Hemolytic-uremic syndrome

Summary

Hemolytic-uremic syndrome (MONDO:0001549) is a disease with 2 cohort genes and 19 clinical trials. Top therapeutic interventions include rituximab.

At a glance

• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemolytic-uremic syndrome
Mondo ID	MONDO:0001549
MeSH	D006463
Orphanet	544458
DOID	DOID:12554
ICD-10-CM	D59.3
NCIT	C75545
SNOMED CT	111407006
UMLS	C0019061
MedGen	42403
GARD	0022233
Is cancer (heuristic)	no

Also known as: acute renal failure, thrombocytopenia, and microangiopathic hemolytic anaemia associated with distorted erythrocytes (‘burr cells’) · acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia associated with distorted erythrocytes (‘burr cells’) · hemolytic uremic syndrome · HUS

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › hemolytic-uremic syndrome

Related subtypes (7): marantic endocarditis, coagulation protein disease, thrombophilia, hemorrhagic disease of newborn, thrombotic microangiopathy, inherited blood coagulation disorder, prekallikrein deficiency

Subtypes (2): infection-related hemolytic uremic syndrome, hereditary hemolytic uremic syndrome

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

2 retrieved; paginated sample, class counts are floors:

1 likely pathogenic, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
548648	NM_003647.3(DGKE):c.888+40A>G	DGKE	Pathogenic	criteria provided, single submitter
2683805	NM_025265.4(TSEN2):c.1100-5T>A	TSEN2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TSEN2	Orphanet:2524	Pontocerebellar hypoplasia type 2
DGKE	Orphanet:329903	Immunoglobulin-mediated membranoproliferative glomerulonephritis
DGKE	Orphanet:357008	Hemolytic uremic syndrome with DGKE deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TSEN2	HGNC:28422	ENSG00000154743	Q8NCE0	tRNA-splicing endonuclease subunit Sen2	clinvar
DGKE	HGNC:2852	ENSG00000153933	P52429	Diacylglycerol kinase epsilon	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSEN2	tRNA-splicing endonuclease subunit Sen2	Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA.
DGKE	Diacylglycerol kinase epsilon	Membrane-bound diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.

Protein-family classification

Druggable: 2 · 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
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSEN2	Enzyme (other)	yes	4.6.1.16	tRNA_splic, tRNA_intron_Endonuc_cat-like, tRNA_intron_Endonuc_N
DGKE	Kinase	yes	2.7.1.107	Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom, PKC_DAG/PE

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
buccal mucosa cell	2
mucosa of transverse colon	1
primordial germ cell in gonad	1
Brodmann (1909) area 23	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSEN2	225	ubiquitous	marker	buccal mucosa cell, mucosa of transverse colon, primordial germ cell in gonad
DGKE	250	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TSEN2	1,088
DGKE	1,045

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TSEN2	Q8NCE0	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DGKE	P52429	86.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Effects of PIP2 hydrolysis	1	228.4×	0.011	DGKE
tRNA processing	1	178.4×	0.011	TSEN2
tRNA processing in the nucleus	1	98.5×	0.014	TSEN2
Metabolism of RNA	1	20.8×	0.047	TSEN2

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
tRNA-type intron splice site recognition and cleavage	1	2808.7×	0.004	TSEN2
glycerolipid metabolic process	1	1053.2×	0.004	DGKE
lipid phosphorylation	1	842.6×	0.004	DGKE
tRNA splicing, via endonucleolytic cleavage and ligation	1	702.2×	0.004	TSEN2
diacylglycerol metabolic process	1	601.9×	0.004	DGKE
tRNA processing	1	421.3×	0.005	TSEN2
phosphatidic acid biosynthetic process	1	255.3×	0.007	DGKE
phosphatidylinositol biosynthetic process	1	183.2×	0.009	DGKE
platelet activation	1	133.8×	0.011	DGKE
modulation of chemical synaptic transmission	1	91.6×	0.014	DGKE
phospholipase C-activating G protein-coupled receptor signaling pathway	1	65.8×	0.018	DGKE
mRNA processing	1	39.4×	0.027	TSEN2
intracellular signal transduction	1	19.1×	0.052	DGKE

Therapeutics

Drugs indicated for this disease

1 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Ravulizumab	Approved (phase 4)
Eculizumab	Phase 3 (in late-stage trials)
Galasomite	Phase 3 (in late-stage trials)

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

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

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
TSEN2	0	0
DGKE	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
DGKE	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TSEN2	4.6.1.16	tRNA-intron lyase
DGKE	2.7.1.107	diacylglycerol kinase (ATP)

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

0 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.

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	1	TSEN2
D	Druggable family + AlphaFold only, no drug	1	DGKE
E	Difficult family or no structure, no drug	0

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TSEN2	0	—
DGKE	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 19.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	11
PHASE3	3
PHASE2	2
PHASE4	1
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03776851	PHASE4	COMPLETED	Erythropoietin in Hemolytic Uremic Syndrome
NCT06389474	PHASE3	RECRUITING	Efficacy of INM004 in Children With STEC-HUS
NCT00004465	PHASE3	TERMINATED	Phase III Randomized Study of SYNSORB Pk in Children With E. Coli-Associated Hemolytic Uremic Syndrome
NCT01433003	PHASE3	WITHDRAWN	The Plasma Large-Volume Exchange RCT
NCT04132375	PHASE2/PHASE3	TERMINATED	Phase 2/3 Study to Evaluate PK, Safety & Efficacy of INM004 in STEC Positive Pediatric Patients for Prevention of HUS
NCT00531089	PHASE2	UNKNOWN	Rituximab in Patients With Relapsed or Refractory TTP-HUS
NCT05569746	PHASE2	COMPLETED	A Study to Assess Safety, Efficacy, and Pharmacokinetics of INM004 in Pediatric Patients With STEC-HUS
NCT03275792	PHASE1	WITHDRAWN	Shiga Toxin Producing Escherichia Coli (STEC) Volume Expansion
NCT04745195	Not specified	RECRUITING	Complement Prospective Evaluation of Thrombotic Microangiopathy on Endothelium
NCT05219110	Not specified	RECRUITING	Hyperhydration in Children With Shiga Toxin-Producing E. Coli Infection
NCT05985122	Not specified	ACTIVE_NOT_RECRUITING	New Analytic Tools for aHUS and C3G Diagnosis
NCT00358306	Not specified	COMPLETED	The Role of Endothelium Dysfunction in Progression of CKD (Chronic Kidney Disease) After AKI (Acute Kidney Injury)
NCT00593229	Not specified	TERMINATED	International Registry and Biorepository for TMA(Thrombotic Microangiopathy)
NCT01406288	Not specified	COMPLETED	Outbreak of Hemolytic Uremic Syndrome Linked to Escherichia Coli of Serotype O104:H4
NCT01561248	Not specified	COMPLETED	Study of Repetitive Intestinal Lavage in Patients With EHEC Associated Hemorrhagic Colitis
NCT01666548	Not specified	COMPLETED	Haemolytic Uraemic Syndrome in Childhood: Clinical, Cognitive and Psychological Aspects
NCT02904863	Not specified	COMPLETED	Study of ‘Vascular Competence’ Profile and Endothelial Activation in the Hemolytic Uremic Syndrome in Children and Adults
NCT03580941	Not specified	UNKNOWN	Usefulness of a Diagnostic Algorithm to Diagnose Thrombotic Microangiopathies in Pregnancy
NCT05991245	Not specified	UNKNOWN	French National Cohort MATRIX Renal and Systemic Thrombotic Microangiopathy

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
RITUXIMAB	4	1