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Atlas / Disease / Metabolic disease

Metabolic disease

disease
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Also known as disorder of metabolic processmetabolic disordermetabolic process disease

Summary

Metabolic disease (MONDO:0005066) is a disease (an umbrella term covering 37 Mondo subtypes) caused by FARS2 (GenCC Definitive), with 9 cohort genes (426 GWAS associations across 60 studies) and 420 clinical trials. Top therapeutic interventions include mipomersen, tenofovir disoproxil, and terazosin.

At a glance

  • Causal gene: FARS2 (GenCC Definitive)
  • Umbrella term: 37 Mondo subtypes
  • Cohort genes: 9
  • GWAS associations: 426
  • ClinVar variants: 8
  • Clinical trials: 420

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namemetabolic disease
Mondo IDMONDO:0005066
EFOEFO:0000589
MeSHD008659
DOIDDOID:0014667
ICD-10-CME70-E88
NCITC3235
SNOMED CT75934005
UMLSC0025517
MedGen44376
Is cancer (heuristic)no

Also known as: disorder of metabolic process · metabolic disease · metabolic disorder · metabolic process disease

Data availability: 8 ClinVar variants · 426 GWAS associations (60 studies) · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 37 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease

Related subtypes (11): psychiatric disorder, premature aging syndrome, disorder of development or morphogenesis, inflammatory disease, disorder of glycosylation, ulcer disease, mitochondrial disease, sleep disorder, perinatal disease, obstetric disorder, disease by molecular mechanism

Subtypes (37): glutaric aciduria, mineral metabolism disease, xanthinuria, chondrocalcinosis, ochronosis disorder, glucose metabolism disease, diabetic kidney disease, xanthoma, diabetic retinopathy, hypertriglyceridemia, gout, lactic acidosis, acquired metabolic disease, lipodystrophy, developmental anomaly of metabolic origin, dopa-responsive dystonia, hypoalphalipoproteinemia, steroid dehydrogenase deficiency-dental anomalies syndrome, inborn errors of metabolism, vitamin B12 deficiency, proteostasis deficiencies, hyperlipidemia, disorder of GPI anchor biosynthesis, bilirubin metabolism disease, hyperlipoproteinemia, carbohydrate metabolism disease, porphyrin metabolism disease, purine metabolism disease, amino acid metabolism disease, pyrimidine metabolism disease, disorder of acid-base balance, disorder of glutamate decarboxylase, tumor lysis syndrome, collagenous sprue, steroid metabolism disease, disorder of organic acid metabolism, skeletal fluorosis

Genetics & variants

GWAS landscape

426 GWAS associations across 60 studies. Top hits map to 17 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs74121e-323APOEC0.42
rs75284196e-294CELSR2A0.22
rs127403747e-262CELSR2G0.21
chr19:449099768e-261T0.31
rs1421309586e-219SMARCA4 - LDLRG0.24
chr19:110856801e-210A0.25
rs730150202e-197SMARCA4 - LDLRG0.22
rs9641846e-193ZPR1G0.22
chr1:1092749682e-191T0.18
rs286017611e-175TRIB1ALC0.15
rs115911472e-156PCSK9G0.58
chr19:110869226e-150T0.2
chr11:1167524978e-144T0.18
rs6689482e-143APOB - TDRD15G0.16
chr8:1254921419e-140C0.13
rs5632901e-131APOB - TDRD15G0.15
chr2:210439024e-126G0.13
chr1:550399741e-119T0.48
rs585429261e-118TM6SF2C0.21
chr6:1605760862e-111T0.21
rs1128756512e-110TRIB1ALG0.13
rs283622868e-102PCSK9C1.14
rs104558721e-98LPAA0.22
rs42993764e-75ABCG8G0.1
chr2:438454372e-74T0.1
rs6518212e-70APOA5?
rs1154787351e-65ABOA0.11
chr2:275080739e-65C0.09
chr5:753607143e-62C0.09
rs12603265e-54GCKRT0.08

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90475715Verma A2024335,94890,622Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473214UK Biobank Whole-Genome Sequencing Consortium2025139,278319,162Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90473221UK Biobank Whole-Genome Sequencing Consortium2025115,511342,929Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90475714Verma A202482,10731,954Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479929Verma A202482,10731,954Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475713Verma A202439,98415,849Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90103393Fitzgerald T202238,221132,536CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.
GCST90435753Zhou W201835,927373,034Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90651134Liu TY202534,642195,375Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90475744Verma A20249,692429,457Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding5
Tier 2: splice/UTR6
Tier 3: regulatory0
Tier 4: intronic/intergenic39

MAF distribution

BucketVariants
common (>=0.05)23
low_freq (0.01-0.05)1
rare (<0.01)2
unknown24

Functional consequences

ConsequenceCount
unknown26
intron_variant10
3_prime_UTR_variant5
missense_variant3
intergenic_variant3
stop_gained2
splice_region_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
chr19:44908822Tier 4: intronic/intergenic
rs74121944908822C>T0.08missense_variantAPOE1e-323Tier 1: coding
rs75284191109274570A>G0.2183_prime_UTR_variantCELSR26e-294Tier 2: splice/UTR
rs127403741109274968G>T0.2223_prime_UTR_variantCELSR27e-262Tier 2: splice/UTR
chr19:449099768e-261Tier 4: intronic/intergenic
rs1421309581911079976G>A0.117intergenic_variantSMARCA4 - LDLR6e-219Tier 4: intronic/intergenic
chr19:110856801e-210Tier 4: intronic/intergenic
rs730150201911081874G>A,C0.12intergenic_variantSMARCA4 - LDLR2e-197Tier 4: intronic/intergenic
rs96418411116778201G>C0.1413_prime_UTR_variantZPR16e-193Tier 2: splice/UTR
chr1:1092749682e-191Tier 4: intronic/intergenic
rs286017618125487789C>G0.413intron_variantTRIB1AL1e-175Tier 4: intronic/intergenic
rs11591147155039974G>A,T0.015missense_variantPCSK92e-156Tier 1: coding
chr19:110869226e-150Tier 4: intronic/intergenic
chr11:1167524978e-144Tier 4: intronic/intergenic
rs668948221068657G>A0.204intron_variantAPOB - TDRD152e-143Tier 4: intronic/intergenic
chr8:1254921419e-140Tier 4: intronic/intergenic
rs563290221065354G>A,C0.283intron_variantAPOB - TDRD151e-131Tier 4: intronic/intergenic
chr2:210439024e-126Tier 4: intronic/intergenic
chr1:550399741e-119Tier 4: intronic/intergenic
rs585429261919268740C>A,T0.075stop_gainedTM6SF21e-118Tier 1: coding
chr6:1605760862e-111Tier 4: intronic/intergenic
rs1128756518125494452G>A,T0.337intron_variantTRIB1AL2e-110Tier 4: intronic/intergenic
rs28362286155063542C>A,T0.007stop_gainedPCSK98e-102Tier 1: coding
rs104558726160589086A>G0.069intron_variantLPA1e-98Tier 4: intronic/intergenic
rs4299376243845437G>C,T0.329intron_variantABCG84e-75Tier 4: intronic/intergenic
chr2:438454372e-74Tier 4: intronic/intergenic
rs65182111116791863C>A,T0.05splice_region_variantAPOA52e-70Tier 2: splice/UTR
rs1154787359133274295A>T0.193intron_variantABO1e-65Tier 4: intronic/intergenic
chr2:275080739e-65Tier 4: intronic/intergenic
chr5:753607143e-62Tier 4: intronic/intergenic

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 2 likely pathogenic, 2 pathogenic, 1 pathogenic/likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
100085NM_000182.5(HADHA):c.1528G>C (p.Glu510Gln)GAREM2Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
4074833NM_025137.4(SPG11):c.2180del (p.Asn727fs)SPG11Pathogeniccriteria provided, single submitter
41353NM_025137.4(SPG11):c.6856C>T (p.Arg2286Ter)SPG11Pathogeniccriteria provided, multiple submitters, no conflicts
4074763NM_001845.6(COL4A1):c.1582G>C (p.Gly528Arg)COL4A1Likely pathogeniccriteria provided, single submitter
375224NM_000317.2(PTS):c.(?-1)(*1_?)delPTSLikely pathogenicno assertion criteria provided
3129404NM_001374828.1(ARID1B):c.5734A>G (p.Ile1912Val)ARID1BUncertain significancecriteria provided, multiple submitters, no conflicts
3338130NM_001876.4(CPT1A):c.-14+11934T>ACPT1AUncertain significanceno assertion criteria provided
66873NM_170707.4(LMNA):c.1892G>A (p.Gly631Asp)LMNAUncertain significancecriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 37 · 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.

GeneClassificationInheritanceDiseaseRecords
FARS2DefinitiveAutosomal recessivemetabolic disease8
MPC2LimitedAutosomal recessivemetabolic disease2

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
FARS2Orphanet:319519Combined oxidative phosphorylation defect type 14
FARS2Orphanet:466722Autosomal recessive spastic paraplegia type 77
SPG11Orphanet:2822Autosomal recessive spastic paraplegia type 11
SPG11Orphanet:300605Juvenile amyotrophic lateral sclerosis
SPG11Orphanet:466775Autosomal recessive Charcot-Marie-Tooth disease type 2X
ARID1BOrphanet:1465Coffin-Siris syndrome
ARID1BOrphanet:2510566q25.2q25.3 microdeletion syndrome
COL4A1Orphanet:36383COL4A1/2-related familial vascular leukoencephalopathy
COL4A1Orphanet:477749Pontine autosomal dominant microangiopathy with leukoencephalopathy
COL4A1Orphanet:481986Familial schizencephaly
COL4A1Orphanet:73229HANAC syndrome
COL4A1Orphanet:75326Familial isolated retinal arteriolar tortuosity
COL4A1Orphanet:899Walker-Warburg syndrome
COL4A1Orphanet:99810Familial porencephaly
CPT1AOrphanet:156Carnitine palmitoyl transferase 1A deficiency
LMNAOrphanet:154Familial isolated dilated cardiomyopathy
LMNAOrphanet:157973Congenital muscular dystrophy due to LMNA mutation
LMNAOrphanet:1662Restrictive dermopathy
LMNAOrphanet:168796Heart-hand syndrome, Slovenian type
LMNAOrphanet:2229Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome
LMNAOrphanet:2348Familial partial lipodystrophy, Dunnigan type
LMNAOrphanet:280365Autosomal semi-dominant severe lipodystrophic laminopathy
LMNAOrphanet:293888Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant
LMNAOrphanet:293899Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant
LMNAOrphanet:293910Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant
LMNAOrphanet:300751Familial dilated cardiomyopathy with conduction defect due to LMNA mutation
LMNAOrphanet:363618LMNA-related cardiocutaneous progeria syndrome
LMNAOrphanet:54260Left ventricular noncompaction
LMNAOrphanet:675396Epithelioid hemangioma
LMNAOrphanet:740Hutchinson-Gilford progeria syndrome
LMNAOrphanet:79084Familial partial lipodystrophy, Köbberling type
LMNAOrphanet:79474Atypical Werner syndrome
LMNAOrphanet:90153Mandibuloacral dysplasia with type A lipodystrophy
LMNAOrphanet:98853Autosomal dominant Emery-Dreifuss muscular dystrophy
LMNAOrphanet:98855Autosomal recessive Emery-Dreifuss muscular dystrophy
LMNAOrphanet:98856Charcot-Marie-Tooth disease type 2B1
PTSOrphanet:136-pyruvoyl-tetrahydropterin synthase deficiency

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence9

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
FARS2HGNC:21062ENSG00000145982O95363Phenylalanine–tRNA ligase, mitochondrialgencc
MPC2HGNC:24515ENSG00000143158O95563Mitochondrial pyruvate carrier 2gencc
SPG11HGNC:11226ENSG00000104133Q96JI7Spatacsinclinvar
ARID1BHGNC:18040ENSG00000049618Q8NFD5AT-rich interactive domain-containing protein 1Bclinvar
COL4A1HGNC:2202ENSG00000187498P02462Collagen alpha-1(IV) chainclinvar
CPT1AHGNC:2328ENSG00000110090P50416Carnitine O-palmitoyltransferase 1, liver isoformclinvar
GAREM2HGNC:27172ENSG00000157833Q75VX8GRB2-associated and regulator of MAPK protein 2clinvar
LMNAHGNC:6636ENSG00000160789P02545Prelamin-A/Cclinvar
PTSHGNC:9689ENSG00000150787Q033936-pyruvoyl tetrahydrobiopterin synthaseclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
FARS2Phenylalanine–tRNA ligase, mitochondrialIs responsible for the charging of tRNA(Phe) with phenylalanine in mitochondrial translation.
MPC2Mitochondrial pyruvate carrier 2Mediates the uptake of pyruvate into mitochondria to maintain the balance between glycolysis and oxidative phosphorylation.
SPG11SpatacsinMay play a role in neurite plasticity by maintaining cytoskeleton stability and regulating synaptic vesicle transport.
ARID1BAT-rich interactive domain-containing protein 1BInvolved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
COL4A1Collagen alpha-1(IV) chainType IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
CPT1ACarnitine O-palmitoyltransferase 1, liver isoformCatalyzes 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.
GAREM2GRB2-associated and regulator of MAPK protein 2Probable adapter protein that may provide a link between cell surface epidermal growth factor receptor and the MAPK/ERK signaling pathway.
LMNAPrelamin-A/CLamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane.
PTS6-pyruvoyl tetrahydrobiopterin synthaseInvolved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 6 · 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.

FamilyGenesFoldFDR
Enzyme (other)34.0×0.066
Other/Unknown61.2×0.380

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
FARS2Enzyme (other)yes6.1.1.20Phenylalanyl-tRNA_Synthase, Phe-tRNA-synth_IIc_mito, Fdx_antiC-bd
MPC2Other/UnknownnoMPC
SPG11Other/UnknownnoSpatacsin, Spatacsin_C_dom
ARID1BOther/UnknownnoARID_dom, BAF250/Osa, BAF250_C
COL4A1Other/UnknownnoCollagen_IV_NC, Collagen, CTDL_fold
CPT1AEnzyme (other)yes2.3.1.21Carn_acyl_trans, CAT-like_dom_sf, CPT_N
GAREM2Other/UnknownnoSAM/pointed_sf, CABIT_dom, GAREM
LMNAOther/UnknownnoLamin_tail_dom, IF_conserved, Lamin_tail_dom_sf
PTSEnzyme (other)yes4.2.3.126-PTP_synth/QueD, PTPS_His_AS, PTPS_Cys_AS

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)9
unknown0

Top tissues across cohort

TissueCohort genes
endothelial cell1
gluteal muscle1
triceps brachii1
adult organism1
male germ cell1
sperm1
bronchial epithelial cell1
calcaneal tendon1
granulocyte1
bone marrow cell1
colonic epithelium1
sural nerve1
placenta1
right coronary artery1
visceral pleura1
ileal mucosa1
jejunal mucosa1
renal medulla1
caudate nucleus1
ganglionic eminence1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
FARS2260ubiquitousmarkertriceps brachii, endothelial cell, gluteal muscle
MPC2298ubiquitousmarkersperm, adult organism, male germ cell
SPG11295ubiquitousmarkerbronchial epithelial cell, granulocyte, calcaneal tendon
ARID1B256ubiquitousmarkerbone marrow cell, colonic epithelium, sural nerve
COL4A1283ubiquitousmarkervisceral pleura, placenta, right coronary artery
CPT1A282ubiquitousmarkerjejunal mucosa, ileal mucosa, renal medulla
GAREM2187ubiquitousyesventricular zone, ganglionic eminence, caudate nucleus
LMNA295ubiquitousmarkernipple, mucosa of stomach, skin of abdomen
PTS298ubiquitousmarkeradrenal tissue, right adrenal gland, left adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
LMNA7,173
COL4A12,909
FARS22,506
CPT1A2,399
ARID1B2,131
PTS1,897
SPG111,691
MPC21,315
GAREM2667

Structural data

PDB: 8 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
LMNAP0254528
MPC2O9556317
FARS2O953639
COL4A1P024624
SPG11Q96JI73
ARID1BQ8NFD52
CPT1AP504161
PTSQ033931

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
GAREM2Q75VX861.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 58. Enrichment computed across 9 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Breakdown of the nuclear lamina1543.8×0.054LMNA
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation1163.1×0.054PTS
Carnitine shuttle1108.8×0.054CPT1A
Anchoring fibril formation1108.8×0.054COL4A1
Depolymerization of the Nuclear Lamina1108.8×0.054LMNA
Formation of the canonical BAF (cBAF) complex190.6×0.054ARID1B
Initiation of Nuclear Envelope (NE) Reformation185.9×0.054LMNA
Scavenging by Class A Receptors185.9×0.054COL4A1
Fibronectin matrix formation181.6×0.054COL4A1
Crosslinking of collagen fibrils181.6×0.054COL4A1
Mitochondrial tRNA aminoacylation174.2×0.054FARS2
IRE1alpha activates chaperones174.2×0.054LMNA
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models174.2×0.054LMNA
Attachment of bacteria to epithelial cells170.9×0.054COL4A1
Nuclear Envelope Breakdown165.3×0.054LMNA
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)165.3×0.054ARID1B
Pyruvate metabolism158.3×0.054MPC2
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression158.3×0.054CPT1A
Laminin interactions154.4×0.054COL4A1
Regulation of endogenous retroelements152.6×0.054ARID1B
Unfolded Protein Response (UPR)151.0×0.054LMNA
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known142.9×0.058ARID1B
tRNA Aminoacylation140.8×0.058FARS2
Regulation of MITF-M-dependent genes involved in pigmentation137.9×0.058ARID1B
Collagen chain trimerization137.1×0.058COL4A1
Signaling by PDGF136.2×0.058COL4A1
NCAM1 interactions135.5×0.058COL4A1
Oncogenic MAPK signaling135.5×0.058LMNA
XBP1(S) activates chaperone genes130.8×0.064LMNA
Assembly of collagen fibrils and other multimeric structures128.6×0.067COL4A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
neuromuscular junction development2117.0×0.013SPG11, COL4A1
phagosome-lysosome fusion involved in apoptotic cell clearance11872.4×0.016SPG11
pyruvate import into mitochondria1624.1×0.016MPC2
localization within membrane1624.1×0.016SPG11
DNA double-strand break attachment to nuclear envelope1624.1×0.016LMNA
phenylalanyl-tRNA aminoacylation1468.1×0.016FARS2
carnitine shuttle1468.1×0.016CPT1A
axo-dendritic transport1468.1×0.016SPG11
establishment or maintenance of microtubule cytoskeleton polarity1468.1×0.016LMNA
renal tubule morphogenesis1468.1×0.016COL4A1
response to tetrachloromethane1468.1×0.016CPT1A
nuclear pore localization1374.5×0.016LMNA
autophagosome organization1374.5×0.016SPG11
negative regulation of mesenchymal cell proliferation1312.1×0.016LMNA
walking behavior1312.1×0.016SPG11
tetrahydrobiopterin biosynthetic process1267.5×0.016PTS
response to stress1267.5×0.016GAREM2
carnitine metabolic process1267.5×0.016CPT1A
corticospinal tract morphogenesis1267.5×0.016SPG11
aflatoxin metabolic process1267.5×0.016CPT1A
retinal blood vessel morphogenesis1267.5×0.016COL4A1
epithelial cell differentiation239.0×0.016COL4A1, CPT1A
protein import into nucleus232.0×0.016SPG11, LMNA
pyruvate decarboxylation to acetyl-CoA1234.1×0.017MPC2
protein localization to nuclear envelope1234.1×0.017LMNA
regulation of protein localization to nucleus1234.1×0.017LMNA
negative regulation of cardiac muscle hypertrophy in response to stress1208.1×0.018LMNA
positive regulation of fatty acid beta-oxidation1170.2×0.020CPT1A
response to alkaloid1170.2×0.020CPT1A
ventricular cardiac muscle cell development1170.2×0.020LMNA

Therapeutics

Drugs indicated for this disease

0 approved, 7 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
AcarbosePhase 3 (in late-stage trials)
FenofibratePhase 3 (in late-stage trials)
MetforminPhase 3 (in late-stage trials)
OMEGA-3-ACID ETHYL ESTERSPhase 3 (in late-stage trials)
RamiprilPhase 3 (in late-stage trials)
RosiglitazonePhase 3 (in late-stage trials)
StannsoporfinPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Dextrose, Soybean Oil.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 3 · Undrugged: 6

Druggability breadth: 7 of 9 evidence-associated genes (78%) 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.

SymbolExample approved molecule
LMNABEPRIDIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
LMNA8234
CPT1A22
MPC212
FARS200
SPG1100
ARID1B00
COL4A100
GAREM200
PTS00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
BEPRIDIL4LMNA
PHENYLBUTAZONE4LMNA
CEFOTAXIME SODIUM4LMNA
DIENESTROL4LMNA
IFOSFAMIDE4LMNA
PROGESTERONE4LMNA
CLOTRIMAZOLE4LMNA
DAPSONE4LMNA
AMINOCAPROIC ACID4LMNA
FLUCONAZOLE4LMNA
COLCHICINE4LMNA
NABUMETONE4LMNA
OXAPROZIN4LMNA
BUMETANIDE4LMNA
GLIPIZIDE4LMNA
BROMFENAC4LMNA
ROPIVACAINE4LMNA
TIZANIDINE4LMNA
METAXALONE4LMNA
CARBAMAZEPINE4LMNA
SALMETEROL XINAFOATE4LMNA
AMIODARONE HYDROCHLORIDE4LMNA
METHYL SALICYLATE4LMNA
DIBUCAINE4LMNA
PHENELZINE4LMNA
HYDROCORTISONE ACETATE4LMNA
BRETYLIUM TOSYLATE4LMNA
IMIPRAMINE4LMNA
FURAZOLIDONE4LMNA
DROPERIDOL4LMNA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

SymbolAssaysType breakdown
CPT1A24Binding:24
LMNA12Binding:9, Functional:3
FARS23Binding:3
MPC21Binding:1
SPG111Binding:1
PTS1ADMET:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
FARS26.1.1.20phenylalanine-tRNA ligase
CPT1A2.3.1.21carnitine O-palmitoyltransferase
PTS4.2.3.126-pyruvoyltetrahydropterin synthase

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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.

CompoundMax phaseCohort target (bioactivity)
BEPRIDIL4LMNA
PHENYLBUTAZONE4LMNA
CEFOTAXIME SODIUM4LMNA
DIENESTROL4LMNA
IFOSFAMIDE4LMNA
PROGESTERONE4LMNA
CLOTRIMAZOLE4LMNA
DAPSONE4LMNA
AMINOCAPROIC ACID4LMNA
FLUCONAZOLE4LMNA
COLCHICINE4LMNA
NABUMETONE4LMNA
OXAPROZIN4LMNA
BUMETANIDE4LMNA
GLIPIZIDE4LMNA
BROMFENAC4LMNA
ROPIVACAINE4LMNA
TIZANIDINE4LMNA
METAXALONE4LMNA
CARBAMAZEPINE4LMNA
SALMETEROL XINAFOATE4LMNA
AMIODARONE HYDROCHLORIDE4LMNA
METHYL SALICYLATE4LMNA
DIBUCAINE4LMNA
PHENELZINE4LMNA
HYDROCORTISONE ACETATE4LMNA
BRETYLIUM TOSYLATE4LMNA
IMIPRAMINE4LMNA
FURAZOLIDONE4LMNA
DROPERIDOL4LMNA

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1LMNA
BPhased (≥1) drug, not yet approved2MPC2, CPT1A
CDruggable family + PDB, no drug2FARS2, PTS
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug4SPG11, ARID1B, COL4A1, GAREM2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
FARS23—
SPG111—
ARID1B0—
COL4A10—
GAREM20—
PTS1—

Clinical trials & evidence

Clinical trials

Clinical trials: 420.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified335
PHASE227
PHASE124
PHASE316
PHASE48
PHASE1/PHASE27
EARLY_PHASE12
PHASE2/PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05855577PHASE4NOT_YET_RECRUITINGMotor Function Efficacy of Pharmacological Treatments Targeting Energy Metabolism, in Parkinson’s Patients
NCT06003153PHASE4RECRUITINGGLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH
NCT00192621PHASE4COMPLETEDSeronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects
NCT01443806PHASE4COMPLETEDCharacterisation of the Human Carboxylesterase 1 (CES1) Mutations in Thailand
NCT02645279PHASE4UNKNOWNComparison of Oral 30 % Dextrose and iv Midazolam Sedation During MRI in Neonates
NCT04653779PHASE4UNKNOWNA Clinical Trial to Evaluate the Preference Regarding Convenience of Medication and Efficacy/Safety of SUGAMET®XR Tablet 5/1000mg
NCT05084079PHASE4UNKNOWNDifferent Initial Insulin Dose Regimens on Time to Achieve Glycemic Targets and Treatment Safety in SIIT
NCT06009653PHASE4WITHDRAWNEffects of Tirzepatide Plus Intensive Lifestyle Therapy on Body Weight and Metabolic Health in Latinos With Obesity
NCT05208281PHASE2/PHASE3RECRUITINGA Multi-cohort Study of Safety, Efficacy, PK and PD of GNR-055 in Patients With Mucopolysaccharidosis Type II
NCT06568471PHASE3RECRUITINGA Study on Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia
NCT06672237PHASE3RECRUITINGA Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT07613307PHASE3NOT_YET_RECRUITINGA Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes Who Observe Ramadan Fasting
NCT00387114PHASE3TERMINATEDEffect of an Anti-Oxidant Treatment on Resistin Serum Levels.A Randomized Study
NCT00546052PHASE3COMPLETEDA 52 Week Study to Evaluate the Effects of Losartan With or Without HCTZ on Plasma Glucose, Metabolic Parameters, Blood Pressure in Hypertensive Patients With Metabolic Syndrome (0954A-331)
NCT00607373PHASE3COMPLETEDStudy to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109PHASE3COMPLETEDAn Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00935766PHASE3TERMINATEDEffect of Fish Oil (Omega-3 Fatty Acids) on Arteries
NCT01286909PHASE3UNKNOWNEfficacy of Laflavon in Lowering Triglycerides and Raising High-Density Lipoprotein (HDL)
NCT01343680PHASE3TERMINATEDTrial of Two Central Venous Catheter (CVC) Flushing Schemes in Pediatric Hematology and Oncology Patients
NCT04371978PHASE3TERMINATEDEfficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19
NCT04809220PHASE3COMPLETEDA Study of Two Doses of Dulaglutide (LY2189265) in Japanese Patients With Type 2 Diabetes
NCT05260021PHASE3COMPLETEDA Study to Evaluate Tirzepatide (LY3298176) in Pediatric and Adolescent Participants With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin or Basal Insulin or Both
NCT05425745PHASE3COMPLETEDEvaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05505994PHASE3UNKNOWNThe Efficacy and Safety of DWP16001 in Combination With Metformin in T2DM Patients Inadequately Controlled on Metformin
NCT05691712PHASE3COMPLETEDA Study of Tirzepatide (LY3298176) in Chinese Participants With Type 2 Diabetes
NCT00920972PHASE1/PHASE2RECRUITINGCampath/Fludarabine/Melphalan Transplant Conditioning for Non-Malignant Diseases
NCT03128996PHASE1/PHASE2RECRUITINGReduced Intensity Conditioning and Familial HLA-Mismatched BMT for Non-Malignant Disorders
NCT04055428PHASE2RECRUITINGNAUTICAL: Effect of Natriuretic Peptide Augmentation on Cardiometabolic Health in Black Individuals
NCT04414046PHASE2RECRUITINGTCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Primary Immunodeficiency and Inherited Metabolic Disorders in Children
NCT06320951PHASE2NOT_YET_RECRUITINGVITAL-IMPACT: Improving Cardiometabolic Health in Black Individuals Through Therapeutic Augmentation of Cyclic Guanosine Mono-Phosphate Signaling Pathway
NCT06575426PHASE1/PHASE2RECRUITINGA Study to Investigate Safety and Effectiveness of Porcine Pancreatic Cells (OPF-310) in Patients With Type 1 Diabetes Mellitus
NCT06843902PHASE2RECRUITINGImproving Coronary Vascular Health in Women
NCT06968208PHASE2NOT_YET_RECRUITINGThe Efficacy and Safety of Puerarin in Obesity Treatment
NCT00001723PHASE2COMPLETEDSafety and Efficacy of Xenical in Children and Adolescents With Obesity-Related Diseases
NCT00119379PHASE2COMPLETEDEffectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults
NCT00362180PHASE2COMPLETEDMeasure Liver Fat Content After ISIS 301012 (Mipomersen) Administration
NCT00446264PHASE2COMPLETEDIslet Allotransplantation With Steroid Free Immunosuppression
NCT00467831PHASE1/PHASE2TERMINATEDPilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
NCT00477594PHASE2COMPLETEDOpen Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00622765PHASE2COMPLETEDA Study of the Safety and Effectiveness of JNJ-16269110 (R256918) in Overweight and Obese Patients

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
MIPOMERSEN48
TENOFOVIR DISOPROXIL43
TERAZOSIN43
INULIN42
LOSARTAN42
TIRZEPATIDE42
ACIPIMOX41
ASCORBIC ACID41
BUSULFAN41
CLOFARABINE41
DEFERASIROX41
DULAGLUTIDE41
ERYTHROMYCIN41
EVINACUMAB41
EVOGLIPTIN41
GONADORELIN ACETATE41
INSULIN LISPRO41
LACTITOL41
LAMIVUDINE41
LINAGLIPTIN41
ORLISTAT41
OSELTAMIVIR41
PHENTERMINE41
PHENTERMINE HYDROCHLORIDE41
PRAVASTATIN41
ROTIGOTINE41
SECRETIN41
SEMAGLUTIDE41
VERICIGUAT41
ZILEUTON41

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot