Paroxysmal nocturnal hemoglobinuria 2

Summary

Paroxysmal nocturnal hemoglobinuria 2 (MONDO:0014166) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	paroxysmal nocturnal hemoglobinuria 2
Mondo ID	MONDO:0014166
OMIM	615399
UMLS	C3809369
MedGen	815699
GARD	0015958
Is cancer (heuristic)	no

Also known as: paroxysmal nocturnal hemoglobinuria 2 · paroxysmal nocturnal hemoglobinuria 2, autosomal dominant, somatic mutation · paroxysmal nocturnal hemoglobinuria caused by mutation in PIGT · paroxysmal nocturnal hemoglobinuria type 2 · PIGT paroxysmal nocturnal hemoglobinuria · PNH2

Data availability: 13 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 2

Related subtypes (1): paroxysmal nocturnal hemoglobinuria 1

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

13 retrieved; paginated sample, class counts are floors:

4 benign, 3 uncertain significance, 3 risk factor, 2 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
548927	NM_015937.6(PIGT):c.197del (p.Tyr66fs)	PIGT	risk factor	no assertion criteria provided
599265	NM_015937.6(PIGT):c.767_770del (p.Lys256fs)	PIGT	risk factor	no assertion criteria provided
64650	NM_015937.6(PIGT):c.1401-2A>G	PIGT	risk factor	no assertion criteria provided
417893	NM_015937.6(PIGT):c.634C>T (p.His212Tyr)	PIGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
547916	NM_015937.6(PIGT):c.949A>G (p.Ile317Val)	PIGT	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1981911	NM_015937.6(PIGT):c.1252C>G (p.Pro418Ala)	PIGT	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891965	NM_015937.6(PIGT):c.62G>T (p.Cys21Phe)	PIGT	Uncertain significance	criteria provided, single submitter
977934	NM_015937.6(PIGT):c.1072G>A (p.Val358Met)	PIGT	Uncertain significance	no assertion criteria provided
1169471	NM_015937.6(PIGT):c.1371G>A (p.Thr457=)	PIGT	Benign	criteria provided, multiple submitters, no conflicts
1250938	NM_015937.6(PIGT):c.594+36dup	PIGT	Benign	criteria provided, multiple submitters, no conflicts
1289322	NM_015937.6(PIGT):c.1400+48T>C	PIGT	Benign	criteria provided, multiple submitters, no conflicts
506300	NM_015937.6(PIGT):c.1620T>C (p.Tyr540=)	PIGT	Benign	criteria provided, multiple submitters, no conflicts
784609	NM_015937.6(PIGT):c.969C>T (p.Thr323=)	PIGT	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · 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

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
PIGT	HGNC:14938	ENSG00000124155	Q969N2	GPI-anchor transamidase component PIGT	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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PIGT	Other/Unknown	no		PIG-T

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
cardia of stomach	1
pylorus	1
stromal cell of endometrium	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PIGT	1,295

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PIGT	Q969N2	4

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
Attachment of GPI anchor to uPAR	1	1268.9×	8e-04	PIGT

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
GPI anchored protein biosynthesis	1	2808.7×	0.001	PIGT
attachment of GPI anchor to protein	1	2106.5×	0.001	PIGT
GPI anchor biosynthetic process	1	495.6×	0.003	PIGT
neuron apoptotic process	1	185.2×	0.007	PIGT
neuron differentiation	1	100.3×	0.010	PIGT

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
PIGT	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: 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PIGT

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)
PIGT	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.