Amebiasis

Summary

Amebiasis (MONDO:0005644) is a disease with 2 cohort genes (1 GWAS associations across 1 studies) and 4 clinical trials. Top therapeutic interventions include nitazoxanide.

At a glance

• Cohort genes: 2
• GWAS associations: 1
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amebiasis
Mondo ID	MONDO:0005644
EFO	EFO:0007144
MeSH	D000562
DOID	DOID:9181
ICD-10-CM	A06
NCIT	C84551
UMLS	C0002438
MedGen	1857
Is cancer (heuristic)	no

Data availability: 1 GWAS association (1 study).

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › parasitic infectious disease › protozoa infectious disease › amebiasis

Related subtypes (14): primary amebic meningoencephalitis, granulomatous amebic encephalitis, trypanosomiasis, giardiasis, protozoal dysentery, trichomoniasis, malaria, Acanthamoeba keratitis, babesiosis, balantidiasis, coccidiosis, theileriasis, leishmaniasis, dientamoebiasis

Subtypes (2): Blastocystis infectious disease, amebic dysentery

Genetics & variants

GWAS landscape

1 GWAS associations across 1 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs58000832	6e-09	CCNY-AS1	C	2.45

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST007109	Wojcik GL	2018	170	0	Genome-Wide Association Study Reveals Genetic Link between Diarrhea-Associated Entamoeba histolytica Infection and Inflammatory Bowel Disease.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs58000832	10	35228708	CAA>C,CA,CAAA,CAAAA,CAAAAAAAA	0.05	intron_variant	CCNY-AS1	6e-09	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CCNY	HGNC:23354	ENSG00000108100	Q8ND76	Cyclin-Y	gwas
CREM	HGNC:2352	ENSG00000095794	Q03060	cAMP-responsive element modulator	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CCNY	Cyclin-Y	Positive regulatory subunit of the cyclin-dependent kinases CDK14/PFTK1 and CDK16.
CREM	cAMP-responsive element modulator	Transcriptional regulator that binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CCNY	Other/Unknown	no		Cyclin_N, Cyclin_Y, Cyclin-like_dom
CREM	Other/Unknown	no		Leuzip_CREB, CREB1-like_pKID, bZIP

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
left testis	2
right testis	2
sperm	1
adrenal tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCNY	260	ubiquitous	marker	sperm, left testis, right testis
CREM	282	ubiquitous	marker	left testis, right testis, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CREM	2,159
CCNY	737

Intra-cohort edges

A	B	Sources
CCNY	CREM	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCNY	Q8ND76	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CREM	Q03060	61.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes	1	475.8×	0.002	CREM

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cyclin-dependent protein serine/threonine kinase activity	1	2808.7×	0.004	CCNY
glycosphingolipid metabolic process	1	1203.7×	0.004	CREM
spermatogenesis	2	35.2×	0.004	CCNY, CREM
cAMP/PKA signal transduction	1	702.2×	0.006	CREM
regulation of canonical Wnt signaling pathway	1	271.8×	0.012	CCNY
G2/M transition of mitotic cell cycle	1	156.0×	0.017	CCNY
rhythmic process	1	125.8×	0.018	CREM
positive regulation of autophagy	1	104.0×	0.019	CCNY
Wnt signaling pathway	1	49.9×	0.035	CCNY
cell division	1	23.1×	0.069	CCNY
regulation of DNA-templated transcription	1	15.8×	0.090	CREM
cell differentiation	1	14.6×	0.090	CREM
negative regulation of transcription by RNA polymerase II	1	8.9×	0.135	CREM
signal transduction	1	8.0×	0.138	CREM
positive regulation of transcription by RNA polymerase II	1	7.4×	0.139	CREM
regulation of transcription by RNA polymerase II	1	5.8×	0.164	CREM

Therapeutics

Drugs indicated for this disease

12 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Atovaquone	Approved (phase 4)
Broxyquinoline	Approved (phase 4)
Clioquinol	Approved (phase 4)
Emetine	Approved (phase 4)
Metronidazole	Approved (phase 4)
Nimorazole	Approved (phase 4)
Nitazoxanide	Approved (phase 4)
Ornidazole	Approved (phase 4)
Quinacrine	Approved (phase 4)
Secnidazole	Approved (phase 4)
Tilbroquinol	Approved (phase 4)
Tinidazole	Approved (phase 4)

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

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 1

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCNY	2	2
CREM	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ISTISOCICLIB	2	CCNY
AT-7519	2	CCNY

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CCNY	196	Binding:196

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CCNY	196

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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)
ISTISOCICLIB	2	CCNY
AT-7519	2	CCNY

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	1	CCNY
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CREM

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)
CREM	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	2
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00366236	PHASE3	COMPLETED	Study of Nitazoxanide in the Treatment of Amebiasis in Adults and Adolescents
NCT00366730	PHASE3	COMPLETED	Study of Nitazoxanide in the Treatment of Amebiasis in Children
NCT00001162	Not specified	TERMINATED	Parasitic Infections of the Gastrointestinal Tract
NCT02734264	Not specified	COMPLETED	Field Studies of Amebiasis in Bangladesh

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NITAZOXANIDE	4	2