very long chain acyl-CoA dehydrogenase deficiency

Summary

very long chain acyl-CoA dehydrogenase deficiency (MONDO:0008723) is a disease caused by ACADVL (GenCC Definitive), with 6 cohort genes and 10 clinical trials. Top therapeutic interventions include triheptanoin, glycerin, and bezafibrate.

At a glance

• Prevalence: 1-9 / 100 000 (Germany) [Orphanet-validated]
• Causal gene: ACADVL (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 2,037
• Phenotypes (HPO): 40
• Clinical trials: 10

Clinical features

Epidemiology

Prevalence records

7 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	2	Germany	Validated
Prevalence at birth	1-9 / 100 000	3.2	Australia	Validated
Prevalence at birth	1-9 / 100 000	1.8	United States	Validated
Prevalence at birth	1-9 / 100 000	2.3	Israel	Validated
Prevalence at birth	1-9 / 100 000	4.3	Specific population	Validated
Prevalence at birth	1-9 / 1 000 000	0.45	Czech Republic	Validated
Point prevalence	1-9 / 100 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

40 HPO clinical features (Orphanet curated; top 40 by frequency):

HPO ID	Term	Frequency
HP:0030781	Increased circulating free fatty acid level	Frequent (30-79%)
HP:0000952	Jaundice	Occasional (5-29%)
HP:0001518	Small for gestational age	Occasional (5-29%)
HP:0001629	Ventricular septal defect	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001655	Patent foramen ovale	Occasional (5-29%)
HP:0001985	Hypoketotic hypoglycemia	Occasional (5-29%)
HP:0002045	Hypothermia	Occasional (5-29%)
HP:0002098	Respiratory distress	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0002876	Episodic tachypnea	Occasional (5-29%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Occasional (5-29%)
HP:0003236	Elevated circulating creatine kinase concentration	Occasional (5-29%)
HP:0009045	Exercise-induced rhabdomyolysis	Occasional (5-29%)
HP:0011968	Feeding difficulties	Occasional (5-29%)
HP:0025502	Overweight	Occasional (5-29%)
HP:0000256	Macrocephaly	Very rare (<1-4%)
HP:0001254	Lethargy	Very rare (<1-4%)
HP:0001513	Obesity	Very rare (<1-4%)
HP:0001545	Anteriorly placed anus	Very rare (<1-4%)
HP:0001644	Dilated cardiomyopathy	Very rare (<1-4%)
HP:0001649	Tachycardia	Very rare (<1-4%)
HP:0001657	Prolonged QT interval	Very rare (<1-4%)
HP:0001663	Ventricular fibrillation	Very rare (<1-4%)
HP:0001678	Atrioventricular block	Very rare (<1-4%)
HP:0001698	Pericardial effusion	Very rare (<1-4%)
HP:0001942	Metabolic acidosis	Very rare (<1-4%)
HP:0001987	Hyperammonemia	Very rare (<1-4%)
HP:0002013	Vomiting	Very rare (<1-4%)
HP:0002090	Pneumonia	Very rare (<1-4%)
HP:0002280	Enlarged cisterna magna	Very rare (<1-4%)
HP:0002789	Tachypnea	Very rare (<1-4%)
HP:0002901	Hypocalcemia	Very rare (<1-4%)
HP:0003075	Hypoproteinemia	Very rare (<1-4%)
HP:0003394	Muscle spasm	Very rare (<1-4%)
HP:0004756	Ventricular tachycardia	Very rare (<1-4%)
HP:0008947	Floppy infant	Very rare (<1-4%)
HP:0011123	Inflammatory abnormality of the skin	Very rare (<1-4%)
HP:0011675	Arrhythmia	Very rare (<1-4%)
HP:0012531	Pain	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	very long chain acyl-CoA dehydrogenase deficiency
Mondo ID	MONDO:0008723
OMIM	201475
Orphanet	26793
DOID	DOID:0080155
ICD-10-CM	E71.310
ICD-11	907810567
NCIT	C98647
SNOMED CT	237997005
UMLS	C3887523
MedGen	854382
GARD	0005508
NORD	1827
Is cancer (heuristic)	no

Also known as: ACADVLD · acyl-CoA dehydrogenase, very long-chain deficiency · acyl-CoA dehydrogenase, very long-chain, deficiency OF · Very Long Chain Acyl CoA Dehydrogenase Deficiency (LCAD) · very long chain acyl-CoA dehydrogenase deficiency · very long-chain acyl-CoA dehydrogenase deficiency · very long-chain acyl-Coenzyme A dehydrogenase deficiency · VLCAD · VLCAD deficiency · VLCADD

Data availability: 2,037 ClinVar variants · 282 ClinGen variant curations · 5 GenCC gene-disease records · 6 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of energy metabolism › disorder of fatty acid and ketone body metabolism › disorder of fatty acid oxidation and ketogenesis › very long chain acyl-CoA dehydrogenase deficiency

Related subtypes (9): carnitine-acylcarnitine translocase deficiency, systemic primary carnitine deficiency disease, 3-hydroxy-3-methylglutaric aciduria, 3-hydroxy-3-methylglutaryl-CoA synthase deficiency, long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, acyl-CoA dehydrogenase 9 deficiency, acyl-CoA dehydrogenase deficiency, 3-hydroxyacyl-CoA dehydrogenase deficiency, long chain acyl-CoA dehydrogenase deficiency

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:

310 likely benign, 154 uncertain significance, 56 likely pathogenic, 39 pathogenic, 23 conflicting classifications of pathogenicity, 11 pathogenic/likely pathogenic, 7 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1036078	NM_000018.4(ACADVL):c.1909_1912dup (p.Ser638fs)	ACADVL	Pathogenic	criteria provided, single submitter
1073342	NM_000018.4(ACADVL):c.642_643del (p.Phe214fs)	ACADVL	Pathogenic	reviewed by expert panel
1208304	NM_000018.4(ACADVL):c.664G>C (p.Gly222Arg)	ACADVL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1321382	NM_000018.4(ACADVL):c.335del (p.Phe112fs)	ACADVL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1391720	NM_000018.4(ACADVL):c.1138C>T (p.Gln380Ter)	ACADVL	Pathogenic	criteria provided, single submitter
1392500	NM_000018.4(ACADVL):c.1093_1094insT (p.Asn365fs)	ACADVL	Pathogenic	criteria provided, single submitter
1414097	NM_000018.4(ACADVL):c.640_643del (p.Phe214fs)	ACADVL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1419913	NM_000018.4(ACADVL):c.406C>T (p.Leu136Phe)	ACADVL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1427529	NM_000018.4(ACADVL):c.277+2T>C	ACADVL	Pathogenic	criteria provided, single submitter
1427626	NM_000018.4(ACADVL):c.1605+1G>C	ACADVL	Pathogenic	criteria provided, single submitter
1437138	NM_000018.4(ACADVL):c.747G>A (p.Trp249Ter)	ACADVL	Pathogenic	criteria provided, single submitter
1437726	NM_000018.4(ACADVL):c.1328T>C (p.Met443Thr)	ACADVL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1440456	NM_000018.4(ACADVL):c.100_104dup (p.Arg37fs)	ACADVL	Pathogenic	criteria provided, multiple submitters, no conflicts
1442492	NM_000018.4(ACADVL):c.1138dup (p.Gln380fs)	ACADVL	Pathogenic	criteria provided, single submitter
1446281	NM_000018.4(ACADVL):c.626dup (p.Thr210fs)	ACADVL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1447373	NM_000018.4(ACADVL):c.488dup (p.Leu163fs)	ACADVL	Pathogenic	criteria provided, single submitter
1452475	NM_000018.4(ACADVL):c.1389del (p.Thr464fs)	ACADVL	Pathogenic	criteria provided, single submitter
1454349	NM_000018.4(ACADVL):c.1151_1154dup (p.Met386fs)	ACADVL	Pathogenic	criteria provided, single submitter
1454452	NM_000018.4(ACADVL):c.655C>A (p.Pro219Thr)	ACADVL	Pathogenic	criteria provided, single submitter
1455065	NM_000018.4(ACADVL):c.1587G>T (p.Leu529Phe)	ACADVL	Pathogenic	criteria provided, single submitter
1455427	NM_000018.4(ACADVL):c.303del (p.Glu104fs)	ACADVL	Pathogenic	criteria provided, single submitter
1457909	NM_000018.4(ACADVL):c.1739_1751del (p.Val580fs)	ACADVL	Pathogenic	criteria provided, single submitter
1458252	NM_000018.4(ACADVL):c.465_466dup (p.Cys156fs)	ACADVL	Pathogenic	criteria provided, single submitter
1458622	NM_000018.4(ACADVL):c.437T>G (p.Val146Gly)	ACADVL	Pathogenic	criteria provided, single submitter
1459642	NM_000018.4(ACADVL):c.1268C>A (p.Ser423Ter)	ACADVL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1460064	NM_000018.4(ACADVL):c.1605+1G>T	ACADVL	Pathogenic	criteria provided, single submitter
1484294	NM_000018.4(ACADVL):c.1316G>C (p.Gly439Ala)	ACADVL	Pathogenic	criteria provided, single submitter
1621	NM_000018.4(ACADVL):c.1080_1182+2del	ACADVL	Pathogenic	no assertion criteria provided
1624	NM_000018.4(ACADVL):c.343del	ACADVL	Pathogenic	reviewed by expert panel
1626	NM_000018.4(ACADVL):c.385GAG[1] (p.Glu130del)	ACADVL	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
ACADVL	Definitive	Autosomal recessive	very long chain acyl-CoA dehydrogenase deficiency	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACADVL	Orphanet:26793	Very long chain acyl-CoA dehydrogenase deficiency
CHRNB1	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
DLG4	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ACADVL	HGNC:92	ENSG00000072778	P49748	Very long-chain acyl-CoA dehydrogenase, mitochondrial	gencc,clinvar
CHRNB1	HGNC:1961	ENSG00000170175	P11230	Acetylcholine receptor subunit beta	clinvar
SPEM2	HGNC:27315	ENSG00000184560	Q0P670	Uncharacterized protein SPEM2	clinvar
DLG4	HGNC:2903	ENSG00000132535	P78352	Disks large homolog 4	clinvar
DVL2	HGNC:3086	ENSG00000004975	O14641	Segment polarity protein dishevelled homolog DVL-2	clinvar
SLC25A35	HGNC:31921	ENSG00000125434	Q3KQZ1	Solute carrier family 25 member 35	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACADVL	Very long-chain acyl-CoA dehydrogenase, mitochondrial	Very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation (FAO), breaking down fatty acids into acetyl-CoA and allowing the production of e…
CHRNB1	Acetylcholine receptor subunit beta	After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
DLG4	Disks large homolog 4	Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins.
DVL2	Segment polarity protein dishevelled homolog DVL-2	Plays a role in the signal transduction pathways mediated by multiple Wnt genes.
SLC25A35	Solute carrier family 25 member 35	Putative antiporter that exchanges dicarboxylates and sulfur oxoanions across the inner membrane of mitochondria.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.33

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
Kinase	1	4.6×	0.543
Scaffold/PPI	1	2.9×	0.543
Enzyme (other)	1	2.0×	0.543
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACADVL	Enzyme (other)	yes	1.3.8.8	Acyl-CoA_DH_CS, AcylCoA_DH/ox_M, AcylCo_DH/oxidase_C
CHRNB1	Other/Unknown	no		Nicotinic_acetylcholine_rcpt, Neurotrans-gated_channel_TM, Neur_channel
SPEM2	Other/Unknown	no		SPEM1_N
DLG4	Kinase	yes		SH3_domain, PDZ, Guanylate_kin-like_dom
DVL2	Scaffold/PPI	no		DEP_dom, DIX, PDZ
SLC25A35	Other/Unknown	no		MCP_transmembrane, MCP_dom_sf, Mito_Carrier_Antiporter

Expression context

Cohort genes with no expression data: 0.

4 cohort genes 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	2
right testis	2
apex of heart	1
right adrenal gland	1
right adrenal gland cortex	1
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1
testis	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
left ovary	1
stromal cell of endometrium	1
ventricular zone	1
kidney epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACADVL	295	ubiquitous	marker	right adrenal gland cortex, apex of heart, right adrenal gland
CHRNB1	137	ubiquitous	marker	gastrocnemius, hindlimb stylopod muscle, muscle of leg
SPEM2	23	tissue_specific	yes	left testis, right testis, testis
DLG4	190	tissue_specific	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
DVL2	278	ubiquitous	marker	ventricular zone, stromal cell of endometrium, left ovary
SLC25A35	186	ubiquitous	marker	kidney epithelium, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DLG4	6,905
DVL2	3,555
ACADVL	2,988
CHRNB1	711
SPEM2	390
SLC25A35	387

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DLG4	P78352	24
DVL2	O14641	15
CHRNB1	P11230	13
ACADVL	P49748	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC25A35	Q3KQZ1	87.99
SPEM2	Q0P670	49.84

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 6 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Beta oxidation of palmitoyl-CoA to myristoyl-CoA	1	1268.9×	0.013	ACADVL
Negative regulation of TCF-dependent signaling by DVL-interacting proteins	1	761.3×	0.013	DVL2
NrCAM interactions	1	543.8×	0.013	DLG4
mitochondrial fatty acid beta-oxidation of saturated fatty acids	1	543.8×	0.013	ACADVL
WNT mediated activation of DVL	1	475.8×	0.013	DVL2
Activation of Ca-permeable Kainate Receptor	1	380.7×	0.013	DLG4
WNT5:FZD7-mediated leishmania damping	1	317.2×	0.013	DVL2
LGI-ADAM interactions	1	271.9×	0.013	DLG4
WNT5A-dependent internalization of FZD4	1	253.8×	0.013	DVL2
RHO GTPases activate CIT	1	200.3×	0.013	DLG4
Ras activation upon Ca2+ influx through NMDA receptor	1	190.3×	0.013	DLG4
Signaling by Hippo	1	181.3×	0.013	DVL2
Trafficking of AMPA receptors	1	181.3×	0.013	DLG4
Unblocking of NMDA receptors, glutamate binding and activation	1	181.3×	0.013	DLG4
Synaptic adhesion-like molecules	1	181.3×	0.013	DLG4
Negative regulation of NMDA receptor-mediated neuronal transmission	1	181.3×	0.013	DLG4
IRE1alpha activates chaperones	1	173.0×	0.013	ACADVL
Long-term potentiation	1	158.6×	0.013	DLG4
Mitochondrial Fatty Acid Beta-Oxidation	1	126.9×	0.015	ACADVL
Unfolded Protein Response (UPR)	1	119.0×	0.015	ACADVL
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	119.0×	0.015	DVL2
PCP/CE pathway	1	100.2×	0.017	DVL2
Signaling by ERBB4	1	90.6×	0.018	DLG4
Assembly and cell surface presentation of NMDA receptors	1	84.6×	0.019	DLG4
Degradation of DVL	1	79.3×	0.019	DVL2
XBP1(S) activates chaperone genes	1	71.8×	0.020	ACADVL
Asymmetric localization of PCP proteins	1	68.0×	0.021	DVL2
Neurexins and neuroligins	1	65.6×	0.021	DLG4
Fatty acid metabolism	1	43.8×	0.030	ACADVL
TCF dependent signaling in response to WNT	1	39.2×	0.032	DVL2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of neuron projection arborization	2	1053.2×	8e-05	DLG4, DVL2
energy derivation by oxidation of organic compounds	1	2106.5×	0.012	ACADVL
convergent extension involved in neural plate elongation	1	1404.3×	0.012	DVL2
regulation of grooming behavior	1	1404.3×	0.012	DLG4
postsynaptic membrane organization	1	1053.2×	0.012	CHRNB1
AMPA glutamate receptor clustering	1	842.6×	0.012	DLG4
NMDA selective glutamate receptor signaling pathway	1	601.9×	0.012	DLG4
segment specification	1	526.6×	0.012	DVL2
receptor localization to synapse	1	526.6×	0.012	DLG4
synaptic vesicle maturation	1	468.1×	0.012	DLG4
behavioral response to nicotine	1	468.1×	0.012	CHRNB1
negative regulation of fatty acid oxidation	1	421.3×	0.012	ACADVL
fatty acid beta-oxidation using acyl-CoA dehydrogenase	1	351.1×	0.012	ACADVL
negative regulation of receptor internalization	1	300.9×	0.012	DLG4
nervous system process	1	300.9×	0.012	CHRNB1
positive regulation of signal transduction by p53 class mediator	1	300.9×	0.012	DVL2
positive regulation of synaptic transmission	1	280.9×	0.012	DLG4
regulation of cholesterol metabolic process	1	280.9×	0.012	ACADVL
cellular response to potassium ion	1	263.3×	0.012	DLG4
locomotory exploration behavior	1	247.8×	0.012	DLG4
regulation of long-term neuronal synaptic plasticity	1	247.8×	0.012	DLG4
muscle cell development	1	234.1×	0.012	CHRNB1
negative regulation of fatty acid biosynthetic process	1	221.7×	0.012	ACADVL
dendritic spine morphogenesis	1	221.7×	0.012	DLG4
vocalization behavior	1	221.7×	0.012	DLG4
synaptic transmission, cholinergic	1	200.6×	0.012	CHRNB1
neurotransmitter receptor localization to postsynaptic specialization membrane	1	200.6×	0.012	DLG4
monoatomic cation transport	1	191.5×	0.012	CHRNB1
protein localization to synapse	1	191.5×	0.012	DLG4
temperature homeostasis	1	162.0×	0.013	ACADVL

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 3

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
CHRNB1	VARENICLINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CHRNB1	10	4
ACADVL	1	2
DLG4	1	3
SPEM2	0	0
DVL2	0	0
SLC25A35	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VARENICLINE	4	CHRNB1
NICOTINE	4	CHRNB1
TROPISETRON	4	CHRNB1
BUPROPION	4	CHRNB1
MECAMYLAMINE	4	CHRNB1
DEXMECAMYLAMINE	3	CHRNB1
CYTISINICLINE	3	CHRNB1
NERINETIDE	3	DLG4
TG100-115	2	ACADVL
RADAFAXINE	2	CHRNB1
GTS-21	2	CHRNB1
TC-2216	1	CHRNB1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CHRNB1	87	Binding:51, Functional:36
DLG4	20	Binding:20
DVL2	3	Binding:3
ACADVL	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ACADVL	1.3.8.8, 1.3.8.9	long-chain acyl-CoA dehydrogenase, very-long-chain acyl-CoA dehydrogenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

12 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)
VARENICLINE	4	CHRNB1
NICOTINE	4	CHRNB1
TROPISETRON	4	CHRNB1
BUPROPION	4	CHRNB1
MECAMYLAMINE	4	CHRNB1
DEXMECAMYLAMINE	3	CHRNB1
CYTISINICLINE	3	CHRNB1
NERINETIDE	3	DLG4
TG100-115	2	ACADVL
RADAFAXINE	2	CHRNB1
GTS-21	2	CHRNB1
TC-2216	1	CHRNB1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CHRNB1
B	Phased (≥1) drug, not yet approved	2	ACADVL, DLG4
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	SPEM2, DVL2, SLC25A35

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SPEM2	0	—
DVL2	3	—
SLC25A35	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE2	3
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00983788	PHASE2	COMPLETED	Effect of Bezafibrate on Muscle Metabolism in Patients With Fatty Acid Oxidation Defects
NCT01494051	PHASE1/PHASE2	COMPLETED	High Protein Diet in Patients With Long-chain Fatty Acid Oxidation Disorders
NCT01886378	PHASE2	COMPLETED	A Study of UX007 (Triheptanoin) in Participants With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)
NCT02214160	PHASE2	COMPLETED	Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin Studies
NCT05411835	EARLY_PHASE1	COMPLETED	Oral Ketones and Exercise Among Patients With Long-chain Fatty Acid Oxidation Disorders
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT02517307	Not specified	COMPLETED	Fatty Acid Oxidation Defects and Insulin Sensitivity
NCT02635269	Not specified	UNKNOWN	Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy
NCT03531554	Not specified	COMPLETED	Acute Nutritional Ketosis in VLCAD Deficiency
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TRIHEPTANOIN	4	2
GLYCERIN	4	1
BEZAFIBRATE	3	1
CHEMBL3739769	0	1