Carpal tunnel syndrome 1

Summary

Carpal tunnel syndrome 1 (MONDO:0020730) is a disease caused by TTR (GenCC Strong), with 1 cohort gene and 521 clinical trials. Top therapeutic interventions include lidocaine, dexmedetomidine, and ibuprofen.

At a glance

• Causal gene: TTR (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 48
• Clinical trials: 521

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	carpal tunnel syndrome 1
Mondo ID	MONDO:0020730
OMIM	115430
DOID	DOID:0070466
UMLS	C5779776
MedGen	1830382
GARD	0025228
Is cancer (heuristic)	no

Also known as: amyotrophy, thenar, of carpal origin · carpal tunnel syndrome · carpal tunnel syndrome, familial · CTS · CTS1

Data availability: 48 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › nerve compression syndrome › carpal tunnel syndrome › carpal tunnel syndrome 1

Related subtypes (1): carpal tunnel syndrome 2

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

48 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 12 conflicting classifications of pathogenicity, 6 likely benign, 5 benign/likely benign, 5 pathogenic/likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13417	NM_000371.4(TTR):c.148G>A (p.Val50Met)	TTR	Pathogenic	criteria provided, multiple submitters, no conflicts
13422	NM_000371.4(TTR):c.290C>A (p.Ser97Tyr)	TTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13426	NM_000371.4(TTR):c.424G>A (p.Val142Ile)	TTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13446	NM_000371.4(TTR):c.262A>T (p.Ile88Leu)	TTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13449	NM_000371.4(TTR):c.400T>C (p.Tyr134His)	TTR	Pathogenic	no assertion criteria provided
13450	NM_000371.4(TTR):c.379A>G (p.Ile127Val)	TTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13468	NM_000371.4(TTR):c.349G>T (p.Ala117Ser)	TTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1230561	NM_000371.4(TTR):c.-15C>T	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1235184	NM_000371.4(TTR):c.-3A>G	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1419301	NM_000371.4(TTR):c.151C>A (p.His51Asn)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178279	NM_000371.4(TTR):c.140A>G (p.Asn47Ser)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
178280	NM_000371.4(TTR):c.190T>C (p.Phe64Leu)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181691	NM_000371.4(TTR):c.439G>T (p.Glu147Ter)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181695	NM_000371.4(TTR):c.280G>C (p.Asp94His)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181696	NM_000371.4(TTR):c.301G>A (p.Ala101Thr)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
181697	NM_000371.4(TTR):c.14G>A (p.Arg5His)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2169602	NM_000371.4(TTR):c.235A>G (p.Thr79Ala)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
246201	NM_000371.4(TTR):c.136A>G (p.Ile46Val)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
43454	NM_000371.4(TTR):c.385G>A (p.Ala129Thr)	TTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1024110	NM_000371.4(TTR):c.200+4A>G	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1040987	NM_000371.4(TTR):c.361G>A (p.Gly121Ser)	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1313300	NM_000371.4(TTR):c.83C>T (p.Ser28Phe)	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1366051	NM_000371.4(TTR):c.314C>T (p.Ser105Phe)	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1423499	NM_000371.4(TTR):c.37G>A (p.Gly13Arg)	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
1765057	NM_000371.4(TTR):c.88T>G (p.Cys30Gly)	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
181698	NM_000371.4(TTR):c.368G>A (p.Arg123His)	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
326544	NM_000371.4(TTR):c.-61G>A	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
326545	NM_000371.4(TTR):c.11_13dup (p.His4dup)	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
326565	NM_000371.4(TTR):c.*143G>C	TTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
404412	NM_000371.4(TTR):c.370C>T (p.Arg124Cys)	TTR	Uncertain significance	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	Strong	Autosomal dominant	carpal tunnel syndrome 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: 521.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	438
PHASE4	37
PHASE2	19
PHASE3	10
PHASE2/PHASE3	5
PHASE1/PHASE2	4
EARLY_PHASE1	4
PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03867539	PHASE4	RECRUITING	Exparel and Education to Avoid Opioids After Carpal Tunnel Release
NCT04460521	PHASE4	RECRUITING	The ACTS Trial: N-acetylcysteine (NAC) and Night-splinting as a Non-operative Treatment for Carpal Tunnel Syndrome
NCT05306548	PHASE4	ACTIVE_NOT_RECRUITING	A Norwegian Trial Comparing Treatment Strategies for Carpal Tunnel Syndrome
NCT05475808	PHASE4	ACTIVE_NOT_RECRUITING	Comparison of the Efficacy of Different Treatment Methods in Patients With Carpal Tunnel Syndrome
NCT07283874	PHASE4	NOT_YET_RECRUITING	Does it Matter the Volume of Injectate on the Outcome of Ultrasound-guided Perineural Injection for Carpal Tunnel Syndrome
NCT00277563	PHASE4	COMPLETED	Short and Long Term Exposure to Unique, Time-Varying Pulsed Electro-Magnetic Fields in Refractory Carpal Tunnel Syndrome
NCT00678314	PHASE4	COMPLETED	Patient Controlled Regional Analgesia Following Carpal Tunnel Release: A Double-Blind Study Using Distal Perineural Catheters
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01310218	PHASE4	COMPLETED	Length of Post Operative Dressing After Carpal Tunnel Release
NCT01588158	PHASE4	TERMINATED	Patient Satisfaction With Pain Relief After Ambulatory Hand Surgery
NCT01751347	PHASE4	COMPLETED	Bupivacaine Versus Lidocaine Local Anesthesia
NCT02038452	PHASE4	COMPLETED	Injection Versus Splinting in Carpal Tunnel Syndrome
NCT02140632	PHASE4	COMPLETED	Efficacy Study of Local Steroid Injection and Wrist Splinting for Carpal Tunnel Syndrome
NCT02652390	PHASE4	COMPLETED	Local Steroid Injection vs Placebo in Carpal Tunnel Syndrome
NCT03196817	PHASE4	UNKNOWN	Non-surgical Treatment of Carpal Tunnel Syndrome: Night Splint Versus Local Corticosteroid Infiltration
NCT03432858	PHASE4	COMPLETED	Preoperative Antibiotics for Carpal Tunnel Release Surgery
NCT03649763	PHASE4	COMPLETED	Onset and Duration of Forearm Nerve Blockade
NCT03792945	PHASE4	COMPLETED	Comparison of the Efficacy of Corticosteroid Injection and ESWT in Patients With CTS
NCT03802448	PHASE4	COMPLETED	Myofascial Release on Electrophysiological Measures of Pregnant Women With CTS
NCT04017390	PHASE4	WITHDRAWN	The Effect of Theraworx Foam in Carpal Tunnel Syndrome
NCT04025203	PHASE4	COMPLETED	Pain Reduction and Changes in Upper Limb Function Produced by Different Treatments in Carpal Tunnel Syndrome
NCT04119739	PHASE4	COMPLETED	Pain Reduction Produced by Different Treatments in Carpal Tunnel Syndrome
NCT04245371	PHASE4	COMPLETED	Lidocaine Patch 1.8% for Moderate to Severe Pain From Carpal Tunnel Syndrome
NCT04285281	PHASE4	COMPLETED	Oral Gabapentin and Median Nerve Mobilization in the Treatment of Carpal Tunnel Syndrome
NCT04328805	PHASE4	COMPLETED	Ibuprofen and Neural Mobilization Treatment in Carpal Tunnel Syndrome.
NCT04515966	PHASE4	UNKNOWN	A Comparison of Ultrasound-guided Steroid Injection With Wrist Splint in Carpal Tunnel Syndrome
NCT04767724	PHASE4	COMPLETED	Extracorporeal Shock Wave Versus Local Corticosteroid Injection for Carpal Tunnel Syndrome
NCT05496764	PHASE4	UNKNOWN	Local Injection of Steroid VS.Glucose 5% in Carpal Tunnel Syndrome
NCT06209957	PHASE4	COMPLETED	Study of Single Platelet-Rich Plasma Local Injection Vs. Single Corticosteroid Local Injection in Carpal Tunnel Syndrome
NCT06249503	PHASE4	COMPLETED	Ultrasound Guided Activated and Non Activated Platelet Rich Plasma Injection Versus Hydro Dissection by Steroids.
NCT06282640	PHASE4	COMPLETED	Comparıson Of Electromyography Results Before And After Vıtamın D Treatment In Patıents Wıth Carpal Tunnel Syndrome
NCT06349265	PHASE4	COMPLETED	Ultrasound-Guided 5% Dextrose Injection for Carpal Tunnel Syndrome
NCT06349824	PHASE4	COMPLETED	Dextrose, Steroid, PRP: Choosing the Right Injection for CRS Relief; a RCT
NCT06778759	PHASE4	COMPLETED	Ibuprofen Arginine and Neural Mobilization Versus Ibuprofen Arginine in the Treatment of Carpal Tunnel Syndrome
NCT06778798	PHASE4	COMPLETED	Gabapentin and Neural Mobilization Pain Reduction Effect Compared to Only Gabapentine
NCT06781489	PHASE4	COMPLETED	Pain Reduction Caused by the Combined Treatment of Physiotherapy, Oral Gabapentin and Oral Ibuprofen Arginine.
NCT07105540	PHASE4	COMPLETED	Comparison of Injection Techniques in Carpal Tunnel Syndrome
NCT06045013	PHASE3	RECRUITING	Ultrasound-guided Dextrose Injection Versus Dextrose With Methylprednisolone in Carpal Tunnel Syndrome
NCT07474714	PHASE3	NOT_YET_RECRUITING	Hyaluronic Acid Injection in Idiopathic Carpal Tunnel Syndrome; is it Effective as Local Corticosteroids
NCT00137735	PHASE3	COMPLETED	Gabapentin for Carpal Tunnel Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
LIDOCAINE	4	7
DEXMEDETOMIDINE	4	6
IBUPROFEN	4	4
AMITRIPTYLINE	4	3
GABAPENTIN	4	3
HYALURONIDASE	4	3
DEXTROSE	4	2
HYALURONATE SODIUM	4	2
METHYLPREDNISOLONE	4	2
METHYLPREDNISOLONE ACETATE	4	2
ROPIVACAINE	4	2
ACETAMINOPHEN	4	1
ACETYLCYSTEINE	4	1
BUPIVACAINE	4	1
CARBAMAZEPINE	4	1
CEFAZOLIN	4	1
CYANOCOBALAMIN	4	1
DALFAMPRIDINE	4	1
MENTHOL	4	1
MEPIVACAINE	4	1
ONABOTULINUMTOXINA	4	1
SODIUM CHLORIDE	4	1
TRIAMCINOLONE ACETONIDE	4	1
TRIAMCINOLONE HEXACETONIDE	4	1
VANCOMYCIN	4	1
OZONE	3	4
PARAFFIN	3	3
ACETYLCARNITINE	3	1
LEVOMENTHOL	3	1
LIPOIC ACID, ALPHA	3	1