Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome
diseaseOn this page
Also known as HUPRA syndromeHUPRAShyperuricemia, pulmonary hypertension, renal failure, and alkalosishyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome
Summary
Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome (MONDO:0013458) is a disease caused by SARS2 (GenCC Strong), with 2 cohort genes.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Causal gene: SARS2 (GenCC Strong)
- Cohort genes: 2
- ClinVar variants: 168
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 4 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome |
| Mondo ID | MONDO:0013458 |
| OMIM | 613845 |
| Orphanet | 363694 |
| UMLS | C3151209 |
| MedGen | 462559 |
| GARD | 0017569 |
| Is cancer (heuristic) | no |
Also known as: HUPRA syndrome · HUPRAS · hyperuricemia, pulmonary hypertension, renal failure, and alkalosis · hyperuricemia, pulmonary hypertension, renal failure, and alkalosis syndrome
Data availability: 168 ClinVar variants · 5 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › hypertensive disorder › pulmonary hypertension › hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome
Related subtypes (5): Braddock syndrome, chronic thromboembolic pulmonary hypertension, pulmonary arterial hypertension, pulmonary hypertension owing to lung disease and/or hypoxia, pulmonary hypertension, neonatal
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
168 retrieved; paginated sample, class counts are floors:
116 uncertain significance, 26 conflicting classifications of pathogenicity, 10 benign, 8 benign/likely benign, 6 likely benign, 1 pathogenic, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 242874 | NM_017827.4(SARS2):c.1042T>C (p.Phe348Leu) | SARS2 | Pathogenic | no assertion criteria provided |
| 30982 | NM_017827.4(SARS2):c.1169A>G (p.Asp390Gly) | SARS2 | Likely pathogenic | criteria provided, single submitter |
| 138961 | NM_017827.4(SARS2):c.248C>T (p.Ser83Leu) | LOC130064387 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1420911 | NM_017827.4(SARS2):c.17C>T (p.Ala6Val) | LOC130064387 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2054564 | NM_017827.4(SARS2):c.176A>C (p.Asp59Ala) | LOC130064387 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 215114 | NM_017827.4(SARS2):c.30G>A (p.Trp10Ter) | LOC130064387 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 138958 | NM_017827.4(SARS2):c.590-5T>A | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 215102 | NM_017827.4(SARS2):c.310C>T (p.Arg104Trp) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 215104 | NM_017827.4(SARS2):c.91A>G (p.Arg31Gly) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 215106 | NM_017827.4(SARS2):c.364-7C>A | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 215107 | NM_017827.4(SARS2):c.390G>A (p.Gln130=) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 215109 | NM_017827.4(SARS2):c.501G>A (p.Ala167=) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2574738 | NM_017827.4(SARS2):c.603A>G (p.Gln201=) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 329210 | NM_017827.4(SARS2):c.1347+10G>A | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 329214 | NM_017827.4(SARS2):c.917-4C>T | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 329216 | NM_017827.4(SARS2):c.888G>A (p.Leu296=) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 329218 | NM_017827.4(SARS2):c.654-11C>G | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 329219 | NM_017827.4(SARS2):c.589+4G>A | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 329221 | NM_017827.4(SARS2):c.534+10G>A | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 3583866 | NM_017827.4(SARS2):c.755G>A (p.Arg252His) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 432690 | NM_017827.4(SARS2):c.694C>T (p.Arg232Cys) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 506542 | NM_017827.4(SARS2):c.1315A>T (p.Thr439Ser) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 559230 | NM_017827.4(SARS2):c.1317C>T (p.Thr439=) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 638611 | NM_017827.4(SARS2):c.1347G>A (p.Thr449=) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 669445 | NM_017827.4(SARS2):c.777G>A (p.Thr259=) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 894086 | NM_017827.4(SARS2):c.1292G>A (p.Arg431His) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 894473 | NM_017827.4(SARS2):c.900G>A (p.Ala300=) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 978825 | NM_017827.4(SARS2):c.1205G>A (p.Arg402His) | SARS2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2048371 | NM_017827.4(SARS2):c.146G>A (p.Arg49His) | LOC130064387 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 329225 | NM_017827.4(SARS2):c.175G>C (p.Asp59His) | LOC130064387 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · Orphanet: 3 · 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 |
|---|---|---|---|---|
| SARS2 | Strong | Autosomal recessive | hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SARS2 | Orphanet:363694 | Hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome |
| SARS1 | Orphanet:2512 | Autosomal recessive primary microcephaly |
| SARS1 | Orphanet:88616 | Autosomal recessive non-syndromic intellectual disability |
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 |
|---|---|---|---|---|---|
| SARS2 | HGNC:17697 | ENSG00000104835 | Q9NP81 | Serine–tRNA ligase, mitochondrial | gencc,clinvar |
| SARS1 | HGNC:10537 | ENSG00000031698 | P49591 | Serine–tRNA ligase, cytoplasmic | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SARS2 | Serine–tRNA ligase, mitochondrial | Catalyzes the attachment of serine to tRNA(Ser). |
| SARS1 | Serine–tRNA ligase, cytoplasmic | Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser). |
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 |
|---|---|---|---|
| Enzyme (other) | 2 | 12.0× | 0.007 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| SARS2 | Enzyme (other) | yes | 6.1.1.11 | aa-tRNA-synt_IIb, Ser-tRNA-ligase_type_1, aa-tRNA-synth_II |
| SARS1 | Enzyme (other) | yes | 6.1.1.11 | aa-tRNA-synt_IIb, Ser-tRNA-ligase_type_1, aa-tRNA-synth_II |
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 |
|---|---|
| apex of heart | 1 |
| metanephros cortex | 1 |
| right lobe of thyroid gland | 1 |
| body of pancreas | 1 |
| frontal pole | 1 |
| islet of Langerhans | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SARS2 | 138 | ubiquitous | marker | apex of heart, right lobe of thyroid gland, metanephros cortex |
| SARS1 | 291 | ubiquitous | marker | islet of Langerhans, body of pancreas, frontal pole |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SARS1 | 2,306 |
| SARS2 | 1,998 |
Structural data
PDB: 2 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SARS1 | P49591 | 9 |
| SARS2 | Q9NP81 | 6 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 9. 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 |
|---|---|---|---|---|
| tRNA Aminoacylation | 2 | 285.5× | 1e-04 | SARS2, SARS1 |
| Translation | 2 | 62.1× | 0.001 | SARS2, SARS1 |
| Mitochondrial tRNA aminoacylation | 1 | 259.6× | 0.010 | SARS2 |
| Cytosolic tRNA aminoacylation | 1 | 219.6× | 0.010 | SARS1 |
| Metabolism of proteins | 2 | 12.4× | 0.012 | SARS2, SARS1 |
| Selenoamino acid metabolism | 1 | 98.5× | 0.015 | SARS1 |
| Selenocysteine synthesis | 1 | 60.1× | 0.021 | SARS1 |
| Metabolism of amino acids and derivatives | 1 | 33.8× | 0.033 | SARS1 |
| Metabolism | 1 | 5.8× | 0.165 | SARS1 |
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 |
|---|---|---|---|---|
| seryl-tRNA aminoacylation | 2 | 8426.0× | 6e-08 | SARS2, SARS1 |
| mitochondrial seryl-tRNA aminoacylation | 1 | 8426.0× | 4e-04 | SARS2 |
| negative regulation of vascular endothelial growth factor production | 1 | 8426.0× | 4e-04 | SARS1 |
| selenocysteine incorporation | 1 | 936.2× | 0.002 | SARS1 |
| tRNA modification | 1 | 300.9× | 0.006 | SARS1 |
| cytoplasmic translation | 1 | 92.6× | 0.015 | SARS1 |
| negative regulation of angiogenesis | 1 | 84.3× | 0.015 | SARS1 |
| translation | 1 | 51.4× | 0.022 | SARS1 |
| negative regulation of transcription by RNA polymerase II | 1 | 8.9× | 0.110 | SARS1 |
Therapeutics
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 |
|---|---|---|
| SARS2 | 0 | 0 |
| SARS1 | 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 |
|---|---|---|
| SARS1 | 2 | ADMET:1, Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| SARS2 | 6.1.1.11 | serine-tRNA ligase |
| SARS1 | 6.1.1.11 | serine-tRNA ligase |
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 | 2 | SARS2, SARS1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| 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) |
|---|---|---|
| SARS2 | 0 | — |
| SARS1 | 2 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.