Cryptosporidiosis

Summary

Cryptosporidiosis (MONDO:0015474) is a disease with 2 cohort genes (3 GWAS associations across 1 studies) and 29 clinical trials. Top therapeutic interventions include nitazoxanide, paromomycin sulfate, and spiramycin.

At a glance

• Cohort genes: 2
• GWAS associations: 3
• Clinical trials: 29

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cryptosporidiosis
Mondo ID	MONDO:0015474
MeSH	D003457
Orphanet	1549, 697096
DOID	DOID:1733
ICD-10-CM	A07.2
ICD-11	1837013982
NCIT	C128408
SNOMED CT	66160001
UMLS	C0010418
MedGen	41362
MedDRA	10011502
Is cancer (heuristic)	no

Also known as: Cryptosporidioses · Cryptosporidium caused disease or disorder · Cryptosporidium disease or disorder · Cryptosporidium infection · Cryptosporidium infectious disease · intestinal cryptosporidiosis

Data availability: 3 GWAS associations (1 study).

Disease family

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

Related subtypes (4): cyclosporiasis, toxoplasmosis, isosporiasis, sarcocystosis

Genetics & variants

GWAS landscape

3 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
rs58296998	4e-08	PRKCA	T	2.4
rs4758351	4e-07	KRT18P58 - OR56A4	A	2.39
rs9937140	8e-07	APOOP5 - LINC02141	G	1.99

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST009861	Wojcik GL	2020	183	0	Genome-Wide Association Study of Cryptosporidiosis in Infants Implicates PRKCA.

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	3

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	2
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs58296998	17	66473763	C>A,T	0.05	intron_variant	PRKCA	4e-08	Tier 4: intronic/intergenic
rs4758351	11	5997956	G>A,T	0.05	intergenic_variant	KRT18P58 - OR56A4	4e-07	Tier 4: intronic/intergenic
rs9937140	16	59784010	A>G,T	0.05	intergenic_variant	APOOP5 - LINC02141	8e-07	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, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
APOOP5	HGNC:48743	ENSG00000260240		apolipoprotein O pseudogene 5	gwas
PRKCA	HGNC:9393	ENSG00000154229	P17252	Protein kinase C alpha type	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRKCA	Protein kinase C alpha type	Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenes…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
APOOP5	Other/Unknown	no
PRKCA	Kinase	yes	2.7.11.13	C2_dom, Prot_kinase_dom, AGC-kinase_C

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
cerebellar vermis	1
male germ line stem cell (sensu Vertebrata) in testis	1
thymus	1
CA1 field of hippocampus	1
lateral globus pallidus	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APOOP5	21		marker	male germ line stem cell (sensu Vertebrata) in testis, cerebellar vermis, thymus
PRKCA	280	ubiquitous	marker	CA1 field of hippocampus, lateral globus pallidus, trigeminal ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKCA	4,530
APOOP5	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKCA	P17252	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 69. 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
Disinhibition of SNARE formation	1	2284.0×	0.008	PRKCA
The phototransduction cascade	1	1268.9×	0.008	PRKCA
HuR (ELAVL1) binds and stabilizes mRNA	1	1268.9×	0.008	PRKCA
ROBO receptors bind AKAP5	1	1268.9×	0.008	PRKCA
EGFR Transactivation by Gastrin	1	1142.0×	0.008	PRKCA
Acetylcholine regulates insulin secretion	1	1142.0×	0.008	PRKCA
Gastrin-CREB signalling pathway via PKC and MAPK	1	878.5×	0.008	PRKCA
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	761.3×	0.008	PRKCA
Depolymerization of the Nuclear Lamina	1	761.3×	0.008	PRKCA
Regulation of mRNA stability by proteins that bind AU-rich elements	1	761.3×	0.008	PRKCA
WNT5A-dependent internalization of FZD4	1	761.3×	0.008	PRKCA
Trafficking of GluR2-containing AMPA receptors	1	671.8×	0.008	PRKCA
Regulation of KIT signaling	1	601.0×	0.008	PRKCA
VEGFR2 mediated cell proliferation	1	571.0×	0.008	PRKCA
Trafficking of AMPA receptors	1	543.8×	0.008	PRKCA
SHC1 events in ERBB2 signaling	1	475.8×	0.008	PRKCA
Nuclear Envelope Breakdown	1	456.8×	0.008	PRKCA
RHO GTPases Activate NADPH Oxidases	1	456.8×	0.008	PRKCA
Syndecan interactions	1	423.0×	0.008	PRKCA
Calmodulin induced events	1	380.7×	0.008	PRKCA
CaM pathway	1	380.7×	0.008	PRKCA
Ca-dependent events	1	368.4×	0.008	PRKCA
Mitotic Prophase	1	368.4×	0.008	PRKCA
Signaling by ERBB2	1	346.1×	0.008	PRKCA
G-protein mediated events	1	326.3×	0.008	PRKCA
DAG and IP3 signaling	1	317.2×	0.008	PRKCA
Inactivation, recovery and regulation of the phototransduction cascade	1	317.2×	0.008	PRKCA
PCP/CE pathway	1	300.5×	0.008	PRKCA
Beta-catenin independent WNT signaling	1	292.8×	0.008	PRKCA
Opioid Signalling	1	265.6×	0.008	PRKCA

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
positive regulation of angiotensin-activated signaling pathway	1	16852.0×	0.002	PRKCA
response to phorbol 13-acetate 12-myristate	1	8426.0×	0.002	PRKCA
positive regulation of dense core granule biogenesis	1	8426.0×	0.002	PRKCA
protein kinase C signaling	1	4213.0×	0.002	PRKCA
positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	2808.7×	0.002	PRKCA
desmosome assembly	1	2407.4×	0.002	PRKCA
regulation of platelet aggregation	1	2407.4×	0.002	PRKCA
mitotic nuclear membrane disassembly	1	1872.4×	0.002	PRKCA
central nervous system neuron axonogenesis	1	1872.4×	0.002	PRKCA
negative regulation of glial cell apoptotic process	1	1872.4×	0.002	PRKCA
positive regulation of lipopolysaccharide-mediated signaling pathway	1	1532.0×	0.003	PRKCA
positive regulation of macrophage differentiation	1	1203.7×	0.003	PRKCA
response to corticosterone	1	1123.5×	0.003	PRKCA
response to reactive oxygen species	1	1053.2×	0.003	PRKCA
positive regulation of bone resorption	1	991.3×	0.003	PRKCA
positive regulation of cardiac muscle hypertrophy	1	732.7×	0.004	PRKCA
positive regulation of exocytosis	1	601.9×	0.004	PRKCA
positive regulation of cytokine production involved in inflammatory response	1	543.6×	0.005	PRKCA
response to interleukin-1	1	510.7×	0.005	PRKCA
positive regulation of mitotic cell cycle	1	468.1×	0.005	PRKCA
regulation of mRNA stability	1	421.3×	0.005	PRKCA
negative regulation of cytokine production involved in inflammatory response	1	421.3×	0.005	PRKCA
response to peptide hormone	1	391.9×	0.005	PRKCA
positive regulation of blood vessel endothelial cell migration	1	391.9×	0.005	PRKCA
positive regulation of smooth muscle cell proliferation	1	330.4×	0.005	PRKCA
response to mechanical stimulus	1	300.9×	0.006	PRKCA
positive regulation of cell adhesion	1	271.8×	0.006	PRKCA
positive regulation of insulin secretion	1	255.3×	0.006	PRKCA
positive regulation of endothelial cell migration	1	251.5×	0.006	PRKCA
positive regulation of synapse assembly	1	244.2×	0.006	PRKCA

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Nitazoxanide	Phase 3 (in late-stage trials)

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

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · 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).

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
PRKCA	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKCA	39	4
APOOP5	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INGENOL MEBUTATE	4	PRKCA
MIDOSTAURIN	4	PRKCA
TAMOXIFEN	4	PRKCA
RUXOLITINIB	4	PRKCA
PACRITINIB	4	PRKCA
BARICITINIB	4	PRKCA
TOFACITINIB	4	PRKCA
CAPIVASERTIB	4	PRKCA
ABEMACICLIB	4	PRKCA
GILTERITINIB	4	PRKCA
SUNITINIB	4	PRKCA
SURAMIN	3	PRKCA
FASUDIL	3	PRKCA
ALVOCIDIB	3	PRKCA
ENZASTAURIN HYDROCHLORIDE	3	PRKCA
AFURESERTIB	3	PRKCA
ENZASTAURIN	3	PRKCA
LESTAURTINIB	3	PRKCA
RUBOXISTAURIN	3	PRKCA
PHORBOL MYRISTATE ACETATE	2	PRKCA
EDELFOSINE	2	PRKCA
UPROSERTIB	2	PRKCA
UCN-01	2	PRKCA
APITOLISIB	2	PRKCA
ZOTIRACICLIB	2	PRKCA
DECERNOTINIB	2	PRKCA
BMS-690514	2	PRKCA
DAROVASERTIB	2	PRKCA
ACETOSIDE	2	PRKCA
BRYOSTATIN 1	2	PRKCA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRKCA	1,148	Binding:1131, Functional:15, ADMET:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRKCA	2.7.11.13	protein kinase C

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PRKCA	1,148

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

30 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)
INGENOL MEBUTATE	4	PRKCA
MIDOSTAURIN	4	PRKCA
TAMOXIFEN	4	PRKCA
RUXOLITINIB	4	PRKCA
PACRITINIB	4	PRKCA
BARICITINIB	4	PRKCA
TOFACITINIB	4	PRKCA
CAPIVASERTIB	4	PRKCA
ABEMACICLIB	4	PRKCA
GILTERITINIB	4	PRKCA
SUNITINIB	4	PRKCA
SURAMIN	3	PRKCA
FASUDIL	3	PRKCA
ALVOCIDIB	3	PRKCA
ENZASTAURIN HYDROCHLORIDE	3	PRKCA
AFURESERTIB	3	PRKCA
ENZASTAURIN	3	PRKCA
LESTAURTINIB	3	PRKCA
RUBOXISTAURIN	3	PRKCA
PHORBOL MYRISTATE ACETATE	2	PRKCA
EDELFOSINE	2	PRKCA
UPROSERTIB	2	PRKCA
UCN-01	2	PRKCA
APITOLISIB	2	PRKCA
ZOTIRACICLIB	2	PRKCA
DECERNOTINIB	2	PRKCA
BMS-690514	2	PRKCA
DAROVASERTIB	2	PRKCA
ACETOSIDE	2	PRKCA
BRYOSTATIN 1	2	PRKCA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRKCA
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	APOOP5

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)
APOOP5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 29.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	17
PHASE2	5
PHASE1	3
PHASE3	2
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06600711	PHASE3	NOT_YET_RECRUITING	Nitazoxanide for Treatment of Cryptosporidium in Children
NCT00004986	PHASE3	TERMINATED	Safety and Effectiveness of Nitazoxanide for the Treatment of Cryptosporidiosis in AIDS Patients
NCT07249463	PHASE2	RECRUITING	Study Testing the Efficacy, Safety, and Tolerability of EDI048 in Cryptosporidium Infection Model in Healthy Adults
NCT07388615	PHASE2	RECRUITING	The Effect of Echinacea (Immulant ®) in the Treatment of CRYPTOSPORIDIOSIS in Immunocompromised Children
NCT00000771	PHASE2	COMPLETED	A Double-Blind, Placebo-Controlled Trial of Paromomycin for Treatment of Cryptosporidiosis in Patients With Advanced HIV Disease and CD4 Counts Under 150 Cells/mm3
NCT00001081	PHASE2	COMPLETED	A Study of Nitazoxanide in Patients With AIDS and Diarrhea Caused by Cryptosporidium
NCT00055107	PHASE1/PHASE2	COMPLETED	Nitazoxanide for the Treatment of Chronic Diarrhea in HIV Infected Children
NCT00057486	PHASE1/PHASE2	TERMINATED	Interleukin 12 (IL-12) for the Treatment of Cryptosporidiosis in AIDS Patients
NCT03341767	PHASE2	TERMINATED	A Phase 2A Evaluation of the Safety, Tolerability, Pharmacokinetics, Efficacy of Clofazimine (CFZ) in Cryptosporidiosis
NCT00000980	PHASE1	COMPLETED	A Study of Spiramycin in the Treatment of Patients With AIDS-Related Diarrhea
NCT00001018	PHASE1	COMPLETED	A Study of Letrazuril in the Treatment of AIDS-Related Diarrhea
NCT00002248	PHASE1	COMPLETED	A Randomized, Multicenter, Double-Blind, Parallel-Group, Placebo-Controlled Trial of the Efficacy and Safety of Bovine Anti-Cryptosporidium Immunoglobulin (BACI) in the Treatment of Cryptosporidium Enteritis in AIDS Patients
NCT02764918	Not specified	ACTIVE_NOT_RECRUITING	Cryptosporidiosis and Enteropathogens in Bangladesh
NCT00001128	Not specified	TERMINATED	Treatment of Chronic Cryptosporidiosis in AIDS Patients
NCT00001162	Not specified	TERMINATED	Parasitic Infections of the Gastrointestinal Tract
NCT00002027	Not specified	COMPLETED	Protocol For the Treatment of Cryptosporidiosis in AIDS Patients With Diclazuril (R64,433)
NCT00002062	Not specified	COMPLETED	Open-Label Compassionate Use Study of Spiramycin for the Treatment of Diarrhea Due to Chronic Cryptosporidiosis in Immunocompromised Patients
NCT00002082	Not specified	COMPLETED	Azithromycin in the Treatment of Cryptosporidiosis in Patients With Acquired Immune Deficiency Syndrome (AIDS): A Randomized, Multi-Center, Placebo-Controlled, Double-Blind Study
NCT00002158	Not specified	UNKNOWN	A Study to Evaluate the Use of Nitazoxanide to Treat Cryptosporidiosis
NCT00002264	Not specified	COMPLETED	The Effectiveness of Cow’s Milk Immune Globulin in the Treatment of AIDS-Related Diarrhea
NCT00002278	Not specified	COMPLETED	A 28-Day Study of Diclazuril in the Treatment of Cryptosporidiosis in Patients With AIDS
NCT00002328	Not specified	COMPLETED	Azithromycin in the Treatment of Cryptosporidiosis in Patients Who Have Not Had Success With Other Drugs
NCT00507871	Not specified	COMPLETED	Transmission and the Respiratory Tract in Cryptosporidiosis
NCT01695304	Not specified	COMPLETED	Trial of Ceramic Water Filters to Reduce Cryptosporidium Infection in Kenya
NCT01699841	Not specified	COMPLETED	Breast Milk Composition and HIV-exposed/Unexposed Early Infant Growth and Infectious Disease Events
NCT04103216	Not specified	COMPLETED	Treatment of Cryptosporidiosis
NCT04332705	Not specified	UNKNOWN	Cryptosporidium Infection and Human Colorectal Cancer
NCT05208970	Not specified	UNKNOWN	Cryptosporidium Species in Sohag Governorate
NCT06379035	Not specified	UNKNOWN	Blastocystis and Cryptosporidium Infection in Colorectal Cancer Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NITAZOXANIDE	4	6
PAROMOMYCIN SULFATE	4	2
SPIRAMYCIN	4	2
CLOFAZIMINE	4	1
ECHINACEA, UNSPECIFIED	3	1
DICLAZURIL	2	2
INTERLEUKIN-12 HUMAN RECOMBINANT	2	1
LETRAZURIL	2	1
CHEMBL4299381	0	3
CHEMBL4303258	0	2
CHEMBL4278112	0	2
CHEMBL4758173	0	2
CHEMBL83521	0	2