Paroxysmal nocturnal hemoglobinuria 1
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Also known as paroxysmal nocturnal hemoglobinuria caused by mutation in PIGAparoxysmal nocturnal hemoglobinuria type 1paroxysmal nocturnal hemoglobinuria, somaticPIGA paroxysmal nocturnal hemoglobinuriaPNH1
Summary
Paroxysmal nocturnal hemoglobinuria 1 (MONDO:0010438) is a disease with 2 cohort genes.
At a glance
- Cohort genes: 2
- ClinVar variants: 21
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | paroxysmal nocturnal hemoglobinuria 1 |
| Mondo ID | MONDO:0010438 |
| OMIM | 300818 |
| UMLS | C3806670 |
| MedGen | 813000 |
| GARD | 0024726 |
| Is cancer (heuristic) | no |
Also known as: paroxysmal nocturnal hemoglobinuria 1 · paroxysmal nocturnal hemoglobinuria caused by mutation in PIGA · paroxysmal nocturnal hemoglobinuria caused by mutation in pIgA · paroxysmal nocturnal hemoglobinuria type 1 · paroxysmal nocturnal hemoglobinuria, somatic · PIGA paroxysmal nocturnal hemoglobinuria · pIgA paroxysmal nocturnal hemoglobinuria · PNH1
Data availability: 21 ClinVar variants.
Disease family
Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › proteinuria › hemoglobinuria › paroxysmal nocturnal hemoglobinuria › paroxysmal nocturnal hemoglobinuria 1
Related subtypes (1): paroxysmal nocturnal hemoglobinuria 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
21 retrieved; paginated sample, class counts are floors:
9 likely pathogenic, 4 conflicting classifications of pathogenicity, 4 uncertain significance, 2 pathogenic/likely pathogenic, 1 pathogenic, 1 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 41400 | NC_000003.12:g.169765160G>C | LOC110806306 | Pathogenic | no assertion criteria provided |
| 132814 | NM_002641.4(PIGA):c.355C>T (p.Arg119Trp) | PIGA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 623369 | NM_002641.4(PIGA):c.145G>A (p.Val49Met) | PIGA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1033523 | NM_002641.4(PIGA):c.986T>C (p.Val329Ala) | PIGA | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1685404 | NM_002641.4(PIGA):c.109A>G (p.Met37Val) | PIGA | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2444337 | NM_002641.4(PIGA):c.1281_1282del (p.Phe428fs) | PIGA | Likely pathogenic | criteria provided, single submitter |
| 2501811 | NM_002641.4(PIGA):c.1188+1G>C | PIGA | Likely pathogenic | no assertion criteria provided |
| 2502420 | NM_002641.4(PIGA):c.196_206del (p.Lys66fs) | PIGA | Likely pathogenic | no assertion criteria provided |
| 2502425 | NM_002641.4(PIGA):c.151_187del (p.Ser51fs) | PIGA | Likely pathogenic | no assertion criteria provided |
| 2502426 | NM_002641.4(PIGA):c.329dup (p.Pro111fs) | PIGA | Likely pathogenic | no assertion criteria provided |
| 2502427 | NM_002641.4(PIGA):c.1139del (p.Ile380fs) | PIGA | Likely pathogenic | no assertion criteria provided |
| 973228 | NM_002641.4(PIGA):c.1355A>T (p.Asp452Val) | PIGA | Likely pathogenic | criteria provided, single submitter |
| 1549539 | NM_002641.4(PIGA):c.849-19C>T | PIGA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 208742 | NM_002641.4(PIGA):c.98A>G (p.His33Arg) | PIGA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 432113 | NM_002641.4(PIGA):c.368C>T (p.Thr123Met) | PIGA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 625990 | NM_002641.4(PIGA):c.248T>C (p.Leu83Pro) | PIGA | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2502424 | NM_002641.4(PIGA):c.167T>C (p.Leu56Pro) | PIGA | Uncertain significance | no assertion criteria provided |
| 2502428 | NM_002641.4(PIGA):c.142G>A (p.Gly48Ser) | PIGA | Uncertain significance | no assertion criteria provided |
| 471950 | NM_002641.4(PIGA):c.1048C>T (p.Pro350Ser) | PIGA | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 548620 | NM_015937.6(PIGT):c.602T>C (p.Leu201Pro) | PIGT | Uncertain significance | criteria provided, single submitter |
| 471952 | NM_002641.4(PIGA):c.525T>C (p.Leu175=) | PIGA | Benign/Likely benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PIGT | Orphanet:369837 | Intellectual disability-seizures-hypophosphatasia-ophthalmic-skeletal anomalies syndrome |
| PIGA | Orphanet:293181 | Epilepsy of infancy with migrating focal seizures |
| PIGA | Orphanet:300496 | Multiple congenital anomalies-hypotonia-seizures syndrome type 2 |
| PIGA | Orphanet:397922 | Ferro-cerebro-cutaneous syndrome |
| PIGA | Orphanet:447 | Paroxysmal nocturnal hemoglobinuria |
| PIGA | Orphanet:697160 | Infantile epileptic spasms syndrome |
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 |
|---|---|---|---|---|---|
| PIGT | HGNC:14938 | ENSG00000124155 | Q969N2 | GPI-anchor transamidase component PIGT | clinvar |
| PIGA | HGNC:8957 | ENSG00000165195 | P37287 | Phosphatidylinositol N-acetylglucosaminyltransferase subunit A | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PIGT | GPI-anchor transamidase component PIGT | Component of the glycosylphosphatidylinositol-anchor (GPI-anchor) transamidase (GPI-T) complex that catalyzes the formation of the linkage between a proprotein and a GPI-anchor and participates in GPI anchored protein biosynthesis. |
| PIGA | Phosphatidylinositol N-acetylglucosaminyltransferase subunit A | Catalytic subunit of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first s… |
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) |
|---|---|---|---|---|
| PIGT | Other/Unknown | no | PIG-T | |
| PIGA | Other/Unknown | no | Glyco_trans_1, PIGA_GPI_anchor_biosynthesis, PIG-A/GPI3 |
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 |
|---|---|
| cardia of stomach | 1 |
| pylorus | 1 |
| stromal cell of endometrium | 1 |
| endometrium epithelium | 1 |
| mucosa of stomach | 1 |
| secondary oocyte | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PIGT | 253 | ubiquitous | marker | cardia of stomach, stromal cell of endometrium, pylorus |
| PIGA | 266 | ubiquitous | marker | secondary oocyte, mucosa of stomach, endometrium epithelium |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PIGA | 2,324 |
| PIGT | 1,295 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| PIGA | PIGT | string_interaction |
Structural data
PDB: 1 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PIGT | Q969N2 | 4 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| PIGA | P37287 | 86.22 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 2. 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 |
|---|---|---|---|---|
| Attachment of GPI anchor to uPAR | 1 | 634.4× | 0.003 | PIGT |
| Synthesis of glycosylphosphatidylinositol (GPI) | 1 | 317.2× | 0.003 | PIGA |
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 |
|---|---|---|---|---|
| GPI anchor biosynthetic process | 2 | 495.6× | 2e-05 | PIGT, PIGA |
| GPI anchored protein biosynthesis | 1 | 1404.3× | 0.002 | PIGT |
| attachment of GPI anchor to protein | 1 | 1053.2× | 0.002 | PIGT |
| neuron apoptotic process | 1 | 92.6× | 0.015 | PIGT |
| cellular response to leukemia inhibitory factor | 1 | 79.5× | 0.015 | PIGA |
| neuron differentiation | 1 | 50.1× | 0.020 | PIGT |
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 |
|---|---|---|
| PIGT | 0 | 0 |
| PIGA | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PIGT | 1 | Binding:1 |
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 | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 2 | PIGT, PIGA |
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) |
|---|---|---|
| PIGT | 1 | — |
| PIGA | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.