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Atlas / Disease / Hemolytic anemia

Hemolytic anemia

disease
On this page

Also known as anaemia hemolyticanemia hemolyticanemia, hemolytic

Summary

Hemolytic anemia (MONDO:0003664) is a disease (an umbrella term covering 11 Mondo subtypes) with 10 cohort genes and 20 clinical trials. The dominant Reactome pathway is Interaction between L1 and Ankyrins (3 cohort genes). Top therapeutic interventions include mitapivat, levamisole, and deferasirox.

At a glance

  • Umbrella term: 11 Mondo subtypes
  • Cohort genes: 10
  • ClinVar variants: 134
  • Clinical trials: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namehemolytic anemia
Mondo IDMONDO:0003664
MeSHD000743
DOIDDOID:583
ICD-10-CMD55-D59
NCITC34376
SNOMED CT61261009
UMLSC0002878
MedGen1916
GARD0023610
Is cancer (heuristic)no

Also known as: anaemia hemolytic · anemia hemolytic · anemia, hemolytic · hemolytic anemia

Data availability: 134 ClinVar variants.

Disease family

An umbrella term covering 11 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › normocytic anemia › hemolytic anemia

Subtypes (11): familial hemolytic anemia, Heinz body anemia, lethal hemolytic anemia-genital anomalies syndrome, hemolytic disease of the newborn with Kell alloimmunization, hereditary elliptocytosis, Shiga toxin-associated hemolytic uremic syndrome, hereditary stomatocytosis, autoimmune hemolytic anemia, 6-phosphogluconate dehydrogenase deficiency, non-autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria

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

134 retrieved; paginated sample, class counts are floors:

52 uncertain significance, 39 conflicting classifications of pathogenicity, 23 benign/likely benign, 15 benign, 2 likely pathogenic, 2 pathogenic, 1 pathogenic/likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
15347NM_000518.4(HBB):c.127T>G (p.Phe43Val)HBBPathogenicno assertion criteria provided
812891NM_003126.4(SPTA1):c.2353C>T (p.Arg785Ter)SPTA1Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
523359NM_001355436.2(SPTB):c.5794_5798+6delSPTBPathogeniccriteria provided, single submitter
15251NM_000518.5(HBB):c.127T>C (p.Phe43Leu)HBBLikely pathogeniccriteria provided, single submitter
812889NM_003126.4(SPTA1):c.4177C>T (p.Gln1393Ter)SPTA1Likely pathogenicno assertion criteria provided
17756NM_000342.3(SLC4A1):c.118G>A (p.Glu40Lys)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
17759NM_000342.4(SLC4A1):c.1972G>A (p.Glu658Lys)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
17782NM_000342.4(SLC4A1):c.1937G>A (p.Arg646Gln)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
17783NM_000342.4(SLC4A1):c.2603C>T (p.Pro868Leu)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
255914NM_000342.4(SLC4A1):c.539G>A (p.Arg180His)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323495NM_000342.4(SLC4A1):c.*351G>TSLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323501NM_000342.4(SLC4A1):c.2630T>C (p.Ile877Thr)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323505NM_000342.4(SLC4A1):c.2208C>T (p.Asn736=)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323513NM_000342.4(SLC4A1):c.876+14G>ASLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323515NM_000342.4(SLC4A1):c.636A>G (p.Ser212=)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323516NM_000342.4(SLC4A1):c.457C>A (p.Leu153Met)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323517NM_000342.4(SLC4A1):c.286C>T (p.Arg96Cys)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323519NM_000342.4(SLC4A1):c.202G>A (p.Glu68Lys)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323520NM_000342.4(SLC4A1):c.173A>G (p.Tyr58Cys)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
323525NM_000342.4(SLC4A1):c.-136C>TSLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
64423NM_000342.4(SLC4A1):c.2701C>T (p.Arg901Trp)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
737923NM_000342.4(SLC4A1):c.2193C>T (p.Ser731=)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
854724NM_000342.4(SLC4A1):c.733G>A (p.Val245Met)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
888574NM_000342.4(SLC4A1):c.349+15C>GSLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
889392NM_000342.4(SLC4A1):c.2401A>C (p.Ser801Arg)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
889445NM_000342.4(SLC4A1):c.1928C>T (p.Ser643Phe)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
889578NM_000342.4(SLC4A1):c.719C>T (p.Pro240Leu)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
889579NM_000342.4(SLC4A1):c.706T>G (p.Phe236Val)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
890020NM_000342.4(SLC4A1):c.2625G>A (p.Pro875=)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
890131NM_000342.4(SLC4A1):c.1671G>A (p.Val557=)SLC4A1Conflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 46 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SLC4A1Orphanet:3202Dehydrated hereditary stomatocytosis
SLC4A1Orphanet:398088Hereditary cryohydrocytosis with normal stomatin
SLC4A1Orphanet:822Hereditary spherocytosis
SLC4A1Orphanet:93608Autosomal dominant distal renal tubular acidosis
SLC4A1Orphanet:93610Distal renal tubular acidosis with anemia
SLC4A1Orphanet:98868Southeast Asian ovalocytosis
SPTA1Orphanet:288Hereditary elliptocytosis
SPTA1Orphanet:822Hereditary spherocytosis
SPTBOrphanet:288Hereditary elliptocytosis
SPTBOrphanet:822Hereditary spherocytosis
PIEZO1Orphanet:3202Dehydrated hereditary stomatocytosis
PIEZO1Orphanet:568062PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis
G6PDOrphanet:466026Class I glucose-6-phosphate dehydrogenase deficiency
GPIOrphanet:712Hemolytic anemia due to glucophosphate isomerase deficiency
HBBOrphanet:2132Hemoglobin C disease
HBBOrphanet:2133Hemoglobin E disease
HBBOrphanet:231214Beta-thalassemia major
HBBOrphanet:231222Beta-thalassemia intermedia
HBBOrphanet:231226Unstable beta globin chain variant disease
HBBOrphanet:231237Delta-beta-thalassemia
HBBOrphanet:231242Hemoglobin C-beta-thalassemia syndrome
HBBOrphanet:231249Hemoglobin E-beta-thalassemia syndrome
HBBOrphanet:232Sickle cell anemia
HBBOrphanet:247511Autosomal dominant secondary polycythemia
HBBOrphanet:251365Sickle cell S-C disease
HBBOrphanet:251370Sickle cell S-D Punjab disease
HBBOrphanet:251375Sickle cell S-E disease
HBBOrphanet:251380Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
HBBOrphanet:330041Hemoglobin M disease
HBBOrphanet:46532Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
HBBOrphanet:695140Sickle cell-beta zero-thalassemia
HBBOrphanet:695147Sickle cell-beta plus-thalassemia
HBBOrphanet:699822Sickle cell S-Lepore disease
HBBOrphanet:700090Sickle cell S-O Arab disease
HBBOrphanet:700107Sickle cell S-other specified hemoglobin variant
HBBOrphanet:700111Homozygous hemoglobin O Arab disease
HBBOrphanet:715125Hemoglobin E-beta-thalassemia intermedia
HBBOrphanet:715128Hemoglobin E-beta-thalassemia major
HBBOrphanet:715135Hemoglobin Lepore-beta-thalassemia intermedia
HBBOrphanet:715140Hemoglobin Lepore-beta-thalassemia major
HBBOrphanet:715143Heterozygous beta-thalassemia intermedia with supernumerary alpha-globin gene
HBBOrphanet:715157Low oxygen affinity beta chain hemoglobin disease
HBBOrphanet:90039Hemoglobin D disease
ANK1Orphanet:2510668p11.2 deletion syndrome
ANK1Orphanet:822Hereditary spherocytosis
PKLROrphanet:766Hemolytic anemia due to red cell pyruvate kinase deficiency

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence10

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SLC4A1HGNC:11027ENSG00000004939P02730Band 3 anion transport proteinclinvar
SPTA1HGNC:11272ENSG00000163554P02549Spectrin alpha chain, erythrocytic 1clinvar
SPTBHGNC:11274ENSG00000070182P11277Spectrin beta chain, erythrocyticclinvar
PIEZO1HGNC:28993ENSG00000103335Q92508Piezo-type mechanosensitive ion channel component 1clinvar
G6PDHGNC:4057ENSG00000160211P11413Glucose-6-phosphate 1-dehydrogenaseclinvar
GNPDA1HGNC:4417ENSG00000113552P46926Glucosamine-6-phosphate deaminase 1clinvar
GPIHGNC:4458ENSG00000105220P06744Glucose-6-phosphate isomeraseclinvar
HBBHGNC:4827ENSG00000244734P68871Hemoglobin subunit betaclinvar
ANK1HGNC:492ENSG00000029534P16157Ankyrin-1clinvar
PKLRHGNC:9020ENSG00000143627P30613Pyruvate kinase PKLRclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SLC4A1Band 3 anion transport proteinFunctions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein.
SPTA1Spectrin alpha chain, erythrocytic 1Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane.
SPTBSpectrin beta chain, erythrocyticSpectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane.
PIEZO1Piezo-type mechanosensitive ion channel component 1Pore-forming subunit of the mechanosensitive non-specific cation Piezo channel required for rapidly adapting mechanically activated (MA) currents and has a key role in sensing touch and tactile pain.
G6PDGlucose-6-phosphate 1-dehydrogenaseCatalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis.
GNPDA1Glucosamine-6-phosphate deaminase 1Catalyzes the reversible conversion of alpha-D-glucosamine 6-phosphate (GlcN-6P) into beta-D-fructose 6-phosphate (Fru-6P) and ammonium ion, a regulatory reaction step in de novo uridine diphosphate-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc…
GPIGlucose-6-phosphate isomeraseIsomerase that catalyzes the conversion of alpha-D-glucose-6-phosphate to beta-D-fructose-6-phosphate, the second step in glycolysis, and the reverse reaction in gluconeogenesis, within the cytoplasm.
HBBHemoglobin subunit betaInvolved in oxygen transport from the lung to the various peripheral tissues.
ANK1Ankyrin-1Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.
PKLRPyruvate kinase PKLRPyruvate kinase that catalyzes the conversion of phosphoenolpyruvate to pyruvate with the synthesis of ATP, and which plays a key role in glycolysis.

Protein-family classification

Druggable: 4 · Difficult: 2 · Unknown: 4 · Druggable fraction: 0.4

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.

FamilyGenesFoldFDR
Enzyme (other)33.6×0.178
Scaffold/PPI23.5×0.221
Kinase12.8×0.410
Other/Unknown40.7×0.907

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SLC4A1Other/UnknownnoAnion_exchange, Anion_exchange_1, HCO3_transpt_euk
SPTA1Scaffold/PPInoSH3_domain, Spectrin_repeat, EF_hand_dom
SPTBOther/UnknownnoActinin_actin-bd_CS, CH_dom, Spectrin_repeat
PIEZO1Other/UnknownnoPiezo, Piezo_cap_dom, Piezo_TM25-28
G6PDEnzyme (other)yes1.1.1.49G6P_DH, G6P_DH_AS, G6P_DH_NAD-bd
GNPDA1Enzyme (other)yes3.5.99.6Glucosamine6P_isomerase, Glc/Gal-6P_isomerase, Glucosamine6P_isomerase_CS
GPIEnzyme (other)yes5.3.1.9G6P_Isomerase, Phosphoglucose_isomerase_CS, G6P_Isomerase_C
HBBOther/UnknownnoGlobin, Hemoglobin_b, Globin-like_sf
ANK1Scaffold/PPInoDeath_dom, ZU5_dom, Ankyrin_rpt
PKLRKinaseyes2.7.1.40Pyr_Knase, Pyrv_Knase-like_insert_dom_sf, Pyrv_Knase_brl

Expression context

Cohort genes with no expression data: 0.

10 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)10
unknown0

Top tissues across cohort

TissueCohort genes
trabecular bone tissue3
bone marrow2
bone marrow cell2
gastrocnemius1
hindlimb stylopod muscle1
muscle of leg1
lower esophagus mucosa1
muscle layer of sigmoid colon1
upper lobe of left lung1
granulocyte1
right testis1
stromal cell of endometrium1
adult organism1
nephron tubule1
type B pancreatic cell1
apex of heart1
right adrenal gland1
right adrenal gland cortex1
monocyte1
vena cava1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SLC4A1161tissue_specificmarkertrabecular bone tissue, bone marrow, bone marrow cell
SPTA1147tissue_specificmarkertrabecular bone tissue, bone marrow, bone marrow cell
SPTB220broadmarkergastrocnemius, hindlimb stylopod muscle, muscle of leg
PIEZO1142ubiquitousmarkermuscle layer of sigmoid colon, lower esophagus mucosa, upper lobe of left lung
G6PD218ubiquitousmarkerstromal cell of endometrium, granulocyte, right testis
GNPDA1298ubiquitousmarkertype B pancreatic cell, nephron tubule, adult organism
GPI286ubiquitousmarkerapex of heart, right adrenal gland, right adrenal gland cortex
HBB284broadmarkermonocyte, trabecular bone tissue, vena cava
ANK1226broadmarkerskeletal muscle tissue of rectus abdominis, triceps brachii, body of tongue
PKLR69tissue_specificmarkerliver, right lobe of liver, duodenum

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

SymbolInteractor count
ANK15,705
GPI4,709
G6PD4,226
PIEZO12,266
GNPDA11,687
SLC4A11,598
SPTA11,551
SPTB1,079
HBB454
PKLR94

Intra-cohort edges

ABSources
ANK1SLC4A1biogrid_interaction, intact, string_interaction
ANK1SPTA1biogrid_interaction, string_interaction
ANK1SPTBbiogrid_interaction, string_interaction
G6PDGPIstring_interaction
GNPDA1GPIstring_interaction
SLC4A1SPTA1intact, string_interaction
SLC4A1SPTBintact
SPTA1SPTBintact, string_interaction

Structural data

PDB: 10 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
HBBP68871350
PKLRP3061358
SLC4A1P0273054
G6PDP1141325
ANK1P1615721
GPIP0674413
SPTBP112776
PIEZO1Q925086
SPTA1P025493
GNPDA1P469261

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 52. Enrichment computed across 10 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Interaction between L1 and Ankyrins3110.5×1e-04SPTA1, SPTB, ANK1
Glycolysis385.7×1e-04GNPDA1, GPI, PKLR
Erythrocytes take up oxygen and release carbon dioxide2253.8×4e-04SLC4A1, HBB
Erythrocytes take up carbon dioxide and release oxygen2175.7×6e-04SLC4A1, HBB
ER to Golgi Anterograde Transport339.8×6e-04SPTA1, SPTB, ANK1
L1CAM interactions336.1×6e-04SPTA1, SPTB, ANK1
COPI-mediated anterograde transport332.9×6e-04SPTA1, SPTB, ANK1
Transport to the Golgi and subsequent modification330.9×7e-04SPTA1, SPTB, ANK1
Asparagine N-linked glycosylation318.0×0.003SPTA1, SPTB, ANK1
NCAM signaling for neurite out-growth254.4×0.003SPTA1, SPTB
Defective SLC4A1 causes hereditary spherocytosis type 4 (HSP4), distal renal tubular acidosis (dRTA) and dRTA with hemolytic anemia (dRTA-HA)11142.0×0.004SLC4A1
Axon guidance313.5×0.005SPTA1, SPTB, ANK1
Nervous system development312.9×0.005SPTA1, SPTB, ANK1
Membrane Trafficking311.1×0.008SPTA1, SPTB, ANK1
Heme assimilation1380.7×0.008HBB
MAPK1/MAPK3 signaling226.2×0.008SPTA1, SPTB
TP53 Regulates Metabolic Genes225.9×0.008G6PD, GPI
Vesicle-mediated transport310.4×0.008SPTA1, SPTB, ANK1
MAPK family signaling cascades220.6×0.011SPTA1, SPTB
NrCAM interactions1163.1×0.016ANK1
Neurofascin interactions1142.8×0.016ANK1
NFE2L2 regulates pentose phosphate pathway genes1142.8×0.016G6PD
O2/CO2 exchange in erythrocytes1126.9×0.016SLC4A1
ChREBP activates metabolic gene expression1126.9×0.016PKLR
CHL1 interactions1126.9×0.016ANK1
Bicarbonate transporters1114.2×0.017SLC4A1
Pentose phosphate pathway195.2×0.020G6PD
Scavenging of heme from plasma187.8×0.020HBB
RAF/MAP kinase cascade212.2×0.020SPTA1, SPTB
Post-translational protein modification35.8×0.022SPTA1, SPTB, ANK1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
negative regulation of glycolytic process through fructose-6-phosphate2561.7×5e-04SLC4A1, GPI
actin filament capping2306.4×9e-04SPTA1, SPTB
glucose 6-phosphate metabolic process2259.3×9e-04G6PD, GPI
erythrocyte development2105.3×0.004SLC4A1, HBB
glycolytic process276.6×0.006GPI, PKLR
response to increased oxygen levels11685.2×0.008SLC4A1
pH elevation11685.2×0.008SLC4A1
ribose phosphate biosynthetic process11685.2×0.008G6PD
response to iron(III) ion1842.6×0.011G6PD
pentose biosynthetic process1842.6×0.011G6PD
positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel1842.6×0.011G6PD
D-glucosamine catabolic process1561.7×0.015GNPDA1
porphyrin-containing compound biosynthetic process1421.3×0.015SPTA1
intracellular monoatomic ion homeostasis1421.3×0.015SLC4A1
pentose-phosphate shunt, oxidative branch1421.3×0.015G6PD
negative regulation of urine volume1421.3×0.015SLC4A1
carbohydrate metabolic process227.2×0.015GNPDA1, GPI
N-acetylglucosamine catabolic process1337.0×0.016GNPDA1
nitric oxide transport1337.0×0.016HBB
protein localization to plasma membrane221.7×0.019SLC4A1, ANK1
N-acetylneuraminate catabolic process1240.7×0.019GNPDA1
maintenance of epithelial cell apical/basal polarity1240.7×0.019ANK1
positive regulation of cell-cell adhesion mediated by integrin1210.7×0.019PIEZO1
pyruvate biosynthetic process1210.7×0.019PKLR
lymphocyte homeostasis1187.2×0.019SPTA1
positive regulation of integrin activation1187.2×0.019PIEZO1
cellular oxidant detoxification1187.2×0.019HBB
hemostasis1168.5×0.019GPI
renal absorption1168.5×0.019HBB
UDP-N-acetylglucosamine biosynthetic process1153.2×0.019GNPDA1

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
VoxelotorApproved (phase 4)

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 7

Druggability breadth: 6 of 10 evidence-associated genes (60%) 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.

SymbolExample approved molecule
G6PDBREXANOLONE
HBBCANDESARTAN CILEXETIL
PKLRMITAPIVAT

Top cohort targets by molecule count

SymbolMoleculesMax phase
HBB234
G6PD84
PKLR34
SLC4A100
SPTA100
SPTB00
PIEZO100
GNPDA100
GPI00
ANK100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
BREXANOLONE4G6PD
APOMORPHINE HYDROCHLORIDE4G6PD
PRASTERONE4G6PD
CANDESARTAN CILEXETIL4HBB
MECHLORETHAMINE HYDROCHLORIDE4HBB
PHENAZOPYRIDINE HYDROCHLORIDE4HBB
MERCAPTOPURINE ANHYDROUS4HBB
AZACITIDINE4HBB
AZATHIOPRINE4HBB
TOPOTECAN HYDROCHLORIDE4HBB
ACYCLOVIR4HBB
FLUOROURACIL4HBB
RAUWOLFIA SERPENTINA4HBB
HYDROQUINONE4HBB
MENADIONE4HBB
THIOTEPA4HBB
THIOGUANINE4HBB
RESERPINE4HBB
MITAPIVAT4PKLR
EBSELEN3G6PD
CURCUMIN3HBB
HYDROXYCAMPTOTHECIN3HBB
SURAMIN3PKLR
PICEID2G6PD
SEPRANOLONE2G6PD
MOLIBRESIB2HBB
FISETIN2HBB
TEROXIRONE2HBB
5-FLUOROURIDINE2HBB
ELLAGIC ACID2HBB, PKLR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

SymbolAssaysType breakdown
PKLR82Binding:69, Functional:12, ADMET:1
HBB68Binding:50, Functional:18
G6PD49Binding:46, ADMET:2, Functional:1
PIEZO117Binding:17
GPI2Binding:2
GNPDA11Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
G6PD1.1.1.49glucose-6-phosphate dehydrogenase (NADP+)
GNPDA13.5.99.6glucosamine-6-phosphate deaminase
GPI5.3.1.9glucose-6-phosphate isomerase
PKLR2.7.1.40pyruvate kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
G6PD1

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.

CompoundMax phaseCohort target (bioactivity)
BREXANOLONE4G6PD
APOMORPHINE HYDROCHLORIDE4G6PD
PRASTERONE4G6PD
CANDESARTAN CILEXETIL4HBB
MECHLORETHAMINE HYDROCHLORIDE4HBB
PHENAZOPYRIDINE HYDROCHLORIDE4HBB
MERCAPTOPURINE ANHYDROUS4HBB
AZACITIDINE4HBB
AZATHIOPRINE4HBB
TOPOTECAN HYDROCHLORIDE4HBB
ACYCLOVIR4HBB
FLUOROURACIL4HBB
RAUWOLFIA SERPENTINA4HBB
HYDROQUINONE4HBB
MENADIONE4HBB
THIOTEPA4HBB
THIOGUANINE4HBB
RESERPINE4HBB
EBSELEN3G6PD
CURCUMIN3HBB
HYDROXYCAMPTOTHECIN3HBB
SURAMIN3PKLR
PICEID2G6PD
SEPRANOLONE2G6PD
MOLIBRESIB2HBB
FISETIN2HBB
TEROXIRONE2HBB
5-FLUOROURIDINE2HBB
ELLAGIC ACID2HBB, PKLR

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)3G6PD, HBB, PKLR
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug2GNPDA1, GPI
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug5SLC4A1, SPTA1, SPTB, PIEZO1, ANK1

Undrugged target profiles

7 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

SymbolChEMBL assaysDrugged partners (top 3)
GPI2G6PD
SLC4A10—
SPTA10—
SPTB0—
PIEZO117—
GNPDA11—
ANK10—

Clinical trials & evidence

Clinical trials

Clinical trials: 20.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified7
PHASE24
PHASE33
PHASE13
PHASE1/PHASE22
PHASE41

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05777993PHASE4ENROLLING_BY_INVITATIONA Study to Provide Continued Access to Mitapivat for Participants Who Previously Completed an Agios-Sponsored Mitapivat Study
NCT00001729PHASE3COMPLETEDCombination Drug Therapy for Patients With Hepatitis C
NCT03548220PHASE3COMPLETEDA Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT03559699PHASE3COMPLETEDA Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT04610866PHASE1/PHASE2ACTIVE_NOT_RECRUITINGSafety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
NCT00110617PHASE2COMPLETEDStudy of Deferasirox Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients
NCT01579110PHASE2UNKNOWNEfficacy and Safety of Levamisole Combined With Standard Prednisolone in Warm Antibody Autoimmune Hemolytic Anemia.
NCT01642979PHASE2UNKNOWNSafety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Classic Paroxysmal Nocturnal Hemoglobinuria
NCT01760096PHASE2UNKNOWNSafety and Efficacy of Levamisole Combined With Cyclosporine A in Patients With Subclinical Paroxysmal Nocturnal Hemoglobinuria and PNH in the Setting of Another Bone Marrow Failure Syndromes(PNH-2013)
NCT03513328PHASE1/PHASE2COMPLETEDConditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT05004259PHASE1COMPLETEDThe Safety of Repurposing Daratumumab for Relapsed or Refractory Autoimmune Antibody Mediated Hemolytic Anemia
NCT06684041PHASE1COMPLETEDA Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Study, and QT Interval Study of HRS-5965 Capsules in Healthy Subjects
NCT07040787PHASE1COMPLETEDInvestigation of Drug-drug Interaction of HRS-5965 With Clopidogrel and Clarithromycin in Healthy Subjects
NCT06708728Not specifiedNOT_YET_RECRUITINGStudy of Acquired Hemolytic Anemia in Adult Hospitalized Patients
NCT00842621Not specifiedCOMPLETEDLong Term Effects of Erythrocyte Lysis
NCT00971984Not specifiedCOMPLETEDDemographic, Clinical and Laboratory Characteristics of Children With Alpha Thalassemia in Northern Israel
NCT02111590Not specifiedCOMPLETEDImmunoglobulin Dosage and Administration Form in CIDP and MMN
NCT03006718Not specifiedCOMPLETEDSCD-PROMIS: A Software Platform to Enhance Self-efficacy and Patient-provider Engagement for Patients With Sickle Cell Pain
NCT04721262Not specifiedCOMPLETEDFerumoxytol Enhanced Hyperfine Low Field Strength MRI
NCT04964323Not specifiedTERMINATEDPyruvate Kinase (PK) Deficiency Global Longitudinal Registry: Patient-Reported Outcomes (PRO)

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
MITAPIVAT44
LEVAMISOLE43
DEFERASIROX41
DEFEROXAMINE41
RIBAVIRIN41
DEXAMISOLE23
CHEMBL463523401

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 71

This page pulls from 71 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmintactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot