GeneBe

PCK1

phosphoenolpyruvate carboxykinase 1

Basic information

Region (hg38): 20:57561080-57568121

Links

ENSG00000124253 ∙ NCBI:5105 ∙ OMIM:614168 ∙ HGNC:8724 ∙ Uniprot:P35558 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • phosphoenolpyruvate carboxykinase deficiency (Supportive), mode of inheritance: AR
  • phosphoenolpyruvate carboxykinase deficiency, cytosolic (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Phosphoenolpyruvate carboxykinase-1 deficiency, cytosolicARBiochemicalIndividuals have been described with manifestations such as early-onset hypoglycemia, and awareness can allow prompt treatment of acute episodes as well as longer-term dietary management (low-fat, high-carbohydrate diet with frequent feedings)Biochemical24863970; 26971250; 28216384

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PCK1 gene.

  • not_provided (140 variants)
  • Inborn_genetic_diseases (96 variants)
  • Phosphoenolpyruvate_carboxykinase_deficiency,_cytosolic (52 variants)
  • PCK1-related_disorder (19 variants)
  • Lynch_syndrome_1 (2 variants)
  • not_specified (1 variants)
  • Phosphoenolpyruvate_carboxykinase_(GTP)_deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCK1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002591.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
5
clinvar
59
clinvar
5
clinvar
 69
missense
1
clinvar
2
clinvar
128
clinvar
14
clinvar
1
clinvar
 146
nonsense
1
clinvar
1
clinvar
1
clinvar
 3
start loss
0
frameshift
2
clinvar
1
clinvar
 3
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total 2 6 136 73 6

Highest pathogenic variant AF is 0.000590074

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PCK1protein_codingprotein_codingENST00000319441 95378
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
8.75e-150.03581256660821257480.000326
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.04303863841.010.00002274114
Missense in Polyphen165180.310.915111846
Synonymous-1.281821611.130.00001111192
Loss of Function0.4272325.30.9090.00000108296

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0006210.000621
Ashkenazi Jewish0.0001040.0000992
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.0004330.000431
Middle Eastern0.00005440.0000544
South Asian0.0004340.000425
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: 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. {ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26971250, ECO:0000269|PubMed:28216384}.;
Disease
DISEASE: Phosphoenolpyruvate carboxykinase deficiency, cytosolic (PCKDC) [MIM:261680]: An autosomal recessive metabolic disorder characterized by impaired gluconeogenesis, hypoglycemia, hypotonia, hepatomegaly, hepatic dysfunction, failure to thrive, lactic acidosis, and elevated tricarboxylic acid intermediates, particularly fumarate, in urine. {ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26971250, ECO:0000269|PubMed:28216384}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
PI3K-Akt signaling pathway - Homo sapiens (human);Citrate cycle (TCA cycle) - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);Glycolysis / Gluconeogenesis - Homo sapiens (human);Insulin resistance - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Proximal tubule bicarbonate reclamation - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Glucagon signaling pathway - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Abacavir Pathway, Pharmacokinetics/Pharmacodynamics;Pyruvate Dehydrogenase Complex Deficiency;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;Gluconeogenesis;Leigh Syndrome;Glycogenosis, Type IA. Von gierke disease;Glycogenosis, Type IC;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;Pyruvate Metabolism;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;Transcriptional regulation of white adipocyte differentiation;Adipogenesis;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);Estrogen Receptor Pathway;Nuclear Receptors Meta-Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Amino Acid metabolism;PPAR signaling pathway;PI3K-Akt Signaling Pathway;Glycolysis and Gluconeogenesis;Metabolism of carbohydrates;Citrate cycle;Glycolysis and Gluconeogenesis;Abacavir metabolism;Abacavir transport and metabolism;Metabolism;TCA cycle;gluconeogenesis;Gluconeogenesis;Glucose metabolism;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

pRec
0.502

Intolerance Scores

loftool
0.718
rvis_EVS
0.28
rvis_percentile_EVS
70.76

Haploinsufficiency Scores

pHI
0.532
hipred
Y
hipred_score
0.532
ghis
0.459

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.999

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Pck1
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name
pck1
Affected structure
glucose homeostasis
Phenotype tag
abnormal
Phenotype quality
process quality

Gene ontology

Biological process
glucose metabolic process;pyruvate metabolic process;gluconeogenesis;oxaloacetate metabolic process;internal protein amino acid acetylation;aging;response to activity;propionate catabolic process;response to lipopolysaccharide;response to insulin;cellular response to insulin stimulus;response to lipid;glucose homeostasis;response to starvation;glycerol biosynthetic process from pyruvate;cellular response to potassium ion starvation;positive regulation of transcription from RNA polymerase II promoter in response to acidic pH;hepatocyte differentiation;response to interleukin-6;cellular response to retinoic acid;cellular response to cAMP;cellular response to fructose stimulus;cellular response to glucose stimulus;cellular response to interleukin-1;cellular response to tumor necrosis factor;cellular response to glucagon stimulus;cellular response to hypoxia;cellular response to dexamethasone stimulus;response to methionine
Cellular component
cytoplasm;mitochondrion;cytosol;extracellular exosome
Molecular function
magnesium ion binding;phosphoenolpyruvate carboxykinase (GTP) activity;GTP binding;GDP binding;manganese ion binding;carboxylic acid binding