Liver failure

Summary

Liver failure (MONDO:0100192) is a disease with 1 cohort gene and 145 clinical trials. Top therapeutic interventions include avatrombopag, buprenorphine, and empagliflozin.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 145

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	liver failure
Mondo ID	MONDO:0100192
MeSH	D017093
NCIT	C26922
UMLS	C0085605
MedGen	88444
Is cancer (heuristic)	no

Also known as: hepatic failure

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › hepatobiliary disorder › liver disorder › liver failure

Related subtypes (31): polycystic echinococcosis, autosomal dominant polycystic liver disease, hepatorenal syndrome, hepatitis, hepatic vascular disorder, hepatic porphyria, hepatopulmonary syndrome, fatty liver disease, cirrhosis of liver, drug-induced liver injury, perinatal jaundice due to hepatocellular damage, Aagenaes syndrome, transient familial neonatal hyperbilirubinemia, hyperbiliverdinemia, transient infantile hypertriglyceridemia and hepatosteatosis, idiopathic copper-associated cirrhosis, familial intrahepatic cholestasis, bile duct cyst, nodular regenerative hyperplasia of the liver, hepatoportal sclerosis, primitive portal vein thrombosis, glycogen storage disease due to liver phosphorylase kinase deficiency, liver and intrahepatic bile duct neoplasm, alcoholic liver disease, early-onset familial noncirrhotic portal hypertension, fibrotic liver disease, intestinal failure–associated liver disease, liver abscess (disease), membranous obstruction of inferior vena cava, liver disease, severe congenital, cystic fibrosis-related liver disease

Subtypes (3): infantile liver failure, acute liver failure, chronic liver failure

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
986742	NM_003680.4(YARS1):c.611A>C (p.Tyr204Ser)	YARS1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
YARS1	Orphanet:100045	Autosomal dominant intermediate Charcot-Marie-Tooth disease type C

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
YARS1	HGNC:12840	ENSG00000134684	P54577	Tyrosine–tRNA ligase, cytoplasmic	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
YARS1	Tyrosine–tRNA ligase, cytoplasmic	Tyrosine–tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr).

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
YARS1	Enzyme (other)	yes	6.1.1.1	aa-tRNA-synth_Ic, Tyr-tRNA-ligase, tRNA-bd_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
islet of Langerhans	1
left adrenal gland	1
right adrenal gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
YARS1	290	ubiquitous	marker	islet of Langerhans, right adrenal gland, left adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
YARS1	4,793

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
YARS1	P54577	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Cytosolic tRNA aminoacylation	1	439.2×	0.007	YARS1
tRNA Aminoacylation	1	285.5×	0.007	YARS1
Translation	1	62.1×	0.021	YARS1
Metabolism of proteins	1	12.4×	0.081	YARS1

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
tyrosyl-tRNA aminoacylation	1	16852.0×	2e-04	YARS1
response to starvation	1	468.1×	0.003	YARS1
apoptotic process	1	28.7×	0.035	YARS1

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Tolcapone	Approved (phase 4)
Filgrastim	Phase 3 (in late-stage trials)
Pentoxifylline	Phase 3 (in late-stage trials)
Somatostatin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Silibinin, Tacrolimus Anhydrous, Terlipressin.

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
YARS1	CAPSAICIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
YARS1	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CAPSAICIN	4	YARS1
CRENOLANIB	3	YARS1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
YARS1	16	Binding:16

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
YARS1	6.1.1.1	tyrosine-tRNA ligase

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

2 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)
CAPSAICIN	4	YARS1
CRENOLANIB	3	YARS1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	YARS1
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: 145.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	87
PHASE2	15
PHASE1/PHASE2	12
PHASE4	11
PHASE1	10
PHASE3	6
PHASE2/PHASE3	3
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04447911	PHASE4	RECRUITING	Effects of the SGLT2 Inhibitor Empagliflozin in Patients With Euvolemic and Hypervolemic Hyponatremia
NCT00522730	PHASE4	COMPLETED	Safety and Tolerance on Lipids of Parenteral and Enteral Nutrition in Critically Ill Patients With Liver Failure
NCT01846455	PHASE4	COMPLETED	Single Dose Pharmacokinetics of Suboxone Study in Hepatic Impaired Subjects
NCT02331745	PHASE4	UNKNOWN	RCT Study on Granulocyte Colony-stimulating Factor(G-CSF) Treatment of Hepatic Failure
NCT03044639	PHASE4	COMPLETED	Parenteral Lipid Emulsions and the Liver Function
NCT03667157	PHASE4	COMPLETED	Liver Function After Intravenous Methylprednisolone Administration
NCT04237246	PHASE4	COMPLETED	Comparative FK506 Drug Levels of Once Daily Advagraf in First Nations and Caucasian Patients With Liver Transplants
NCT04347902	PHASE4	COMPLETED	Lipid Emulsions and Liver Function - Results After 5 Years.
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05441150	PHASE4	UNKNOWN	Intravenous Ketamine Infusion on Postoperative Analgesia of Living Liver Donors
NCT05480787	PHASE4	UNKNOWN	Pharmacokinetic Study of Continuous Infusion of Remazolam in Mechanically Ventilated Patients in ICU
NCT00162552	PHASE3	COMPLETED	Clinical Trial of Pentoxifylline in Patient With Cirrhosis
NCT00695617	PHASE2/PHASE3	UNKNOWN	Citrate Anticoagulation During MARS Treatment
NCT01160978	PHASE2/PHASE3	COMPLETED	Donor Simvastatin Treatment in Organ Transplantation
NCT01785082	PHASE3	COMPLETED	Fast-track LiveR: Study for the Early Identification of Low-risk Patients After Partial Liver Resection by the LiMAx-test
NCT02552901	PHASE3	WITHDRAWN	Cardiox Liver Function Test Pivotal Trial
NCT02584283	PHASE3	COMPLETED	Dual Hypothermic Oxygenated Perfusion of DCD Liver Grafts in Preventing Biliary Complications After Transplantation
NCT02837939	PHASE2/PHASE3	WITHDRAWN	Transfer Factor Efficacy in the Management of Cirrhosis-associated Immune Dysfunction
NCT02882347	PHASE3	UNKNOWN	The Effect of Somatostatin for Treatment of Post Hepatectomy Liver Failure (PHLF)
NCT04221672	PHASE3	UNKNOWN	The Effect of Terlipressin on Recovery of Liver Function After Hepatectomy
NCT05234190	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Clinical Activity of QEL-001 in A2-mismatch Liver Transplant Patients
NCT05726032	PHASE2	RECRUITING	Empagliflozin in Patients With Cirrhosis and Ascites
NCT05989958	PHASE1/PHASE2	RECRUITING	The Safety ,Tolerability and Efficacy Study of HepaCure in Chinese Subjects with Acute-On-Chronic Liver Failure
NCT07053488	PHASE1/PHASE2	RECRUITING	CRISPR-Edited HLA Donor Liver Transplant to Reduce Rejection
NCT07312864	PHASE1/PHASE2	RECRUITING	Safety and Tolerability Study of a Novel Bioartificial Liver in Liver Failure and Small-for-Size Syndrome
NCT00420134	PHASE1/PHASE2	COMPLETED	Improvement of Liver Function in Liver Cirrhosis Patients After Autologous Mesenchymal Stem Cell Injection:a Phase I-II Clinical Trial
NCT00608244	PHASE2	COMPLETED	Pharmacokinetics of LCP-Tacro in Stable Liver Transplant Patients
NCT00772148	PHASE2	COMPLETED	Pharmacokinetics of LCP-Tacro™ Once Daily and Prograf® Twice A Day in Adult De Novo Liver Transplant Patients
NCT00805610	PHASE1/PHASE2	WITHDRAWN	Hepatocyte Transplantation in Liver Failure
NCT00915681	PHASE2	TERMINATED	Intravenous Milk Thistle (Silibinin-Legalon) for Hepatic Failure Induced by Amatoxin/Amanita Mushroom Poisoning
NCT01022476	PHASE1/PHASE2	COMPLETED	Raltegravir in Patients With End Stage Liver Disease and in Transplant Recipients
NCT01218464	PHASE1/PHASE2	UNKNOWN	Safety and Efficacy of Human Mesenchymal Stem Cells for Treatment of Liver Failure
NCT01221454	PHASE2	UNKNOWN	Allogenic Bone Marrow Stem Cell Transplantation in Liver Failure
NCT01254994	PHASE2	COMPLETED	The Efficacy and Safety of Entecavir Treatment of Patients With Acute on Chronic Hepatitis B Liver Failure
NCT01322906	PHASE2	UNKNOWN	Allogeneic Bone Marrow Mesenchymal Stem Cells Transplantation in Patients With Liver Failure Caused by Hepatitis B Virus (HBV)
NCT01394497	PHASE2	COMPLETED	Use of N-Acetylcysteine During Liver Procurement
NCT01423708	PHASE2	UNKNOWN	Everolimus in de Novo Liver Transplantation: a Multicentre Randomized Study
NCT01429038	PHASE1/PHASE2	COMPLETED	Mesenchymal Stem Cells After Renal or Liver Transplantation
NCT01698723	PHASE2	UNKNOWN	A Trial of Ribavirin in Patients With ACLF Due to Hepatitis E Virus
NCT01724398	PHASE1/PHASE2	UNKNOWN	Umbilical Cord Mesenchymal Stem Cells Transplantation Combined With Plasma Exchange for Patients With Liver Failure

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AVATROMBOPAG	4	1
BUPRENORPHINE	4	1
EMPAGLIFLOZIN	4	1
LOFEXIDINE	4	1
PENTOXIFYLLINE	4	1
PROMETHAZINE	4	1
RALTEGRAVIR POTASSIUM	4	1
REMIMAZOLAM	4	1
ROCURONIUM	4	1
SACITUZUMAB GOVITECAN	4	1
TENOFOVIR ALAFENAMIDE	4	1
TERLIPRESSIN	4	1
VASOPRESSIN	4	1
WATER	4	1
VELIPARIB	3	2
GLUTATHIONE	3	1
LATREPIRDINE	3	1
MALTODEXTRIN	3	1
SILIBININ	3	1
SILYBIN A	3	1
SOMATOSTATIN	3	1
CIMLANOD	2	1
ICENTICAFTOR	2	1
CHEMBL452845	0	1
CHEMBL5177502	0	1
CHEMBL3739556	0	1
CHEMBL4067090	0	1
SCEPTRIN	0	1
SILYBIN B	0	1