PC

pyruvate carboxylase, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 11:66848417-66958386

Links

ENSG00000173599 ∙ NCBI:5091 ∙ OMIM:608786 ∙ HGNC:8636 ∙ Uniprot:P11498 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pyruvate carboxylase deficiency disease (Definitive), mode of inheritance: AR
• pyruvate carboxylase deficiency disease (Definitive), mode of inheritance: AR
• pyruvate carboxylase deficiency, infantile form (Supportive), mode of inheritance: AR
• pyruvate carboxylase deficiency, severe neonatal type (Supportive), mode of inheritance: AR
• pyruvate carboxylase deficiency, benign type (Supportive), mode of inheritance: AR
• pyruvate carboxylase deficiency disease (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pyruvate carboxylase deficiency	AR	Biochemical	In acute episodes, acidosis correction and glucose-containing rehydration are beneficial; Dietary (eg, with high-carbohydrate, low-protein diet, with avoidance of fasting/ketogenic diet) and medical (eg, with supplementation/substrate therapy with citrate, aspartic acid, biotin, triheptanoin) therapy may be beneficial; Liver transplant may be required in some individuals	Biochemical; Neurologic	5771860; 817914; 826106; 6422151; 6424438; 3101494; 1909777; 9585612; 12112657; 16325442; 17403843; 18676167; 19306334; 20301764; 37207470

ClinVar

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

• Pyruvate carboxylase deficiency (57 variants)
• Global developmental delay (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PC 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			3	543	7	553
missense	3	9	191	40	2	245
nonsense	13	16				29
start loss						0
frameshift	33	50				83
inframe indel	1	1	8			10
splice donor/acceptor (+/-2bp)	8	18				26
splice region			10	78	4	92
non coding	1	1	53	237	9	301
Total	59	95	255	820	18

Highest pathogenic variant AF is 0.0000263

Variants in PC

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

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

Position	Type	Phenotype	Significance	ClinVar
11-66848526-G-A		Pyruvate carboxylase deficiency	Uncertain significance (Jun 14, 2016)
11-66848546-T-C		Pyruvate carboxylase deficiency	Uncertain significance (Jan 12, 2018)
11-66848696-A-G		Pyruvate carboxylase deficiency	Uncertain significance (Jan 13, 2018)
11-66848711-C-T		Pyruvate carboxylase deficiency	Uncertain significance (Jan 13, 2018)
11-66848714-C-T		Pyruvate carboxylase deficiency	Uncertain significance (Jan 12, 2018)
11-66848734-G-GA		Pyruvate carboxylase deficiency	Uncertain significance (Jun 14, 2016)
11-66848738-G-A		Pyruvate carboxylase deficiency	Uncertain significance (Jan 12, 2018)
11-66848793-C-A		Pyruvate carboxylase deficiency	Benign (Jan 13, 2018)
11-66848798-C-T		Pyruvate carboxylase deficiency	Uncertain significance (Jan 12, 2018)
11-66848810-C-T		Pyruvate carboxylase deficiency	Conflicting classifications of pathogenicity (Jun 10, 2019)
11-66848811-C-T		Pyruvate carboxylase deficiency	Uncertain significance (Jan 13, 2018)
11-66848856-G-A		Pyruvate carboxylase deficiency	Uncertain significance (Jan 12, 2018)
11-66848884-C-T		Pyruvate carboxylase deficiency • not specified	Conflicting classifications of pathogenicity (Jan 12, 2018)
11-66848886-G-A		PC-related disorder	Benign (Mar 03, 2015)
11-66848905-G-A		Pyruvate carboxylase deficiency	Conflicting classifications of pathogenicity (Jan 31, 2024)
11-66848905-G-T		Pyruvate carboxylase deficiency	Likely benign (Sep 09, 2023)
11-66848908-C-T		Pyruvate carboxylase deficiency	Likely benign (Mar 26, 2022)
11-66848910-C-T		Pyruvate carboxylase deficiency	Uncertain significance (Aug 30, 2023)
11-66848914-G-A		Pyruvate carboxylase deficiency	Likely benign (Feb 20, 2023)
11-66848916-T-G		not specified	Uncertain significance (Aug 19, 2015)
11-66848917-G-A		Pyruvate carboxylase deficiency	Likely benign (Sep 12, 2022)
11-66848922-C-A		Pyruvate carboxylase deficiency	Uncertain significance (Feb 27, 2022)
11-66848922-C-T		Pyruvate carboxylase deficiency	Conflicting classifications of pathogenicity (Jan 08, 2024)
11-66848923-G-A		Pyruvate carboxylase deficiency • PC-related disorder	Likely benign (Feb 01, 2024)
11-66848932-C-T		Pyruvate carboxylase deficiency	Likely benign (Jun 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PC	protein_coding	protein_coding	ENST00000393960	20	110144

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0138	0.986	125712	0	34	125746	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.06	516	752	0.686	0.0000525	7619
Missense in Polyphen		171	320.53	0.53349		3198
Synonymous	-1.39	359	327	1.10	0.0000244	2463
Loss of Function	4.64	13	47.5	0.274	0.00000267	531

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000272	0.000272
Finnish	0.000290	0.000277
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.000272	0.000272
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. Catalyzes in a tissue specific manner, the initial reactions of glucose (liver, kidney) and lipid (adipose tissue, liver, brain) synthesis from pyruvate.
• Disease: DISEASE: Pyruvate carboxylase deficiency (PC deficiency) [MIM:266150]: Leads to lactic acidosis, mental retardation and death. It occurs in three forms: mild or type A, severe neonatal or type B, and a very mild lacticacidemia. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Pyruvate metabolism - Homo sapiens (human);Warburg Effect;Pyruvate Dehydrogenase Complex Deficiency;Pyruvate Carboxylase Deficiency;Primary Hyperoxaluria Type I;Lactic Acidemia;Transfer of Acetyl Groups into Mitochondria;The oncogenic action of Succinate;The oncogenic action of Fumarate;Primary hyperoxaluria II, PH2;Pyruvate kinase deficiency;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Gluconeogenesis;Citric Acid Cycle;Alanine Metabolism;Leigh Syndrome;Glycogenosis, Type IA. Von gierke disease;Glycogenosis, Type IC;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;Glycogen Storage Disease Type 1A (GSD1A) or Von Gierke Disease;Pyruvate Metabolism;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency);Triosephosphate isomerase;Fructose-1,6-diphosphatase deficiency;Phosphoenolpyruvate carboxykinase deficiency 1 (PEPCK1);Glycogenosis, Type IB;Alanine and aspartate metabolism;TCA Cycle and Deficiency of Pyruvate Dehydrogenase complex (PDHc);Fatty Acid Biosynthesis;Amino Acid metabolism;Glycolysis and Gluconeogenesis;Biotin transport and metabolism;Metabolism of carbohydrates;Citrate cycle;Alanine Aspartate Asparagine metabolism;Glycolysis Gluconeogenesis;Glycolysis and Gluconeogenesis;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;gluconeogenesis;Gluconeogenesis;Glucose metabolism (Consensus)

Recessive Scores

• pRec: 0.818

Intolerance Scores

• loftool: 0.00882
• rvis_EVS: -1.74
• rvis_percentile_EVS: 2.39

Haploinsufficiency Scores

• pHI: 0.194
• hipred: Y
• hipred_score: 0.694
• ghis: 0.508

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.974

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pcx
• Phenotype: growth/size/body region 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: pcxa
• Affected structure: habituation
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: pyruvate metabolic process;gluconeogenesis;lipid metabolic process;biotin metabolic process;negative regulation of gene expression;viral RNA genome packaging;positive regulation by host of viral release from host cell;positive regulation by host of viral process
• Cellular component: cytoplasm;mitochondrion;mitochondrial matrix;cytosol
• Molecular function: pyruvate carboxylase activity;protein binding;ATP binding;biotin binding;identical protein binding;metal ion binding