variant ABeta2M amyloidosis

Summary

variant ABeta2M amyloidosis (MONDO:0017810) is a disease caused by B2M (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: B2M (GenCC Strong)
• Cohort genes: 1
• Phenotypes (HPO): 24

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0001917	Renal amyloidosis	Frequent (30-79%)
HP:0012185	Constrictive median neuropathy	Frequent (30-79%)
HP:0012622	Chronic kidney disease	Frequent (30-79%)
HP:0000157	Abnormality of the tongue	Occasional (5-29%)
HP:0002176	Spinal cord compression	Occasional (5-29%)
HP:0002756	Pathologic fracture	Occasional (5-29%)
HP:0003365	Arthralgia of the hip	Occasional (5-29%)
HP:0005244	Gastrointestinal infarctions	Occasional (5-29%)
HP:0007141	Sensorimotor neuropathy	Occasional (5-29%)
HP:0010286	Abnormal salivary gland morphology	Occasional (5-29%)
HP:0011805	Abnormal skeletal muscle morphology	Occasional (5-29%)
HP:0011915	Cardiovascular calcification	Occasional (5-29%)
HP:0012065	Multiple bony cystic lesions	Occasional (5-29%)
HP:0012280	Hepatic amyloidosis	Occasional (5-29%)
HP:0012309	Cutaneous amyloidosis	Occasional (5-29%)
HP:0012332	Abnormal autonomic nervous system physiology	Occasional (5-29%)
HP:0012664	Reduced left ventricular ejection fraction	Occasional (5-29%)
HP:0025015	Abnormal vascular morphology	Occasional (5-29%)
HP:0030834	Shoulder pain	Occasional (5-29%)
HP:0030836	Wrist pain	Occasional (5-29%)
HP:0030839	Knee pain	Occasional (5-29%)
HP:0030843	Cardiac amyloidosis	Occasional (5-29%)
HP:0031368	Intestinal perforation	Occasional (5-29%)
HP:0100292	Amyloidosis of peripheral nerves	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	variant ABeta2M amyloidosis
Mondo ID	MONDO:0017810
Orphanet	314652
DOID	DOID:0080929
ICD-11	1466418791
SNOMED CT	722292000
UMLS	C4302669
MedGen	928338
GARD	0021382
Is cancer (heuristic)	no

Also known as: autosomal dominant beta2-microglobulinic amyloidosis

Data availability: 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › proteostasis deficiencies › amyloidosis › ABeta2M amyloidosis › variant ABeta2M amyloidosis

Related subtypes (1): wild type ABeta2M 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
B2M	Strong	Autosomal dominant	variant ABeta2M amyloidosis	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
B2M	Orphanet:314652	Variant ABeta2M amyloidosis
B2M	Orphanet:34592	Immunodeficiency by defective expression of MHC class I

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
B2M	HGNC:914	ENSG00000166710	P61769	Beta-2-microglobulin	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
B2M	Beta-2-microglobulin	Component of the class I major histocompatibility complex (MHC).

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
B2M	Antibody/Immunoglobulin	yes		Ig/MHC_CS, Ig_C1-set, Ig-like_dom

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
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
B2M	134	ubiquitous	marker	granulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
B2M	415

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
B2M	P61769	1,226

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 32. 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
Modulation by Mtb of host immune system	1	1631.4×	0.008	B2M
Nef mediated downregulation of MHC class I complex cell surface expression	1	1142.0×	0.008	B2M
Infection with Mycobacterium tuberculosis	1	1142.0×	0.008	B2M
Endosomal/Vacuolar pathway	1	1038.2×	0.008	B2M
Nef-mediates down modulation of cell surface receptors by recruiting them to clathrin adapters	1	634.4×	0.008	B2M
The role of Nef in HIV-1 replication and disease pathogenesis	1	634.4×	0.008	B2M
DAP12 interactions	1	475.8×	0.008	B2M
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	1	393.8×	0.008	B2M
DAP12 signaling	1	368.4×	0.008	B2M
Host Interactions of HIV factors	1	335.9×	0.008	B2M
Bacterial Infection Pathways	1	335.9×	0.008	B2M
Antigen processing-Cross presentation	1	317.2×	0.008	B2M
ER-Phagosome pathway	1	129.8×	0.016	B2M
Interferon gamma signaling	1	125.5×	0.016	B2M
Interferon Signaling	1	120.2×	0.016	B2M
HIV Infection	1	119.0×	0.016	B2M
SARS-CoV-2-host interactions	1	119.0×	0.016	B2M
Amyloid fiber formation	1	102.9×	0.017	B2M
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.018	B2M
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.018	B2M
SARS-CoV-2 Infection	1	80.4×	0.019	B2M
Class I MHC mediated antigen processing & presentation	1	70.1×	0.021	B2M
SARS-CoV Infections	1	55.4×	0.025	B2M
Cytokine Signaling in Immune system	1	40.8×	0.033	B2M
Viral Infection Pathways	1	30.8×	0.041	B2M
Adaptive Immune System	1	29.8×	0.041	B2M
Innate Immune System	1	25.5×	0.046	B2M
Infectious disease	1	24.8×	0.046	B2M
Neutrophil degranulation	1	23.1×	0.048	B2M
Disease	1	13.1×	0.080	B2M

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 iron ion transport	1	16852.0×	8e-04	B2M
antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent	1	8426.0×	8e-04	B2M
regulation of iron ion transport	1	8426.0×	8e-04	B2M
cellular response to iron(III) ion	1	8426.0×	8e-04	B2M
negative regulation of forebrain neuron differentiation	1	8426.0×	8e-04	B2M
peptide antigen assembly with MHC class I protein complex	1	2808.7×	0.001	B2M
regulation of erythrocyte differentiation	1	2808.7×	0.001	B2M
cellular response to iron ion	1	2407.4×	0.001	B2M
response to molecule of bacterial origin	1	2106.5×	0.001	B2M
antigen processing and presentation of endogenous peptide antigen via MHC class I	1	2106.5×	0.001	B2M
cellular response to nicotine	1	2106.5×	0.001	B2M
negative regulation of receptor-mediated endocytosis	1	1872.4×	0.001	B2M
transferrin transport	1	1532.0×	0.002	B2M
positive regulation of T cell cytokine production	1	1296.3×	0.002	B2M
positive regulation of cellular senescence	1	1296.3×	0.002	B2M
T cell mediated cytotoxicity	1	1123.5×	0.002	B2M
peptide antigen assembly with MHC class II protein complex	1	1053.2×	0.002	B2M
positive regulation of receptor-mediated endocytosis	1	802.5×	0.002	B2M
protein refolding	1	624.1×	0.003	B2M
negative regulation of neurogenesis	1	624.1×	0.003	B2M
amyloid fibril formation	1	601.9×	0.003	B2M
multicellular organismal-level iron ion homeostasis	1	581.1×	0.003	B2M
antigen processing and presentation of exogenous peptide antigen via MHC class II	1	543.6×	0.003	B2M
positive regulation of T cell mediated cytotoxicity	1	510.7×	0.003	B2M
positive regulation of immune response	1	481.5×	0.003	B2M
positive regulation of T cell activation	1	443.5×	0.003	B2M
T cell differentiation in thymus	1	411.0×	0.003	B2M
negative regulation of epithelial cell proliferation	1	290.6×	0.004	B2M
intracellular iron ion homeostasis	1	244.2×	0.004	B2M
learning or memory	1	240.7×	0.004	B2M

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
B2M	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
B2M	5	Binding:5

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	B2M
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)
B2M	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.