ADan amyloidosis

Summary

ADan amyloidosis (MONDO:0007297) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ADan amyloidosis
Mondo ID	MONDO:0007297
MeSH	C538209
OMIM	117300
Orphanet	97346
DOID	DOID:0070030
ICD-11	2086401830, 54507082
UMLS	C1861735
MedGen	396208
GARD	0009169
Is cancer (heuristic)	no

Also known as: cerebellar ataxia, cataract, deafness, and dementia Or psychosis · cerebral amyloid angiopathy, ITM2B-related, type 2 · familial Danish dementia · familial dementia, Danish type · FDD · Heredopathia Ophthalmootoencephalica · HOOE

Data availability: 3 ClinVar variants · 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 › ADan amyloidosis

Related subtypes (3): ACys amyloidosis, ABri amyloidosis, cerebral amyloid angiopathy, APP-related

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

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
5980	NM_021999.5(ITM2B):c.787_796dup (p.Ser266fs)	ITM2B	Pathogenic	no assertion criteria provided
1353049	NM_021999.5(ITM2B):c.92C>G (p.Pro31Arg)	ITM2B	Uncertain significance	criteria provided, multiple submitters, no conflicts
975900	NM_021999.5(ITM2B):c.50A>G (p.Lys17Arg)	ITM2B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · 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
ITM2B	Strong	Autosomal dominant	ABri amyloidosis	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITM2B	Orphanet:397758	Retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies
ITM2B	Orphanet:97345	ABri amyloidosis
ITM2B	Orphanet:97346	ADan 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
ITM2B	HGNC:6174	ENSG00000136156	Q9Y287	Integral membrane protein 2B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITM2B	Integral membrane protein 2B	Plays a regulatory role in the processing of the amyloid-beta A4 precursor protein (APP) and acts as an inhibitor of the amyloid-beta peptide aggregation and fibrils deposition.

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)
ITM2B	Other/Unknown	no		BRICHOS_dom, ITM2

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
germinal epithelium of ovary	1
metanephric glomerulus	1
renal glomerulus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITM2B	295	ubiquitous	marker	renal glomerulus, metanephric glomerulus, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITM2B	1,917

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITM2B	Q9Y287	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Amyloid fiber formation	1	102.9×	0.019	ITM2B
Metabolism of proteins	1	12.4×	0.081	ITM2B

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
negative regulation of amyloid precursor protein biosynthetic process	1	2106.5×	9e-04	ITM2B
nervous system development	1	45.9×	0.022	ITM2B

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
ITM2B	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	ITM2B

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)
ITM2B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.