MCID: PPC001
MIFTS: 35

Pepck 1 Deficiency

Categories: Liver diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Pepck 1 Deficiency

MalaCards integrated aliases for Pepck 1 Deficiency:

Name: Pepck 1 Deficiency 20
Phosphoenolpyruvate Carboxykinase Deficiency 20 58 70
Phosphoenolpyruvate Carboxykinase Deficiency 29 6
Phosphoenolpyruvate Carboxykinase-1 Deficiency 20
Phosphoenolpyruvate Carboxylase Deficiency 20
Phosphopyruvate Carboxylase Deficiency 20
Pep Carboxykinase Deficiency 20
Pepck Deficiency 58

Characteristics:

Orphanet epidemiological data:

58
phosphoenolpyruvate carboxykinase deficiency
Inheritance: Autosomal recessive,Mitochondrial inheritance; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: infantile;

Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

MESH via Orphanet 45 C536654
ICD10 via Orphanet 33 E74.4
UMLS via Orphanet 71 C0268194
Orphanet 58 ORPHA2880
UMLS 70 C0268194

Summaries for Pepck 1 Deficiency

GARD : 20 PEPCK1 deficiency is a rare inborn error of metabolism disorder, characterized by the deficiency of the enzyme PEPCK1, one of the enzymes needed for gluconeogenesis, the process by which organisms produce sugars (namely glucose) from non-carbohydrate precursors (such as amino acids ). The symptoms described in the few cases reported in the medical literature suggest that there may be variation in the severity of the symptoms ranging from severe early-onset cases, to milder late-onset presentations. In severe cases symptoms may include persistent and very low levels of blood's sugar in newborns (neonatal hypoglycemia ), failure to thrive, build-up of lactic acid in the blood ( lactic acidosis ), liver enlargement (hepatomegaly) and liver failure leading to neurological degeneration. Milder cases present during childhood with fewer and less serious liver problems. Infections and fasting may trigger the symptoms. PEPCK1 deficiency inheritance is autosomal recessive. It is caused by mutations in the PEPCK1 gene. Some researchers believe that the severity of the disease depend upon the mutations resulting in less or more PEPCK1 activity (the more active the enzyme is, the less severe the disease is, and vice versa). Treatment depend on the symptoms and may include giving extra carbohydrates during heavy exercise and illness or other times of fasting (formal sick day regimen) by the dietitian. PEPCK1 is the cytosolic form of the phosphoenolpyruvate carboxykinase (PEPCK) enzyme, the other being the mitochondrial ( PEPCK2 ).

MalaCards based summary : Pepck 1 Deficiency, also known as phosphoenolpyruvate carboxykinase deficiency, is related to phosphoenolpyruvate carboxykinase deficiency, mitochondrial and hypoglycemia, and has symptoms including seizures and cyanosis. An important gene associated with Pepck 1 Deficiency is PCK1 (Phosphoenolpyruvate Carboxykinase 1), and among its related pathways/superpathways are Glucose metabolism and Glucose / Energy Metabolism. Affiliated tissues include liver, and related phenotypes are Decreased shRNA abundance (Z-score < -2) and Decreased shRNA abundance (Z-score < -2)

Wikipedia : 73 Phosphoenolpyruvate carboxykinase (PEPCK) is an enzyme in the lyase family used in the metabolic pathway... more...

Related Diseases for Pepck 1 Deficiency

Graphical network of the top 20 diseases related to Pepck 1 Deficiency:



Diseases related to Pepck 1 Deficiency

Symptoms & Phenotypes for Pepck 1 Deficiency

UMLS symptoms related to Pepck 1 Deficiency:


seizures; cyanosis

GenomeRNAi Phenotypes related to Pepck 1 Deficiency according to GeneCards Suite gene sharing:

26 (show all 28)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-105 9.98 NRL
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-114 9.98 PCK1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-12 9.98 PCK1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-127 9.98 PCK1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-147 9.98 NRL
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-149 9.98 PCK1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-151 9.98 PCK1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-152 9.98 PCK1
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 9.98 PCK1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-22 9.98 NRL PCK1
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-28 9.98 PCK1
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-47 9.98 NRL
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-49 9.98 NRL PCK1
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-56 9.98 PCK1
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-70 9.98 NRL
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-71 9.98 PCK1
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-87 9.98 NRL
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 9.98 PCK1
19 Decreased shRNA abundance (Z-score < -2) GR00366-A-91 9.98 PCK1
20 Increased shRNA abundance (Z-score > 2) GR00366-A-106 9.28 NRL
21 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.28 NRL
22 Increased shRNA abundance (Z-score > 2) GR00366-A-196 9.28 NRL
23 Increased shRNA abundance (Z-score > 2) GR00366-A-25 9.28 PCK1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-27 9.28 PCK1
25 Increased shRNA abundance (Z-score > 2) GR00366-A-4 9.28 NRL
26 Increased shRNA abundance (Z-score > 2) GR00366-A-5 9.28 NRL
27 Increased shRNA abundance (Z-score > 2) GR00366-A-72 9.28 NRL
28 Increased shRNA abundance (Z-score > 2) GR00366-A-90 9.28 PCK1

Drugs & Therapeutics for Pepck 1 Deficiency

Search Clinical Trials , NIH Clinical Center for Pepck 1 Deficiency

Genetic Tests for Pepck 1 Deficiency

Genetic tests related to Pepck 1 Deficiency:

# Genetic test Affiliating Genes
1 Phosphoenolpyruvate Carboxykinase (gtp) Deficiency 29

Anatomical Context for Pepck 1 Deficiency

MalaCards organs/tissues related to Pepck 1 Deficiency:

40
Liver

Publications for Pepck 1 Deficiency

Articles related to Pepck 1 Deficiency:

(show all 11)
# Title Authors PMID Year
1
Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal pattern of urine metabolites and liver dysfunction. 20 61
28216384 2017
2
Three rare diseases in one Sib pair: RAI1, PCK1, GRIN2B mutations associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA receptor glutamate insensitivity. 6
24863970 2014
3
Gluconeogenesis in infancy and childhood. II. Studies on the glucose production from alanine in three cases of persistent neonatal hypoglycaemia. 20
1274563 1976
4
Cytosolic Phosphoenolpyruvate Carboxykinase Deficiency: Cause of Hypoglycemia-Induced Seizure and Death. 61
33445193 2021
5
Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis. 61
26971250 2016
6
[Phosphoenolpyruvate carboxykinase deficiency]. 61
9590066 1998
7
Mitochondrial phosphoenolpyruvate carboxykinase deficiency. 61
2044592 1991
8
Hepatic phosphoenolpyruvate carboxykinase deficiency: a neonatal case with reduced activity of pyruvate carboxylase. 61
2515381 1989
9
Mitochondrial phosphoenolpyruvate carboxykinase deficiency. 61
3089795 1986
10
The genetic heterogeneity of lactic acidosis: occurrence of recognizable inborn errors of metabolism in pediatric population with lactic acidosis. 61
6775276 1980
11
Two cases of phosphoenolpyruvate carboxykinase deficiency. 61
176867 1976

Variations for Pepck 1 Deficiency

ClinVar genetic disease variations for Pepck 1 Deficiency:

6 (show top 50) (show all 103)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PCK1 PCK1, 12-BP DEL, NT369 Deletion Pathogenic 440852 GRCh37:
GRCh38:
2 NRL , PCK2 NM_004563.4(PCK2):c.577C>T (p.Arg193Ter) SNV Pathogenic 451808 rs753706965 GRCh37: 14:24567800-24567800
GRCh38: 14:24098591-24098591
3 NRL , PCK2 NM_004563.4(PCK2):c.1468+2T>C SNV Pathogenic 440999 rs148019349 GRCh37: 14:24572466-24572466
GRCh38: 14:24103257-24103257
4 NRL , PCK2 NM_004563.4(PCK2):c.1125dup (p.Thr376fs) Duplication Pathogenic 1032910 GRCh37: 14:24569308-24569309
GRCh38: 14:24100099-24100100
5 NRL , PCK2 NM_004563.4(PCK2):c.1469-1G>A SNV Pathogenic 452765 rs376278710 GRCh37: 14:24572718-24572718
GRCh38: 14:24103509-24103509
6 NRL , PCK2 NM_004563.4(PCK2):c.1234+1G>T SNV Pathogenic 503636 rs138881435 GRCh37: 14:24569423-24569423
GRCh38: 14:24100214-24100214
7 PCK1 NM_002591.4(PCK1):c.961+1G>A SNV Likely pathogenic 931905 GRCh37: 20:56138784-56138784
GRCh38: 20:57563728-57563728
8 PCK1 NM_002591.4(PCK1):c.724G>A (p.Gly242Arg) SNV Likely pathogenic 807457 rs373906233 GRCh37: 20:56138197-56138197
GRCh38: 20:57563141-57563141
9 PCK1 NM_002591.4(PCK1):c.7C>T (p.Pro3Ser) SNV Conflicting interpretations of pathogenicity 788182 rs147120329 GRCh37: 20:56136474-56136474
GRCh38: 20:57561418-57561418
10 NRL , PCK2 NM_004563.4(PCK2):c.68C>G (p.Ser23Ter) SNV Conflicting interpretations of pathogenicity 374449 rs61752842 GRCh37: 14:24566139-24566139
GRCh38: 14:24096930-24096930
11 PCK1 NM_002591.4(PCK1):c.925G>A (p.Gly309Arg) SNV Conflicting interpretations of pathogenicity 338886 rs201186470 GRCh37: 20:56138747-56138747
GRCh38: 20:57563691-57563691
12 PCK1 NM_002591.4(PCK1):c.1642G>A (p.Ala548Thr) SNV Uncertain significance 338891 rs148684857 GRCh37: 20:56140633-56140633
GRCh38: 20:57565577-57565577
13 PCK1 NM_002591.4(PCK1):c.414C>A (p.Thr138=) SNV Uncertain significance 897622 GRCh37: 20:56137759-56137759
GRCh38: 20:57562703-57562703
14 PCK1 NM_002591.4(PCK1):c.955G>A (p.Ala319Thr) SNV Uncertain significance 897687 GRCh37: 20:56138777-56138777
GRCh38: 20:57563721-57563721
15 PCK1 NM_002591.4(PCK1):c.1152G>A (p.Thr384=) SNV Uncertain significance 707924 rs141878699 GRCh37: 20:56139415-56139415
GRCh38: 20:57564359-57564359
16 PCK1 NM_002591.4(PCK1):c.*608A>C SNV Uncertain significance 897763 GRCh37: 20:56141468-56141468
GRCh38: 20:57566412-57566412
17 PCK1 NM_002591.4(PCK1):c.474C>T (p.Ile158=) SNV Uncertain significance 898782 GRCh37: 20:56137819-56137819
GRCh38: 20:57562763-57562763
18 PCK1 NM_002591.4(PCK1):c.521C>T (p.Thr174Met) SNV Uncertain significance 898783 GRCh37: 20:56137866-56137866
GRCh38: 20:57562810-57562810
19 PCK1 NM_002591.4(PCK1):c.1211C>T (p.Ser404Leu) SNV Uncertain significance 898847 GRCh37: 20:56139562-56139562
GRCh38: 20:57564506-57564506
20 PCK1 NM_002591.4(PCK1):c.1320T>C (p.Gly440=) SNV Uncertain significance 898848 GRCh37: 20:56140097-56140097
GRCh38: 20:57565041-57565041
21 PCK1 NM_002591.4(PCK1):c.1448G>A (p.Arg483Gln) SNV Uncertain significance 779639 rs41302559 GRCh37: 20:56140439-56140439
GRCh38: 20:57565383-57565383
22 PCK1 NM_002591.4(PCK1):c.1553G>A (p.Arg518Gln) SNV Uncertain significance 898849 GRCh37: 20:56140544-56140544
GRCh38: 20:57565488-57565488
23 NRL , PCK2 NM_004563.4(PCK2):c.1907G>A (p.Arg636His) SNV Uncertain significance 1030819 GRCh37: 14:24573157-24573157
GRCh38: 14:24103948-24103948
24 NRL , PCK2 NM_004563.4(PCK2):c.1756G>A (p.Gly586Ser) SNV Uncertain significance 618263 rs61737098 GRCh37: 14:24573006-24573006
GRCh38: 14:24103797-24103797
25 NRL , PCK2 NM_004563.4(PCK2):c.287G>A (p.Arg96His) SNV Uncertain significance 1032911 GRCh37: 14:24567423-24567423
GRCh38: 14:24098214-24098214
26 NRL , PCK2 NM_004563.4(PCK2):c.157C>T (p.Arg53Cys) SNV Uncertain significance 1032912 GRCh37: 14:24566228-24566228
GRCh38: 14:24097019-24097019
27 PCK1 NM_002591.4(PCK1):c.*358_*359TG[21] Microsatellite Uncertain significance 338906 rs141075201 GRCh37: 20:56141217-56141218
GRCh38: 20:57566161-57566162
28 PCK1 NM_002591.4(PCK1):c.*358_*359TG[20] Microsatellite Uncertain significance 338905 rs141075201 GRCh37: 20:56141217-56141218
GRCh38: 20:57566161-57566162
29 PCK1 NM_002591.4(PCK1):c.*358_*359TG[17] Microsatellite Uncertain significance 338908 rs141075201 GRCh37: 20:56141218-56141219
GRCh38: 20:57566162-57566163
30 PCK1 NM_002591.4(PCK1):c.*358_*359TG[14] Microsatellite Uncertain significance 338912 rs141075201 GRCh37: 20:56141218-56141225
GRCh38: 20:57566162-57566169
31 PCK1 NM_002591.4(PCK1):c.*357_*360del Deletion Uncertain significance 338903 rs147972610 GRCh37: 20:56141216-56141219
GRCh38: 20:57566160-57566163
32 PCK1 NM_002591.4(PCK1):c.*358_*359TG[15] Microsatellite Uncertain significance 338911 rs141075201 GRCh37: 20:56141218-56141223
GRCh38: 20:57566162-57566167
33 PCK1 NM_002591.4(PCK1):c.228G>T (p.Trp76Cys) SNV Uncertain significance 338873 rs139008325 GRCh37: 20:56137130-56137130
GRCh38: 20:57562074-57562074
34 PCK1 NM_002591.4(PCK1):c.*358_*359TG[24] Microsatellite Uncertain significance 338907 rs141075201 GRCh37: 20:56141217-56141218
GRCh38: 20:57566161-57566162
35 PCK1 NM_002591.4(PCK1):c.*357_*362del Deletion Uncertain significance 338904 rs760440639 GRCh37: 20:56141216-56141221
GRCh38: 20:57566160-57566165
36 PCK1 NM_002591.4(PCK1):c.*349_*350AT[6] Microsatellite Uncertain significance 338901 rs201179319 GRCh37: 20:56141207-56141208
GRCh38: 20:57566151-57566152
37 PCK1 NM_002591.4(PCK1):c.*358_*359TG[16] Microsatellite Uncertain significance 338910 rs141075201 GRCh37: 20:56141218-56141221
GRCh38: 20:57566162-57566165
38 PCK1 NM_002591.4(PCK1):c.*358_*359TG[19] Microsatellite Uncertain significance 338909 rs141075201 GRCh37: 20:56141217-56141218
GRCh38: 20:57566161-57566162
39 PCK1 NM_002591.4(PCK1):c.1537C>T (p.His513Tyr) SNV Uncertain significance 81729 rs267606016 GRCh37: 20:56140528-56140528
GRCh38: 20:57565472-57565472
40 PCK1 NM_002591.4(PCK1):c.1658C>T (p.Thr553Met) SNV Uncertain significance 338893 rs762446688 GRCh37: 20:56140649-56140649
GRCh38: 20:57565593-57565593
41 PCK1 NM_002591.4(PCK1):c.556G>A (p.Asp186Asn) SNV Uncertain significance 338880 rs11552146 GRCh37: 20:56137901-56137901
GRCh38: 20:57562845-57562845
42 PCK1 NM_002591.4(PCK1):c.*202G>A SNV Uncertain significance 338899 rs886056795 GRCh37: 20:56141062-56141062
GRCh38: 20:57566006-57566006
43 PCK1 NM_002591.4(PCK1):c.-64C>T SNV Uncertain significance 338866 rs886056793 GRCh37: 20:56136236-56136236
GRCh38: 20:57561180-57561180
44 PCK1 NM_002591.4(PCK1):c.102C>T (p.Asn34=) SNV Uncertain significance 338869 rs200771350 GRCh37: 20:56136569-56136569
GRCh38: 20:57561513-57561513
45 PCK1 NM_002591.4(PCK1):c.203G>T (p.Arg68Leu) SNV Uncertain significance 338872 rs147273759 GRCh37: 20:56136670-56136670
GRCh38: 20:57561614-57561614
46 PCK1 NM_002591.4(PCK1):c.*249G>T SNV Uncertain significance 338900 rs886056796 GRCh37: 20:56141109-56141109
GRCh38: 20:57566053-57566053
47 PCK1 NM_002591.4(PCK1):c.1207A>G (p.Asn403Asp) SNV Uncertain significance 338890 rs368426390 GRCh37: 20:56139558-56139558
GRCh38: 20:57564502-57564502
48 PCK1 NM_002591.4(PCK1):c.-54C>T SNV Uncertain significance 338867 rs886056794 GRCh37: 20:56136246-56136246
GRCh38: 20:57561190-57561190
49 PCK1 NM_002591.4(PCK1):c.954C>T (p.Asp318=) SNV Uncertain significance 338887 rs147943264 GRCh37: 20:56138776-56138776
GRCh38: 20:57563720-57563720
50 PCK1 NM_002591.4(PCK1):c.141C>T (p.Asp47=) SNV Uncertain significance 338870 rs45559338 GRCh37: 20:56136608-56136608
GRCh38: 20:57561552-57561552

Expression for Pepck 1 Deficiency

Search GEO for disease gene expression data for Pepck 1 Deficiency.

Pathways for Pepck 1 Deficiency

Pathways related to Pepck 1 Deficiency according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.13 PCK2 PCK1
2 11.97 PCK2 PCK1
3
Show member pathways
11.91 PCK2 PCK1
4
Show member pathways
11.57 PCK2 PCK1
5 11.52 PCK2 PCK1
6
Show member pathways
11.41 PCK2 PCK1
7 11.35 PCK2 PCK1
8
Show member pathways
11.27 PCK2 PCK1
9 11.04 PCK2 PCK1
10 10.79 PCK2 PCK1
11 9.98 PCK2 PCK1

GO Terms for Pepck 1 Deficiency

Biological processes related to Pepck 1 Deficiency according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 response to lipopolysaccharide GO:0032496 9.51 PCK2 PCK1
2 cellular response to tumor necrosis factor GO:0071356 9.49 PCK2 PCK1
3 cellular response to insulin stimulus GO:0032869 9.48 PCK2 PCK1
4 cellular response to glucose stimulus GO:0071333 9.46 PCK2 PCK1
5 gluconeogenesis GO:0006094 9.43 PCK2 PCK1
6 response to starvation GO:0042594 9.4 PCK2 PCK1
7 cellular response to dexamethasone stimulus GO:0071549 9.37 PCK2 PCK1
8 response to lipid GO:0033993 9.32 PCK2 PCK1
9 hepatocyte differentiation GO:0070365 9.26 PCK2 PCK1
10 oxaloacetate metabolic process GO:0006107 9.16 PCK2 PCK1
11 glycerol biosynthetic process from pyruvate GO:0046327 8.96 PCK2 PCK1
12 propionate catabolic process GO:0019543 8.62 PCK2 PCK1

Molecular functions related to Pepck 1 Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GTP binding GO:0005525 9.4 PCK2 PCK1
2 lyase activity GO:0016829 9.37 PCK2 PCK1
3 manganese ion binding GO:0030145 9.32 PCK2 PCK1
4 carboxy-lyase activity GO:0016831 9.26 PCK2 PCK1
5 purine nucleotide binding GO:0017076 9.16 PCK2 PCK1
6 phosphoenolpyruvate carboxykinase (GTP) activity GO:0004613 8.96 PCK2 PCK1
7 phosphoenolpyruvate carboxykinase activity GO:0004611 8.62 PCK2 PCK1

Sources for Pepck 1 Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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