Inherited lipid metabolism disorder

Summary

Inherited lipid metabolism disorder (MONDO:0002525) is a disease (an umbrella term covering 29 Mondo subtypes) with 2 cohort genes and 934 clinical trials. Top therapeutic interventions include pitavastatin, simvastatin, and atorvastatin.

At a glance

• Umbrella term: 29 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 934

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inherited lipid metabolism disorder
Mondo ID	MONDO:0002525
Orphanet	309005
DOID	DOID:3146
NCIT	C97092
SNOMED CT	267431006, 402788005
UMLS	C0154251
MedGen	57587
GARD	0021314
MedDRA	10061227
Is cancer (heuristic)	no

Also known as: disorder of lipid metabolism · dyslipidaemia · dyslipidemia · lipid metabolism disorder

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 29 Mondo subtypes.

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

Related subtypes (92): thiopurine metabolic disease, hypercalcemia, infantile, hypermanganesemia with dystonia, abdominal obesity-metabolic syndrome, plasma protein metabolism disease, lysosomal storage disease, striatonigral degeneration, inborn metal metabolism disorder, inborn vitamin metabolic disorder, chondrocalcinosis 2, Ehlers-Danlos syndrome, spondylodysplastic type, fish eye disease, aromatase excess syndrome, spondyloepiphyseal dysplasia with congenital joint dislocations, hypertriglyceridemia 1, autosomal dominant myoglobinuria, diastrophic dysplasia, hemolytic anemia due to diphosphoglycerate mutase deficiency, multiple epiphyseal dysplasia type 4, atelosteogenesis type II, inherited threoninemia, inborn glycerol kinase deficiency, achondrogenesis type IB, diabetes mellitus, noninsulin-dependent, 1, diabetes mellitus, noninsulin-dependent, 2, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, diabetes mellitus, noninsulin-dependent, 3, hypercholesterolemia, familial, 4, hypoalphalipoproteinemia, primary, 1, autosomal recessive proximal renal tubular acidosis, diabetes mellitus, noninsulin-dependent, 4, normophosphatemic familial tumoral calcinosis, apolipoprotein c-III deficiency, hypotonia-failure to thrive-microcephaly syndrome, chondrodysplasia with joint dislocations, gPAPP type, gluthathione peroxidase deficiency, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diabetes mellitus, noninsulin-dependent, 5, congenital disorder of glycosylation, monogenic diabetes, 2-hydroxyglutaric aciduria, familial hypoparathyroidism, familial intrahepatic cholestasis, inborn aminoacylase deficiency, disorder of lysosomal-related organelles, inborn disorder of porphyrin metabolism, disorder of metabolite absorption and transport, autosomal dominant proximal renal tubular acidosis, neurodegeneration with brain iron accumulation, ferro-cerebro-cutaneous syndrome, familial hypocalciuric hypercalcemia, hypophosphatasia, hereditary amyloidosis, peroxisomal disease, inborn disorder of amino acid and other organic acid metabolism, inborn carbohydrate metabolic disorder, inborn disorder of energy metabolism, inborn disorder of biogenic amine metabolism and transport, inborn disorder of purine or pyrimidine metabolism, spondyloepimetaphyseal dysplasia, PAPSS2 type, hereditary lipodystrophy, hereditary recurrent myoglobinuria, DNA repair disease, 4-hydroxyphenylacetic aciduria, 5-nucleotidase syndrome, antigen-peptide-transporter 2 deficiency, APO A-i deficiency, cardiomyopathy hypogonadism metabolic anomalies, deficiency of coenzyme q cytochrome c reductase, defective apolipoprotein b-100, sulfide quinone oxidoreductase deficiency, congenital disorder of deglycosylation, hypoalphalipoproteinemia, primary, 2, uridine-cytidineuria, NAD(P)HX dehydratase deficiency, inborn disorder of aspartate family metabolism, weinstein kliman scully syndrome, glycoprotein metabolism disease, inherited thyroid metabolism disease, tumoral calcinosis, hyperphosphatemic, familial, 2, tumoral calcinosis, hyperphosphatemic, familial, 3, combined ApoA-I and ApoC-III deficiency, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome, tumoral calcinosis, hyperphosphatemic, familial, 1, Waldenstrom macroglobulinemia, mucopolysaccharidosis or mucopolysaccharidosis-like disorder, disorder of peptide and amine metabolism, CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis, Lane Hamilton syndrome, SQSTM1-related multisystem proteinopathy, hypertriglyceridemia 2, autosomal dominant dopa-responsive dystonia

Subtypes (29): cortisone reductase deficiency, familial hyperlipidemia, hypolipoproteinemia, steroid inherited metabolic disorder, corticosterone methyloxidase type 1 deficiency, lipoid proteinosis, 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency, vitamin D hydroxylation-deficient rickets, type 1B, mitochondrial trifunctional protein deficiency, pancreatic triacylglycerol lipase deficiency, glucocorticoid resistance, syndromic dyslipidemia, inborn disorder of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation, disorder of plasmalogens biosynthesis, disorder of phospholipids, sphingolipids and fatty acids biosynthesis, inborn disorder of ketolysis, lysosomal lipid storage disorder, sterol metabolism disorder, disorder of sphingolipid biosynthesis, glycosylphosphatidylinositol biosynthesis defect 18, neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, developmental and epileptic encephalopathy, 77, developmental and epileptic encephalopathy, 80, developmental and epileptic encephalopathy, 55, inherited fatty acid metabolism disorder, glycosylphosphatidylinositol biosynthesis defect 16, glycosylphosphatidylinositol biosynthesis defect 15, glycosylphosphatidylinositol biosynthesis defect 17, CYP7B1-related disorder of oxysterol accumulation

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
4686642	NM_005577.4(LPA):c.4193G>A (p.Gly1398Asp)	LPA	Uncertain significance	criteria provided, single submitter
4686643	NM_013262.4(MYLIP):c.732A>C (p.Glu244Asp)	MYLIP	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYLIP	HGNC:21155	ENSG00000007944	Q8WY64	E3 ubiquitin-protein ligase MYLIP	clinvar
LPA	HGNC:6667	ENSG00000198670	P08519	Apolipoprotein(a)	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYLIP	E3 ubiquitin-protein ligase MYLIP	E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8.
LPA	Apolipoprotein(a)	Apo(a) is the main constituent of lipoprotein(a) (Lp(a)).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Protease	1	18.3×	0.108
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYLIP	Transcription factor	no		FERM_domain, Ez/rad/moesin-like, Znf_RING
LPA	Protease	yes		Kringle, Trypsin_dom, Peptidase_S1A

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
nipple	1
oocyte	1
secondary oocyte	1
adrenal tissue	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYLIP	275	ubiquitous	marker	oocyte, secondary oocyte, nipple
LPA	100	tissue_specific	marker	liver, right lobe of liver, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYLIP	1,592
LPA	1,200

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYLIP	Q8WY64	35
LPA	P08519	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Plasma lipoprotein assembly, remodeling, and clearance	2	228.4×	3e-04	MYLIP, LPA
NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake	1	1142.0×	0.005	MYLIP
LDL remodeling	1	951.7×	0.005	LPA
Transport of small molecules	2	25.1×	0.006	MYLIP, LPA
VLDLR internalisation and degradation	1	356.9×	0.008	MYLIP
Plasma lipoprotein remodeling	1	237.9×	0.008	LPA
Plasma lipoprotein clearance	1	237.9×	0.008	MYLIP
NR1H2 and NR1H3-mediated signaling	1	196.9×	0.009	MYLIP
Signaling by Nuclear Receptors	1	51.0×	0.030	MYLIP
Class I MHC mediated antigen processing & presentation	1	35.0×	0.040	MYLIP
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.068	MYLIP
Adaptive Immune System	1	14.9×	0.077	MYLIP
Immune System	1	6.5×	0.160	MYLIP
Signal Transduction	1	5.1×	0.187	MYLIP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of low-density lipoprotein particle receptor catabolic process	1	8426.0×	0.002	MYLIP
negative regulation of low-density lipoprotein particle clearance	1	766.0×	0.008	MYLIP
blood circulation	1	255.3×	0.017	LPA
protein destabilization	1	145.3×	0.018	MYLIP
lipid transport	1	131.7×	0.018	LPA
negative regulation of neuron projection development	1	118.7×	0.018	MYLIP
positive regulation of protein catabolic process	1	101.5×	0.018	MYLIP
cholesterol homeostasis	1	78.0×	0.021	MYLIP
lipid metabolic process	1	45.8×	0.031	LPA
ubiquitin-dependent protein catabolic process	1	37.1×	0.035	MYLIP
nervous system development	1	23.0×	0.051	MYLIP
protein ubiquitination	1	20.7×	0.052	MYLIP
proteolysis	1	17.1×	0.058	LPA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MYLIP	0	0
LPA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	LPA
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MYLIP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYLIP	0	—
LPA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 934.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	512
PHASE3	116
PHASE4	100
PHASE1	99
PHASE2	81
PHASE2/PHASE3	11
PHASE1/PHASE2	9
EARLY_PHASE1	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05365425	PHASE4	RECRUITING	Choline Fenofibrate and Carotid Atherosclerosis in Patients With Type 2 Diabetes and Combined Dyslipidemia
NCT05365438	PHASE4	RECRUITING	Atmeg (Atorvastatin and Omega-3 Combination) and Carotid Atherosclerosis in Patients With Type 2 Diabetes and Combined Dyslipidemia
NCT05537948	PHASE4	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Pitavastatin and PCSK9 Inhibitors in Liver Transplant Patients
NCT05749874	PHASE4	ACTIVE_NOT_RECRUITING	Effects of Berberine on Preventing Cardiovascular Disease and Diabetes Mellitus
NCT05845424	PHASE4	RECRUITING	High-intensity Statin and Ezetimibe Therapy for Asymptomatic Patients With Positive Coronary Calcium
NCT05910476	PHASE4	ACTIVE_NOT_RECRUITING	Comparative Study of Rosuvastatin/Ezetimib 20/10 mg and Atovastatin/Ezetimib 40/10 mg (TOLERANT Trial)
NCT06186037	PHASE4	RECRUITING	Clinical Comparison of Low-dose Rosuvastatin Plus Ezetimibe Combination Therapy and High-dose Rosuvastatin Monotherapy in Patients With Minimal to Intermediate Coronary Artery Disease Without Percutaneous Coronary Intervention
NCT06463561	PHASE4	RECRUITING	CPAP Effect on Lipid Profile and Hyperuricemia in Patients With Dyslipidemia and Moderate-severe Obstructive Sleep Apnea
NCT06845345	PHASE4	ENROLLING_BY_INVITATION	Effect of an Early Time Restricted Eating Mediterranean Diet Compared to Naltrexone/Bupropion on Liver Fibrosis in People With Cardiometabolic Risk Factors in a Hospital Outpatient Clinic (MEDFAST-study)
NCT07314775	PHASE4	NOT_YET_RECRUITING	Yangxin Dawayimixike Honey Paste for Carotid Atherosclerotic Plaque With Dyslipidemia: A Randomized Controlled Clinical Study
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00125125	PHASE4	COMPLETED	Fluvastatin in Adults With Dislipidemia With History of Muscle Problems
NCT00150384	PHASE4	COMPLETED	Clinical Utility of Caduet in Achieving Blood Pressure and Lipid Endpoints in a Specific Patient Population
NCT00171262	PHASE4	COMPLETED	Trial to Evaluate the Efficacy of Fluvastatin on Certain Markers
NCT00171327	PHASE4	COMPLETED	Efficacy and Safety of Fluvastatin or Valsartan and Their Combination in Dyslipidemic Patients With Hypertension and Endothelial Dysfunction
NCT00192621	PHASE4	COMPLETED	Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects
NCT00194402	PHASE4	COMPLETED	SLIM: Combined Effects of Slo-Niacin and Atorvastatin on Lipoproteins and Inflammatory Markers in Hyperlipidemia
NCT00249938	PHASE4	COMPLETED	Evaluation of Combination Cholesterol Treatments in Patients With High Cholesterol.
NCT00264394	PHASE4	COMPLETED	Cardiovascular Risk Factor Management in HIV Infection
NCT00282659	PHASE4	COMPLETED	The Use of Magnesium to Improve Blood Pressure, Cholesterol, and Glucose Control
NCT00330980	PHASE4	COMPLETED	Effects of Statin Medications on Mental Processes, Behavior, and Serotonin Levels
NCT00332761	PHASE4	COMPLETED	Caduet in an Untreated Subject Population
NCT00345657	PHASE4	COMPLETED	Efficacy Study of Extended-Release Niacin/Lovastatin Versus Usual Care
NCT00346697	PHASE4	COMPLETED	Omega-3 Fatty Acids for High Triglycerides in HIV-infected Patients
NCT00350038	PHASE4	COMPLETED	Irbesartan, Ciprofibrate and Their Combination Onto the Endothelial Functions
NCT00385658	PHASE4	COMPLETED	Efficacy of Fluvastatin and Fenofibrate in Comparison to Simvastatin and Ezetimibe in Patients With Metabolic Syndrome
NCT00412113	PHASE4	COMPLETED	A Multi-Risk Factor Strategy vs a Guideline-Based Approach in Achieving Blood Pressure and Lipid Goals in Hypertensives at Extra Risk
NCT00441480	PHASE4	COMPLETED	Effect of Plant Sterols Esterified to Fish Oil Fatty Acids on Plasma Lipid Levels
NCT00442325	PHASE4	COMPLETED	Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets
NCT00442845	PHASE4	COMPLETED	Establish The Benefits Of Using Various Starting Doses Of Atorvastatin On Achievement Of Cholesterol Targets (ACTFAST)
NCT00447070	PHASE4	COMPLETED	Effect of Atazanavir on Endothelial Function in HIV-Infected Patients
NCT00506961	PHASE4	COMPLETED	Evaluate the Efficacy and Safety of Rosuvastatin Versus Simvastatin in Type 2 Diabetic Patients With Dyslipidemia
NCT00540293	PHASE4	COMPLETED	Lipitor Korean Atorvastatin Goal Achievement Across Risk Levels Study
NCT00541554	PHASE4	UNKNOWN	Reversal of Antipsychotic-Induced Hyperprolactinemia, Weight Gain, Hyperglycemia and Dyslipidemia
NCT00644670	PHASE4	COMPLETED	A Study Of The Efficacy Of Atorvastatin For Lowering Cholesterol In High-Risk Patients With High Cholesterol
NCT00644709	PHASE4	COMPLETED	A Study Of Atorvastatin For The Treatment Of High Cholesterol In Patients At High Risk Of Coronary Heart Disease (CHD)
NCT00645151	PHASE4	COMPLETED	A Study Of The Efficacy Of Atorvastatin In Lowering Cholesterol In Latin American Patients With High Cholesterol
NCT00647543	PHASE4	COMPLETED	Atorvastatin Study For The Treatment Of High Cholesterol In Patients From Thailand
NCT00651963	PHASE4	COMPLETED	Open Label Study Evaluating The Use Of Combination Therapy Of Ezetimibe And Statins In Patients With Dyslipidemia In Colombia (0653-141)(COMPLETED)
NCT00665834	PHASE4	COMPLETED	Comparison of Rosuvastatin and Atorvastatin in Patients With Acute Coronary Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PITAVASTATIN	4	36
SIMVASTATIN	4	28
ATORVASTATIN	4	18
FENOFIBRATE	4	14
ROSUVASTATIN	4	14
EZETIMIBE	4	11
CHOLINE FENOFIBRATE	4	10
NIACIN	4	10
MIPOMERSEN	4	8
EVOLOCUMAB	4	7
PERINDOPRIL	4	6
FLUVASTATIN	4	5
ALIROCUMAB	4	4
AMLODIPINE	4	4
PRAVASTATIN	4	4
RIMONABANT	4	4
BEMPEDOIC ACID	4	3
LAROPIPRANT	4	3
TELMISARTAN	4	3
ARTENIMOL	4	2
FISH OIL	4	2
LEVOTHYROXINE	4	2
LOVASTATIN	4	2
OLMESARTAN MEDOXOMIL	4	2
SAFFLOWER OIL	4	2
ARIPIPRAZOLE	4	1
ATAZANAVIR	4	1
BERBERINE	4	1
BUPROPION HYDROCHLORIDE	4	1
CANNABIDIOL	4	1