PCK2

phosphoenolpyruvate carboxykinase 2, mitochondrial

Basic information

Region (hg38): 14:24094053-24110598

Links

ENSG00000100889 ∙ NCBI:5106 ∙ OMIM:614095 ∙ HGNC:8725 ∙ Uniprot:Q16822 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• phosphoenolpyruvate carboxykinase deficiency, mitochondrial (Limited), mode of inheritance: AR
• phosphoenolpyruvate carboxykinase deficiency (Supportive), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PCK2 gene.

• Phosphoenolpyruvate carboxykinase deficiency, mitochondrial (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PCK2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	26	7	35
missense			110	10	5	125
nonsense			5			5
start loss						0
frameshift			6			6
inframe indel						0
splice donor/acceptor (+/-2bp)	1		4	1		6
splice region			4	2	1	7
non coding				11	2	13
Total	1	0	127	48	14

Highest pathogenic variant AF is 0.000171

Variants in PCK2

This is a list of pathogenic ClinVar variants found in the PCK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-24094411-C-T			Benign (Jan 29, 2024)
14-24094416-T-G			Uncertain significance (May 11, 2023)
14-24094417-G-C		not specified	Uncertain significance (Mar 30, 2024)
14-24094422-G-A		not specified	Uncertain significance (Jul 12, 2023)
14-24094423-C-A			Likely benign (Jan 07, 2024)
14-24094439-G-A		Retinitis pigmentosa 27	Uncertain significance (Mar 29, 2024)
14-24096872-T-C			Likely benign (Feb 13, 2023)
14-24096879-G-A			Likely benign (Nov 21, 2023)
14-24096930-C-G		not specified • Phosphoenolpyruvate carboxykinase deficiency, mitochondrial	Conflicting classifications of pathogenicity (Jan 09, 2024)
14-24096935-C-T		not specified	Uncertain significance (Dec 15, 2023)
14-24096936-G-A			Uncertain significance (Dec 11, 2023)
14-24096954-G-A		not specified	Uncertain significance (Dec 11, 2023)
14-24096956-G-A		not specified	Uncertain significance (Oct 05, 2022)
14-24096983-C-T			Uncertain significance (Dec 05, 2022)
14-24097012-C-T			Conflicting classifications of pathogenicity (Jan 08, 2024)
14-24097019-C-A			Uncertain significance (Jan 14, 2023)
14-24097019-C-T		Phosphoenolpyruvate carboxykinase deficiency, mitochondrial • not specified	Uncertain significance (Dec 15, 2022)
14-24097024-G-T			Likely benign (Nov 27, 2023)
14-24097041-T-C			Uncertain significance (Jun 06, 2023)
14-24097049-T-G		not specified	Uncertain significance (Dec 01, 2022)
14-24097052-G-A		PCK2-related disorder	Benign (Jan 16, 2024)
14-24097059-C-G		not specified	Uncertain significance (Nov 22, 2022)
14-24097080-C-T		not specified	Likely benign (Sep 09, 2021)
14-24097093-G-A			Uncertain significance (Feb 17, 2022)
14-24097112-C-T			Uncertain significance (Feb 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PCK2	protein_coding	protein_coding	ENST00000216780	10	16546

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.75e-23	0.000368	124495	2	1251	125748	0.00499

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.203	418	407	1.03	0.0000251	4144
Missense in Polyphen		204	197.53	1.0328		2008
Synonymous	0.693	139	150	0.928	0.00000859	1331
Loss of Function	-0.244	34	32.5	1.05	0.00000213	280

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00896	0.00894
Ashkenazi Jewish	0.00	0.00
East Asian	0.000870	0.000870
Finnish	0.000235	0.000231
European (Non-Finnish)	0.00782	0.00777
Middle Eastern	0.000870	0.000870
South Asian	0.00193	0.00190
Other	0.00572	0.00572

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:0000250}.
• Disease: DISEASE: 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. 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);Adipogenesis;Transcription factor regulation in adipogenesis;PPAR signaling pathway;PI3K-Akt Signaling Pathway;DNA Damage Response (only ATM dependent);Metabolism of carbohydrates;Citrate cycle;Glycolysis and Gluconeogenesis;Metabolism;TCA cycle;Glucocorticoid receptor regulatory network;gluconeogenesis;Gluconeogenesis;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.818

Intolerance Scores

• loftool: 0.999
• rvis_EVS: 0.27
• rvis_percentile_EVS: 70.75

Haploinsufficiency Scores

• pHI: 0.211
• hipred: N
• hipred_score: 0.213
• ghis: 0.432

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pck2

Gene ontology

• Biological process: pyruvate metabolic process;gluconeogenesis;propionate catabolic process;cellular response to insulin stimulus;response to lipid;response to starvation;glycerol biosynthetic process from pyruvate;hepatocyte differentiation;cellular response to glucose stimulus;cellular response to dexamethasone stimulus
• Cellular component: mitochondrion;mitochondrial matrix;cytosol
• Molecular function: phosphoenolpyruvate carboxykinase activity;phosphoenolpyruvate carboxykinase (GTP) activity;protein binding;GTP binding;manganese ion binding