apolipoprotein A-II amyloidosis

Summary

apolipoprotein A-II amyloidosis (MONDO:0016533) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	apolipoprotein A-II amyloidosis
Mondo ID	MONDO:0016533
Orphanet	238269
UMLS	C5679845
MedGen	1842484
GARD	0020631
Is cancer (heuristic)	no

Also known as: AApoAII amyloidosis · familial amyloid nephropathy due to apolipoprotein A-II variant · familial renal amyloidosis due to apolipoprotein A-II variant · hereditary amyloid nephropathy due to apolipoprotein A-II variant · hereditary renal amyloidosis due to apolipoprotein A-II variant

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › hereditary amyloidosis › familial visceral amyloidosis › apolipoprotein A-II amyloidosis

Related subtypes (3): AApoAI amyloidosis, ALys amyloidosis, AFib amyloidosis

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
17936	NM_001643.2(APOA2):c.-323C>T	APOA2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
APOA2	Supportive	Autosomal dominant	apolipoprotein A-II amyloidosis	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APOA2	Orphanet:238269	AApoAII amyloidosis

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
APOA2	HGNC:601	ENSG00000158874	P02652	Apolipoprotein A-II	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APOA2	Apolipoprotein A-II	May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
APOA2	Other/Unknown	no		ApoA-II, ApoA-II_sf

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
colonic epithelium	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APOA2	160	tissue_specific	marker	right lobe of liver, liver, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APOA2	1,921

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
APOA2	P02652	75.92

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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
Chylomicron assembly	1	1142.0×	0.008	APOA2
Chylomicron remodeling	1	1142.0×	0.008	APOA2
Plasma lipoprotein assembly	1	713.8×	0.009	APOA2
Plasma lipoprotein remodeling	1	475.8×	0.010	APOA2
Metabolism of fat-soluble vitamins	1	380.7×	0.010	APOA2
Visual phototransduction	1	259.6×	0.010	APOA2
Retinoid metabolism and transport	1	248.3×	0.010	APOA2
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.010	APOA2
Regulation of lipid metabolism by PPARalpha	1	141.0×	0.015	APOA2
Metabolism of vitamins and cofactors	1	116.5×	0.015	APOA2
Post-translational protein phosphorylation	1	100.2×	0.015	APOA2
Sensory Perception	1	95.2×	0.015	APOA2
PPARA activates gene expression	1	94.4×	0.015	APOA2
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	86.5×	0.016	APOA2
Metabolism of lipids	1	31.6×	0.040	APOA2
Transport of small molecules	1	25.1×	0.047	APOA2
Post-translational protein modification	1	19.2×	0.058	APOA2
Metabolism of proteins	1	12.4×	0.085	APOA2
Metabolism	1	11.6×	0.086	APOA2

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	APOA2
peptidyl-methionine modification	1	5617.3×	0.001	APOA2
triglyceride-rich lipoprotein particle remodeling	1	5617.3×	0.001	APOA2
negative regulation of cholesterol import	1	5617.3×	0.001	APOA2
regulation of intestinal cholesterol absorption	1	4213.0×	0.001	APOA2
negative regulation of cholesterol transport	1	4213.0×	0.001	APOA2
cellular response to lipoprotein particle stimulus	1	3370.4×	0.001	APOA2
negative regulation of cytokine production involved in immune response	1	2808.7×	0.001	APOA2
negative regulation of very-low-density lipoprotein particle remodeling	1	2808.7×	0.001	APOA2
diacylglycerol catabolic process	1	2808.7×	0.001	APOA2
high-density lipoprotein particle clearance	1	2407.4×	0.001	APOA2
positive regulation of lipid catabolic process	1	1872.4×	0.001	APOA2
high-density lipoprotein particle assembly	1	1685.2×	0.001	APOA2
phospholipid catabolic process	1	1203.7×	0.002	APOA2
phospholipid efflux	1	1123.5×	0.002	APOA2
low-density lipoprotein particle remodeling	1	1053.2×	0.002	APOA2
lipoprotein metabolic process	1	936.2×	0.002	APOA2
reverse cholesterol transport	1	936.2×	0.002	APOA2
negative regulation of lipid catabolic process	1	842.6×	0.002	APOA2
phosphatidylcholine biosynthetic process	1	802.5×	0.002	APOA2
high-density lipoprotein particle remodeling	1	802.5×	0.002	APOA2
cholesterol transport	1	732.7×	0.002	APOA2
cholesterol efflux	1	526.6×	0.003	APOA2
triglyceride metabolic process	1	443.5×	0.003	APOA2
positive regulation of phagocytosis	1	318.0×	0.004	APOA2
response to glucose	1	255.3×	0.005	APOA2
positive regulation of interleukin-8 production	1	244.2×	0.005	APOA2
cholesterol metabolic process	1	195.9×	0.006	APOA2
cholesterol homeostasis	1	156.0×	0.007	APOA2
regulation of protein stability	1	125.8×	0.008	APOA2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
APOA2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	1	APOA2

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)
APOA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.