Encephalopathy, acute, infection-induced, susceptibility to, 4

Summary

Encephalopathy, acute, infection-induced, susceptibility to, 4 (MONDO:0013633) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 243

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	encephalopathy, acute, infection-induced, susceptibility to, 4
Mondo ID	MONDO:0013633
OMIM	614212
UMLS	C3280160
MedGen	481790
Is cancer (heuristic)	no

Also known as: CPT2 encephalopathy, acute, infection-induced · encephalopathy, acute, infection-induced caused by mutation in CPT2 · encephalopathy, acute, infection-induced, 4, susceptibility to · encephalopathy, acute, infection-induced, susceptibility to, 4 · encephalopathy, acute, infection-induced, susceptibility to, type 4 · IIAE4

Data availability: 243 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › encephalitis, acute, infection-induced, susceptibility to › encephalopathy, acute, infection-induced, susceptibility to, 4

Related subtypes (6): encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 10, encephalitis, acute, infection (viral)-induced, susceptibility to, 11, encephalopathy, acute, infection-induced, susceptibility to, 9, encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8, immunodeficiency 83, susceptibility to viral infections, encephalitis, acute, infection-induced, susceptibility to, 12

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

243 retrieved; paginated sample, class counts are floors:

99 uncertain significance, 44 pathogenic/likely pathogenic, 34 conflicting classifications of pathogenicity, 26 likely pathogenic, 19 likely benign, 10 pathogenic, 9 benign/likely benign, 1 benign, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
1067729	NM_000098.3(CPT2):c.1436A>G (p.Tyr479Cys)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073763	NM_000098.3(CPT2):c.28_29insAGCAAG (p.Trp10Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1074855	NM_000098.3(CPT2):c.350_354del (p.Phe117fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076646	NM_000098.3(CPT2):c.1660C>T (p.Arg554Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
130889	NM_000098.3(CPT2):c.452G>A (p.Arg151Gln)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1358726	NM_000098.3(CPT2):c.451C>T (p.Arg151Trp)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1437709	NM_000098.3(CPT2):c.213_214del (p.Leu72fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451403	NM_000098.3(CPT2):c.1339C>T (p.Gln447Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1460363	NM_000098.3(CPT2):c.896_906dup (p.Arg303fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
166953	NM_000098.3(CPT2):c.886C>T (p.Arg296Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
188753	NM_000098.3(CPT2):c.1369A>T (p.Lys457Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1944741	NM_000098.3(CPT2):c.1437C>G (p.Tyr479Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1959706	NM_000098.3(CPT2):c.257del (p.Ser86fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
203659	NM_000098.3(CPT2):c.370C>T (p.Arg124Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
203663	NM_000098.3(CPT2):c.1511C>T (p.Pro504Leu)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2048995	NM_000098.3(CPT2):c.1806del (p.Phe602fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680939	NM_000098.3(CPT2):c.1143_1144del (p.Arg382fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680944	NM_000098.3(CPT2):c.1444_1447del (p.Thr482fs)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
2700153	NM_000098.3(CPT2):c.975_976del (p.Cys326fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2733898	NM_000098.3(CPT2):c.1273_1274del (p.Thr425fs)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
371697	NM_000098.3(CPT2):c.110_111dup (p.Ser38fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371712	NM_000098.3(CPT2):c.1545_1548del (p.Phe516fs)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
371729	NM_000098.3(CPT2):c.1345C>T (p.Gln449Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371730	NM_000098.3(CPT2):c.75del (p.Ser26fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371750	NM_000098.3(CPT2):c.1414C>T (p.Gln472Ter)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371762	NM_000098.3(CPT2):c.1046dup (p.Asn349fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372351	NM_000098.3(CPT2):c.852del (p.Glu285fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
429340	NM_000098.3(CPT2):c.1324dup (p.Thr442fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
495549	NM_000098.3(CPT2):c.98del (p.Gln33fs)	CPT2	Pathogenic	criteria provided, multiple submitters, no conflicts
529859	NM_000098.3(CPT2):c.725_726del (p.His242fs)	CPT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · 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
CPT2	Limited	Unknown	encephalopathy, acute, infection-induced, susceptibility to, 4	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CPT2	Orphanet:228302	Carnitine palmitoyl transferase II deficiency, myopathic form
CPT2	Orphanet:228305	Carnitine palmitoyl transferase II deficiency, severe infantile form
CPT2	Orphanet:228308	Carnitine palmitoyl transferase II deficiency, neonatal form
CPT2	Orphanet:263524	Acute necrotizing encephalopathy of childhood

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
CPT2	HGNC:2330	ENSG00000157184	P23786	Carnitine O-palmitoyltransferase 2, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CPT2	Carnitine O-palmitoyltransferase 2, mitochondrial	Involved in the intramitochondrial synthesis of acylcarnitines from accumulated acyl-CoA metabolites.

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)
CPT2	Enzyme (other)	yes	2.3.1.21	Carn_acyl_trans, CAT-like_dom_sf, Cho/carn_acyl_trans_1_2

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
jejunal mucosa	1
mucosa of transverse colon	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPT2	254	ubiquitous	marker	mucosa of transverse colon, jejunal mucosa, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CPT2	2,303

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CPT2	P23786	94.52

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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×	0.003	CPT2
PPARA activates gene expression	1	94.4×	0.011	CPT2

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×	0.001	CPT2
carnitine metabolic process	1	2407.4×	0.001	CPT2
long-chain fatty acid metabolic process	1	624.1×	0.003	CPT2
fatty acid beta-oxidation	1	374.5×	0.004	CPT2
positive regulation of cold-induced thermogenesis	1	163.6×	0.007	CPT2
in utero embryonic development	1	72.0×	0.014	CPT2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CPT2	PERHEXILINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CPT2	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PERHEXILINE	4	CPT2
TEGLICAR	2	CPT2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CPT2	12	Binding:12

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CPT2	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)
PERHEXILINE	4	CPT2
TEGLICAR	2	CPT2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CPT2
B	Phased (≥1) drug, not yet approved	0
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: 0.