Pyruvate kinase deficiency of red cells

Summary

Pyruvate kinase deficiency of red cells (MONDO:0009950) is a disease caused by PKLR (GenCC Definitive), with 3 cohort genes and 14 clinical trials. Top therapeutic interventions include mitapivat and ascorbic acid.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: PKLR (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 143
• Phenotypes (HPO): 15
• Clinical trials: 14

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	5	Europe	Validated
Point prevalence	1-9 / 100 000	5.1	Specific population	Validated
Point prevalence	1-9 / 1 000 000	0.96	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

15 HPO clinical features (Orphanet curated; top 15 by frequency):

HPO ID	Term	Frequency
HP:0001744	Splenomegaly	Very frequent (80-99%)
HP:0001903	Anemia	Very frequent (80-99%)
HP:0001923	Reticulocytosis	Very frequent (80-99%)
HP:0004870	Chronic hemolytic anemia	Very frequent (80-99%)
HP:0008282	Unconjugated hyperbilirubinemia	Very frequent (80-99%)
HP:0025109	Reduced red cell pyruvate kinase level	Very frequent (80-99%)
HP:0001789	Hydrops fetalis	Frequent (30-79%)
HP:0003281	Increased circulating ferritin concentration	Frequent (30-79%)
HP:0003452	Increased serum iron	Frequent (30-79%)
HP:0004804	Congenital hemolytic anemia	Frequent (30-79%)
HP:0006579	Prolonged neonatal jaundice	Frequent (30-79%)
HP:0001877	Abnormal erythrocyte morphology	Occasional (5-29%)
HP:0004447	Poikilocytosis	Occasional (5-29%)
HP:0011273	Anisocytosis	Occasional (5-29%)
HP:0012463	Elevated transferrin saturation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pyruvate kinase deficiency of red cells
Mondo ID	MONDO:0009950
MeSH	C564858
OMIM	266200
Orphanet	766
DOID	DOID:0111077
NCIT	C99037
SNOMED CT	124331002
UMLS	C0340968
MedGen	473069
GARD	0007514
NORD	1642
Is cancer (heuristic)	no

Also known as: anemia, congenital, nonspherocytic hemolytic, 2, pyruvate kinase deficient · hemolytic anaemia due to pyruvate Kinase deficiency · hemolytic anaemia due to red cell pyruvate kinase deficiency · hemolytic anemia due to pyruvate Kinase deficiency · hemolytic anemia due to red cell pyruvate kinase deficiency · PK deficiency · Pyruvate Kinase Deficiency · pyruvate kinase deficiency · pyruvate kinase deficiency of erythrocyte · pyruvate kinase deficiency of erythrocytes · pyruvate kinase deficiency of red cells

Data availability: 143 ClinVar variants · 5 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › congenital anemia › congenital nonspherocytic hemolytic anemia › pyruvate kinase deficiency of red cells

Related subtypes (9): anemia, nonspherocytic hemolytic, gamma-glutamylcysteine synthetase deficiency, glutathione synthetase deficiency without 5-oxoprolinuria, non-spherocytic hemolytic anemia due to hexokinase deficiency, hemolytic anemia due to pyrimidine 5’ nucleotidase deficiency, hemolytic anemia due to adenylate kinase deficiency, hemolytic anemia due to glucophosphate isomerase deficiency, hemolytic anemia due to glutathione reductase deficiency, hemolytic anemia due to erythrocyte adenosine deaminase overproduction

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

143 retrieved; paginated sample, class counts are floors:

59 uncertain significance, 29 conflicting classifications of pathogenicity, 21 likely pathogenic, 17 pathogenic, 10 pathogenic/likely pathogenic, 4 benign, 3 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1163643	NM_000298.6(PKLR):c.993C>A (p.Asp331Glu)	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1163645	NM_000298.6(PKLR):c.826del (p.Val276fs)	PKLR	Pathogenic	criteria provided, multiple submitters, no conflicts
1163647	NM_000298.6(PKLR):c.307del (p.Arg103fs)	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1187215	NM_000298.6(PKLR):c.1178A>G (p.Asn393Ser)	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1505	PKLR, 1-BP DEL	PKLR	Pathogenic	no assertion criteria provided
1507	NM_000298.6(PKLR):c.1151C>T (p.Thr384Met)	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1509	NM_000298.6(PKLR):c.1261C>A (p.Gln421Lys)	PKLR	Pathogenic	no assertion criteria provided
1510	NM_000298.6(PKLR):c.1436G>A (p.Arg479His)	PKLR	Pathogenic	criteria provided, multiple submitters, no conflicts
1511	NM_000298.6(PKLR):c.1529G>A (p.Arg510Gln)	PKLR	Pathogenic	criteria provided, multiple submitters, no conflicts
1513	NM_000298.6(PKLR):c.1456C>T (p.Arg486Trp)	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1514	NM_000298.6(PKLR):c.389C>A (p.Ser130Tyr)	PKLR	Pathogenic	no assertion criteria provided
1515	NC_000001.11:g.155301478C>G	PKLR	Pathogenic	no assertion criteria provided
1516	NM_000298.6(PKLR):c.1318G>T (p.Glu440Ter)	PKLR	Pathogenic	criteria provided, single submitter
1517	NM_000298.6(PKLR):c.1269G>A (p.Ala423=)	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1687397	NM_000298.6(PKLR):c.1015del (p.Asp339fs)	PKLR	Pathogenic	criteria provided, single submitter
1705384	NM_000298.6(PKLR):c.808C>T (p.Arg270Ter)	PKLR	Pathogenic	criteria provided, multiple submitters, no conflicts
2202852	NM_000298.6(PKLR):c.1462C>T (p.Arg488Ter)	PKLR	Pathogenic	criteria provided, multiple submitters, no conflicts
2437867	NM_000298.6(PKLR):c.1022G>C (p.Gly341Ala)	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
280113	NM_000298.6(PKLR):c.721G>T (p.Glu241Ter)	PKLR	Pathogenic	criteria provided, multiple submitters, no conflicts
292815	NM_000298.6(PKLR):c.391_393del (p.Ile131del)	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2956937	NM_000298.6(PKLR):c.694+2T>G	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3235888	NM_000298.6(PKLR):c.695-1G>A	PKLR	Pathogenic	criteria provided, single submitter
3341365	NM_000298.6(PKLR):c.603G>A (p.Trp201Ter)	PKLR	Pathogenic	criteria provided, single submitter
3376903	NM_000298.6(PKLR):c.1618+1del	PKLR	Pathogenic	criteria provided, single submitter
3775965	NM_000298.6(PKLR):c.403del (p.Arg135fs)	PKLR	Pathogenic	criteria provided, single submitter
522658	NM_000298.6(PKLR):c.331G>A (p.Gly111Arg)	PKLR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
983093	NM_000298.6(PKLR):c.1594C>T (p.Arg532Trp)	PKLR	Pathogenic	criteria provided, multiple submitters, no conflicts
1299505	NM_000298.6(PKLR):c.224T>C (p.Leu75Pro)	PKLR	Likely pathogenic	criteria provided, single submitter
1380720	NM_000298.6(PKLR):c.1595G>C (p.Arg532Pro)	PKLR	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431446	NM_000298.6(PKLR):c.1511G>T (p.Arg504Leu)	PKLR	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 5 · 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
PKLR	Definitive	Autosomal recessive	pyruvate kinase deficiency of red cells	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PKLR	Orphanet:766	Hemolytic anemia due to red cell pyruvate kinase deficiency
NTRK1	Orphanet:146	Differentiated thyroid carcinoma
NTRK1	Orphanet:642	Hereditary sensory and autonomic neuropathy type 4
NTRK1	Orphanet:64752	Hereditary sensory and autonomic neuropathy type 5
NTRK1	Orphanet:99361	Isolated familial medullary thyroid carcinoma

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PKLR	HGNC:9020	ENSG00000143627	P30613	Pyruvate kinase PKLR	gencc,clinvar
HCN3	HGNC:19183	ENSG00000143630	Q9P1Z3	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3	clinvar
NTRK1	HGNC:8031	ENSG00000198400	P04629	High affinity nerve growth factor receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PKLR	Pyruvate kinase PKLR	Pyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which plays a key role in glycolysis.
HCN3	Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3	Hyperpolarization-activated ion channel that are permeable to sodium and potassium ions, with an about 3:1 preference for potassium ions.
NTRK1	High affinity nerve growth factor receptor	Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons.

Protein-family classification

Druggable: 3 · 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	2	18.5×	0.008
Ion channel	1	37.2×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PKLR	Kinase	yes	2.7.1.40	Pyr_Knase, Pyrv_Knase-like_insert_dom_sf, Pyrv_Knase_brl
HCN3	Ion channel	yes		cNMP-bd_dom, K_chnl_volt-dep_EAG/ELK/ERG, Ion_trans_dom
NTRK1	Kinase	yes	2.7.10.1	Cys-rich_flank_reg_C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
duodenum	1
liver	1
right lobe of liver	1
cerebellum	1
cortical plate	1
right hemisphere of cerebellum	1
apex of heart	1
dorsal root ganglion	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PKLR	69	tissue_specific	marker	liver, right lobe of liver, duodenum
HCN3	132	ubiquitous	marker	cortical plate, right hemisphere of cerebellum, cerebellum
NTRK1	160	broad	marker	dorsal root ganglion, apex of heart, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NTRK1	9,181
HCN3	899
PKLR	94

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NTRK1	P04629	65
PKLR	P30613	58
HCN3	Q9P1Z3	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TRKA activation by NGF	1	1903.3×	0.004	NTRK1
PLC-gamma1 signalling	1	1268.9×	0.004	NTRK1
Signalling to STAT3	1	1268.9×	0.004	NTRK1
HCN channels	1	951.7×	0.004	HCN3
NGF-independant TRKA activation	1	761.3×	0.004	NTRK1
Signalling to p38 via RIT and RIN	1	761.3×	0.004	NTRK1
ARMS-mediated activation	1	543.8×	0.004	NTRK1
ChREBP activates metabolic gene expression	1	423.0×	0.004	PKLR
PI3K/AKT activation	1	423.0×	0.004	NTRK1
Frs2-mediated activation	1	317.2×	0.005	NTRK1
Retrograde neurotrophin signalling	1	271.9×	0.005	NTRK1
Signalling to RAS	1	223.9×	0.006	NTRK1
Regulation of gene expression in beta cells	1	173.0×	0.007	PKLR
Pyruvate metabolism	1	135.9×	0.008	PKLR
Glycolysis	1	95.2×	0.011	PKLR
SARS-CoV-1-host interactions	1	58.6×	0.017	PKLR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
programmed cell death involved in cell development	1	2808.7×	0.010	NTRK1
olfactory nerve development	1	1872.4×	0.010	NTRK1
behavioral response to formalin induced pain	1	1872.4×	0.010	NTRK1
response to hydrostatic pressure	1	1404.3×	0.010	NTRK1
mechanoreceptor differentiation	1	1123.5×	0.010	NTRK1
regulation of SA node cell action potential	1	936.2×	0.010	HCN3
pyruvate biosynthetic process	1	702.2×	0.010	PKLR
cellular response to nicotine	1	702.2×	0.010	NTRK1
regulation of membrane depolarization	1	624.1×	0.010	HCN3
peptidyl-tyrosine autophosphorylation	1	624.1×	0.010	NTRK1
axonogenesis involved in innervation	1	561.7×	0.010	NTRK1
response to metal ion	1	510.7×	0.010	PKLR
nerve growth factor signaling pathway	1	432.1×	0.010	NTRK1
cellular response to epinephrine stimulus	1	432.1×	0.010	PKLR
positive regulation of programmed cell death	1	374.5×	0.010	NTRK1
detection of mechanical stimulus involved in sensory perception of pain	1	374.5×	0.010	NTRK1
Sertoli cell development	1	374.5×	0.010	NTRK1
neurotrophin TRK receptor signaling pathway	1	351.1×	0.010	NTRK1
response to ATP	1	330.4×	0.010	PKLR
sympathetic nervous system development	1	312.1×	0.010	NTRK1
positive regulation of Ras protein signal transduction	1	295.6×	0.010	NTRK1
detection of temperature stimulus involved in sensory perception of pain	1	280.9×	0.010	NTRK1
response to electrical stimulus	1	216.1×	0.012	NTRK1
positive regulation of synaptic transmission, glutamatergic	1	208.1×	0.012	NTRK1
sodium ion import across plasma membrane	1	208.1×	0.012	HCN3
response to axon injury	1	170.2×	0.014	NTRK1
response to cAMP	1	170.2×	0.014	PKLR
cellular response to nerve growth factor stimulus	1	156.0×	0.014	NTRK1
peptidyl-tyrosine phosphorylation	1	140.4×	0.015	NTRK1
glycolytic process	1	127.7×	0.016	PKLR

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 3 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PKLR	MITAPIVAT
NTRK1	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NTRK1	66	4
PKLR	3	4
HCN3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MITAPIVAT	4	PKLR
PONATINIB	4	NTRK1
FEDRATINIB	4	NTRK1
AXITINIB	4	NTRK1
SORAFENIB	4	NTRK1
RUXOLITINIB	4	NTRK1
ENTRECTINIB	4	NTRK1
CABOZANTINIB	4	NTRK1
CERITINIB	4	NTRK1
BOSUTINIB	4	NTRK1
LORLATINIB	4	NTRK1
ABEMACICLIB	4	NTRK1
LAROTRECTINIB	4	NTRK1
LAROTRECTINIB SULFATE	4	NTRK1
REPOTRECTINIB	4	NTRK1
NINTEDANIB	4	NTRK1
SUNITINIB	4	NTRK1
QUIZARTINIB	4	NTRK1
CRIZOTINIB	4	NTRK1
MIDOSTAURIN	4	NTRK1
AMITRIPTYLINE	4	NTRK1
SURAMIN	3	PKLR
CRENOLANIB	3	NTRK1
LINIFANIB	3	NTRK1
DEFACTINIB	3	NTRK1
ENTOSPLETINIB	3	NTRK1
SITRAVATINIB	3	NTRK1
ALISERTIB	3	NTRK1
DOVITINIB	3	NTRK1
LESTAURTINIB	3	NTRK1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
NTRK1	1,194	Binding:1182, ADMET:7, Functional:5
PKLR	82	Binding:69, Functional:12, ADMET:1
HCN3	3	Binding:1, ADMET:1, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PKLR	2.7.1.40	pyruvate kinase
NTRK1	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
NTRK1	1,194

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

29 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.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	NTRK1
FEDRATINIB	4	NTRK1
AXITINIB	4	NTRK1
SORAFENIB	4	NTRK1
RUXOLITINIB	4	NTRK1
ENTRECTINIB	4	NTRK1
CABOZANTINIB	4	NTRK1
CERITINIB	4	NTRK1
BOSUTINIB	4	NTRK1
LORLATINIB	4	NTRK1
ABEMACICLIB	4	NTRK1
LAROTRECTINIB	4	NTRK1
LAROTRECTINIB SULFATE	4	NTRK1
REPOTRECTINIB	4	NTRK1
NINTEDANIB	4	NTRK1
SUNITINIB	4	NTRK1
QUIZARTINIB	4	NTRK1
CRIZOTINIB	4	NTRK1
MIDOSTAURIN	4	NTRK1
AMITRIPTYLINE	4	NTRK1
SURAMIN	3	PKLR
CRENOLANIB	3	NTRK1
LINIFANIB	3	NTRK1
DEFACTINIB	3	NTRK1
ENTOSPLETINIB	3	NTRK1
SITRAVATINIB	3	NTRK1
ALISERTIB	3	NTRK1
DOVITINIB	3	NTRK1
LESTAURTINIB	3	NTRK1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	PKLR, NTRK1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	HCN3
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)
HCN3	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE3	3
PHASE2	2
PHASE1	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05777993	PHASE4	ENROLLING_BY_INVITATION	A Study to Provide Continued Access to Mitapivat for Participants Who Previously Completed an Agios-Sponsored Mitapivat Study
NCT03548220	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT03559699	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT03853798	PHASE3	COMPLETED	Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007
NCT02476916	PHASE2	COMPLETED	A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency
NCT06422351	PHASE2	SUSPENDED	Clinical Trial to Evaluate the Efficacy of Gene Therapy for Pyruvate Kinase Deficiency
NCT07612345	PHASE1	NOT_YET_RECRUITING	High-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study
NCT04105166	PHASE1	COMPLETED	Gene Therapy for Pyruvate Kinase Deficiency (PKD)
NCT03481738	Not specified	ACTIVE_NOT_RECRUITING	Pyruvate Kinase Deficiency Global Longitudinal Registry
NCT02053480	Not specified	COMPLETED	Pyruvate Kinase Deficiency Natural History Study
NCT03866590	Not specified	COMPLETED	Pyruvate Kinase Deficiency Epidemiological Study (PIECE)
NCT04902833	Not specified	COMPLETED	Acquired Pyruvate Kinase Deficiency In Clonal Myeloid Neoplasms
NCT04964323	Not specified	TERMINATED	Pyruvate Kinase (PK) Deficiency Global Longitudinal Registry: Patient-Reported Outcomes (PRO)
NCT04995315	Not specified	COMPLETED	Pyruvate Kinase Deficiency Global Longitudinal Registry Substudy of Protocol AG348-C-008

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MITAPIVAT	4	5
ASCORBIC ACID	4	1