HBD

Summary

HBD (hemoglobin subunit delta, HGNC:4829) is a protein-coding gene on chromosome 11p15.4, encoding Hemoglobin subunit delta (P02042). Involved in oxygen transport from the lung to the various peripheral tissues.

The delta (HBD) and beta (HBB) genes are normally expressed in the adult: two alpha chains plus two beta chains constitute HbA, which in normal adult life comprises about 97% of the total hemoglobin. Two alpha chains plus two delta chains constitute HbA-2, which with HbF comprises the remaining 3% of adult hemoglobin. Five beta-like globin genes are found within a 45 kb cluster on chromosome 11 in the following order: 5’-epsilon–Ggamma–Agamma–delta–beta-3’. Mutations in the delta-globin gene are associated with beta-thalassemia.

Source: NCBI Gene 3045 — RefSeq curated summary.

At a glance

• Gene–disease (curated): delta-beta-thalassemia (Supportive, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 77 total — 12 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_000519

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4829
Approved symbol	HBD
Name	hemoglobin subunit delta
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	HBK
Ensembl gene	ENSG00000223609
Ensembl biotype	protein_coding
OMIM	142000
Entrez	3045

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000292901, ENST00000417377, ENST00000429817, ENST00000643122, ENST00000650601

RefSeq mRNA: 1 — MANE Select: NM_000519 NM_000519

CCDS: CCDS31376

Canonical transcript exons

ENST00000650601 — 3 exons

Exon	Start	End
ENSE00001057389	5233991	5234213
ENSE00001484514	5232838	5233092
ENSE00001762970	5234342	5234483

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 99.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 55.3773 / max 46249.4645, expressed in 171 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118354	52.5409	150
118356	1.2864	43
118359	0.5146	20
118357	0.4010	17
118365	0.2669	49
118355	0.1733	16
118358	0.0653	7
118351	0.0614	11
118360	0.0344	4
118366	0.0143	6

Top tissues by expression

279 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	99.98	gold quality
bone marrow	UBERON:0002371	99.51	gold quality
bone marrow cell	CL:0002092	99.41	gold quality
monocyte	CL:0000576	97.86	gold quality
mononuclear cell	CL:0000842	97.65	gold quality
bone element	UBERON:0001474	97.30	gold quality
blood	UBERON:0000178	96.60	gold quality
leukocyte	CL:0000738	94.26	gold quality
vena cava	UBERON:0004087	90.26	gold quality
endothelial cell	CL:0000115	88.73	silver quality
periodontal ligament	UBERON:0008266	82.77	gold quality
spleen	UBERON:0002106	80.04	gold quality
decidua	UBERON:0002450	77.86	silver quality
gluteal muscle	UBERON:0002000	73.48	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.70	gold quality
superficial temporal artery	UBERON:0001614	71.47	silver quality
apex of heart	UBERON:0002098	70.63	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	70.35	gold quality
germinal epithelium of ovary	UBERON:0001304	70.21	silver quality
placenta	UBERON:0001987	70.12	gold quality
stromal cell of endometrium	CL:0002255	69.58	gold quality
olfactory bulb	UBERON:0002264	69.48	gold quality
choroid plexus epithelium	UBERON:0003911	69.43	silver quality
right lung	UBERON:0002167	69.32	gold quality
right lobe of liver	UBERON:0001114	67.98	gold quality
frontal pole	UBERON:0002795	67.44	gold quality
diaphragm	UBERON:0001103	67.37	gold quality
middle frontal gyrus	UBERON:0002702	67.09	gold quality
paraflocculus	UBERON:0005351	67.07	gold quality
upper lobe of left lung	UBERON:0008952	66.87	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 18.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	15188.65
E-GEOD-150728	yes	12226.99
E-MTAB-9221	yes	9290.52
E-MTAB-8495	yes	5152.62
E-CURD-55	yes	4409.66
E-MTAB-8884	yes	2675.68
E-HCAD-8	yes	2605.48
E-CURD-112	yes	2214.57
E-HCAD-1	yes	1214.84
E-GEOD-76312	yes	1072.14
E-MTAB-9067	yes	722.11
E-CURD-126	yes	531.82
E-HCAD-4	yes	174.52
E-HCAD-6	yes	59.65
E-HCAD-9	yes	14.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL11A, ELF4, GATA1, KLF1, KLF2, NFE2

miRNA regulators (miRDB)

16 targeting HBD, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-5000-5P	97.40	66.11	1055
HSA-MIR-1182	96.41	64.89	336
HSA-MIR-6806-5P	96.37	68.74	587
HSA-MIR-584-5P	95.82	68.05	848

Literature-anchored findings (GeneRIF, showing 26)

• The 5’ breakapoint of the (deltabeta)(0) thalassemia deletion in a compound heterozygote was located in the second intron of the delta globin gene. (PMID:11860449)
• Hb A2-Monreale [delta146(HC3)His–>Arg]is a novel delta chain variant. (PMID:11939506)
• alternate mRNA species in adult erythroid cells; mRNA encodes an additional 145 nt in the upstream untranslated region, suggesting an alternative site of transcriptional initiation and transcription through the previously defined promoter (PMID:15234005)
• The atomic coordinates of the delta-chain of hemoglobin A2 (R2 state) are used to model the structure of hemoglobin homotetramer delta 4, which occurs in rare hemoglobin H disease. (PMID:15449937)
• Deletion pf this geneis a common, and possibly the predominant beta-thalassemia mutation of the Austroasiatic Lao Theung population. (PMID:15757827)
• characterization of the delta-globin gene alleles and of RFLP-haplotypes, SNPs and one microsatellite associated with them in 231 carriers originating principally from East Sicily; Seventeen alleles were identified, of which five were new (PMID:18221842)
• Borderline HbA(2) is not a rare event in a population with a high prevalence of beta-thalassemia carriers (PMID:18603555)
• Unusually low levels of HBA2 in a compound heterozygote can be explained from the functional inhibition of the HBD gene, in cis to the HBG1 gene, bearing the nd-HPFH mutation. (PMID:18615450)
• Hb A2 IVS-I-5 (G > C) beta-thalassemia mutation phenotype in 289 carriers was reported. (PMID:18932068)
• Data report the study of 23 double heterozygotes for beta- and delta-thalassemia defects or variants. Eight delta-globin and seven beta-globin alleles were detected. All the alleles were associated with RFLP haplotype background. (PMID:19609526)
• Studies present five new hemoglobin (Hb) variants, Hb Canuts, Hb Ambroise Pare, Hb Beaujolais, Hb Monplaisir and Hb(A2)-North Africa. (PMID:19657833)
• Family study reporting normal Hemoglobin A expression in a beta-goblin carrier (beta(+) IVSI-5 (G to C) mutation) with microcytosis and hypochromiadue, due to co-inheritance of mutation in the delta-globin gene (delta codon 12 (AAT–>AAA) HbA2-NYU). (PMID:21194254)
• This report describes a novel missense mutation in delta-globin (HBD: c.323G>A, Gly > Asp) in an Indian family with heterozygous beta-thalassemia with normal HbA(2) levels. (PMID:22477537)
• A functional promoter polymorphism of the delta-globin gene is a specific marker of the Arab-Indian haplotype (PMID:22641479)
• Twenty-one different mutations were detected, and of these 12 have not been previously described. (PMID:23215833)
• Data indicate that a delta-globin mutation was suspected in both patients. (PMID:23806011)
• The expression of the activated delta-globin gene in a beta-thalassemia mice model greatly improves the phenotype, validating the delta-globin chain as a therapeutic target for beta-hemoglobinopathies. (PMID:23872310)
• Blood donor homozygous for Hb D Los Angeles. (PMID:25217459)
• Association of polymorphisms in the HBG1-HBD intergenic region with HbF levels. (PMID:32068918)
• delta-Globin Chain Variants Associated with Decreased Hb A2 Levels: A National Reference Laboratory Experience. (PMID:33054450)
• delta-Hemoglobinopathies in Thailand: screening, molecular basis, genotype-phenotype interaction, and implication for prevention and control of thalassemia. (PMID:33834283)
• Delta-globin gene expression improves sickle cell disease in a humanised mouse model. (PMID:34046885)
• Analysis of delta-globin gene alleles in Tunisians: description of three new delta-thalassemia mutations. (PMID:34341901)
• Molecular characterization of a novel homozygous deletion in beta-globin cluster causing (deltabeta)[0]-Thalassemia among Tunisian family. (PMID:36214153)
• Detecting rare thalassemia in children with anemia using third-generation sequencing. (PMID:37548329)
• Mutational spectrum of HBD gene in the Chinese population: Description of 36 mutations including 11 novel variants. (PMID:37605839)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	hbae5	ENSDARG00000045142
danio_rerio	hbaa2	ENSDARG00000069735
danio_rerio	si:ch211-5k11.8	ENSDARG00000079078
danio_rerio	hbae3	ENSDARG00000079305
danio_rerio	hbae1.2	ENSDARG00000088330
danio_rerio	hbae1.3	ENSDARG00000089124
danio_rerio	hbae1.1	ENSDARG00000089475
danio_rerio	hbaa1	ENSDARG00000097011
drosophila_melanogaster	glob1	FBGN0027657
caenorhabditis_elegans		WBGENE00008996
caenorhabditis_elegans		WBGENE00077763

Paralogs (11): HBQ1 (ENSG00000086506), HBZ (ENSG00000130656), CYGB (ENSG00000161544), HBA2 (ENSG00000188536), HBG2 (ENSG00000196565), MB (ENSG00000198125), HBA1 (ENSG00000206172), HBM (ENSG00000206177), HBE1 (ENSG00000213931), HBG1 (ENSG00000213934), HBB (ENSG00000244734)

Protein

Protein identifiers

Hemoglobin subunit delta — P02042 (reviewed: P02042)

Alternative names: Delta-globin, Hemoglobin delta chain

All UniProt accessions (5): A0N071, C9JRG0, E9PEW8, E9PFT6, P02042

UniProt curated annotations — full annotation on UniProt →

Function. Involved in oxygen transport from the lung to the various peripheral tissues.

Subunit / interactions. Heterotetramer of two alpha chains and two delta chains in adult hemoglobin A2 (HbA2). HbA2 represents less than 3.5% of adult hemoglobin.

Tissue specificity. Red blood cells.

Similarity. Belongs to the globin family.

RefSeq proteins (1): NP_000510* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000971	Globin	Domain
IPR002337	Hemoglobin_b	Family
IPR009050	Globin-like_sf	Homologous_superfamily
IPR012292	Globin/Proto	Homologous_superfamily
IPR050056	Hemoglobin_oxygen_transport	Family

Pfam: PF00042

UniProt features (63 total): sequence variant 43, helix 11, binding site 2, modified residue 2, turn 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1SHR	X-RAY DIFFRACTION	1.88
1SI4	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02042-F1	96.81	0.97

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 64 (distal binding residue); 93 (proximal binding residue)

Post-translational modifications (2): 2, 51

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 109 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GNF2_PRDX2, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MYELOID_CELL_DEVELOPMENT, GOBP_ERYTHROCYTE_HOMEOSTASIS, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, HUMMERICH_MALIGNANT_SKIN_TUMOR_UP, GNF2_ANK1, GOBP_ONE_CARBON_COMPOUND_TRANSPORT, GOBP_GAS_TRANSPORT, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP, GOBP_OXYGEN_TRANSPORT, GNF2_SPTA1, WELCH_GATA1_TARGETS, MODULE_88

GO Biological Process (3): carbon dioxide transport (GO:0015670), oxygen transport (GO:0015671), erythrocyte development (GO:0048821)

GO Molecular Function (6): oxygen carrier activity (GO:0005344), oxygen binding (GO:0019825), heme binding (GO:0020037), hemoglobin alpha binding (GO:0031721), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), hemoglobin complex (GO:0005833), haptoglobin-hemoglobin complex (GO:0031838), blood microparticle (GO:0072562), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
gas transport	2
protein-containing complex	2
one-carbon compound transport	1
erythrocyte differentiation	1
myeloid cell development	1
oxygen transport	1
oxygen binding	1
molecular carrier activity	1
small molecule binding	1
tetrapyrrole binding	1
hemoglobin binding	1
cation binding	1
binding	1
cytoplasm	1
cytosol	1
extracellular region	1

Protein interactions and networks

STRING

1058 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HBD	DEFB103A	P81534	720
HBD	DEFB4A	O15263	716
HBD	EXOC6	Q8TAG9	713
HBD	DEFB1	P60022	669
HBD	BCL11A	Q9H165	649
HBD	DEFB104A	Q8WTQ1	579
HBD	AHSP	Q9NZD4	576
HBD	CCR6	P51684	576
HBD	CCRL2	O00421	575
HBD	OR51B6	Q9H340	556
HBD	SLC25A37	Q9NYZ2	549
HBD	CYP11B1	P15538	543
HBD	KLF1	Q13351	533
HBD	HP	P00737	524
HBD	CYP2B6	P20813	513

IntAct

61 interactions, top by confidence:

A	B	Type	Score
HBZ	HBD	psi-mi:“MI:0915”(physical association)	0.720
HBD	HBQ1	psi-mi:“MI:0915”(physical association)	0.720
HBQ1	HBD	psi-mi:“MI:0915”(physical association)	0.720
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
HBD	HBA1	psi-mi:“MI:0915”(physical association)	0.560
HBD	NME4	psi-mi:“MI:0915”(physical association)	0.560
CCDC26	HBD	psi-mi:“MI:0915”(physical association)	0.560
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
INSL6	MYCBP2	psi-mi:“MI:0914”(association)	0.530
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
TNFSF8	NME4	psi-mi:“MI:0914”(association)	0.350
UPF3A	CASC3	psi-mi:“MI:0914”(association)	0.350
GDPD1	CP	psi-mi:“MI:0914”(association)	0.350
MERTK	LANCL1	psi-mi:“MI:0914”(association)	0.350
rs27_rs27l_human	HBD	psi-mi:“MI:0914”(association)	0.350

BioGRID (87): HBQ1 (Two-hybrid), HBZ (Two-hybrid), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS), HBD (Affinity Capture-MS)

ESM2 similar proteins: B2KHZ4, D0VX08, P02042, P02048, P02049, P02055, P02059, P02060, P02061, P02070, P02072, P02074, P08535, P09840, P09909, P10893, P11756, P11758, P14388, P14391, P14392, P15449, P18982, P18983, P18989, P19886, P21201, P23602, P24660, P26916, P28781, P60524, P60525, P60526, P61772, P61773, P61774, P61775, P68011, P68012

Diamond homologs: B2KHZ4, B3EWE2, D0VX08, P02024, P02025, P02026, P02028, P02029, P02030, P02032, P02033, P02035, P02036, P02038, P02039, P02040, P02042, P02044, P02047, P02048, P02049, P02051, P02055, P02057, P02058, P02061, P07412, P08259, P08535, P09840, P09909, P10893, P11752, P11754, P11756, P11758, P13557, P13558, P14388, P14391

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NFE2	“up-regulates quantity by expression”	HBD	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

77 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	1
Uncertain significance	30
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
15044	NM_000519.3(HBD):c.410G>A (p.Gly137Asp)	Pathogenic
15065	NM_000519.4(HBD):c.179del (p.Lys60fs)	Pathogenic
15068	NC_000011.10:g.5232765C>T	Pathogenic
15071	NM_000519.4(HBD):c.92G>C (p.Arg31Thr)	Pathogenic
15072	NC_000011.10:g.5234560A>G	Pathogenic
15073	NM_000519.4(HBD):c.316-2A>G	Pathogenic
15076	NM_000519.4(HBD):c.113G>A (p.Trp38Ter)	Pathogenic
15084	NM_000519.4(HBD):c.315+6T>A	Pathogenic
15085	NC_000011.10:g.5234559T>A	Pathogenic
15087	NC_000011.10:g.5234514T>C	Pathogenic
686921	GRCh37/hg19 11p15.4(chr11:5254694-5262112)x1	Pathogenic
815400	GRCh37/hg19 11p15.4(chr11:5112523-5336304)x1	Pathogenic
2573436	NC_000011.9:g.(5248030_5248159)_(5254322_5255220)del	Likely pathogenic

SpliceAI

187 predictions. Top by Δscore:

Variant	Effect	Δscore
11:5233986:CTCA:C	donor_loss	1.0000
11:5233987:TCA:T	donor_loss	1.0000
11:5233988:CA:C	donor_loss	1.0000
11:5233989:A:AC	donor_gain	1.0000
11:5233989:AC:A	donor_gain	1.0000
11:5233990:C:CC	donor_gain	1.0000
11:5233990:C:CT	donor_loss	1.0000
11:5233990:CC:C	donor_gain	1.0000
11:5233985:ACTC:A	donor_loss	0.9900
11:5234213:TC:T	acceptor_loss	0.9900
11:5234214:C:CC	acceptor_gain	0.9900
11:5234214:CT:C	acceptor_loss	0.9900
11:5234215:T:G	acceptor_loss	0.9900
11:5234357:C:CT	donor_gain	0.9900
11:5233093:C:CC	acceptor_gain	0.9800
11:5233979:T:TA	donor_gain	0.9800
11:5233989:ACC:A	donor_gain	0.9800
11:5233990:CCC:C	donor_gain	0.9800
11:5233990:CCCTG:C	donor_gain	0.9800
11:5234209:GTAAT:G	acceptor_gain	0.9800
11:5234324:TATA:T	donor_gain	0.9800
11:5234325:ATAA:A	donor_gain	0.9800
11:5233089:AGAG:A	acceptor_gain	0.9700
11:5233090:GAG:G	acceptor_gain	0.9700
11:5233092:GC:G	acceptor_loss	0.9700
11:5233093:C:A	acceptor_loss	0.9700
11:5233094:T:C	acceptor_loss	0.9700
11:5233990:CCCT:C	donor_gain	0.9700
11:5234210:TAAT:T	acceptor_gain	0.9700
11:5234220:G:GC	acceptor_gain	0.9700

AlphaMissense

960 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:5233994:G:C	F104L	0.999
11:5233994:G:T	F104L	0.999
11:5233996:A:G	F104L	0.999
11:5232972:A:G	Y146H	0.998
11:5233995:A:G	F104S	0.998
11:5234177:A:C	F43L	0.998
11:5234177:A:T	F43L	0.998
11:5234179:A:G	F43L	0.998
11:5234027:G:C	H93Q	0.997
11:5234027:G:T	H93Q	0.997
11:5234029:G:C	H93D	0.997
11:5234112:C:A	G65V	0.997
11:5234112:C:T	G65D	0.997
11:5234168:A:C	F46L	0.997
11:5234168:A:T	F46L	0.997
11:5234170:A:G	F46L	0.997
11:5233995:A:C	F104C	0.996
11:5233996:A:C	F104V	0.996
11:5233997:G:C	N103K	0.996
11:5233997:G:T	N103K	0.996
11:5234029:G:T	H93N	0.996
11:5233085:C:T	G108D	0.995
11:5233086:C:G	G108R	0.995
11:5234116:G:C	H64D	0.995
11:5234399:A:T	V12D	0.995
11:5233996:A:T	F104I	0.994
11:5234007:T:C	D100G	0.994
11:5234016:A:G	L97P	0.994
11:5234031:A:G	L92P	0.994
11:5233085:C:A	G108V	0.993

dbSNP variants (sampled 300 via entrez): RS1000187587 (11:5233887 T>C), RS1000194743 (11:5233858 C>A,T), RS1000495996 (11:5233637 C>G,T), RS1001087198 (11:5232397 G>C,T), RS1001642288 (11:5233518 T>C), RS1001869234 (11:5235129 A>C,T), RS1001875925 (11:5234865 A>G), RS1003393762 (11:5236163 T>C), RS1003543880 (11:5236335 G>A,C), RS1004325971 (11:5236070 G>A), RS1005038187 (11:5236026 T>C), RS1005337172 (11:5232855 T>C), RS1008675883 (11:5235407 G>A), RS1008792087 (11:5235654 A>G), RS1009248450 (11:5235367 C>T)

Disease associations

OMIM: gene MIM:142000 | disease phenotypes: MIM:103900

GenCC curated gene-disease

Disease	Classification	Inheritance
delta-beta-thalassemia	Supportive	Autosomal recessive

Mondo (4): delta-beta-thalassemia (MONDO:0016489), thalassemia (MONDO:0000984), glucocorticoid-remediable aldosteronism (MONDO:0007080), hemoglobinopathy (MONDO:0044348)

Orphanet (3): Delta-beta-thalassemia (Orphanet:231237), Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome (Orphanet:251380), Familial hyperaldosteronism type I (Orphanet:403)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0001903	Anemia
HP:0001935	Microcytic anemia
HP:0011902	Abnormal hemoglobin

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000532_1	Beta thalassemia/hemoglobin E disease	3.000000e-15
GCST001779_5	Hematology traits	5.000000e-11
GCST001782_4	Mean corpuscular hemoglobin concentration	1.000000e-13
GCST003122_3	Hemoglobin levels	4.000000e-86
GCST003122_7	Hemoglobin levels	1.000000e-25
GCST007005_5	Logical memory (immediate recall) in normal cognition	3.000000e-06
GCST007006_9	Logical memory (delayed recall) in normal cognition	1.000000e-07
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004509	hemoglobin measurement
EFO:0005845	hemoglobin A2 measurement
EFO:0004576	fetal hemoglobin measurement
EFO:0004874	memory performance

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D013789	Thalassemia	C15.378.050.141.150.875; C15.378.420.826; C16.320.070.875; C16.320.365.826
C562716	Delta-Beta Thalassemia (supp.)
C563177	Glucocorticoid-Remediable Aldosteronism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment, affects expression, increases abundance	3
Progesterone	affects cotreatment, increases expression	2
ginger extract	affects cotreatment, affects expression, increases abundance	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
hydroquinone	affects binding, decreases reaction	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Clorgyline	increases expression	1
Demecolcine	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Ozone	affects expression, increases abundance	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	increases expression	1
Valproic Acid	affects expression	1
Vincristine	decreases expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

7 cell lines: 5 transformed cell line, 2 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_BT41	GM20480	Transformed cell line	Male
CVCL_BT42	GM20481	Transformed cell line	Male
CVCL_GY15	GM01368	Finite cell line	Male
CVCL_GY94	LAZ-177	Transformed cell line	Sex unspecified
CVCL_HM35	GM02568	Transformed cell line	Male
CVCL_M994	GM02064	Transformed cell line	Male
CVCL_N053	GM06342	Finite cell line	Male

Clinical trials (associated diseases)

154 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00346242	PHASE4	COMPLETED	Evaluation of Efficacy of Zoledronic Acid in Patients With Haemoglobin Syndromes (Thalassemia and Sicle Cell Anaemia) and Risk of Skeletal Events
NCT00707850	PHASE4	COMPLETED	Pegasys® Plus Ribavirin in Thalassemic Patients With Hepatitis C Virus Infection
NCT01250951	PHASE4	COMPLETED	This Study Will Evaluate Efficacy and Safety of Deferasirox in Patients With Myelodysplastic Syndromes (MDS), Thalassemia and Rare Anemia Types Having Transfusion-induced Iron Overload.
NCT02069886	PHASE4	WITHDRAWN	Effect of Deferasirox on Endocrine Complications in Subjects With Transfusion Dependent Thalassemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT03032666	PHASE4	COMPLETED	Sofosbuvir/Ledipasvir for Hepatitis C Genotype 1-6 in Patients With Transfusion-Dependent Thalassemia: An Open Label Trial
NCT03095326	PHASE4	COMPLETED	Pneumococcal Vaccination for Splenectomised Thalassemia Major Patients in Indonesia
NCT03117192	PHASE4	COMPLETED	Zinc Supplementation on Cellular Immunity in Thalassemia Major
NCT03374111	PHASE4	UNKNOWN	Colla Corii Asini Treating Anemia in Pregnant Women With Thalassemia(Presenting the Syndrome of Blood Deficiency)
NCT03392298	PHASE4	UNKNOWN	Study on the Mechanism of Colla Corri Asini in the Treatment of Thalassemia Patients With Pregnancy Anemia
NCT03402191	PHASE4	UNKNOWN	L-arginine Versus Sildenafil in Children With Beta Thalassemia Associated With Pulmonary Hypertension
NCT00673608	PHASE4	COMPLETED	Magnetic Resonance Imaging (MRI) Assessments of the Heart and Liver Iron Load in Patients With Transfusion Induced Iron Overload
NCT00887081	PHASE4	UNKNOWN	Interferon and Ribavirin Treatment in Patients With Hemoglobinopathies
NCT00235391	PHASE3	COMPLETED	Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload
NCT01395199	PHASE3	COMPLETED	Amlodipine in the Prevention and Treatment of Iron Overload in Patients With Thalassemia Major
NCT04208529	PHASE3	ENROLLING_BY_INVITATION	A Long-term Follow-up Study in Participants Who Received CTX001
NCT05356195	PHASE3	ACTIVE_NOT_RECRUITING	Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Transfusion-Dependent β-Thalassemia (TDT)
NCT05477563	PHASE3	RECRUITING	Evaluation of Efficacy and Safety of a Single Dose of CTX001 in Participants With Transfusion-Dependent β-Thalassemia and Severe Sickle Cell Disease
NCT06609226	PHASE3	RECRUITING	A Research Study Looking at Long-term Treatment With Etavopivat in People With Sickle Cell Disease or Thalassaemia
NCT00000585	PHASE3	COMPLETED	Penicillin Prophylaxis in Sickle Cell Disease (PROPS)
NCT00000586	PHASE3	COMPLETED	Multicenter Study of Hydroxyurea in Patients With Sickle Cell Anemia (MSH)
NCT00000592	PHASE3	COMPLETED	Stroke Prevention in Sickle Cell Anemia (STOP 1)
NCT05329649	PHASE3	ACTIVE_NOT_RECRUITING	Evaluation of Safety and Efficacy of CTX001 in Pediatric Participants With Severe Sickle Cell Disease (SCD)
NCT00000588	PHASE2	COMPLETED	Chelation Therapy of Iron Overload With Pyridoxal Isonicotinoyl Hydrazone
NCT00000595	PHASE2	COMPLETED	Evaluation of Subcutaneous Desferrioxamine as Treatment for Transfusional Hemochromatosis
NCT00034528	PHASE2	TERMINATED	Stem Cell Transplantation After Reduced-Dose Chemotherapy for Patients With Sickle Cell Disease or Thalassemia
NCT00040417	PHASE2	TERMINATED	Bone Marrow Transplant From Donor Using Less Toxic Conditioning for Patient With High Risk Hemoglobinopathies
NCT00040469	PHASE2	TERMINATED	Bone Marrow Transplant From Related Donor for Patients With High Risk Hemoglobinopathies
NCT00125788	PHASE2	COMPLETED	L-Glutamine Therapy for Sickle Cell Anemia and Sickle ß0 Thalassemia
NCT00153985	PHASE2	COMPLETED	Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies
NCT00502788	PHASE2	COMPLETED	Evaluating the Safety of Two Medications to Treat Hepatitis C in People With Thalassemia (The HepC Study)
NCT00586209	PHASE2	TERMINATED	L-Glutamine Therapy for Sickle Cell Anemia
NCT00661726	PHASE2	COMPLETED	Evaluating the Safety and Effectiveness of Decitabine in People With Thalassemia Intermedia
NCT00901199	PHASE2	COMPLETED	Combined Chelation Therapy in Patients With Transfusion Dependent Thalassemia and Iron Overload
NCT00957931	PHASE2	COMPLETED	Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs
NCT01005576	PHASE2	COMPLETED	Reduced Intensity Transplant Conditioning Regimen for Severe Thalassemia
NCT01048905	PHASE2	COMPLETED	Glutamine Therapy for Hemolysis-Associated Pulmonary Hypertension
NCT02105766	PHASE2	ACTIVE_NOT_RECRUITING	Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People With Higher Risk of Transplant Failure
NCT02512679	PHASE2	TERMINATED	Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
NCT02995707	PHASE2	UNKNOWN	The Effective and Safety of Thalidomide in NTDT