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Atlas / Disease / Familial amyloid neuropathy

Familial amyloid neuropathy

disease
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Also known as amyloid neuropathies, familialATTRv amyloidosisfamilial amyloid polyneuropathyfamilial transthyretin-related amyloidosisfamilial TTR-related amyloidosishATTRhereditary transthyretin amyloid polyneuropathyhereditary TTR amyloid polyneuropathyhereditary TTR amyloidosisparamyloidosis

Summary

Familial amyloid neuropathy (MONDO:0007100) is a disease caused by TTR (GenCC Definitive), with 1 cohort gene and 15 clinical trials. Top therapeutic interventions include diflunisal, inotersen, and tafamidis meglumine.

At a glance

  • Prevalence: 1-9 / 1 000 000 (Worldwide) [Orphanet-validated]
  • Causal gene: TTR (GenCC Definitive)
  • Cohort genes: 1
  • Phenotypes (HPO): 36
  • Clinical trials: 15

Clinical features

Epidemiology

Prevalence records

41 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

TypeClassValueGeographyValidation
Point prevalence1-9 / 1 000 0000.2222WorldwideValidated
Lifetime Prevalence1-9 / 1 000 0000.1445SwitzerlandValidated
Point prevalence1-9 / 1 000 0000.1474ArgentinaValidated
Point prevalence1-9 / 1 000 0000.147AustraliaValidated
Point prevalence1-9 / 1 000 0000.1511AustriaValidated
Point prevalence1-9 / 1 000 0000.1484BangladeshValidated
Point prevalence1-9 / 1 000 0000.1504BelgiumValidated
Point prevalence1-9 / 1 000 0000.5694BulgariaValidated
Point prevalence1-9 / 1 000 0000.1476CanadaValidated
Point prevalence1-9 / 1 000 0000.1481ChinaValidated
Point prevalence1-9 / 100 0004.25CyprusValidated
Point prevalence1-9 / 1 000 0000.1509Czech RepublicValidated
Point prevalence1-9 / 1 000 0000.1403DenmarkValidated
Point prevalence1-9 / 1 000 0000.149EcuadorValidated
Point prevalence1-9 / 1 000 0000.1454FinlandValidated
Point prevalence1-9 / 1 000 0000.7514FranceValidated
Point prevalence1-9 / 1 000 0000.1486GermanyValidated
Point prevalence1-9 / 1 000 0000.1481GreeceValidated
Point prevalence1-9 / 1 000 0000.153HungaryValidated
Point prevalence1-9 / 1 000 0000.1481IndiaValidated

Signs & symptoms

Clinical features (HPO)

36 HPO clinical features (Orphanet curated; top 36 by frequency):

HPO IDTermFrequency
HP:0002019ConstipationFrequent (30-79%)
HP:0002578GastroparesisFrequent (30-79%)
HP:0003202Skeletal muscle atrophyFrequent (30-79%)
HP:0004926Orthostatic hypotension due to autonomic dysfunctionFrequent (30-79%)
HP:0007141Sensorimotor neuropathyFrequent (30-79%)
HP:0011675ArrhythmiaFrequent (30-79%)
HP:0012185Constrictive median neuropathyFrequent (30-79%)
HP:0012332Abnormal autonomic nervous system physiologyFrequent (30-79%)
HP:0012722Heart blockFrequent (30-79%)
HP:0031327Transthyretin cardiac amyloidosisFrequent (30-79%)
HP:0100832Vitreous floatersFrequent (30-79%)
HP:0000016Urinary retentionFrequent (30-79%)
HP:0000112NephropathyFrequent (30-79%)
HP:0000501GlaucomaFrequent (30-79%)
HP:0000802ImpotenceFrequent (30-79%)
HP:0000970AnhidrosisFrequent (30-79%)
HP:0001097Keratoconjunctivitis siccaFrequent (30-79%)
HP:0001635Congestive heart failureFrequent (30-79%)
HP:0001712Left ventricular hypertrophyFrequent (30-79%)
HP:0001723Restrictive cardiomyopathyFrequent (30-79%)
HP:0002014DiarrheaFrequent (30-79%)
HP:0002017Nausea and vomitingFrequent (30-79%)
HP:0000083Renal insufficiencyOccasional (5-29%)
HP:0000100Nephrotic syndromeOccasional (5-29%)
HP:0001324Muscle weaknessOccasional (5-29%)
HP:0001824Weight lossOccasional (5-29%)
HP:0004610Lumbar spinal canal stenosisOccasional (5-29%)
HP:0009027Foot dorsiflexor weaknessOccasional (5-29%)
HP:0010829Impaired temperature sensitionOccasional (5-29%)
HP:0011970Cerebral amyloid angiopathyOccasional (5-29%)
HP:0012531PainOccasional (5-29%)
HP:0025309Abnormal pupil shapeOccasional (5-29%)
HP:0031006AcroparesthesiaOccasional (5-29%)
HP:0031189Wrist dropOccasional (5-29%)
HP:0033748HypoesthesiaOccasional (5-29%)
HP:0100550Tendon ruptureOccasional (5-29%)

Identifiers

Disease identifiers

FieldValue
Canonical namefamilial amyloid neuropathy
Mondo IDMONDO:0007100
EFOEFO:0004129
MeSHC567782
OMIM105210
Orphanet271861
DOIDDOID:0050638, DOID:0050761
ICD-11807065795
NCITC84554
SNOMED CT42295001
UMLSC0206245
MedGen104815
GARD0021017
Is cancer (heuristic)no

Also known as: amyloid neuropathies, familial · ATTRv amyloidosis · familial amyloid neuropathy · familial amyloid polyneuropathy · familial transthyretin-related amyloidosis · familial TTR-related amyloidosis · hATTR · hereditary transthyretin amyloid polyneuropathy · hereditary TTR amyloid polyneuropathy · hereditary TTR amyloidosis · paramyloidosis

Data availability: 3 GenCC gene-disease records · 8 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › hereditary amyloidosis › familial amyloid neuropathy

Related subtypes (8): cerebral amyloid angiopathy, Finnish type amyloidosis, familial visceral amyloidosis, familial primary localized cutaneous amyloidosis, variant ABeta2M amyloidosis, ITM2B amyloidosis, pulmonary amyloidosis, APP-related brain and vascular amyloidosis

Subtypes (4): amyloidosis, hereditary systemic 1, amyloidosis, hereditary systemic 3, amyloidosis, hereditary systemic 5, amyloidosis, hereditary systemic 6

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: 8 · 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.

GeneClassificationInheritanceDiseaseRecords
TTRDefinitiveAutosomal dominantfamilial amyloid neuropathy8

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
TTROrphanet:597939Euthyroid dysprealbuminemic hyperthyroxinemia
TTROrphanet:85447ATTRV30M amyloidosis
TTROrphanet:85451ATTRV122I amyloidosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
TTRHGNC:12405ENSG00000118271P02766Transthyretingencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
TTRTransthyretinThyroid hormone-binding protein.

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.

FamilyGenesFoldFDR
Other/Unknown11.8×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
TTROther/UnknownnoTransthyretin/HIU_hydrolase, Transthyretin/HIU_hydrolase_d, Thyroxine_BS

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
choroid plexus epithelium1
right lobe of liver1
type B pancreatic cell1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
TTR185broadmarkerchoroid plexus epithelium, type B pancreatic cell, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
TTR4,528

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
TTRP02766462

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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.

PathwayCohort genesFoldFDRSample cohort genes
Defective visual phototransduction due to STRA6 loss of function13806.7×0.002TTR
The canonical retinoid cycle in rods (twilight vision)1519.1×0.006TTR
Retinoid metabolism and transport1248.3×0.008TTR
Non-integrin membrane-ECM interactions1154.3×0.010TTR
Amyloid fiber formation1102.9×0.012TTR
Neutrophil degranulation123.1×0.043TTR

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 termCohort genesFoldFDRSample cohort genes
negative regulation of glomerular filtration14213.0×8e-04TTR
purine nucleobase metabolic process12407.4×8e-04TTR
phototransduction, visible light11296.3×0.001TTR
retinoid metabolic process1495.6×0.002TTR

Therapeutics

Drugs indicated for this disease

4 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
Eplontersen SodiumApproved (phase 4)
Patisiran SodiumApproved (phase 4)
VutrisiranApproved (phase 4)
Vutrisiran SodiumApproved (phase 4)
AcoramidisPhase 3 (in late-stage trials)
EplontersenPhase 3 (in late-stage trials)
InotersenPhase 3 (in late-stage trials)
PatisiranPhase 3 (in late-stage trials)
RevusiranPhase 3 (in late-stage trials)
TafamidisPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Diflunisal, Taurolithocholic Acid.

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.

SymbolExample approved molecule
TTRTRICLABENDAZOLE

Top cohort targets by molecule count

SymbolMoleculesMax phase
TTR294

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
TRICLABENDAZOLE4TTR
AMLEXANOX4TTR
TOLCAPONE4TTR
DICLOFENAC4TTR
LEVOTHYROXINE4TTR
TAFAMIDIS4TTR
BENZIODARONE4TTR
BITHIONOL4TTR
BENZBROMARONE4TTR
ACORAMIDIS4TTR
GEMFIBROZIL4TTR
MECLOFENAMIC ACID4TTR
DASATINIB4TTR
DEXTROTHYROXINE4TTR
TRICLOSAN4TTR
DIFLUNISAL4TTR
CAFFEIC ACID3TTR
RESVERATROL3TTR
EPIGALOCATECHIN GALLATE3TTR
DIACEREIN3TTR
TOLFENAMIC ACID2TTR
LUTEOLIN2TTR
FLUFENAMIC ACID2TTR
XANTHOHUMOL2TTR
GENISTEIN2TTR
NIFLUMIC ACID2TTR
DAIDZEIN2TTR
PTEROSTILBENE2TTR
ACECLOFENAC2TTR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
TTR423Binding:391, Functional:32

Cohort genes with high screening signal

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

SymbolChEMBL assays
TTR423

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

28 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.

CompoundMax phaseCohort target (bioactivity)
TRICLABENDAZOLE4TTR
AMLEXANOX4TTR
TOLCAPONE4TTR
DICLOFENAC4TTR
LEVOTHYROXINE4TTR
TAFAMIDIS4TTR
BENZIODARONE4TTR
BITHIONOL4TTR
BENZBROMARONE4TTR
ACORAMIDIS4TTR
GEMFIBROZIL4TTR
MECLOFENAMIC ACID4TTR
DASATINIB4TTR
DEXTROTHYROXINE4TTR
TRICLOSAN4TTR
CAFFEIC ACID3TTR
RESVERATROL3TTR
EPIGALOCATECHIN GALLATE3TTR
DIACEREIN3TTR
TOLFENAMIC ACID2TTR
LUTEOLIN2TTR
FLUFENAMIC ACID2TTR
XANTHOHUMOL2TTR
GENISTEIN2TTR
NIFLUMIC ACID2TTR
DAIDZEIN2TTR
PTEROSTILBENE2TTR
ACECLOFENAC2TTR

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1TTR
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

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: 15.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified5
PHASE2/PHASE34
PHASE34
PHASE1/PHASE21
PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06672237PHASE3RECRUITINGA Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT00294671PHASE2/PHASE3COMPLETEDThe Effect of Diflunisal on Familial Amyloidosis
NCT00409175PHASE2/PHASE3COMPLETEDSafety and Efficacy Study of Fx-1006A in Patients With Familial Amyloidosis
NCT00791492PHASE2/PHASE3COMPLETEDAn Extension of Study Fx-005 Evaluating Long-Term Safety And Clinical Outcomes Of Fx-1006A In Patients With Transthyretin Amyloid Polyneuropathy
NCT01737398PHASE2/PHASE3COMPLETEDEfficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy
NCT01960348PHASE3COMPLETEDAPOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis
NCT02175004PHASE3COMPLETEDExtension Study Assessing Long Term Safety and Efficacy of IONIS-TTR Rx in Familial Amyloid Polyneuropathy (FAP)
NCT02319005PHASE3COMPLETEDENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)
NCT02191826PHASE1/PHASE2COMPLETEDStudy of SOM0226 in Familial Amyloid Polyneuropathy
NCT02595983PHASE2COMPLETEDThe Study of an Investigational Drug, Revusiran (ALN-TTRSC), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis in Patients Whose Disease Has Continued to Worsen Following Liver Transplant
NCT06465810Not specifiedRECRUITINGNon-interventional Study of Patients With Transthyretin (ATTR) Amyloidosis
NCT02939820Not specifiedAPPROVED_FOR_MARKETINGExpanded Access Protocol of Patisiran for Patients With Hereditary ATTR Amyloidosis (hATTR)
NCT03190577Not specifiedCOMPLETEDAssessment of the Prevalence of TTR Amyloid Neuropathy in a Population of Patients With Neuropathy of Unknown Aetiology
NCT03431896Not specifiedCOMPLETEDMonitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis
NCT03720275Not specifiedCOMPLETEDEarly and Systematic Screening in Chronic Neuropathy

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
DIFLUNISAL43
INOTERSEN42
TAFAMIDIS MEGLUMINE42
PATISIRAN32
REVUSIRAN32
NEXIGURAN21
ZICLUMERAN21

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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This page pulls from 72 datasets indexed by BioBTree:

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