Pyruvate carboxylase deficiency, infantile form

Summary

Pyruvate carboxylase deficiency, infantile form (MONDO:0018141) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pyruvate carboxylase deficiency, infantile form
Mondo ID	MONDO:0018141
Orphanet	353308
UMLS	C5679928
MedGen	1842180
GARD	0017536
Is cancer (heuristic)	no

Also known as: pyruvate carboxylase deficiency type A

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › glucose metabolism disease › disorder of gluconeogenesis › pyruvate carboxylase deficiency disease › pyruvate carboxylase deficiency, infantile form

Related subtypes (2): pyruvate carboxylase deficiency, severe neonatal type, pyruvate carboxylase deficiency, benign type

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PC	Definitive	Autosomal recessive	pyruvate carboxylase deficiency disease	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PC	Orphanet:353308	Pyruvate carboxylase deficiency, infantile type
PC	Orphanet:353314	Pyruvate carboxylase deficiency, severe neonatal type
PC	Orphanet:353320	Pyruvate carboxylase deficiency, benign type

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PC	HGNC:8636	ENSG00000173599	P11498	Pyruvate carboxylase, mitochondrial	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PC	Pyruvate carboxylase, mitochondrial	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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PC	Enzyme (other)	yes	6.4.1.1	Biotin_lipoyl, PYR_CT, Biotin_BS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
liver	1
right frontal lobe	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PC	204	ubiquitous	marker	right lobe of liver, liver, right frontal lobe

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PC	2,984

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PC	P11498	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective HLCS causes multiple carboxylase deficiency	1	1631.4×	0.002	PC
Biotin transport and metabolism	1	1038.2×	0.002	PC
Gluconeogenesis	1	439.2×	0.002	PC
Pyruvate metabolism	1	407.9×	0.002	PC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
viral RNA genome packaging	1	8426.0×	9e-04	PC
NAD+ metabolic process	1	1872.4×	0.001	PC
NADP+ metabolic process	1	1532.0×	0.001	PC
host-mediated activation of viral process	1	1404.3×	0.001	PC
viral release from host cell	1	936.2×	0.002	PC
gluconeogenesis	1	324.1×	0.004	PC
lipid metabolic process	1	91.6×	0.012	PC
negative regulation of gene expression	1	69.1×	0.014	PC

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PC	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PC	10	Binding:10

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PC	6.4.1.1	pyruvate carboxylase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	PC
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PC	10	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.