carnitine palmitoyl transferase 1A deficiency

Summary

carnitine palmitoyl transferase 1A deficiency (MONDO:0009705) is a disease caused by CPT1A (GenCC Definitive), with 1 cohort gene and 2 clinical trials.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CPT1A (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 1,055
• Phenotypes (HPO): 21
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		60	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Prevalence at birth	1-9 / 1 000 000	0.3	Israel	Validated
Prevalence at birth	1-9 / 1 000 000	0.5	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

21 HPO clinical features (Orphanet curated; top 21 by frequency):

HPO ID	Term	Frequency
HP:0000708	Atypical behavior	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001315	Reduced tendon reflexes	Very frequent (80-99%)
HP:0001399	Hepatic failure	Very frequent (80-99%)
HP:0001939	Abnormality of metabolism/homeostasis	Very frequent (80-99%)
HP:0001943	Hypoglycemia	Very frequent (80-99%)
HP:0002167	Abnormality of speech or vocalization	Very frequent (80-99%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Very frequent (80-99%)
HP:0003202	Skeletal muscle atrophy	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0001254	Lethargy	Frequent (30-79%)
HP:0001259	Coma	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0004374	Hemiplegia/hemiparesis	Frequent (30-79%)
HP:0007185	Loss of consciousness	Frequent (30-79%)
HP:0008279	Transient hyperlipidemia	Frequent (30-79%)
HP:0001639	Hypertrophic cardiomyopathy	Occasional (5-29%)
HP:0001645	Sudden cardiac death	Occasional (5-29%)
HP:0001947	Renal tubular acidosis	Occasional (5-29%)
HP:0011675	Arrhythmia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	carnitine palmitoyl transferase 1A deficiency
Mondo ID	MONDO:0009705
MeSH	C535588
OMIM	255120
Orphanet	156
DOID	DOID:0090129
NCIT	C98871
SNOMED CT	238001003
UMLS	C1829703
MedGen	316820
GARD	0001120
NORD	894
Is cancer (heuristic)	no

Also known as: Carnitine palmitoyl transferase 1 deficiency · carnitine palmitoyl transferase 1A deficiency · Carnitine palmitoyl transferase IA deficiency · carnitine palmitoyl transferase IA deficiency · Carnitine Palmitoyltransferase 1A Deficiency · Carnitine palmitoyltransferase 1A deficiency · carnitine palmitoyltransferase I deficiency · cpt deficiency, hepatic, type IA · CPT1A deficiency · CPT1A disorder of carnitine cycle and carnitine transport · disorder of carnitine cycle and carnitine transport caused by mutation in CPT1A · hepatic carnitine palmitoyl transferase 1 deficiency · hepatic carnitine palmitoyl transferase I deficiency · hepatic carnitine palmitoyltransferase 1 deficiency · hepatic CPT1 · L-CPT 1 deficiency · L-CPT1 deficiency · L-CPTI deficiency

Data availability: 1,055 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inherited lipid metabolism disorder › inherited fatty acid metabolism disorder › carnitine palmitoyl transferase 1A deficiency

Related subtypes (2): disorder of fatty acid oxidation and ketogenesis, inherited lipoic acid biosynthesis defect

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

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

341 likely benign, 139 uncertain significance, 47 likely pathogenic, 35 pathogenic, 15 benign, 13 pathogenic/likely pathogenic, 9 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070019	NC_000011.9:g.(?68560773)(68562389_?)del	CPT1A	Pathogenic	criteria provided, single submitter
1070426	NM_001876.4(CPT1A):c.1015C>T (p.Arg339Ter)	CPT1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1071607	NM_001876.4(CPT1A):c.76G>T (p.Glu26Ter)	CPT1A	Pathogenic	criteria provided, single submitter
1073716	NM_001876.4(CPT1A):c.1895T>A (p.Leu632Ter)	CPT1A	Pathogenic	criteria provided, single submitter
1075591	NM_001876.4(CPT1A):c.1709_1710del (p.Val570fs)	CPT1A	Pathogenic	criteria provided, single submitter
1378009	NM_001876.4(CPT1A):c.668T>G (p.Leu223Ter)	CPT1A	Pathogenic	criteria provided, single submitter
1383563	NM_001876.4(CPT1A):c.742del (p.Leu248fs)	CPT1A	Pathogenic	criteria provided, single submitter
1391751	NM_001876.4(CPT1A):c.1367C>A (p.Ser456Ter)	CPT1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1395198	NM_001876.4(CPT1A):c.924G>A (p.Trp308Ter)	CPT1A	Pathogenic	criteria provided, single submitter
1405623	NM_001876.4(CPT1A):c.2018_2022del (p.Pro672_Phe673insTer)	CPT1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1443299	NM_001876.4(CPT1A):c.589G>T (p.Glu197Ter)	CPT1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452946	NM_001876.4(CPT1A):c.1762_1766dup (p.Tyr589Ter)	CPT1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454023	NM_001876.4(CPT1A):c.1328dup (p.Leu444fs)	CPT1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455519	NC_000011.9:g.(?68525112)(68582942_?)del	CPT1A	Pathogenic	criteria provided, single submitter
1455520	NC_000011.9:g.(?68548098)(68548223_?)del	CPT1A	Pathogenic	criteria provided, single submitter
1456102	NM_001876.4(CPT1A):c.1573dup (p.Glu525fs)	CPT1A	Pathogenic	criteria provided, multiple submitters, no conflicts
1456264	NM_001876.4(CPT1A):c.530del (p.Pro177fs)	CPT1A	Pathogenic	criteria provided, single submitter
1456414	NM_001876.4(CPT1A):c.1984dup (p.Val662fs)	CPT1A	Pathogenic	criteria provided, single submitter
1694466	NM_001876.4(CPT1A):c.544_545del (p.Thr182fs)	CPT1A	Pathogenic	criteria provided, single submitter
1705365	NM_001876.4(CPT1A):c.1164-2A>G	CPT1A	Pathogenic	criteria provided, single submitter
189151	NM_001876.4(CPT1A):c.1364A>C (p.Lys455Thr)	CPT1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1960705	NM_001876.4(CPT1A):c.1855del (p.Met619fs)	CPT1A	Pathogenic	criteria provided, single submitter
1969741	NM_001876.4(CPT1A):c.2T>G (p.Met1Arg)	CPT1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1975306	NM_001876.4(CPT1A):c.1796_1797del (p.Glu599fs)	CPT1A	Pathogenic	criteria provided, single submitter
1993872	NM_001876.4(CPT1A):c.1882_1885del (p.Gln628fs)	CPT1A	Pathogenic	criteria provided, single submitter
1995273	NM_001876.4(CPT1A):c.1670dup (p.Ile558fs)	CPT1A	Pathogenic	criteria provided, single submitter
1996250	NM_001876.4(CPT1A):c.1493del (p.Tyr498fs)	CPT1A	Pathogenic	criteria provided, single submitter
1998547	NM_001876.4(CPT1A):c.1925del (p.His642fs)	CPT1A	Pathogenic	criteria provided, single submitter
1999606	NM_001876.4(CPT1A):c.704G>A (p.Trp235Ter)	CPT1A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2019097	NM_001876.4(CPT1A):c.1767C>G (p.Tyr589Ter)	CPT1A	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
CPT1A	Definitive	Autosomal recessive	carnitine palmitoyl transferase 1A deficiency	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CPT1A	Orphanet:156	Carnitine palmitoyl transferase 1A deficiency

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
CPT1A	HGNC:2328	ENSG00000110090	P50416	Carnitine O-palmitoyltransferase 1, liver isoform	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CPT1A	Carnitine O-palmitoyltransferase 1, liver isoform	Catalyzes the transfer of the acyl group of long-chain fatty acid-CoA conjugates onto carnitine, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion.

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)
CPT1A	Enzyme (other)	yes	2.3.1.21	Carn_acyl_trans, CAT-like_dom_sf, CPT_N

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
ileal mucosa	1
jejunal mucosa	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPT1A	282	ubiquitous	marker	jejunal mucosa, ileal mucosa, renal medulla

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CPT1A	2,399

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CPT1A	P50416	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Carnitine shuttle	1	761.3×	0.004	CPT1A
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	1	407.9×	0.004	CPT1A
PPARA activates gene expression	1	94.4×	0.011	CPT1A

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
carnitine shuttle	1	4213.0×	0.002	CPT1A
response to tetrachloromethane	1	4213.0×	0.002	CPT1A
carnitine metabolic process	1	2407.4×	0.002	CPT1A
aflatoxin metabolic process	1	2407.4×	0.002	CPT1A
positive regulation of fatty acid beta-oxidation	1	1532.0×	0.002	CPT1A
response to alkaloid	1	1532.0×	0.002	CPT1A
cellular response to fatty acid	1	702.2×	0.004	CPT1A
long-chain fatty acid metabolic process	1	624.1×	0.004	CPT1A
eating behavior	1	601.9×	0.004	CPT1A
positive regulation of innate immune response	1	526.6×	0.004	CPT1A
liver regeneration	1	510.7×	0.004	CPT1A
triglyceride metabolic process	1	443.5×	0.004	CPT1A
regulation of insulin secretion	1	391.9×	0.004	CPT1A
fatty acid beta-oxidation	1	374.5×	0.004	CPT1A
response to nutrient	1	295.6×	0.005	CPT1A
glucose metabolic process	1	255.3×	0.005	CPT1A
fatty acid metabolic process	1	193.7×	0.006	CPT1A
epithelial cell differentiation	1	175.5×	0.007	CPT1A
response to ethanol	1	146.5×	0.008	CPT1A
response to hypoxia	1	95.8×	0.011	CPT1A
response to xenobiotic stimulus	1	69.1×	0.014	CPT1A

Therapeutics

Drug target analysis

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

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
CPT1A	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TEGLICAR	2	CPT1A
OXFENICINE	2	CPT1A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CPT1A	24	Binding:24

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CPT1A	2.3.1.21	carnitine O-palmitoyltransferase

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
TEGLICAR	2	CPT1A
OXFENICINE	2	CPT1A

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	1	CPT1A
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan