaired gluconeogenesis. It is a rare disease with less than 10 cases reported in the literature. Clinical characteristics include hypotonia, hepatomegaly, failure to thrive, lactic acidosis and hypoglycemia. Autopsy reveals fatty infiltration of both the liver and kidneys. The disorder is transmitted as an autosomal recessive trait. The gene represented in this entry may be involved in disease pathogenesis.

Cofactor. Binds 1 Mn(2+) ion per subunit.

Pathway. Carbohydrate biosynthesis; gluconeogenesis.

Miscellaneous. In eukaryotes there are two isozymes: a cytoplasmic one and a mitochondrial one.

Similarity. Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q16822-1	1	yes
Q16822-2	2
Q16822-3	3

RefSeq proteins (4): NP_001018083, NP_001278485, NP_001294983, NP_004554* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008209	PEP_carboxykinase_GTP	Family
IPR008210	PEP_carboxykinase_N	Homologous_superfamily
IPR013035	PEP_carboxykinase_C	Homologous_superfamily
IPR018091	PEP_carboxykin_GTP_CS	Conserved_site
IPR035077	PEP_carboxykinase_GTP_C	Domain
IPR035078	PEP_carboxykinase_GTP_N	Domain

Pfam: PF00821, PF17297

Enzyme classification (BRENDA)

• EC 4.1.1.32 — phosphoenolpyruvate carboxykinase (GTP) (BRENDA: 33 organisms, 128 substrates, 87 inhibitors, 232 Km, 37 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GDP	0.003–20.6	44
CO2	0.0133–46	43
OXALOACETATE	0.004–2.5	41
PHOSPHOENOLPYRUVATE	0.0185–9.6	38
GTP	0.0074–1.6	25
IDP	0.013–2.5	15
ITP	0.05–40	11
2’-DEOXYGUANOSINE 5’-DIPHOSPHATE	0.053–0.19	3
2’-DEOXYGUANOSINE 5’-TRIPHOSPHATE	0.71–1.05	3
(Z)-3-FLUOROPHOSPHOENOLPYRUVATE	0.03	1
ADP	2.23	1
ATP	0.465	1

Catalyzed reactions (Rhea)

• oxaloacetate + GTP = phosphoenolpyruvate + GDP + CO2 (RHEA:10388)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (41 total): binding site 20, sequence variant 7, modified residue 6, sequence conflict 4, splice variant 2, transit peptide 1, chain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16822-F1	94.04	0.91

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Lyases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Citric acid cycle related proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of carbohydrate metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH enhanced · IF enhanced

Functional residue map

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

Ligand- & substrate-binding residues (20)

Position	Role
308	GDP
309	GDP
310	GDP
329	Mn(2+)
355	GDP
421	phosphoenolpyruvate
423	phosphoenolpyruvate
454	GDP
534	GDP
543	GDP
104	phosphoenolpyruvate
548	GDP
551	GDP
255	phosphoenolpyruvate
262	Mn(2+)
282	Mn(2+)
305	GDP
306	GDP
306	Mn(2+)
307	GDP

Post-translational modifications (6)

Type	Positions
Phosphothreonine	42, 196
N6-acetyllysine	88
Phosphoserine	115, 304
N6-succinyllysine	457

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-70263	Gluconeogenesis	curated
R-HSA-70326	Glucose metabolism	—
R-HSA-1430728	Metabolism	—
R-HSA-71387	Metabolism of carbohydrates and carbohydrate derivatives	—

MSigDB gene sets: 389 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, WANG_CLIM2_TARGETS_UP, GRUETZMANN_PANCREATIC_CANCER_DN, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_RESPONSE_TO_CORTICOSTEROID, GNF2_HPN, GOBP_POLYOL_METABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KYNG_DNA_DAMAGE_DN, KYNG_DNA_DAMAGE_BY_4NQO

GO Biological Process (8): gluconeogenesis (GO:0006094), oxaloacetate metabolic process (GO:0006107), cellular response to insulin stimulus (GO:0032869), response to starvation (GO:0042594), hepatocyte differentiation (GO:0070365), cellular response to glucose stimulus (GO:0071333), cellular response to dexamethasone stimulus (GO:0071549), positive regulation of ferroptosis (GO:0160020)

GO Molecular Function (13): phosphoenolpyruvate carboxykinase activity (GO:0004611), phosphoenolpyruvate carboxykinase (GTP) activity (GO:0004613), protein serine/threonine kinase activity (GO:0004674), GTP binding (GO:0005525), manganese ion binding (GO:0030145), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), lyase activity (GO:0016829), carboxy-lyase activity (GO:0016831), purine nucleotide binding (GO:0017076), metal ion binding (GO:0046872)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Glucose metabolism	1
Metabolism of carbohydrates and carbohydrate derivatives	1
Metabolism	1

GO top-level categories

37 GO namespaces:

Category	Terms
catalytic activity	2
glucose metabolic process	1
hexose biosynthetic process	1
dicarboxylic acid metabolic process	1
response to insulin	1
cellular response to peptide hormone stimulus	1
response to stress	1
response to nutrient levels	1
liver development	1
epithelial cell differentiation	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
cellular response to glucocorticoid stimulus	1
response to dexamethasone	1
cellular response to ketone	1
positive regulation of programmed cell death	1
ferroptosis	1
regulation of ferroptosis	1
carboxy-lyase activity	1
phosphoenolpyruvate carboxykinase activity	1
protein kinase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
transition metal ion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
carbon-carbon lyase activity	1
nucleotide binding	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 24 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of ferroptosis	BP	direct assay
mitochondrion	CC	direct assay
manganese ion binding	MF	direct assay
phosphoenolpyruvate carboxykinase (GTP) activity	MF	direct assay
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 16 of 2,020 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PCK2	G6PC1	P35575	918
PCK2	PC	P11498	836
PCK2	INS	P01308	767
PCK2	FBP1	P09467	762
PCK2	G6PC3	Q9BUM1	732
PCK2	G6PC2	Q9NQR9	730
PCK2	PPARGC1A	Q9UBK2	700
PCK2	PPARG	P37231	667
PCK2	FOXO1	Q12778	640
PCK2	ACOX1	Q15067	638
PCK2	UCP2	P55851	630
PCK2	PPARA	Q07869	630
PCK2	SREBF1	P36956	615
PCK2	ADIPOQ	Q15848	615
PCK2	GCK	P35557	608
PCK2	IRS1	P35568	608

IntAct

Human interaction partners of PCK2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
IGHA1	association	0.530	1
BBS2	association	0.510	2
SMAD3	physical association	0.510	2
APOD	physical association	0.400	1
EP300	physical association	0.370	1
LONP1	association	0.350	1
PIGR	association	0.350	1
PLPBP	association	0.350	1

BioGRID (168 interactions; top human partners by supporting records): AHNAK2 (Affinity Capture-MS; 2 records), ALAS1 (Affinity Capture-MS; 2 records), BPIFA1 (Affinity Capture-MS; 2 records), BPIFB1 (Affinity Capture-MS; 2 records), DMBT1 (Affinity Capture-MS; 2 records), GAP43 (Affinity Capture-MS; 2 records), HSPD1 (Affinity Capture-MS; 2 records), IGHA1 (Affinity Capture-MS; 2 records), IGHA2 (Affinity Capture-MS; 2 records), LACRT (Affinity Capture-MS; 2 records), MUC5B (Affinity Capture-MS; 2 records), NDUFS6 (Affinity Capture-MS; 2 records), PCK1 (Affinity Capture-MS; 2 records), RAF1 (Affinity Capture-MS; 2 records), RCOR3 (Affinity Capture-MS; 2 records)

SIGNOR signaling

7 signaling interactions:

A	Effect	B	Mechanism
CEBPB	“up-regulates quantity by expression”	PCK2	“transcriptional regulation”
NR0B2	“down-regulates quantity by repression”	PCK2	“transcriptional regulation”
PPARGC1A	“up-regulates quantity by expression”	PCK2	“transcriptional regulation”
NCOA1	“up-regulates quantity by expression”	PCK2	“transcriptional regulation”
RELA	“down-regulates quantity by repression”	PCK2	“transcriptional regulation”
PCK2	“down-regulates quantity”	oxaloacetate(2-)	“chemical modification”
PCK2	“up-regulates quantity”	phosphonatoenolpyruvate	“chemical modification”

Disease & clinical

Genetic variants

Variant evidence for PCK2: 33 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	7
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 793):

Position(s)	Effect	Δscore	Sites
14:24097138–24097139	donor_loss	1.0000	5
14:24098679–24098680	donor_loss	1.0000	4
14:24099550	acceptor_gain	1.0000
14:24099555	acceptor_gain	1.0000
14:24099556–24099557	acceptor_loss	1.0000	6
14:24099669	donor_gain	1.0000
14:24102747	acceptor_gain	1.0000
14:24102751–24102752	acceptor_loss	1.0000	3
14:24102891–24102892	donor_loss	1.0000	2
14:24103158–24103159	acceptor_loss	1.0000	4

AlphaMissense

1,662 missense substitutions predicted likely pathogenic (of 4,175 scored), across 397 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M191	9	0.894	0.981
M500	9	0.891	0.972
M283	9	0.882	0.985
D329	8	0.998	1.000
H282	8	0.995	0.998
D328	8	0.991	0.998
D101	8	0.986	0.996
F351	8	0.986	0.998
D496	8	0.986	0.996
F535	8	0.983	0.999
F302	8	0.982	0.993
F503	8	0.982	0.999
N551	8	0.975	0.994
D180	8	0.972	0.991
S304	8	0.972	0.998
H212	8	0.967	0.992
N256	8	0.954	0.998
N533	8	0.943	0.999
F424	8	0.934	0.998
N377	8	0.927	0.998

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Liver Hepatocellular Carcinoma)

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.12e-07
Ovary Serous Cystadenocarcinoma (validation)	favorable	0.000215
Liver Hepatocellular Carcinoma (validation)	favorable	0.000355
Colon Adenocarcinoma (TCGA)	favorable	0.000662

Disease associations

OMIM: gene MIM:614095 | disease phenotypes:

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
peripheral neuropathy	Moderate	Autosomal recessive
phosphoenolpyruvate carboxykinase deficiency	Supportive	Autosomal recessive
phosphoenolpyruvate carboxykinase deficiency, mitochondrial	Limited	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Leukodystrophy, childhood onset	amber
Mitochondrial disorders	amber

Mondo (3): phosphoenolpyruvate carboxykinase deficiency, mitochondrial (MONDO:0009864), phosphoenolpyruvate carboxykinase deficiency (MONDO:0017320), peripheral neuropathy (MONDO:0005244)

HPO phenotypes

27 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000799	Renal steatosis
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001325	Hypoglycemic coma
HP:0001397	Hepatic steatosis
HP:0001399	Hepatic failure
HP:0001410	Decreased liver function
HP:0001943	Hypoglycemia
HP:0001987	Hyperammonemia
HP:0001988	Recurrent hypoglycemia
HP:0001998	Neonatal hypoglycemia
HP:0002013	Vomiting
HP:0002151	Increased circulating lactate concentration
HP:0002173	Hypoglycemic seizures
HP:0002329	Drowsiness
HP:0003128	Lactic acidosis
HP:0003217	Hyperglutaminemia
HP:0003648	Lacticaciduria
HP:0005959	Impaired gluconeogenesis
HP:0006846	Acute encephalopathy
HP:0012402	Increased urine alpha-ketoglutarate concentration
HP:0012758	Neurodevelopmental delay
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031964	Elevated circulating alanine aminotransferase concentration
HP:0034648	Elevated urine fumaric acid level

GWAS associations

1 associations:

Study	Trait	p-value
GCST010418_3	Liver fibrosis and steatohepatitis severity (MRI cT1 measure)	3e-11

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0006845	liver disease biomarker
EFO:0010821	liver fat measurement

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
C564890	Phosphoenolpyruvate Carboxykinase Deficiency, Mitochondrial *(supp.)*
C536654	Phosphoenolpyruvate carboxykinase deficiency *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3096 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.40	Kd	397.9	nM	CHEMBL3752910
6.40	ED50	397.9	nM	CHEMBL3752910
6.37	Kd	428.9	nM	CHEMBL5653589
6.37	ED50	428.9	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148946: Binding affinity to human PCK2 incubated for 45 mins by Kinobead based pull down assay	kd	0.3979	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148946: Binding affinity to human PCK2 incubated for 45 mins by Kinobead based pull down assay	kd	0.4289	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, affects cotreatment, affects expression, decreases expression	6
sodium arsenite	decreases expression, increases expression	5
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	5
Cyclosporine	affects expression, increases expression	5
Particulate Matter	increases abundance, increases expression, affects cotreatment, affects expression, decreases expression	5
Aflatoxin B1	affects expression, decreases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
Cisplatin	affects expression, affects cotreatment, increases expression	3
Copper	increases expression, affects binding	3
mono-(2-ethylhexyl)phthalate	increases expression	2
perfluorooctane sulfonic acid	increases expression	2
bisphenol AF	decreases expression, increases expression	2
Troglitazone	decreases expression, increases expression	2
Ethanol	increases expression, affects cotreatment, decreases expression, increases abundance	2
Atrazine	decreases expression, increases expression	2
Endosulfan	affects cotreatment, decreases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Fenofibrate	increases expression	2
Tunicamycin	increases expression, decreases expression	2
Thapsigargin	decreases expression, increases expression	2
Genistein	increases expression	2
GSK-J4	decreases expression	1
afuresertib	increases expression	1
bisphenol F	increases expression	1
moringin	decreases expression, affects cotreatment	1
perfluoropentanoic acid	increases expression	1
fluorotelomer sulfonic acids	increases expression	1
perfluorotridecanoic acid	increases expression	1
methyleugenol	decreases expression	1
benzo(b)fluoranthene	affects cotreatment, affects expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4415381	Binding	Binding affinity to PCKGM in human PC9 cells incubated for 1 hr by ABPP-SILAC assay	Development of Novel Irreversible Pyruvate Kinase M2 Inhibitors. — *J Med Chem*

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1GB	Abcam MCF-7 PCK2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00380965	Phase 4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	Phase 4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	Phase 4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	Phase 4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	Phase 4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	Phase 4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	Phase 4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	Phase 4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	Phase 4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	Phase 4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	Phase 4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT00058071	Phase 3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	Phase 3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	Phase 3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	Phase 3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	Phase 3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	Phase 3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	Phase 3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	Phase 3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	Phase 3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	Phase 3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	Phase 3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	Phase 3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	Phase 3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	Phase 3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	Phase 3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	Phase 3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	Phase 3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	Phase 3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	Phase 3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	Phase 3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	Phase 3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	Phase 3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	Phase 3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	Phase 3	COMPLETED	Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
NCT06071936	Phase 3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	Phase 3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	Phase 3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06072573	Phase 3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT07287592	Phase 3	NOT_YET_RECRUITING	Glutamine for the Prophylaxis of Vincristine-induced Neuropathy in Children and Adolescents With Cancer.
NCT00006072	Phase 2	UNKNOWN	A Study of Rituxan in the Treatment of Polyneuropathies Associated With Serum IgM Autoantibodies
NCT00365768	Phase 2	COMPLETED	Glutamine in Treating Neuropathy Caused by Vincristine in Young Patients With Lymphoma, Leukemia, or Solid Tumors
NCT00475904	Phase 2	COMPLETED	A Comparison of EpiCept™ NP-1 Topical Cream vs. Oral Gabapentin in Postherpetic Neuralgia (PHN)
NCT00528593	Phase 2	WITHDRAWN	Epoetin Alfa for HIV-Associated Neuropathy Trial
NCT00603265	Phase 2	COMPLETED	Safety and Efficacy Study of ADL5859 in Participants With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
NCT00665652	Phase 2	TERMINATED	Study of Lenalidomide as a Treatment for Neuropathy Associated With Monoclonal Gammopathy of Undetermined Significance
NCT00863057	Phase 2	TERMINATED	Combination Pain Therapy in HIV Neuropathy
NCT00891618	Phase 2	COMPLETED	Acupuncture for Chemo-Induced Peripheral Neuropathy
NCT00952848	Phase 2	COMPLETED	Electrical Stimulation Therapy Using the MC5-A Scrambler in Reducing Peripheral Neuropathy Caused by Chemotherapy
NCT01135251	Phase 2	COMPLETED	Safety and Preliminary Evidence of Efficacy of Escalating Doses of Dimiracetam in AIDS Patients With Painful Neuropathy
NCT01278004	Phase 2	COMPLETED	Chemotherapy Induced Painful Peripheral Neuropathy Ethosuximide (The CIN-E Study)
NCT01290224	Phase 2	COMPLETED	MC5-A Scrambler Therapy in Reducing Peripheral Neuropathy Caused by Chemotherapy
NCT01451853	Phase 2	WITHDRAWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01480297	Phase 2	COMPLETED	Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy
NCT01506453	Phase 2	COMPLETED	Therapeutic Interventions For Pain Induced By Vincristine Treatment For Childhood Acute Lymphoblastic Leukemia (ALL)
NCT01523574	Phase 2	COMPLETED	Vitamin E for Oxaliplatin-induced Peripheral Neuropathy Prophylaxis
NCT01637077	Phase 2	COMPLETED	Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel
NCT01655823	Phase 2	TERMINATED	The Purpose of This Study is to Determine if Tetrodotoxin (TTX) is Effective in the Treatment of Pain Resulting From Chemotherapy Treatment
NCT01774058	Phase 2	UNKNOWN	The Arterial Measurement of the Blood Flow Volume After Iloprost Stimulation
NCT01783522	Phase 2	TERMINATED	Glutamine in Preventing Peripheral Neuropathy in Patients With Multiple Myeloma Receiving Bortezomib

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PCK2 across ~30M SureChEMBL compounds — explore on Sugi Predict.