apolipoprotein A-I deficiency

Summary

apolipoprotein A-I deficiency (MONDO:0700513) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 2
• Phenotypes (HPO): 9

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		30	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Point prevalence	<1 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0002621	Atherosclerosis	Very frequent (80-99%)
HP:0003119	Abnormal circulating lipid concentration	Very frequent (80-99%)
HP:0003233	Decreased HDL cholesterol concentration	Very frequent (80-99%)
HP:0007759	Opacification of the corneal stroma	Very frequent (80-99%)
HP:0000622	Blurred vision	Frequent (30-79%)
HP:0000991	Xanthomatosis	Frequent (30-79%)
HP:0001114	Xanthelasma	Frequent (30-79%)
HP:0001681	Angina pectoris	Frequent (30-79%)
HP:0005181	Premature coronary artery atherosclerosis	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	apolipoprotein A-I deficiency
Mondo ID	MONDO:0700513
Orphanet	425
UMLS	C0342898
MedGen	137983
GARD	0028051
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › hypoalphalipoproteinemia › apolipoprotein A-I deficiency

Related subtypes (5): Tangier disease, LCAT deficiency, combined ApoA-I and ApoC-III deficiency, familial apolipoprotein gene cluster deletion syndrome, apolipoprotein A-II deficiency

Subtypes (2): hypoalphalipoproteinemia, primary, 1, hypoalphalipoproteinemia, primary, 2

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:

1 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
17919	NC_000011.10:g.(?116800700)(116841000_?)del	APOA1-AS	Pathogenic	no assertion criteria provided
17916	NM_000039.3(APOA1):c.566C>G (p.Pro189Arg)	APOA1	Uncertain significance	criteria provided, single submitter

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
APOA1	Orphanet:425	Apolipoprotein A-I deficiency
APOA1	Orphanet:93560	AApoAI amyloidosis

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
APOA1-AS	HGNC:40079	ENSG00000235910		APOA1 antisense RNA	clinvar
APOA1	HGNC:600	ENSG00000118137	P02647	Apolipoprotein A-I	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APOA1	Apolipoprotein A-I	Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
APOA1-AS	Other/Unknown	no
APOA1	Other/Unknown	no		ApoA_E, Apolipoprotein_A1/A4/E

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
colonic epithelium	1
corpus callosum	1
male germ line stem cell (sensu Vertebrata) in testis	1
jejunal mucosa	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APOA1-AS	131		marker	corpus callosum, male germ line stem cell (sensu Vertebrata) in testis, colonic epithelium
APOA1	170	broad	marker	jejunal mucosa, right lobe of liver, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APOA1	3,608
APOA1-AS	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APOA1	P02647	31

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 45. Enrichment computed across 2 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×	0.006	APOA1
HDL clearance	1	2284.0×	0.006	APOA1
HDL assembly	1	1427.5×	0.006	APOA1
Chylomicron assembly	1	1142.0×	0.006	APOA1
Chylomicron remodeling	1	1142.0×	0.006	APOA1
HDL remodeling	1	1142.0×	0.006	APOA1
Scavenging by Class B Receptors	1	1038.2×	0.006	APOA1
Scavenging of heme from plasma	1	878.5×	0.006	APOA1
Plasma lipoprotein assembly	1	713.8×	0.007	APOA1
ABC transporters in lipid homeostasis	1	601.0×	0.007	APOA1
Scavenging by Class A Receptors	1	601.0×	0.007	APOA1
Binding and Uptake of Ligands by Scavenger Receptors	1	543.8×	0.007	APOA1
Plasma lipoprotein remodeling	1	475.8×	0.007	APOA1
Plasma lipoprotein clearance	1	475.8×	0.007	APOA1
ABC transporter disorders	1	439.2×	0.007	APOA1
Metabolism of fat-soluble vitamins	1	380.7×	0.007	APOA1
Dengue virus activates/modulates innate and adaptive immune responses	1	335.9×	0.008	APOA1
Visual phototransduction	1	259.6×	0.010	APOA1
Retinoid metabolism and transport	1	248.3×	0.010	APOA1
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.010	APOA1
Heme signaling	1	215.5×	0.010	APOA1
Maturation of DENV proteins	1	211.5×	0.010	APOA1
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.012	APOA1
Regulation of lipid metabolism by PPARalpha	1	141.0×	0.013	APOA1
Disorders of transmembrane transporters	1	139.3×	0.013	APOA1
ABC-family protein mediated transport	1	121.5×	0.014	APOA1
Metabolism of vitamins and cofactors	1	116.5×	0.014	APOA1
Platelet activation, signaling and aggregation	1	105.7×	0.015	APOA1
Amyloid fiber formation	1	102.9×	0.015	APOA1
Post-translational protein phosphorylation	1	100.2×	0.015	APOA1

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
protein oxidation	1	5617.3×	0.001	APOA1
peptidyl-methionine modification	1	5617.3×	0.001	APOA1
regulation of intestinal cholesterol absorption	1	4213.0×	0.001	APOA1
positive regulation of phospholipid efflux	1	4213.0×	0.001	APOA1
acylglycerol homeostasis	1	3370.4×	0.001	APOA1
negative regulation of cell adhesion molecule production	1	3370.4×	0.001	APOA1
cellular response to lipoprotein particle stimulus	1	3370.4×	0.001	APOA1
negative regulation of cytokine production involved in immune response	1	2808.7×	0.001	APOA1
glucocorticoid metabolic process	1	2808.7×	0.001	APOA1
negative regulation of very-low-density lipoprotein particle remodeling	1	2808.7×	0.001	APOA1
lipoprotein biosynthetic process	1	2808.7×	0.001	APOA1
vitamin transport	1	2808.7×	0.001	APOA1
negative regulation of response to cytokine stimulus	1	2808.7×	0.001	APOA1
cholesterol import	1	2808.7×	0.001	APOA1
high-density lipoprotein particle clearance	1	2407.4×	0.001	APOA1
positive regulation of cholesterol metabolic process	1	2106.5×	0.001	APOA1
negative regulation of heterotypic cell-cell adhesion	1	1872.4×	0.001	APOA1
amyloid-beta formation	1	1872.4×	0.001	APOA1
high-density lipoprotein particle assembly	1	1685.2×	0.001	APOA1
regulation of Cdc42 protein signal transduction	1	1404.3×	0.002	APOA1
blood vessel endothelial cell migration	1	1404.3×	0.002	APOA1
phospholipid efflux	1	1123.5×	0.002	APOA1
phospholipid homeostasis	1	991.3×	0.002	APOA1
reverse cholesterol transport	1	936.2×	0.002	APOA1
phosphatidylcholine biosynthetic process	1	802.5×	0.002	APOA1
high-density lipoprotein particle remodeling	1	802.5×	0.002	APOA1
cholesterol transport	1	732.7×	0.002	APOA1
adrenal gland development	1	674.1×	0.002	APOA1
negative chemotaxis	1	648.1×	0.003	APOA1
positive regulation of cholesterol efflux	1	624.1×	0.003	APOA1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
APOA1-AS	0	0
APOA1	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
APOA1	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	APOA1-AS, APOA1

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)
APOA1-AS	0	—
APOA1	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.