Familial hemolytic anemia

Summary

Familial hemolytic anemia (MONDO:0003689) is a disease (an umbrella term covering 23 Mondo subtypes) with 8 cohort genes (14 GWAS associations across 10 studies) and 2 clinical trials. Top therapeutic interventions include alemtuzumab.

At a glance

• Umbrella term: 23 Mondo subtypes
• Cohort genes: 8
• GWAS associations: 14
• ClinVar variants: 12
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial hemolytic anemia
Mondo ID	MONDO:0003689
MeSH	D000745
DOID	DOID:589
NCIT	C34379
SNOMED CT	42601008
UMLS	C0002881
MedGen	1919
GARD	0006167
Is cancer (heuristic)	no

Also known as: anaemia hemolytic congenital · anemia hemolytic congenital · congenital hemolytic anemia · hereditary hemolytic anemia

Data availability: 12 ClinVar variants · 14 GWAS associations (10 studies).

Disease family

An umbrella term covering 23 Mondo subtypes.

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

Related subtypes (10): 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

Subtypes (23): congenital nonspherocytic hemolytic anemia, elliptocytosis 2, southeast Asian ovalocytosis, overhydrated hereditary stomatocytosis, cryohydrocytosis, dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, abetalipoproteinemia, hemolytic anemia due to diphosphoglycerate mutase deficiency, glycogen storage disease VII, cutaneous porphyria, hereditary cryohydrocytosis with reduced stomatin, familial pseudohyperkalemia, renal tubular acidosis, distal, 4, with hemolytic anemia, elliptocytosis 1, glycogen storage disease due to aldolase A deficiency, primary CD59 deficiency, triosephosphate isomerase deficiency, dehydrated hereditary stomatocytosis 2, Rh deficiency syndrome, hereditary spherocytosis, congenital dyserythropoietic anemia, X-linked congenital hemolytic anemia, hemolytic disease of fetus and newborn, RH-induced

Genetics & variants

GWAS landscape

14 GWAS associations across 10 studies. Top hits map to 8 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs334	1e-323	HBB	T	2.24
rs77362408	1e-323	OR52S1P - OR52E3P	C	1.71
rs11549407	6e-224	HBB	G	2.15
rs372755452	7e-195	LUC7L	?
rs73404549	5e-44	HBG2, HBE1	?	11.03
rs13331259	2e-36	FAM234A	A	0.48
chr11:4653841	7e-19		C	1.82
chr11:2488091	1e-17		C	3.03
chr11:7296587	6e-16		A	2.77
rs144517644	2e-13	BRSK2	C	2.81
rs1050828	9e-13	G6PD	?	3.45
rs540546007	2e-11	XKR4	G	3.31

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475778	Verma A	2024	2,972	117,170	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479966	Verma A	2024	2,972	117,170	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475779	Verma A	2024	1,029	448,955	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481653	Verma A	2024	675	120,789	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651122	Liu TY	2025	669	215,243	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90476487	Verma A	2024	245	59,451	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435802	Zhou W	2018	156	390,026	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90435804	Zhou W	2018	83	390,026	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90837516	Koyama S	2025	0	0	Genetics and context for precision health in Greater Boston.
GCST90837540	Koyama S	2025	0	0	Genetics and context for precision health in Greater Boston.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	9

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	3
rare (<0.01)	5
unknown	1

Functional consequences

Consequence	Count
intron_variant	5
unknown	3
missense_variant	2
intergenic_variant	1
stop_gained	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs334	11	5227002	T>A,C,G	0.052	missense_variant	HBB	1e-323	Tier 1: coding
rs77362408	11	5078417	C>A,G	0.025	intergenic_variant	OR52S1P - OR52E3P	1e-323	Tier 4: intronic/intergenic
rs11549407	11	5226774	G>A,C,T	0	stop_gained	HBB	6e-224	Tier 1: coding
rs372755452	16	199622	AG>A		intron_variant	LUC7L	7e-195	Tier 4: intronic/intergenic
rs73404549	11	5299424	C>T	0.05	intron_variant	HBG2, HBE1	5e-44	Tier 4: intronic/intergenic
rs13331259	16	249924	A>G	0.02	intron_variant	FAM234A	2e-36	Tier 4: intronic/intergenic
chr11:4653841				0.011			7e-19	Tier 4: intronic/intergenic
chr11:2488091				0.002			1e-17	Tier 4: intronic/intergenic
chr11:7296587				0.001			6e-16	Tier 4: intronic/intergenic
rs144517644	11	1458438	C>A,T	0.001	intron_variant	BRSK2	2e-13	Tier 4: intronic/intergenic
rs1050828	X	154536002	C>T	0.05	missense_variant	G6PD	9e-13	Tier 1: coding
rs540546007	8	55158953	G>A,T	0	intron_variant	XKR4	2e-11	Tier 4: intronic/intergenic

ClinVar germline variants

12 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 2 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
544823	NM_003126.4(SPTA1):c.3291G>A (p.Trp1097Ter)	SPTA1	Pathogenic	criteria provided, single submitter
544826	NM_001360016.2(G6PD):c.448G>A (p.Val150Ile)	G6PD	Likely pathogenic	criteria provided, multiple submitters, no conflicts
544819	NM_003126.4(SPTA1):c.6600+5G>T	SPTA1	Likely pathogenic	criteria provided, single submitter
544820	NM_003126.4(SPTA1):c.1688G>A (p.Arg563Gln)	SPTA1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
544818	NM_001355436.2(SPTB):c.6271C>A (p.Pro2091Thr)	SPTB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
544827	NM_022437.3(ABCG8):c.-27G>A	ABCG5	Uncertain significance	criteria provided, single submitter
544828	NM_000064.4(C3):c.1921G>A (p.Asp641Asn)	C3	Uncertain significance	criteria provided, multiple submitters, no conflicts
544824	NM_172351.3(CD46):c.402T>G (p.Ile134Met)	CD46	Uncertain significance	criteria provided, multiple submitters, no conflicts
544825	NM_001142864.4(PIEZO1):c.1126C>G (p.Pro376Ala)	PIEZO1	Uncertain significance	criteria provided, single submitter
544815	NM_001355436.2(SPTB):c.6737C>T (p.Ala2246Val)	PLEKHG3	Uncertain significance	criteria provided, single submitter
544814	NM_001355436.2(SPTB):c.6706C>A (p.Leu2236Met)	SPTB	Uncertain significance	criteria provided, single submitter
258956	NM_003126.4(SPTA1):c.6672A>C (p.Glu2224Asp)	SPTA1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPTA1	Orphanet:288	Hereditary elliptocytosis
SPTA1	Orphanet:822	Hereditary spherocytosis
SPTB	Orphanet:288	Hereditary elliptocytosis
SPTB	Orphanet:822	Hereditary spherocytosis
C3	Orphanet:280133	Complement component 3 deficiency
C3	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
ABCG5	Orphanet:2882	Sitosterolemia
ABCG5	Orphanet:391665	Homozygous familial hypercholesterolemia
PIEZO1	Orphanet:3202	Dehydrated hereditary stomatocytosis
PIEZO1	Orphanet:568062	PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis
G6PD	Orphanet:466026	Class I glucose-6-phosphate dehydrogenase deficiency
CD46	Orphanet:244242	HELLP syndrome
CD46	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SPTA1	HGNC:11272	ENSG00000163554	P02549	Spectrin alpha chain, erythrocytic 1	clinvar
SPTB	HGNC:11274	ENSG00000070182	P11277	Spectrin beta chain, erythrocytic	clinvar
C3	HGNC:1318	ENSG00000125730	P01024	Complement C3	clinvar
ABCG5	HGNC:13886	ENSG00000138075	Q9H222	ATP-binding cassette sub-family G member 5	clinvar
PLEKHG3	HGNC:20364	ENSG00000126822	A1L390	Pleckstrin homology domain-containing family G member 3	clinvar
PIEZO1	HGNC:28993	ENSG00000103335	Q92508	Piezo-type mechanosensitive ion channel component 1	clinvar
G6PD	HGNC:4057	ENSG00000160211	P11413	Glucose-6-phosphate 1-dehydrogenase	clinvar
CD46	HGNC:6953	ENSG00000117335	P15529	Membrane cofactor protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPTA1	Spectrin alpha chain, erythrocytic 1	Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane.
SPTB	Spectrin beta chain, erythrocytic	Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane.
C3	Complement C3	Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adapt…
ABCG5	ATP-binding cassette sub-family G member 5	ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane.
PLEKHG3	Pleckstrin homology domain-containing family G member 3	Plays a role in controlling cell polarity and cell motility by selectively binding newly polymerized actin and activating RAC1 and CDC42 to enhance local actin polymerization.
PIEZO1	Piezo-type mechanosensitive ion channel component 1	Pore-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.
G6PD	Glucose-6-phosphate 1-dehydrogenase	Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis.
CD46	Membrane cofactor protein	Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue.

Protein-family classification

Druggable: 4 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.5

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
Complement	2	67.0×	0.002
Transporter	1	9.7×	0.164
Scaffold/PPI	2	4.3×	0.164
Enzyme (other)	1	1.5×	0.627
Other/Unknown	2	0.5×	0.984

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SPTA1	Scaffold/PPI	no		SH3_domain, Spectrin_repeat, EF_hand_dom
SPTB	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
C3	Complement	yes	3.4.21.47	Anaphylatoxin/fibulin, Netrin_domain, Macroglobln_a2
ABCG5	Transporter	yes		ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM
PLEKHG3	Scaffold/PPI	no		DH_dom, PH_domain, PH-like_dom_sf
PIEZO1	Other/Unknown	no		Piezo, Piezo_cap_dom, Piezo_TM25-28
G6PD	Enzyme (other)	yes	1.1.1.49	G6P_DH, G6P_DH_AS, G6P_DH_NAD-bd
CD46	Complement	yes		Sushi_SCR_CCP_dom, CD46, Sushi/SCR/CCP_sf

Expression context

Cohort genes with no expression data: 0.

8 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
palpebral conjunctiva	2
right lobe of liver	2
bone marrow	1
bone marrow cell	1
trabecular bone tissue	1
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1
parietal pleura	1
duodenum	1
jejunal mucosa	1
popliteal artery	1
sural nerve	1
tibial artery	1
lower esophagus mucosa	1
muscle layer of sigmoid colon	1
upper lobe of left lung	1
granulocyte	1
right testis	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPTA1	147	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell
SPTB	220	broad	marker	gastrocnemius, hindlimb stylopod muscle, muscle of leg
C3	289	ubiquitous	marker	parietal pleura, right lobe of liver, palpebral conjunctiva
ABCG5	61	tissue_specific	marker	jejunal mucosa, right lobe of liver, duodenum
PLEKHG3	247	ubiquitous	marker	sural nerve, popliteal artery, tibial artery
PIEZO1	142	ubiquitous	marker	muscle layer of sigmoid colon, lower esophagus mucosa, upper lobe of left lung
G6PD	218	ubiquitous	marker	stromal cell of endometrium, granulocyte, right testis
CD46	295	ubiquitous	marker	palpebral conjunctiva, adrenal tissue, mucosa of paranasal sinus

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
G6PD	4,226
C3	3,199
PIEZO1	2,266
ABCG5	1,996
CD46	1,780
SPTA1	1,551
SPTB	1,079
PLEKHG3	855

Intra-cohort edges

A	B	Sources
C3	CD46	intact, string_interaction
SPTA1	SPTB	intact, string_interaction

Structural data

PDB: 7 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C3	P01024	75
G6PD	P11413	25
ABCG5	Q9H222	8
CD46	P15529	7
SPTB	P11277	6
PIEZO1	Q92508	6
SPTA1	P02549	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLEKHG3	A1L390	55.28

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 53. Enrichment computed across 8 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interaction between L1 and Ankyrins	2	92.1×	0.009	SPTA1, SPTB
NCAM signaling for neurite out-growth	2	68.0×	0.009	SPTA1, SPTB
Regulation of Complement cascade	2	58.3×	0.009	C3, CD46
Defective ABCG8 causes GBD4 and sitosterolemia	1	713.8×	0.012	ABCG5
Defective ABCG5 causes sitosterolemia	1	713.8×	0.012	ABCG5
ER to Golgi Anterograde Transport	2	33.2×	0.012	SPTA1, SPTB
MAPK1/MAPK3 signaling	2	32.8×	0.012	SPTA1, SPTB
L1CAM interactions	2	30.1×	0.012	SPTA1, SPTB
COPI-mediated anterograde transport	2	27.4×	0.012	SPTA1, SPTB
MAPK family signaling cascades	2	25.7×	0.012	SPTA1, SPTB
Transport to the Golgi and subsequent modification	2	25.7×	0.012	SPTA1, SPTB
Alternative complement activation	1	285.5×	0.015	C3
NFE2L2 regulates pentose phosphate pathway genes	1	178.4×	0.023	G6PD
Activation of C3 and C5	1	158.6×	0.024	C3
RAF/MAP kinase cascade	2	15.3×	0.024	SPTA1, SPTB
Asparagine N-linked glycosylation	2	15.0×	0.024	SPTA1, SPTB
Pentose phosphate pathway	1	119.0×	0.026	G6PD
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes	1	84.0×	0.033	PIEZO1
Complement cascade	1	79.3×	0.033	CD46
ABC transporters in lipid homeostasis	1	75.1×	0.033	ABCG5
Axon guidance	2	11.3×	0.033	SPTA1, SPTB
Nervous system development	2	10.7×	0.033	SPTA1, SPTB
ABC transporter disorders	1	54.9×	0.040	ABCG5
Purinergic signaling in leishmaniasis infection	1	52.9×	0.040	C3
Membrane Trafficking	2	9.3×	0.040	SPTA1, SPTB
NR1H2 and NR1H3-mediated signaling	1	49.2×	0.040	ABCG5
Vesicle-mediated transport	2	8.7×	0.040	SPTA1, SPTB
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	44.6×	0.042	PIEZO1
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	38.6×	0.047	ABCG5
Signal Transduction	3	3.8×	0.064	SPTA1, SPTB, ABCG5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
actin filament capping	2	383.0×	0.001	SPTA1, SPTB
complement activation, classical pathway	2	135.9×	0.004	C3, CD46
obsolete sequestering of extracellular ligand from receptor	1	2106.5×	0.008	CD46
ribose phosphate biosynthetic process	1	2106.5×	0.008	G6PD
response to iron(III) ion	1	1053.2×	0.008	G6PD
regulation of triglyceride biosynthetic process	1	1053.2×	0.008	C3
negative regulation of intestinal phytosterol absorption	1	1053.2×	0.008	ABCG5
pentose biosynthetic process	1	1053.2×	0.008	G6PD
negative regulation of intestinal cholesterol absorption	1	1053.2×	0.008	ABCG5
complement-dependent cytotoxicity	1	1053.2×	0.008	C3
positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	1	1053.2×	0.008	G6PD
positive regulation of T cell proliferation	2	64.8×	0.008	SPTA1, CD46
positive regulation of type IIa hypersensitivity	1	702.2×	0.008	C3
positive regulation of activation of membrane attack complex	1	702.2×	0.008	C3
oviduct epithelium development	1	702.2×	0.008	C3
vertebrate eye-specific patterning	1	702.2×	0.008	C3
porphyrin-containing compound biosynthetic process	1	526.6×	0.009	SPTA1
pentose-phosphate shunt, oxidative branch	1	526.6×	0.009	G6PD
complement-mediated synapse pruning	1	526.6×	0.009	C3
sterol transport	1	351.1×	0.014	ABCG5
negative regulation of complement activation, classical pathway	1	300.9×	0.014	CD46
positive regulation of apoptotic cell clearance	1	300.9×	0.014	C3
positive regulation of D-glucose transmembrane transport	1	263.3×	0.014	C3
positive regulation of cell-cell adhesion mediated by integrin	1	263.3×	0.014	PIEZO1
positive regulation of transforming growth factor beta production	1	263.3×	0.014	CD46
lymphocyte homeostasis	1	234.1×	0.014	SPTA1
positive regulation of integrin activation	1	234.1×	0.014	PIEZO1
positive regulation of memory T cell differentiation	1	234.1×	0.014	CD46
actin cytoskeleton organization	2	19.8×	0.014	SPTA1, SPTB
pentose-phosphate shunt	1	191.5×	0.015	G6PD

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 8 evidence-associated genes (50%) 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
G6PD	BREXANOLONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
G6PD	8	4
SPTA1	0	0
SPTB	0	0
C3	0	0
ABCG5	0	0
PLEKHG3	0	0
PIEZO1	0	0
CD46	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BREXANOLONE	4	G6PD
APOMORPHINE HYDROCHLORIDE	4	G6PD
PRASTERONE	4	G6PD
EBSELEN	3	G6PD
PICEID	2	G6PD
SEPRANOLONE	2	G6PD
PREGNENOLONE	1	G6PD
16.ALPHA.-BROMOEPIANDROSTERONE	1	G6PD

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
G6PD	49	Binding:46, ADMET:2, Functional:1
PIEZO1	17	Binding:17
C3	15	Binding:15
PLEKHG3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
C3	3.4.21.47	alternative-complement-pathway C3/C5 convertase
G6PD	1.1.1.49	glucose-6-phosphate dehydrogenase (NADP+)

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
G6PD	1

Chemical tractability of cohort targets

8 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)
BREXANOLONE	4	G6PD
APOMORPHINE HYDROCHLORIDE	4	G6PD
PRASTERONE	4	G6PD
EBSELEN	3	G6PD
PICEID	2	G6PD
SEPRANOLONE	2	G6PD
PREGNENOLONE	1	G6PD
16.ALPHA.-BROMOEPIANDROSTERONE	1	G6PD

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	G6PD
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	C3, ABCG5, CD46
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	SPTA1, SPTB, PLEKHG3, PIEZO1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SPTA1	0	—
SPTB	0	—
C3	15	—
ABCG5	0	—
PLEKHG3	1	—
PIEZO1	17	—
CD46	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00061568	PHASE1/PHASE2	UNKNOWN	Improving the Results of Bone Marrow Transplantation for Patients With Severe Congenital Anemias
NCT04902833	Not specified	COMPLETED	Acquired Pyruvate Kinase Deficiency In Clonal Myeloid Neoplasms

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALEMTUZUMAB	4	1