Hypoalphalipoproteinemia

Summary

Hypoalphalipoproteinemia (MONDO:0017773) is a disease (an umbrella term covering 6 Mondo subtypes) with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include niacin.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypoalphalipoproteinemia
Mondo ID	MONDO:0017773
MeSH	D052456
Orphanet	31153
ICD-11	1731667610
NCIT	C84774
SNOMED CT	190785000
UMLS	C0151691
MedGen	57731
GARD	0018801
MedDRA	10065156
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 6 Mondo subtypes.

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

Related subtypes (36): 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, 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

Subtypes (6): Tangier disease, LCAT deficiency, combined ApoA-I and ApoC-III deficiency, apolipoprotein A-I deficiency, familial apolipoprotein gene cluster deletion syndrome, apolipoprotein A-II 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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
364389	NM_005502.4(ABCA1):c.5398A>C (p.Asn1800His)	ABCA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABCA1	Orphanet:31150	Tangier disease
ABCA1	Orphanet:425	Apolipoprotein A-I 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
ABCA1	HGNC:29	ENSG00000165029	O95477	Phospholipid-transporting ATPase ABCA1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABCA1	Phospholipid-transporting ATPase ABCA1	Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP.

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
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABCA1	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM

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
adrenal tissue	1
left adrenal gland	1
skin of hip	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABCA1	272	ubiquitous	marker	adrenal tissue, skin of hip, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ABCA1	3,551

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ABCA1	O95477	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. 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
Defective ABCA1 causes TGD	1	5710.0×	0.003	ABCA1
HDL assembly	1	1427.5×	0.006	ABCA1
Plasma lipoprotein assembly	1	713.8×	0.007	ABCA1
ABC transporter disorders	1	439.2×	0.008	ABCA1
NR1H2 and NR1H3-mediated signaling	1	393.8×	0.008	ABCA1
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	308.6×	0.009	ABCA1
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.010	ABCA1
Regulation of lipid metabolism by PPARalpha	1	141.0×	0.013	ABCA1
Disorders of transmembrane transporters	1	139.3×	0.013	ABCA1
Signaling by Nuclear Receptors	1	102.0×	0.015	ABCA1
PPARA activates gene expression	1	94.4×	0.015	ABCA1
Metabolism of lipids	1	31.6×	0.042	ABCA1
Transport of small molecules	1	25.1×	0.049	ABCA1
Disease	1	13.1×	0.087	ABCA1
Metabolism	1	11.6×	0.092	ABCA1
Signal Transduction	1	10.2×	0.098	ABCA1

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
response to vitamin B3	1	8426.0×	0.001	ABCA1
regulation of high-density lipoprotein particle assembly	1	8426.0×	0.001	ABCA1
positive regulation of high-density lipoprotein particle assembly	1	8426.0×	0.001	ABCA1
signal release	1	5617.3×	0.001	ABCA1
peptide secretion	1	4213.0×	0.001	ABCA1
response to laminar fluid shear stress	1	4213.0×	0.001	ABCA1
lipoprotein biosynthetic process	1	2808.7×	0.002	ABCA1
high-density lipoprotein particle assembly	1	1685.2×	0.002	ABCA1
export across plasma membrane	1	1685.2×	0.002	ABCA1
negative regulation of cholesterol storage	1	1532.0×	0.002	ABCA1
regulation of Cdc42 protein signal transduction	1	1404.3×	0.002	ABCA1
negative regulation of macrophage derived foam cell differentiation	1	1296.3×	0.002	ABCA1
intracellular cholesterol transport	1	1296.3×	0.002	ABCA1
protein transmembrane transport	1	1296.3×	0.002	ABCA1
phospholipid efflux	1	1123.5×	0.002	ABCA1
phospholipid homeostasis	1	991.3×	0.002	ABCA1
reverse cholesterol transport	1	936.2×	0.002	ABCA1
cellular response to low-density lipoprotein particle stimulus	1	887.0×	0.002	ABCA1
cellular response to cholesterol	1	842.6×	0.002	ABCA1
phagocytosis, engulfment	1	674.1×	0.002	ABCA1
platelet dense granule organization	1	674.1×	0.002	ABCA1
positive regulation of cholesterol efflux	1	624.1×	0.002	ABCA1
phospholipid translocation	1	624.1×	0.002	ABCA1
cellular response to cytokine stimulus	1	543.6×	0.003	ABCA1
cholesterol efflux	1	526.6×	0.003	ABCA1
lysosome organization	1	306.4×	0.004	ABCA1
protein secretion	1	263.3×	0.005	ABCA1
endosomal transport	1	244.2×	0.005	ABCA1
cellular response to xenobiotic stimulus	1	240.7×	0.005	ABCA1
cellular response to retinoic acid	1	234.1×	0.005	ABCA1

Therapeutics

Drug target analysis

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

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
ABCA1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ABCA1	2	Binding:2

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

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	ABCA1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ABCA1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE4	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01942291	PHASE4	COMPLETED	Short-term Effect of Extended-release Niacin on Endothelial Function.
NCT02697136	PHASE3	TERMINATED	CER-001 Therapy as a Novel Approach to Treat Genetic Orphan Diseases
NCT00458055	Not specified	COMPLETED	High-Density Lipoprotein (HDL) Treatment Study
NCT01342666	Not specified	COMPLETED	Tomato Consumption and High Density Lipoprotein-cholesterol

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NIACIN	4	1