HBD (hemoglobin subunit delta)

Gene

• Entrez ID: 3045
• Gene name: Hemoglobin subunit delta
• Gene symbol: HBD
• Synonyms (NCBI Gene): HBK
• Chromosome: 11
• Chromosome location: 11p15.4
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs34224604	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs34430836	G>C	Pathogenic, other	Coding sequence variant, missense variant
rs34975911	A>G	Pathogenic	Upstream transcript variant
rs35152987	C>A,T	Pathogenic, other	Coding sequence variant, missense variant
rs35324967	C>A,G,T	Pathogenic	Downstream transcript variant
rs35518301	T>C	Pathogenic	Upstream transcript variant
rs35654785	C>G	Pathogenic	Coding sequence variant, missense variant
rs35661168	T>A	Pathogenic	Upstream transcript variant
rs35887507	C>G,T	Pathogenic	Coding sequence variant, missense variant, stop gained
rs63750345	A>T	Pathogenic	Intron variant

Transcription factors

Transcription factor	Regulation	Reference
ELF4	Activation	15286431

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005344	Function	Oxygen carrier activity	IBA
GO:0005344	Function	Oxygen carrier activity	IEA
GO:0005515	Function	Protein binding	IPI	25416956, 32296183, 32814053
GO:0005829	Component	Cytosol	TAS
GO:0005833	Component	Hemoglobin complex	IBA
GO:0005833	Component	Hemoglobin complex	IEA
GO:0005833	Component	Hemoglobin complex	IPI	15449937
GO:0005833	Component	Hemoglobin complex	TAS	7555018
GO:0015670	Process	Carbon dioxide transport	NAS	15449937
GO:0015671	Process	Oxygen transport	IBA
GO:0015671	Process	Oxygen transport	IDA	11307949
GO:0015671	Process	Oxygen transport	IEA
GO:0019825	Function	Oxygen binding	IEA
GO:0020037	Function	Heme binding	IBA
GO:0020037	Function	Heme binding	IEA
GO:0031721	Function	Hemoglobin alpha binding	IBA
GO:0031838	Component	Haptoglobin-hemoglobin complex	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0048821	Process	Erythrocyte development	IBA
GO:0072562	Component	Blood microparticle	HDA	22516433

Other IDs

• MIM: 142000
• HGNC: 4829
• e!Ensembl: ENSG00000223609

Protein

• UniProt ID: P02042
• Protein name: Hemoglobin subunit delta (Delta-globin) (Hemoglobin delta chain)
• Protein function: Involved in oxygen transport from the lung to the various peripheral tissues.
• PDB: 1SHR, 1SI4
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00042	Globin	8 → 112	Globin	Domain

• Tissue specificity: TISSUE SPECIFICITY: Red blood cells.
• Sequence:

  MVHLTPEEKTAVNALWGKVNVDAVGGEALGRLLVVYPWTQRFFESFGDLSSPDAVMGNPK
  VKAHGKKVLGAFSDGLAHLDNLKGTFSQLSELHCDKLHVDPENFRLLGNVLVCVLARNFG
  KEFTPQMQAAYQKVVAGVANALAHKYH

• Sequence length: 147

Pathways

Reactome:

Factors involved in megakaryocyte development and platelet production

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
delta Thalassemia	Pathogenic	rs35324967, rs35654785, rs34975911, rs36023765, rs34430836, rs63750345, rs35661168	RCV000016219 RCV000016223 RCV000016224 RCV000016225 RCV000016226 RCV000016237 RCV000016238	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Delta-0-thalassemia	Pathogenic	rs34224604, rs35887507	RCV004797763 RCV000016229	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Delta-plus-thalassemia	Pathogenic	rs35518301	RCV000016240	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HEMOGLOBIN A(2) BABINGA	Pathogenic	rs35849348	RCV000016189	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HEMOGLOBIN A(2) GROVETOWN	Pathogenic	rs34430836	RCV000016227	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hepatocellular carcinoma	Pathogenic	rs36023765	RCV005887529	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CHLORACNE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DELTA ZERO THALASSEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DELTA-BETA THALASSEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Delta-beta-thalassemia	Conflicting classifications of pathogenicity	ClinVar CTD, Orphanet CTD, Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
DELTA-THALASSEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL HYPERALDOSTERONISM TYPE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Fetal hemoglobin quantitative trait locus 1	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Glucocorticoid-remediable aldosteronism	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HBD-related disorder	Uncertain significance; Conflicting classifications of pathogenicity; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) ADRIA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) AGRINIO	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) CAMPANIA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) CANADA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) CAPRI	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) COBURG	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) CORFU	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) FITZROY	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) FLATBUSH	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) HONAI	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) INDONESIA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) LUCANIA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) MANZANARES	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) MELBOURNE	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) METAPONTO	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) MONREALE	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) NIIGATA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) NINIVE	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) NYU	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) PARKVILLE	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) PELENDRI	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) PUGLIA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) ROOSEVELT	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) SANT' ANTIOCO	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) SPHAKIA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) TROODOS	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) VICTORIA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) WRENS	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) YIALOUSA	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) YOKOSHIMA	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2) ZAGREB	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN A(2)-PRIME	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN B(2)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN E DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN FLATBUSH (GEORGIA)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN LEPORE-BETA-THALASSEMIA SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN NYU	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEPORE-BETA-THALASSEMIA SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thalassemia	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Erythroblastic Leukemia	Erythroblastic Leukemia	BEFREE	1732019		★☆☆☆☆ Found in Text Mining only
alpha Thalassemia	Alpha thalassemia	Pubtator	32901995, 35741722	Associate	★☆☆☆☆ Found in Text Mining only
alpha-Thalassemia	alpha Thalassemia	LHGDN	15449937		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	Pubtator	37548329	Associate	★☆☆☆☆ Found in Text Mining only
Anemia hypochromic microcytic	Hypochromic microcytic anemia	Pubtator	4078867	Associate	★☆☆☆☆ Found in Text Mining only
Anemia Iron Deficiency	Iron deficiency anemia	Pubtator	32901995	Associate	★☆☆☆☆ Found in Text Mining only
Anemia Sickle Cell	Sickle cell anemia	Pubtator	14587045	Associate	★☆☆☆☆ Found in Text Mining only
Anemia, Sickle Cell	Anemia	BEFREE	7708766, 8916973		★☆☆☆☆ Found in Text Mining only
beta Thalassemia	beta Thalassemia	BEFREE	10473880, 1349739, 1398286, 17145605, 17916081, 19609526, 25352644, 30309760, 6288819, 6820119		★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	10814985, 14587045, 17222202, 22801970, 2458154, 30777047, 32068918, 32770585, 32901995, 34828427, 35741722, 40140352, 4078867, 7682618	Associate	★☆☆☆☆ Found in Text Mining only
Beta thalassemia intermedia	beta Thalassemia	BEFREE	23872310		★☆☆☆☆ Found in Text Mining only
beta^+^ Thalassemia	beta Thalassemia	BEFREE	10473880, 1349739, 1398286, 17145605, 17916081, 19609526, 25352644, 30309760, 6288819, 6820119		★☆☆☆☆ Found in Text Mining only
beta^0^ Thalassemia	beta Thalassemia	BEFREE	14587045, 17222202, 17339197, 25218786, 2767680, 6820119, 7682618, 923569		★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Brain Neoplasms	BEFREE	26935297		★☆☆☆☆ Found in Text Mining only
Carcinoma Basal Cell	Basal cell carcinoma	Pubtator	16796735	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	24732135	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Basal Cell	Carcinoma	BEFREE	16796735		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	26038828		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	26038828	Associate	★☆☆☆☆ Found in Text Mining only
Delta-Beta Thalassemia	Delta-Beta Thalassemia	ORPHANET_DG	1301204		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Delta-Beta Thalassemia	Delta-Beta Thalassemia	BEFREE	1520881, 2458154, 2982369, 6179097, 6323412		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Delta-beta-thalassemia	Delta-Beta Thalassemia	Orphanet			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
delta-Thalassemia	Delta-Thalassemia	BEFREE	1309671, 1742490, 6292847		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
delta-Thalassemia	Delta-Thalassemia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
delta^0^ Thalassemia	Delta-Thalassemia	BEFREE	6307432, 6323412		★☆☆☆☆ Found in Text Mining only
delta^0^ Thalassemia	Delta-Thalassemia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	36339449	Associate	★☆☆☆☆ Found in Text Mining only
Distal myopathy Nonaka type	Distal myopathy	Pubtator	37797812	Inhibit	★☆☆☆☆ Found in Text Mining only
Glycogen Storage Disease 0 Muscle	Glycogen storage disease	Pubtator	17222202	Associate	★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	28007020	Associate	★☆☆☆☆ Found in Text Mining only
Hemoglobin E disease	Hemoglobin E Disease	GWASCAT_DG	20183929		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hemoglobin F Disease	Hemoglobinopathy	BEFREE	2982369, 31044540, 6179097		★☆☆☆☆ Found in Text Mining only
Hemoglobin Lepore-beta-thalassemia syndrome	Hemoglobin Lepore-Beta-Thalassemia Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hemoglobinopathies	Hemoglobinopathy	Pubtator	21220744, 22028795, 35741722, 6275383	Associate	★☆☆☆☆ Found in Text Mining only
Hemoglobinopathies	Hemoglobinopathy	BEFREE	23872310, 25218786, 27461962		★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory bowel disease	Pubtator	21042595	Associate	★☆☆☆☆ Found in Text Mining only
Intrahepatic Cholestasis of Pregnancy	Intrahepatic cholestasis of pregnancy	Pubtator	37054625	Associate	★☆☆☆☆ Found in Text Mining only
Iron deficiency anemia	Iron deficiency anemia	BEFREE	25043855		★☆☆☆☆ Found in Text Mining only
Iron-Refractory Iron Deficiency Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative	Myeloid Leukemia	BEFREE	2456661		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	16796735		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	26038828		★☆☆☆☆ Found in Text Mining only
MELORHEOSTOSIS, ISOLATED	Melorheostosis	BEFREE	3470293, 7524502		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	29534847		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	34504491	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29303375		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	29534847		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	26694100, 29132311	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteoporosis	Osteoporosis	Pubtator	37874452	Associate	★☆☆☆☆ Found in Text Mining only
Thalassemia	Thalassemia	Pubtator	1742490, 26516624, 31044540, 34828427, 37548329, 40140352	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Thalassemia Intermedia	Thalassemia	BEFREE	17222202		★☆☆☆☆ Found in Text Mining only