Primary hyperoxaluria type 3

Summary

Primary hyperoxaluria type 3 (MONDO:0013327) is a disease caused by HOGA1 (GenCC Definitive), with 1 cohort gene and 6 clinical trials. Top therapeutic interventions include nedosiran sodium, stiripentol, and nedosiran.

At a glance

• Prevalence: (Worldwide) [Orphanet-validated]
• Causal gene: HOGA1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 308
• Phenotypes (HPO): 9
• Clinical trials: 6

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

9 HPO clinical features (Orphanet curated; top 9 by frequency):

HPO ID	Term	Frequency
HP:0000121	Nephrocalcinosis	Very frequent (80-99%)
HP:0000790	Hematuria	Very frequent (80-99%)
HP:0003110	Abnormality of urine homeostasis	Very frequent (80-99%)
HP:0003159	Hyperoxaluria	Very frequent (80-99%)
HP:0008672	Calcium oxalate nephrolithiasis	Very frequent (80-99%)
HP:0012211	Abnormal renal physiology	Very frequent (80-99%)
HP:0012531	Pain	Very frequent (80-99%)
HP:0100515	Pollakisuria	Very frequent (80-99%)
HP:0100518	Dysuria	Very frequent (80-99%)

Identifiers

Disease identifiers

Field	Value
Canonical name	primary hyperoxaluria type 3
Mondo ID	MONDO:0013327
OMIM	613616
Orphanet	93600
DOID	DOID:0111672
NCIT	C123214
SNOMED CT	734990008
UMLS	C3150878
MedGen	462228
GARD	0010738
Is cancer (heuristic)	no

Also known as: HOGA1 primary hyperoxaluria · HP3 · hyperoxaluria, primary, type III · PH III · primary hyperoxaluria caused by mutation in HOGA1 · primary hyperoxaluria type III

Data availability: 308 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › primary hyperoxaluria › primary hyperoxaluria type 3

Related subtypes (2): primary hyperoxaluria type 1, primary hyperoxaluria type 2

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

308 retrieved; paginated sample, class counts are floors:

119 uncertain significance, 64 likely pathogenic, 33 conflicting classifications of pathogenicity, 29 pathogenic/likely pathogenic, 24 pathogenic, 19 likely benign, 14 benign, 6 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070213	NM_138413.4(HOGA1):c.70del (p.Val24fs)	HOGA1	Pathogenic	criteria provided, single submitter
1070518	NM_138413.4(HOGA1):c.189del (p.Lys63fs)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073203	NM_138413.4(HOGA1):c.812G>A (p.Arg271His)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1369845	NM_138413.4(HOGA1):c.2T>G (p.Met1Arg)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1380813	NM_138413.4(HOGA1):c.388del (p.Ala130fs)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1411084	NM_138413.4(HOGA1):c.834+2T>C	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1479002	NM_138413.4(HOGA1):c.290G>A (p.Arg97His)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1518588	NM_138413.4(HOGA1):c.733G>T (p.Val245Phe)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204266	NM_138413.4(HOGA1):c.134C>T (p.Pro45Leu)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204267	NM_138413.4(HOGA1):c.221T>G (p.Val74Gly)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204268	NM_138413.4(HOGA1):c.117C>A (p.Tyr39Ter)	HOGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
204269	NM_138413.4(HOGA1):c.208C>T (p.Arg70Ter)	HOGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
204270	NM_138413.4(HOGA1):c.337G>A (p.Glu113Lys)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204271	NM_138413.4(HOGA1):c.346C>T (p.Gln116Ter)	HOGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
204273	NM_138413.4(HOGA1):c.569C>T (p.Pro190Leu)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204274	NM_138413.4(HOGA1):c.728C>A (p.Ala243Asp)	HOGA1	Pathogenic	no assertion criteria provided
204275	NM_138413.4(HOGA1):c.733G>A (p.Val245Ile)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204276	NM_138413.4(HOGA1):c.763C>T (p.Arg255Ter)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204279	NM_138413.4(HOGA1):c.907C>T (p.Arg303Cys)	HOGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
204280	NM_138413.4(HOGA1):c.227G>A (p.Gly76Asp)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204284	NM_138413.4(HOGA1):c.973G>A (p.Gly325Ser)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204285	NM_138413.4(HOGA1):c.700+5G>T	HOGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
204286	NM_138413.4(HOGA1):c.834G>A (p.Ala278=)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
204287	NM_138413.4(HOGA1):c.158del (p.Asp53fs)	HOGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
2149465	NM_138413.4(HOGA1):c.860G>A (p.Gly287Glu)	HOGA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2664097	NM_138413.4(HOGA1):c.926T>C (p.Leu309Pro)	HOGA1	Pathogenic	criteria provided, single submitter
2664379	NM_138413.4(HOGA1):c.3G>A (p.Met1Ile)	HOGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
2664380	NM_138413.4(HOGA1):c.186_187del (p.His62fs)	HOGA1	Pathogenic	criteria provided, multiple submitters, no conflicts
2664383	NM_138413.4(HOGA1):c.238G>T (p.Glu80Ter)	HOGA1	Pathogenic	criteria provided, single submitter
2664401	NM_138413.4(HOGA1):c.85G>T (p.Glu29Ter)	HOGA1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
HOGA1	Definitive	Autosomal recessive	primary hyperoxaluria type 3	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HOGA1	Orphanet:93600	Primary hyperoxaluria type 3

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
HOGA1	HGNC:25155	ENSG00000241935	Q86XE5	4-hydroxy-2-oxoglutarate aldolase, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HOGA1	4-hydroxy-2-oxoglutarate aldolase, mitochondrial	Catalyzes the final step in the metabolic pathway of hydroxyproline.

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)
HOGA1	Enzyme (other)	yes	4.1.3.16	DapA-like, Aldolase_TIM, Schiff_base-form_aldolases_AS

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
adult mammalian kidney	1
kidney epithelium	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HOGA1	164	broad	marker	kidney epithelium, right lobe of liver, adult mammalian kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HOGA1	1,135

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HOGA1	Q86XE5	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Glyoxylate metabolism and glycine degradation	1	761.3×	0.001	HOGA1

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
oxalate metabolic process	1	16852.0×	3e-04	HOGA1
glyoxylate catabolic process	1	4213.0×	4e-04	HOGA1
trans-4-hydroxy-L-proline catabolic process	1	3370.4×	4e-04	HOGA1
glyoxylate metabolic process	1	2808.7×	4e-04	HOGA1
pyruvate biosynthetic process	1	2106.5×	5e-04	HOGA1

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
HOGA1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HOGA1	5	Binding:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HOGA1	4.1.3.16	4-Hydroxy-2-oxoglutarate aldolase

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

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	HOGA1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
HOGA1	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	2
Not specified	2
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04042402	PHASE3	ACTIVE_NOT_RECRUITING	Long Term Extension Study in Patients With Primary Hyperoxaluria
NCT06465472	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Stiripentol in Patients 6 Years and Older With Primary Hyperoxaluria Type 1, 2 or 3
NCT05001269	PHASE2	COMPLETED	Nedosiran in Pediatric Patients From Birth to 11 Years of Age With PH and Relatively Intact Renal Function
NCT04555486	PHASE1	COMPLETED	Study to Evaluate Safety, Tolerability, PK and PD of DCR-PHXC in PH Type 3 Patients
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04542590	Not specified	COMPLETED	Natural History of Patients With PH3 and a History of Stone Events

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
NEDOSIRAN SODIUM	4	2
STIRIPENTOL	4	1
NEDOSIRAN	2	1