Liver cancer

Summary

Liver cancer (MONDO:0002691) is a cancer (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene (19 GWAS associations across 14 studies; 1 CIViC-evidence somatic driver) and 804 clinical trials. Molecularly, ARID1A Loss confers sensitivity to Sorafenib in Liver Cancer (CIViC Level D). Top therapeutic interventions include sorafenib, dexmedetomidine, and chlorotrianisene.

At a glance

• Classification: Cancer
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 19
• Clinical trials: 804
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	liver cancer
Mondo ID	MONDO:0002691
DOID	DOID:3571
ICD-11	1605020868
NCIT	C34803
SNOMED CT	93870000
UMLS	C0345904
MedGen	87520
GARD	0027613
Anatomy (UBERON)	UBERON:0002107
Is cancer (heuristic)	yes

Also known as: cancer of liver · hepatic cancer · liver cancer · malignant liver neoplasm · malignant neoplasm of liver · malignant neoplasm of liver, not specified as primary or secondary · malignant neoplasm of liver, primary · malignant tumour of liver · primary cancer of liver · primary liver cancer · primary malignant liver neoplasm · primary malignant neoplasm of liver · primary tumor of the liver · primary tumour of the liver

Data availability: 19 GWAS associations (14 studies).

Disease family

An umbrella term covering 5 Mondo subtypes.

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

Related subtypes (14): gastric cancer, jaw cancer, gastrointestinal lymphoma, gallbladder cancer, oral cavity cancer, pharynx cancer, intestinal cancer, spleen cancer, digestive system carcinoma, esophageal cancer, malignant pancreatic neoplasm, malignant tumor of floor of mouth, digestive system melanoma, gastroesophageal cancer

Subtypes (5): liver sarcoma, biliary tract cancer, liver lymphoma, calcifying nested epithelial stromal tumor of the liver, carcinoma of liver and intrahepatic biliary tract

Genetics & variants

GWAS landscape

19 GWAS associations across 14 studies. Top hits map to 6 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs738408	2e-41	PNPLA3	C	0.34
rs738409	5e-40	PNPLA3	C	0.4
rs56255430	3e-20	MAU2 - GATAD2A	A	0.37
rs3828802	2e-17	HLA-DQB1	?
rs28891471	5e-14	HLA-DQB1 - MTCO3P1	T	0.25
rs35624376	2e-12	KLHL8	T	0.2
rs8103142	3e-12	IFNL3	T	0.16
rs28891474	4e-12	HLA-DQB1 - MTCO3P1	G	0.21
rs559235319	3e-11	CASC9	G	2.47
rs144048895	2e-09	LMCD1-AS1	?	2.62
rs148887053	1e-08	YPEL1 - MAPK1	?	2.57

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90432143	Jiang Y	2023	116,382	213,325	A cross-disorder study to identify causal relationships, shared genetic variants, and genes across 21 digestive disorders.
GCST90475568	Verma A	2024	3,353	446,757	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651193	Liu TY	2025	3,017	211,360	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90475569	Verma A	2024	2,852	447,587	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651195	Liu TY	2025	2,811	211,360	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90477183	Verma A	2024	1,121	120,439	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479785	Verma A	2024	1,121	120,439	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477185	Verma A	2024	977	120,676	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479784	Verma A	2024	977	120,676	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90477182	Verma A	2024	674	59,072	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	0
Tier 3: regulatory	2
Tier 4: intronic/intergenic	7

MAF distribution

Bucket	Variants
common (>=0.05)	8
low_freq (0.01-0.05)	0
rare (<0.01)	1
unknown	2

Functional consequences

Consequence	Count
intergenic_variant	4
missense_variant	2
intron_variant	2
synonymous_variant	1
regulatory_region_variant	1
TF_binding_site_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs738408	22	43928850	C>A,G,T	0.224	synonymous_variant	PNPLA3	2e-41	Tier 4: intronic/intergenic
rs738409	22	43928847	C>A,G,T	0.225	missense_variant	PNPLA3	5e-40	Tier 1: coding
rs56255430	19	19367068	A>C,T	0.067	intron_variant	MAU2 - GATAD2A	3e-20	Tier 4: intronic/intergenic
rs3828802	6	32668296	A>G	0.05	regulatory_region_variant	HLA-DQB1	2e-17	Tier 3: regulatory
rs28891471	6	32674696	T>G	0.257	intergenic_variant	HLA-DQB1 - MTCO3P1	5e-14	Tier 4: intronic/intergenic
rs35624376	4	87237936	T>C	0.236	intergenic_variant	KLHL8	2e-12	Tier 4: intronic/intergenic
rs8103142	19	39244466	T>C	0.383	missense_variant	IFNL3	3e-12	Tier 1: coding
rs28891474	6	32674788	G>T	0.256	intergenic_variant	HLA-DQB1 - MTCO3P1	4e-12	Tier 4: intronic/intergenic
rs559235319	8	75351134	G>A	0.001	intergenic_variant	CASC9	3e-11	Tier 4: intronic/intergenic
rs144048895	3	8481603	TA>T,TAA		intron_variant	LMCD1-AS1	2e-09	Tier 4: intronic/intergenic
rs148887053	22	21745132	C>T		TF_binding_site_variant	YPEL1 - MAPK1	1e-08	Tier 3: regulatory

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ARID1A	LoF	BL,BLCA,BRCA,CCRCC,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,GBC,GBM,HCC,LGGNOS,LUAD,LUNG,LUSC,MBL,MLYM,MT,NHL,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PRAD,RCC,SCLC,SKIN,STAD,UCEC,UCS,UTUC	CIViC #6559

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ARID1A	Orphanet:1465	Coffin-Siris syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ARID1A	HGNC:11110	ENSG00000117713	O14497	AT-rich interactive domain-containing protein 1A	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARID1A	AT-rich interactive domain-containing protein 1A	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

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)
ARID1A	Other/Unknown	no		ARID_dom, ARM-like, ARM-type_fold

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
bone marrow cell	1
embryo	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARID1A	286	ubiquitous	marker	bone marrow cell, ventricular zone, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARID1A	3,476

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ARID1A	O14497	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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
Positive Regulation of CDH1 Gene Transcription	1	951.7×	0.010	ARID1A
Formation of the canonical BAF (cBAF) complex	1	634.4×	0.010	ARID1A
Formation of the embryonic stem cell BAF (esBAF) complex	1	601.0×	0.010	ARID1A
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	1	456.8×	0.010	ARID1A
Regulation of endogenous retroelements	1	368.4×	0.010	ARID1A
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.010	ARID1A
Regulation of MITF-M-dependent genes involved in pigmentation	1	265.6×	0.010	ARID1A
MITF-M-dependent gene expression	1	181.3×	0.013	ARID1A
RMTs methylate histone arginines	1	146.4×	0.013	ARID1A
Transcriptional regulation by RUNX1	1	146.4×	0.013	ARID1A
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)	1	117.7×	0.014	ARID1A
MITF-M-regulated melanocyte development	1	114.2×	0.014	ARID1A
Chromatin organization	1	81.6×	0.018	ARID1A
Chromatin modifying enzymes	1	72.3×	0.018	ARID1A
Epigenetic regulation of gene expression	1	71.4×	0.018	ARID1A
RNA Polymerase II Transcription	1	22.5×	0.053	ARID1A
Gene expression (Transcription)	1	17.8×	0.063	ARID1A
Generic Transcription Pathway	1	15.1×	0.069	ARID1A
Developmental Biology	1	14.5×	0.069	ARID1A

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
nucleosome disassembly	1	802.5×	0.005	ARID1A
regulation of G0 to G1 transition	1	674.1×	0.005	ARID1A
regulation of nucleotide-excision repair	1	601.9×	0.005	ARID1A
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.005	ARID1A
positive regulation of T cell differentiation	1	455.5×	0.005	ARID1A
transcription initiation-coupled chromatin remodeling	1	383.0×	0.005	ARID1A
positive regulation of myoblast differentiation	1	366.4×	0.005	ARID1A
positive regulation of stem cell population maintenance	1	343.9×	0.005	ARID1A
positive regulation of double-strand break repair	1	343.9×	0.005	ARID1A
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.005	ARID1A
positive regulation of cell differentiation	1	267.5×	0.005	ARID1A
chromatin remodeling	1	73.0×	0.017	ARID1A
nervous system development	1	45.9×	0.025	ARID1A
positive regulation of DNA-templated transcription	1	27.9×	0.038	ARID1A
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ARID1A

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
ARID1A	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
ARID1A	6	Binding:6

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).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ARID1A

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)
ARID1A	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 804.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	418
PHASE2	128
PHASE1	104
PHASE1/PHASE2	67
PHASE3	40
PHASE4	24
PHASE2/PHASE3	12
EARLY_PHASE1	11

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04731558	PHASE4	RECRUITING	Pre- Vs Postoperative Thromboprophylaxis for Liver Resection
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT05957822	PHASE4	RECRUITING	Goal-directed vs Preemptive Tranexamic Acid Administration in Non-cardiac Surgery
NCT06084234	PHASE4	RECRUITING	National Liver Cancer Screening Trial
NCT06353126	PHASE4	RECRUITING	DEB-TACE Prior to Liver Transplantation in the Treatment of HCC
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00510627	PHASE4	WITHDRAWN	Study Comparing Radio Frequency Ablation Plus Chemotherapy and Chemotherapy Alone in Patients With Secondary Liver Metastases
NCT00554905	PHASE4	UNKNOWN	Radiofrequency Ablation With or With Transcatheter Arterial Embolization for Hepatocellular Carcinoma
NCT00555334	PHASE4	UNKNOWN	Nucleoid as an Adjuvant Therapy After Radiofrequency Ablation for Hepatocellular Carcinoma
NCT00556803	PHASE4	UNKNOWN	TACE as an Adjuvant Therapy After Radiofrequency Ablation (RFA) for Hepatocellular Carcinoma
NCT00557024	PHASE4	UNKNOWN	Radiotherapy as an Adjuvant Therapy After Radiofrequency Ablation for Hepatocellular Carcinoma
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01882218	PHASE4	WITHDRAWN	Direct Peritoneal Resuscitation Plus Conventional Resuscitation
NCT02016391	PHASE4	COMPLETED	Effects of Dexmedetomidine During Radiofrequency Ablation of Abdominal Tumours
NCT02044224	PHASE4	COMPLETED	Effects of Dexmedetomidine During IRE Procedures for Solid Tumours
NCT02321202	PHASE4	COMPLETED	Omega-3 Fatty Acid-Based Parenteral Nutrition Improves Postoperative Recovery for Cirrhotic Patients With Liver Cancer
NCT02853500	PHASE4	WITHDRAWN	Effect of Surefire Infusion Device on Tumor Response to Regional Intra-arterial Therapy for Primary Liver Malignancies
NCT03215355	PHASE4	WITHDRAWN	Improving CBCT for Liver IG-SBRT Using Gadoxetate Disodium
NCT03843229	PHASE4	UNKNOWN	Clinical Trial of Cinobufacini Combined With Transarterial Chemoembolization (TACE) on Primary Liver Cancer
NCT04288323	PHASE4	COMPLETED	Gadolinium Contrast-enhanced Abbreviated MRI (AMRI) vs. Standard Ultrasound for Hepatocellular Carcinoma (HCC) Surveillance in Patients With Cirrhosis
NCT04707547	PHASE4	COMPLETED	Immune Profile and Prognosis of Malignant Liver Tumors With Radiofrequency Ablation (RFA) Therapy
NCT04769713	PHASE4	UNKNOWN	Hepatic Hilar Nerve Block Versus Sham in Pain Control During Liver Ablation and TACE Procedures
NCT05717400	PHASE4	TERMINATED	Improving Response to Immunotherapy in Patients With Advanced Hepatocellular Carcinoma and Chronic Hepatitis C Virus Infection With Direct-Acting Antiviral Therapy
NCT06173466	PHASE4	COMPLETED	Postoperative Analgesia With Liposomal Bupivacaine Versus Standard Bupivacaine Combined With Dexamethasone
NCT02523443	PHASE3	ACTIVE_NOT_RECRUITING	Patient Controlled Epidural Analgesia Versus Intravenous Patient Controlled Analgesia for Post-Operative Pain Control in Patients Undergoing Elective Liver Resection
NCT03383458	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Nivolumab in Participants With Hepatocellular Carcinoma Who Are at High Risk of Recurrence After Curative Hepatic Resection or Ablation
NCT03949231	PHASE3	RECRUITING	Infusion of PD1/PDL1/CTLA4 Inhibitors Via Hepatic Arterial for Immunotherapy of Hepatocellular Carcinoma
NCT04868149	PHASE3	RECRUITING	Clinical Outcome and Future Liver Remnant Regenerative Response in Laparoscopic Versus Open ALPPS
NCT05744219	PHASE3	RECRUITING	Improved Recovery by Iron Following Surgery With Blood Loss, the IRIS-trial
NCT06478108	PHASE2/PHASE3	RECRUITING	Interventional Software for Multi-immunotherapy of Solid Tumors
NCT06851663	PHASE2/PHASE3	RECRUITING	Trop2-targeted immunoPET Imaging of Solid Tumors
NCT00003424	PHASE3	COMPLETED	Tamoxifen in Treating Patients With Primary Liver Cancer
NCT00003912	PHASE3	COMPLETED	Chemotherapy in Treating Children With Liver Cancer
NCT00012324	PHASE3	COMPLETED	Nolatrexed Dihydrochloride Compared With Doxorubicin in Treating Patients With Recurrent or Unresectable Liver Cancer
NCT00027768	PHASE3	UNKNOWN	Radioactive Iodine in Treating Patients Who Have Undergone Surgery for Liver Cancer
NCT00041275	PHASE3	COMPLETED	Megestrol in Treating Patients With Liver Cancer That Cannot Be Removed By Surgery
NCT00079027	PHASE3	UNKNOWN	Doxorubicin By Infusion or Chemoembolization in Treating Patients With Advanced Unresectable Hepatocellular Carcinoma (Liver Cancer)
NCT00109954	PHASE3	COMPLETED	Hepatic Arterial Chemoembolization With Cisplatin or Internal Radiation Therapy in Treating Patients With Advanced Liver Cancer That Cannot Be Removed By Surgery
NCT00151671	PHASE2/PHASE3	TERMINATED	Effect of a Perioperative Oral Nutritional Supplementation on Patients Undergoing Hepatic Surgery for Liver Cancer
NCT00199173	PHASE3	COMPLETED	Comparing Hepatic Intra-arterial Injection of Yttrium-90 Microspheres Versus Fluorouracil (5FU) in Colorectal Cancer Metastatic to the Liver Only

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
SORAFENIB	4	15
DEXMEDETOMIDINE	4	6
CHLOROTRIANISENE	4	5
DOXORUBICIN	4	4
EPIRUBICIN HYDROCHLORIDE	4	4
SUNITINIB MALATE	4	4
GEMCITABINE HYDROCHLORIDE	4	3
ARSENIC TRIOXIDE	4	2
ETHIODIZED OIL	4	2
FLOXURIDINE	4	2
MITOMYCIN	4	2
NICOTINE	4	2
OXALIPLATIN	4	2
PRAVASTATIN	4	2
RILUZOLE	4	2
SODIUM THIOSULFATE	4	2
TREMELIMUMAB	4	2
ALDESLEUKIN	4	1
AMIFOSTINE	4	1
ATEZOLIZUMAB	4	1
BEVACIZUMAB	4	1
BRODALUMAB	4	1
BUPROPION HYDROCHLORIDE	4	1
CANNABIDIOL	4	1
CAPECITABINE	4	1
CARBOPLATIN	4	1
CISPLATIN	4	1
CITALOPRAM	4	1
DASATINIB	4	1
DASATINIB ANHYDROUS	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
ARID1A Loss	Sorafenib	Sensitivity/Response	CIViC D	EID7328