ATTRV122I amyloidosis

Summary

ATTRV122I amyloidosis (MONDO:0019441) is a disease with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 25
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

25 HPO clinical features (Orphanet curated; top 25 by frequency):

HPO ID	Term	Frequency
HP:0001692	Atrial arrhythmia	Very frequent (80-99%)
HP:0003115	Abnormal EKG	Very frequent (80-99%)
HP:0030843	Cardiac amyloidosis	Very frequent (80-99%)
HP:0031185	Increased circulating NT-proBNP concentration	Very frequent (80-99%)
HP:0410174	Increased troponin T level in blood	Very frequent (80-99%)
HP:0001639	Hypertrophic cardiomyopathy	Frequent (30-79%)
HP:0001640	Cardiomegaly	Frequent (30-79%)
HP:0001723	Restrictive cardiomyopathy	Frequent (30-79%)
HP:0005150	Abnormal atrioventricular conduction	Frequent (30-79%)
HP:0011675	Arrhythmia	Frequent (30-79%)
HP:0012664	Reduced left ventricular ejection fraction	Frequent (30-79%)
HP:0001297	Stroke	Occasional (5-29%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0001681	Angina pectoris	Occasional (5-29%)
HP:0001712	Left ventricular hypertrophy	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0001907	Thromboembolism	Occasional (5-29%)
HP:0003416	Spinal canal stenosis	Occasional (5-29%)
HP:0012185	Constrictive median neuropathy	Occasional (5-29%)
HP:0012332	Abnormal autonomic nervous system physiology	Occasional (5-29%)
HP:0025028	Abnormality of enteric nervous system morphology	Occasional (5-29%)
HP:0100550	Tendon rupture	Occasional (5-29%)
HP:0001271	Polyneuropathy	Very rare (<1-4%)
HP:0001650	Aortic valve stenosis	Very rare (<1-4%)
HP:0009830	Peripheral neuropathy	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	ATTRV122I amyloidosis
Mondo ID	MONDO:0019441
Orphanet	85451
ICD-11	1449168185
SNOMED CT	715655000
UMLS	C4275067
MedGen	907865
GARD	0016755
Is cancer (heuristic)	no

Also known as: ATTRV122I-related amyloidosis

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

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › restrictive cardiomyopathy › familial restrictive cardiomyopathy › ATTRV122I amyloidosis

Related subtypes (9): cardiomyopathy, familial restrictive, 1, Gaucher disease type I, glycogen storage disease II, idiopathic hypereosinophilic syndrome, cardiomyopathy, familial restrictive, 2, cardiomyopathy, familial restrictive, 3, dilated cardiomyopathy 1KK, atrial standstill, cardiomyopathy, familial restrictive, 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

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13426	NM_000371.4(TTR):c.424G>A (p.Val142Ile)	TTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

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.

Gene	Classification	Inheritance	Disease	Records
TTR	Definitive	Autosomal dominant	amyloidosis, hereditary systemic 1	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TTR	Orphanet:597939	Euthyroid dysprealbuminemic hyperthyroxinemia
TTR	Orphanet:85447	ATTRV30M amyloidosis
TTR	Orphanet:85451	ATTRV122I 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
TTR	HGNC:12405	ENSG00000118271	P02766	Transthyretin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TTR	Transthyretin	Thyroid 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.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TTR	Other/Unknown	no		Transthyretin/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)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
choroid plexus epithelium	1
right lobe of liver	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TTR	185	broad	marker	choroid 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)

Symbol	Interactor count
TTR	4,528

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TTR	P02766	462

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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective visual phototransduction due to STRA6 loss of function	1	3806.7×	0.002	TTR
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.006	TTR
Retinoid metabolism and transport	1	248.3×	0.008	TTR
Non-integrin membrane-ECM interactions	1	154.3×	0.010	TTR
Amyloid fiber formation	1	102.9×	0.012	TTR
Neutrophil degranulation	1	23.1×	0.043	TTR

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 glomerular filtration	1	4213.0×	8e-04	TTR
purine nucleobase metabolic process	1	2407.4×	8e-04	TTR
phototransduction, visible light	1	1296.3×	0.001	TTR
retinoid metabolic process	1	495.6×	0.002	TTR

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
TTR	TRICLABENDAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TTR	29	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TRICLABENDAZOLE	4	TTR
AMLEXANOX	4	TTR
TOLCAPONE	4	TTR
DICLOFENAC	4	TTR
LEVOTHYROXINE	4	TTR
TAFAMIDIS	4	TTR
BENZIODARONE	4	TTR
BITHIONOL	4	TTR
BENZBROMARONE	4	TTR
ACORAMIDIS	4	TTR
GEMFIBROZIL	4	TTR
MECLOFENAMIC ACID	4	TTR
DASATINIB	4	TTR
DEXTROTHYROXINE	4	TTR
TRICLOSAN	4	TTR
DIFLUNISAL	4	TTR
CAFFEIC ACID	3	TTR
RESVERATROL	3	TTR
EPIGALOCATECHIN GALLATE	3	TTR
DIACEREIN	3	TTR
TOLFENAMIC ACID	2	TTR
LUTEOLIN	2	TTR
FLUFENAMIC ACID	2	TTR
XANTHOHUMOL	2	TTR
GENISTEIN	2	TTR
NIFLUMIC ACID	2	TTR
DAIDZEIN	2	TTR
PTEROSTILBENE	2	TTR
ACECLOFENAC	2	TTR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TTR	423	Binding:391, Functional:32

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TTR	423

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

29 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)
TRICLABENDAZOLE	4	TTR
AMLEXANOX	4	TTR
TOLCAPONE	4	TTR
DICLOFENAC	4	TTR
LEVOTHYROXINE	4	TTR
TAFAMIDIS	4	TTR
BENZIODARONE	4	TTR
BITHIONOL	4	TTR
BENZBROMARONE	4	TTR
ACORAMIDIS	4	TTR
GEMFIBROZIL	4	TTR
MECLOFENAMIC ACID	4	TTR
DASATINIB	4	TTR
DEXTROTHYROXINE	4	TTR
TRICLOSAN	4	TTR
DIFLUNISAL	4	TTR
CAFFEIC ACID	3	TTR
RESVERATROL	3	TTR
EPIGALOCATECHIN GALLATE	3	TTR
DIACEREIN	3	TTR
TOLFENAMIC ACID	2	TTR
LUTEOLIN	2	TTR
FLUFENAMIC ACID	2	TTR
XANTHOHUMOL	2	TTR
GENISTEIN	2	TTR
NIFLUMIC ACID	2	TTR
DAIDZEIN	2	TTR
PTEROSTILBENE	2	TTR
ACECLOFENAC	2	TTR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TTR
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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06034405	Not specified	RECRUITING	Analysis of Lumbar Spine Stenosis Specimens for Identification of Transthyretin Cardiac Amyloidosis