ABetaL34V amyloidosis

Summary

ABetaL34V amyloidosis (MONDO:0017945) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 11

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

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

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0000726	Dementia	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001259	Coma	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001297	Stroke	Very frequent (80-99%)
HP:0001342	Cerebral hemorrhage	Very frequent (80-99%)
HP:0003401	Paresthesia	Very frequent (80-99%)
HP:0003474	Somatic sensory dysfunction	Very frequent (80-99%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0002076	Migraine	Frequent (30-79%)
HP:0100659	Abnormality of the cerebral vasculature	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	ABetaL34V amyloidosis
Mondo ID	MONDO:0017945
Orphanet	324703
UMLS	C5679882
MedGen	1842835
GARD	0017489
Is cancer (heuristic)	no

Also known as: ABeta amyloidosis, Piedmont type · ABetaL34V-related amyloidosis · HCHWA, Piedmont type · hereditary cerebral haemorrhage with amyloidosis, Piedmont type · hereditary cerebral hemorrhage with amyloidosis, Piedmont type

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebrovascular disorder › cerebral amyloid angiopathy › cerebral amyloid angiopathy, APP-related › ABetaL34V amyloidosis

Related subtypes (5): ABeta amyloidosis, dutch type, ABeta amyloidosis, Iowa type, ABeta amyloidosis, Italian type, ABetaA21G amyloidosis, ABeta amyloidosis, Arctic type

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 7 · 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
APP	Supportive	Autosomal dominant	ABeta amyloidosis, dutch type	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APP	Orphanet:100006	ABeta amyloidosis, Dutch type
APP	Orphanet:1020	Early-onset autosomal dominant Alzheimer disease
APP	Orphanet:324703	ABetaL34V amyloidosis
APP	Orphanet:324708	ABeta amyloidosis, Iowa type
APP	Orphanet:324713	ABeta amyloidosis, Italian type
APP	Orphanet:324718	ABetaA21G amyloidosis
APP	Orphanet:324723	ABeta amyloidosis, Arctic type

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
APP	HGNC:620	ENSG00000142192	P05067	Amyloid-beta precursor protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APP	Amyloid-beta precursor protein	Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.

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)
APP	Other/Unknown	no		Kunitz_BPTI, Amyloid_glyco_extra, Amyloid_glyco

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
Brodmann (1909) area 9	1
prefrontal cortex	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APP	295	ubiquitous	marker	prefrontal cortex, renal medulla, Brodmann (1909) area 9

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APP	11,686

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APP	P05067	256

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 69. 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
Aggregated β-amyloid induces FXII autocatalysis	1	5710.0×	0.011	APP
Aggregated β-amyloid interacts with fibrinogen	1	2855.0×	0.011	APP
Formyl peptide receptors bind formyl peptides and many other ligands	1	1427.5×	0.011	APP
Inflammasomes	1	1142.0×	0.011	APP
Cell recruitment (pro-inflammatory response)	1	1142.0×	0.011	APP
Neurodegenerative Diseases	1	878.5×	0.011	APP
Defective Intrinsic Pathway for Apoptosis	1	761.3×	0.011	APP
Advanced glycosylation endproduct receptor signaling	1	713.8×	0.011	APP
The NLRP3 inflammasome	1	671.8×	0.011	APP
Diseases of programmed cell death	1	634.4×	0.011	APP
Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models	1	519.1×	0.011	APP
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	475.8×	0.011	APP
TRAF6 mediated NF-kB activation	1	456.8×	0.011	APP
Purinergic signaling in leishmaniasis infection	1	423.0×	0.011	APP
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	356.9×	0.011	APP
Lysosome Vesicle Biogenesis	1	326.3×	0.011	APP
TAK1-dependent IKK and NF-kappa-B activation	1	300.5×	0.011	APP
Interleukin-1 family signaling	1	271.9×	0.011	APP
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1	253.8×	0.011	APP
trans-Golgi Network Vesicle Budding	1	253.8×	0.011	APP
Regulation of clotting cascade	1	233.1×	0.011	APP
Toll Like Receptor 10 (TLR10) Cascade	1	215.5×	0.011	APP
Toll Like Receptor 5 (TLR5) Cascade	1	215.5×	0.011	APP
MyD88 cascade initiated on plasma membrane	1	203.9×	0.011	APP
Toll Like Receptor 3 (TLR3) Cascade	1	193.6×	0.011	APP
TRIF (TICAM1)-mediated TLR4 signaling	1	190.3×	0.011	APP
Protein localization	1	190.3×	0.011	APP
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1	190.3×	0.011	APP
MyD88 dependent cascade initiated on endosome	1	190.3×	0.011	APP
MyD88-independent TLR4 cascade	1	184.2×	0.011	APP

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
collateral sprouting in absence of injury	1	5617.3×	0.002	APP
astrocyte activation involved in immune response	1	4213.0×	0.002	APP
axo-dendritic transport	1	4213.0×	0.002	APP
microglia development	1	4213.0×	0.002	APP
cellular response to norepinephrine stimulus	1	4213.0×	0.002	APP
regulation of spontaneous synaptic transmission	1	4213.0×	0.002	APP
axon midline choice point recognition	1	3370.4×	0.002	APP
swimming behavior	1	3370.4×	0.002	APP
hippocampal neuron apoptotic process	1	3370.4×	0.002	APP
positive regulation of amyloid fibril formation	1	3370.4×	0.002	APP
mating behavior	1	2808.7×	0.002	APP
regulation of synapse structure or activity	1	2808.7×	0.002	APP
response to insulin-like growth factor stimulus	1	2808.7×	0.002	APP
cellular response to manganese ion	1	2407.4×	0.002	APP
NMDA selective glutamate receptor signaling pathway	1	2407.4×	0.002	APP
modulation of excitatory postsynaptic potential	1	2106.5×	0.002	APP
ionotropic glutamate receptor signaling pathway	1	1296.3×	0.003	APP
negative regulation of long-term synaptic potentiation	1	1296.3×	0.003	APP
neuron remodeling	1	1203.7×	0.003	APP
neuron projection maintenance	1	1123.5×	0.003	APP
astrocyte activation	1	991.3×	0.003	APP
regulation of long-term neuronal synaptic plasticity	1	991.3×	0.003	APP
positive regulation of protein metabolic process	1	991.3×	0.003	APP
intracellular copper ion homeostasis	1	936.2×	0.003	APP
response to lead ion	1	936.2×	0.003	APP
regulation of Wnt signaling pathway	1	887.0×	0.003	APP
positive regulation of T cell migration	1	732.7×	0.003	APP
regulation of neuron apoptotic process	1	702.2×	0.003	APP
positive regulation of glycolytic process	1	674.1×	0.003	APP
positive regulation of long-term synaptic potentiation	1	674.1×	0.003	APP

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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.

Symbol	Example approved molecule
APP	FLORBETAPIR F 18

Top cohort targets by molecule count

Symbol	Molecules	Max phase
APP	40	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLORBETAPIR F 18	4	APP
FLORBETAPIR	4	APP
METHYLENE BLUE CATION	4	APP
FLUTEMETAMOL F 18	4	APP
TRETINOIN	4	APP
METHYLENE BLUE ANHYDROUS	4	APP
CLIOQUINOL	4	APP
DONEPEZIL	4	APP
FLORBETABEN F18	4	APP
NIACIN	4	APP
FLUTEMETAMOL	4	APP
GENTIAN VIOLET	4	APP
AMODIAQUINE	4	APP
CARVEDILOL	4	APP
CHLOROQUINE	4	APP
TACRINE	4	APP
RETINOL	4	APP
CURCUMIN	3	APP
CAFFEIC ACID	3	APP
TRAMIPROSATE	3	APP
RESVERATROL	3	APP
FLUTAFURANOL	3	APP
EPIGALOCATECHIN GALLATE	3	APP
LANABECESTAT	3	APP
QUERCETIN	3	APP
EDETIC ACID	3	APP
PARAROSANILINE	2	APP
LUTEOLIN	2	APP
PITTSBURGH COMPOUND B	2	APP
AFTOBETIN	2	APP

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
APP	1,744	Binding:1699, Functional:44, ADMET:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
APP	1,744

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

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.

Compound	Max phase	Cohort target (bioactivity)
FLORBETAPIR F 18	4	APP
FLORBETAPIR	4	APP
METHYLENE BLUE CATION	4	APP
FLUTEMETAMOL F 18	4	APP
TRETINOIN	4	APP
METHYLENE BLUE ANHYDROUS	4	APP
CLIOQUINOL	4	APP
DONEPEZIL	4	APP
FLORBETABEN F18	4	APP
NIACIN	4	APP
FLUTEMETAMOL	4	APP
GENTIAN VIOLET	4	APP
AMODIAQUINE	4	APP
CARVEDILOL	4	APP
CHLOROQUINE	4	APP
TACRINE	4	APP
RETINOL	4	APP
CURCUMIN	3	APP
CAFFEIC ACID	3	APP
TRAMIPROSATE	3	APP
RESVERATROL	3	APP
FLUTAFURANOL	3	APP
EPIGALOCATECHIN GALLATE	3	APP
LANABECESTAT	3	APP
QUERCETIN	3	APP
EDETIC ACID	3	APP
PARAROSANILINE	2	APP
LUTEOLIN	2	APP
PITTSBURGH COMPOUND B	2	APP
AFTOBETIN	2	APP

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	APP
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.