Hereditary spherocytosis

Summary

Hereditary spherocytosis (MONDO:0019350) is a disease (an umbrella term covering 5 Mondo subtypes) caused by ANK1 (GenCC Definitive), with 7 cohort genes and 3 clinical trials. The dominant Reactome pathway is Interaction between L1 and Ankyrins (3 cohort genes).

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Causal gene: ANK1 (GenCC Definitive)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 7
• ClinVar variants: 18
• Phenotypes (HPO): 27
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000		Europe	Validated
Point prevalence	1-5 / 10 000	50	Germany	Validated
Prevalence at birth	1-5 / 10 000	20	United States	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0005502	Increased red cell osmotic fragility	Very frequent (80-99%)
HP:0000952	Jaundice	Frequent (30-79%)
HP:0000980	Pallor	Frequent (30-79%)
HP:0001081	Cholelithiasis	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0001923	Reticulocytosis	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0002904	Hyperbilirubinemia	Frequent (30-79%)
HP:0004444	Spherocytosis	Frequent (30-79%)
HP:0005525	Spontaneous hemolytic crises	Frequent (30-79%)
HP:0011900	Hypofibrinogenemia	Frequent (30-79%)
HP:0025548	Increased mean corpuscular hemoglobin concentration	Frequent (30-79%)
HP:0100724	Hypercoagulability	Frequent (30-79%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001723	Restrictive cardiomyopathy	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0001978	Extramedullary hematopoiesis	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0003326	Myalgia	Occasional (5-29%)
HP:0025143	Chills	Occasional (5-29%)
HP:0040186	Maculopapular exanthema	Occasional (5-29%)
HP:0001510	Growth delay	Very rare (<1-4%)
HP:0001997	Gout	Very rare (<1-4%)
HP:0003270	Abdominal distention	Very rare (<1-4%)
HP:0200042	Skin ulcer	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	hereditary spherocytosis
Mondo ID	MONDO:0019350
MeSH	D013103
Orphanet	822
DOID	DOID:12971
ICD-10-CM	D58.0
ICD-11	1305248013
NCIT	C97074
SNOMED CT	55995005
UMLS	C0037889
MedGen	52450
GARD	0006639
MedDRA	10019904
NORD	777
Is cancer (heuristic)	no

Also known as: congenital spherocytic hemolytic anaemia · congenital spherocytosis · hereditary spherocytosis · Minkowski-Chauffard disease · spherocytic anaemia

Data availability: 18 ClinVar variants · 7 GenCC gene-disease records · 33 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

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

Related subtypes (22): 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, congenital dyserythropoietic anemia, X-linked congenital hemolytic anemia, hemolytic disease of fetus and newborn, RH-induced

Subtypes (5): hereditary spherocytosis type 2, hereditary spherocytosis type 1, hereditary spherocytosis type 3, hereditary spherocytosis type 4, hereditary spherocytosis type 5

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

18 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 5 likely pathogenic, 3 pathogenic, 1 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1030630	NM_003126.4(SPTA1):c.4339-99C>T	SPTA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
996360	NM_003126.4(SPTA1):c.6788+11C>T	SPTA1	Pathogenic	criteria provided, multiple submitters, no conflicts
522602	NM_001355436.2(SPTB):c.6095T>C (p.Leu2032Pro)	SPTB	Pathogenic	no assertion criteria provided
624571	NM_001355436.2(SPTB):c.4063G>T (p.Glu1355Ter)	SPTB	Pathogenic	criteria provided, single submitter
2505368	NM_000037.4(ANK1):c.1638C>A (p.Tyr546Ter)	ANK1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3362889	NM_000037.4(ANK1):c.3072T>A (p.Tyr1024Ter)	ANK1	Likely pathogenic	criteria provided, single submitter
2505370	NM_000175.5(GPI):c.283-2A>G	GPI	Likely pathogenic	criteria provided, single submitter
2505369	NM_001355436.2(SPTB):c.2163_2164dup (p.Ser722fs)	SPTB	Likely pathogenic	criteria provided, single submitter
523132	NM_001355436.2(SPTB):c.6194_6195dup (p.Ala2066fs)	SPTB	Likely pathogenic	criteria provided, single submitter
2439043	NM_000037.4(ANK1):c.3829G>C (p.Val1277Leu)	ANK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2683016	NM_000037.4(ANK1):c.1054A>G (p.Arg352Gly)	ANK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2749545	NM_000037.4(ANK1):c.5299G>A (p.Glu1767Lys)	ANK1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779468	NM_000037.4(ANK1):c.2190G>C (p.Lys730Asn)	ANK1	Uncertain significance	criteria provided, single submitter
3779469	NM_000037.4(ANK1):c.2248G>A (p.Val750Met)	ANK1	Uncertain significance	criteria provided, single submitter
3779473	NM_000037.4(ANK1):c.2717C>T (p.Ala906Val)	ANK1	Uncertain significance	criteria provided, single submitter
3779478	NM_000037.4(ANK1):c.3964C>T (p.Arg1322Cys)	ANK1	Uncertain significance	criteria provided, single submitter
3893687	NM_000342.4(SLC4A1):c.1527_1541del (p.Ser510_Arg514del)	SLC4A1	Uncertain significance	criteria provided, single submitter
1326902	NM_001355436.2(SPTB):c.4520G>T (p.Gly1507Val)	SPTB	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 46 · Orphanet: 14 · 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
ANK1	Definitive	Autosomal dominant	hereditary spherocytosis	8
SPTA1	Definitive	Autosomal recessive	hereditary spherocytosis type 3	13
EPB42	Strong	Autosomal recessive	hereditary spherocytosis type 5	3
SLC4A1	Strong	Autosomal dominant	hereditary spherocytosis type 4	15
SPTB	Strong	Autosomal dominant	hereditary spherocytosis type 2	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC4A1	Orphanet:3202	Dehydrated hereditary stomatocytosis
SLC4A1	Orphanet:398088	Hereditary cryohydrocytosis with normal stomatin
SLC4A1	Orphanet:822	Hereditary spherocytosis
SLC4A1	Orphanet:93608	Autosomal dominant distal renal tubular acidosis
SLC4A1	Orphanet:93610	Distal renal tubular acidosis with anemia
SLC4A1	Orphanet:98868	Southeast Asian ovalocytosis
SPTA1	Orphanet:288	Hereditary elliptocytosis
SPTA1	Orphanet:822	Hereditary spherocytosis
SPTB	Orphanet:288	Hereditary elliptocytosis
SPTB	Orphanet:822	Hereditary spherocytosis
ANK1	Orphanet:251066	8p11.2 deletion syndrome
ANK1	Orphanet:822	Hereditary spherocytosis
EPB42	Orphanet:822	Hereditary spherocytosis
GPI	Orphanet:712	Hemolytic anemia due to glucophosphate isomerase deficiency

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC4A1	HGNC:11027	ENSG00000004939	P02730	Band 3 anion transport protein	gencc,clinvar
SPTA1	HGNC:11272	ENSG00000163554	P02549	Spectrin alpha chain, erythrocytic 1	gencc,clinvar
SPTB	HGNC:11274	ENSG00000070182	P11277	Spectrin beta chain, erythrocytic	gencc,clinvar
ANK1	HGNC:492	ENSG00000029534	P16157	Ankyrin-1	gencc,clinvar
EPB42	HGNC:3381	ENSG00000166947	P16452	Protein 4.2	gencc
GNPDA1	HGNC:4417	ENSG00000113552	P46926	Glucosamine-6-phosphate deaminase 1	clinvar
GPI	HGNC:4458	ENSG00000105220	P06744	Glucose-6-phosphate isomerase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC4A1	Band 3 anion transport protein	Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein.
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.
ANK1	Ankyrin-1	Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.
EPB42	Protein 4.2	Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.
GNPDA1	Glucosamine-6-phosphate deaminase 1	Catalyzes 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…
GPI	Glucose-6-phosphate isomerase	Isomerase 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.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.43

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
Scaffold/PPI	2	4.9×	0.220
Enzyme (other)	2	3.4×	0.220
Antibody/Immunoglobulin	1	4.2×	0.289
Other/Unknown	2	0.5×	0.968

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC4A1	Other/Unknown	no		Anion_exchange, Anion_exchange_1, HCO3_transpt_euk
SPTA1	Scaffold/PPI	no		SH3_domain, Spectrin_repeat, EF_hand_dom
SPTB	Other/Unknown	no		Actinin_actin-bd_CS, CH_dom, Spectrin_repeat
ANK1	Scaffold/PPI	no		Death_dom, ZU5_dom, Ankyrin_rpt
EPB42	Antibody/Immunoglobulin	yes	2.3.2.13	Transglutaminase_N, Transglutaminase-like, Transglutaminase_C
GNPDA1	Enzyme (other)	yes	3.5.99.6	Glucosamine6P_isomerase, Glc/Gal-6P_isomerase, Glucosamine6P_isomerase_CS
GPI	Enzyme (other)	yes	5.3.1.9	G6P_Isomerase, Phosphoglucose_isomerase_CS, G6P_Isomerase_C

Expression context

Cohort genes with no expression data: 0.

7 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bone marrow	3
bone marrow cell	3
trabecular bone tissue	2
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1
body of tongue	1
skeletal muscle tissue of rectus abdominis	1
triceps brachii	1
blood	1
adult organism	1
nephron tubule	1
type B pancreatic cell	1
apex of heart	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC4A1	161	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell
SPTA1	147	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell
SPTB	220	broad	marker	gastrocnemius, hindlimb stylopod muscle, muscle of leg
ANK1	226	broad	marker	skeletal muscle tissue of rectus abdominis, triceps brachii, body of tongue
EPB42	91	tissue_specific	marker	blood, bone marrow, bone marrow cell
GNPDA1	298	ubiquitous	marker	type B pancreatic cell, nephron tubule, adult organism
GPI	286	ubiquitous	marker	apex of heart, right adrenal gland, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 10.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANK1	5,705
GPI	4,709
GNPDA1	1,687
SLC4A1	1,598
SPTA1	1,551
SPTB	1,079
EPB42	923

Intra-cohort edges

A	B	Sources
ANK1	EPB42	string_interaction
ANK1	SLC4A1	biogrid_interaction, intact, string_interaction
ANK1	SPTA1	biogrid_interaction, string_interaction
ANK1	SPTB	biogrid_interaction, string_interaction
EPB42	SLC4A1	biogrid_interaction, intact, string_interaction
EPB42	SPTA1	string_interaction
GNPDA1	GPI	string_interaction
SLC4A1	SPTA1	intact, string_interaction
SLC4A1	SPTB	intact
SPTA1	SPTB	intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLC4A1	P02730	54
ANK1	P16157	21
EPB42	P16452	13
GPI	P06744	13
SPTB	P11277	6
SPTA1	P02549	3
GNPDA1	P46926	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 36. Enrichment computed across 7 evidence-associated genes (6 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 6 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	3	184.2×	1e-05	SPTA1, SPTB, ANK1
ER to Golgi Anterograde Transport	3	66.4×	1e-04	SPTA1, SPTB, ANK1
L1CAM interactions	3	60.1×	1e-04	SPTA1, SPTB, ANK1
COPI-mediated anterograde transport	3	54.9×	1e-04	SPTA1, SPTB, ANK1
Transport to the Golgi and subsequent modification	3	51.4×	1e-04	SPTA1, SPTB, ANK1
Asparagine N-linked glycosylation	3	30.1×	5e-04	SPTA1, SPTB, ANK1
Glycolysis	2	95.2×	8e-04	GNPDA1, GPI
NCAM signaling for neurite out-growth	2	90.6×	8e-04	SPTA1, SPTB
Axon guidance	3	22.6×	8e-04	SPTA1, SPTB, ANK1
Nervous system development	3	21.5×	9e-04	SPTA1, SPTB, ANK1
Membrane Trafficking	3	18.5×	0.001	SPTA1, SPTB, ANK1
Vesicle-mediated transport	3	17.4×	0.001	SPTA1, SPTB, ANK1
Defective SLC4A1 causes hereditary spherocytosis type 4 (HSP4), distal renal tubular acidosis (dRTA) and dRTA with hemolytic anemia (dRTA-HA)	1	1903.3×	0.001	SLC4A1
MAPK1/MAPK3 signaling	2	43.8×	0.002	SPTA1, SPTB
MAPK family signaling cascades	2	34.3×	0.003	SPTA1, SPTB
Post-translational protein modification	3	9.6×	0.006	SPTA1, SPTB, ANK1
NrCAM interactions	1	271.9×	0.008	ANK1
RAF/MAP kinase cascade	2	20.4×	0.008	SPTA1, SPTB
Neurofascin interactions	1	237.9×	0.008	ANK1
Erythrocytes take up oxygen and release carbon dioxide	1	211.5×	0.008	SLC4A1
O2/CO2 exchange in erythrocytes	1	211.5×	0.008	SLC4A1
CHL1 interactions	1	211.5×	0.008	ANK1
Bicarbonate transporters	1	190.3×	0.008	SLC4A1
Developmental Biology	3	7.2×	0.008	SPTA1, SPTB, ANK1
Erythrocytes take up carbon dioxide and release oxygen	1	146.4×	0.010	SLC4A1
Metabolism of proteins	3	6.2×	0.012	SPTA1, SPTB, ANK1
Gluconeogenesis	1	73.2×	0.018	GPI
SLC transporter disorders	1	34.0×	0.037	SLC4A1
Disorders of transmembrane transporters	1	23.2×	0.053	SLC4A1
R-HSA-425393	1	21.6×	0.053	SLC4A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of glycolytic process through fructose-6-phosphate	2	802.5×	1e-04	SLC4A1, GPI
actin filament capping	2	437.7×	3e-04	SPTA1, SPTB
response to increased oxygen levels	1	2407.4×	0.007	SLC4A1
pH elevation	1	2407.4×	0.007	SLC4A1
D-glucosamine catabolic process	1	802.5×	0.009	GNPDA1
porphyrin-containing compound biosynthetic process	1	601.9×	0.009	SPTA1
intracellular monoatomic ion homeostasis	1	601.9×	0.009	SLC4A1
hemoglobin metabolic process	1	601.9×	0.009	EPB42
negative regulation of urine volume	1	601.9×	0.009	SLC4A1
carbohydrate metabolic process	2	38.8×	0.009	GNPDA1, GPI
regulation of cell shape	2	35.1×	0.009	SPTA1, EPB42
protein localization to plasma membrane	2	31.1×	0.009	SLC4A1, ANK1
N-acetylglucosamine catabolic process	1	481.5×	0.010	GNPDA1
N-acetylneuraminate catabolic process	1	343.9×	0.012	GNPDA1
maintenance of epithelial cell apical/basal polarity	1	343.9×	0.012	ANK1
actin cytoskeleton organization	2	22.6×	0.013	SPTA1, SPTB
lymphocyte homeostasis	1	267.5×	0.014	SPTA1
hemostasis	1	240.7×	0.014	GPI
UDP-N-acetylglucosamine biosynthetic process	1	218.9×	0.014	GNPDA1
plasma membrane phospholipid scrambling	1	218.9×	0.014	SLC4A1
monoatomic anion transport	1	200.6×	0.014	SLC4A1
modification of postsynaptic actin cytoskeleton	1	200.6×	0.014	SPTB
erythrocyte homeostasis	1	185.2×	0.014	GPI
glucose 6-phosphate metabolic process	1	185.2×	0.014	GPI
fructose 6-phosphate metabolic process	1	160.5×	0.016	GPI
plasma membrane organization	1	126.7×	0.019	SPTA1
erythrocyte maturation	1	120.4×	0.019	EPB42
bicarbonate transport	1	114.6×	0.019	SLC4A1
response to muscle stretch	1	109.4×	0.019	GPI
response to immobilization stress	1	104.7×	0.019	GPI

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 7

Druggability breadth: 2 of 7 evidence-associated genes (29%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SLC4A1	0	0
SPTA1	0	0
SPTB	0	0
ANK1	0	0
EPB42	0	0
GNPDA1	0	0
GPI	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
GPI	2	Binding:2
GNPDA1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EPB42	2.3.2.13	protein-glutamine gamma-glutamyltransferase
GNPDA1	3.5.99.6	glucosamine-6-phosphate deaminase
GPI	5.3.1.9	glucose-6-phosphate isomerase

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; 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	3	EPB42, GNPDA1, GPI
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	SLC4A1, SPTA1, SPTB, ANK1

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)
SLC4A1	0	—
SPTA1	0	—
SPTB	0	—
ANK1	0	—
EPB42	0	—
GNPDA1	1	—
GPI	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01141621	Not specified	TERMINATED	The Dallas Hereditary Spherocytosis Cohort Study
NCT01276561	Not specified	WITHDRAWN	Single Incision Versus Standard Laparoscopic Splenectomy
NCT04451785	Not specified	COMPLETED	Hereditary Spherocytosis and Vascular Function