HBG1 (hemoglobin subunit gamma 1)

Gene

• Entrez ID: 3047
• Gene name: Hemoglobin subunit gamma 1
• Gene symbol: HBG1
• Synonyms (NCBI Gene): HBG-T2, HBGA, HBGR, HSGGL1, PRO2979
• Chromosome: 11
• Chromosome location: 11p15.4
• Summary: The gamma globin genes (HBG1 and HBG2) are normally expressed in the fetal liver, spleen and bone marrow. Two gamma chains together with two alpha chains constitute fetal hemoglobin (HbF) which is normally replaced by adult hemoglobin (HbA) at birth. In s

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs35321913	G>C	Pathogenic	Upstream transcript variant
rs35378915	C>T	Pathogenic	Upstream transcript variant
rs35710727	A>G	Pathogenic	Upstream transcript variant
rs35983258	G>A	Pathogenic	Upstream transcript variant
rs281860601	G>A,C,T	Pathogenic	Upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT736102	hsa-miR-3619-5p	Microarray, qRT-PCR	31541070
MIRT2241119	hsa-miR-214	CLIP-seq
MIRT2241120	hsa-miR-4291	CLIP-seq
MIRT2241121	hsa-miR-4695-3p	CLIP-seq
MIRT2241122	hsa-miR-761	CLIP-seq
MIRT2241123	hsa-miR-922	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
GATA1	Unknown	12609092;16200778;2336386
KLF3	Unknown	12621553
POU2F1	Repression	2336386

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005344	Function	Oxygen carrier activity	IBA
GO:0005344	Function	Oxygen carrier activity	IDA	22096240
GO:0005344	Function	Oxygen carrier activity	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005833	Component	Hemoglobin complex	IBA
GO:0005833	Component	Hemoglobin complex	IEA
GO:0005833	Component	Hemoglobin complex	IPI	6683087, 11514664
GO:0005833	Component	Hemoglobin complex	ISS
GO:0015670	Process	Carbon dioxide transport	NAS	881729, 7543751
GO:0015671	Process	Oxygen transport	IBA
GO:0015671	Process	Oxygen transport	IDA	7543751, 22096240
GO:0015671	Process	Oxygen transport	IEA
GO:0015671	Process	Oxygen transport	NAS	881729
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

Other IDs

• MIM: 142200
• HGNC: 4831
• e!Ensembl: ENSG00000213934

Protein

• UniProt ID: P69891
• Protein name: Hemoglobin subunit gamma-1 (Gamma-1-globin) (Hb F Agamma) (Hemoglobin gamma-1 chain) (Hemoglobin gamma-A chain)
• Protein function: Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
• PDB: 1I3D, 1I3E
• 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:

  MGHFTEEDKATITSLWGKVNVEDAGGETLGRLLVVYPWTQRFFDSFGNLSSASAIMGNPK
  VKAHGKKVLTSLGDAIKHLDDLKGTFAQLSELHCDKLHVDPENFKLLGNVLVTVLAIHFG
  KEFTPEVQASWQKMVTAVASALSSRYH

• 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
British HPFH	Pathogenic	rs35710727	RCV000016175	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Greek HPFH	Pathogenic	rs35378915	RCV000016173	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary persistence of fetal hemoglobin	Pathogenic	rs35378915, rs35710727, rs35983258, rs35321913, rs281860601, rs1554921759	RCV001814965 RCV001814966 RCV001814967 RCV001814968 RCV001814969 RCV001814970	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Sardinian HPFH	Pathogenic	rs35378915	RCV000016172	★★★★☆ 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-BETA THALASSEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DELTA-BETA-THALASSEMIA	—	CTD, Orphanet CTD, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Fetal hemoglobin quantitative trait locus 1	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HBG1 POLYMORPHISM	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HBG1-related disorder	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (BASKENT)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (BEECH ISLAND)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (BONAIRE)	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (CALLUNA)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (COBB)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (DAMMAM)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (DICKINSON)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (FOREST PARK)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (FUKUYAMA)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (HULL)	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (IWATA)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (IZUMI)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (JAMAICA)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (JIANGSU)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (KOTOBUKI)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (KUALA LUMPUR)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (MACEDONIA-I)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (PENDERGRASS)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (PORDENONE)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (SARDINIA)	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (SIENA)	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (TEXAS I)	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (VICTORIA JUBILEE)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (WOODSTOCK)	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (XIN-SU)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (XINJIANG)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F (YAMAGUCHI)	other	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEMOGLOBIN F DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Erythroblastic Leukemia	Erythroblastic Leukemia	BEFREE	10373600, 1689192, 1709381, 17114178, 1848707, 1993224, 2339058, 2369550, 2445753, 2457030, 29046485, 30257864, 3165297, 3463509, 7828600, 8108408, 8353292, 8400240		★☆☆☆☆ Found in Text Mining only
Acute Megakaryocytic Leukemias	Megakaryocytic Leukemia	BEFREE	7647001		★☆☆☆☆ Found in Text Mining only
alpha Thalassemia	Alpha thalassemia	Pubtator	17488699	Associate	★☆☆☆☆ Found in Text Mining only
alpha-Thalassemia	alpha Thalassemia	BEFREE	16519704, 17488699, 18951049, 3332112, 9163586		★☆☆☆☆ Found in Text Mining only
alpha^+^ Thalassemia	alpha Thalassemia	BEFREE	16519704, 17488699, 18951049, 3332112, 9163586		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	BEFREE	10688844, 20712788, 21390308, 26603726, 28190779, 7686036		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	Pubtator	20712788, 21390308, 26603726, 29333458, 6584911	Associate	★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia Sickle Cell	Sickle cell anemia	Pubtator	10373600, 15287957, 15537646, 15828874, 17662889, 18667698, 19327156, 19346141, 20495075, 20602015, 20932329, 22537182, 24157834, 2462713, 26509275, 26849705, 2723072, 27405777, 27525524, 28800727, 28971909, 2917199, 2920205, 29437638, 29519807, 30412705, 30911135, 32068918, 32917636, 33958780, 34069401, 34706496, 35147495, 35240686, 35667093, 36560719, 37895276, 40665149, 6205021, 6248872, 8608254, 8630419	Associate	★☆☆☆☆ Found in Text Mining only
Anemia, Sickle Cell	Anemia	BEFREE	10373600, 12124399, 1379347, 15040425, 15287957, 15534852, 15537646, 16378095, 16513230, 16607652, 1688883, 17662889, 18667698, 19346141, 19474450, 19777196, 2039830, 20602015, 20932329, 22042865, 23416702, 24112139, 24371119, 2441778, 2473801, 25681747, 2580306, 25931013, 25986606, 2723072, 27525524, 27718361, 28776729, 28971909, 29046485, 29255069, 29610478, 29884740, 30038942, 30125603, 30412705, 30911135, 31273412, 31688634, 31698466, 6248872, 9236157, 9768357		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	35138035	Associate	★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	23361909		★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	11172039, 11559936, 12176917, 12210807, 15287957, 16304356, 17614826, 17654503, 19327156, 19346141, 20495075, 20712788, 20716049, 20932329, 21390308, 21725495, 22287841, 2418679, 2430648, 25842369, 26024726, 26377036, 26509275, 27525524, 28303002, 28669403, 28851297, 29186860, 29333458, 30911135, 31406232, 32068918, 33216968, 33227819, 33368182, 33879818, 34091621, 34398996, 35240686, 35269949, 35667093, 35839944, 36333351, 36614221, 36639729, 37895276, 38218889, 3828530, 40197981, 6210198, 6327288, 7677966, 8630419, 9163586	Associate	★☆☆☆☆ Found in Text Mining only
beta Thalassemia	beta Thalassemia	BEFREE	11559936, 12411297, 12738678, 1384315, 1483699, 16338486, 16513230, 16803575, 16814578, 16939628, 1725229, 17614826, 18951049, 1932755, 19346141, 19777196, 23233592, 23416702, 2458154, 2473801, 27525524, 30010219, 31115947, 31789406, 6183586, 698126, 7686036, 7703040, 993355		★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	1932755	Stimulate	★☆☆☆☆ Found in Text Mining only
Beta thalassemia intermedia	beta Thalassemia	BEFREE	12411297, 16803575, 17654503		★☆☆☆☆ Found in Text Mining only
beta^+^ Thalassemia	beta Thalassemia	BEFREE	12411297, 12738678, 1384315, 1483699, 16338486, 16513230, 16803575, 16814578, 16939628, 17614826, 1932755, 19346141, 19777196, 23233592, 23416702, 2473801, 27525524, 30010219, 31115947, 31789406, 6183586, 698126, 7686036, 7703040, 993355		★☆☆☆☆ Found in Text Mining only
beta^0^ Thalassemia	beta Thalassemia	BEFREE	11559936, 21144779, 2415188, 2423109, 2430648, 2456521, 26897028, 3778425, 3828530, 6327288, 7680922		★☆☆☆☆ Found in Text Mining only
Congenital heart disease	Congenital Heart Disease	BEFREE	26823361		★☆☆☆☆ Found in Text Mining only
Delta-Beta Thalassemia	Delta-Beta Thalassemia	ORPHANET_DG	18932066		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Delta-Beta Thalassemia	Delta-Beta Thalassemia	BEFREE	2452784, 2822174, 2982369, 6179097, 6196781		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Delta-beta-thalassemia	Delta-Beta Thalassemia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastroenteritis	Gastroenteritis	Pubtator	36560739	Associate	★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	26823361	Associate	★☆☆☆☆ Found in Text Mining only
Hematologic Diseases	Hematologic disease	Pubtator	15287957	Associate	★☆☆☆☆ Found in Text Mining only
Hematological Disease	Hematological Disease	BEFREE	15287957, 19777196		★☆☆☆☆ Found in Text Mining only
Hemoglobin C Disease	Hemoglobin c disease	Pubtator	29437638	Associate	★☆☆☆☆ Found in Text Mining only
Hemoglobin F Disease	Hemoglobinopathy	BEFREE	11074532, 11285460, 12093744, 1571556, 15944728, 1688466, 1688505, 1689192, 1693523, 16952470, 17114178, 17183675, 18096417, 2291547, 23337982, 2430647, 2451123, 2458313, 2458563, 2462941, 2467208, 2474800, 2478223, 2481268, 2578619, 2578620, 2578805, 27525524, 27718361, 2982369, 30355263, 3165297, 3181130, 3463509, 3601670, 6175332, 6179097, 6196781, 7592674, 7679879, 7686501, 7687430, 7687855, 9668525		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hemoglobin F Disease	Hemoglobinopathy	ORPHANET_DG	24144231, 6210198		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hemoglobinopathies	Hemoglobinopathy	BEFREE	10087991, 10090929, 10575551, 11074532, 12393583, 12533814, 16292549, 18379999, 20837550, 21075284, 24371119, 24589262, 24589264, 26603726, 29389946, 7579419		★☆☆☆☆ Found in Text Mining only
Hemoglobinopathies	Hemoglobinopathy	Pubtator	11421306, 19460472, 26509275, 26603726, 28669403, 32107331, 32755585, 33050052, 33272312, 33938942, 35192776, 37989316, 38218889	Associate	★☆☆☆☆ Found in Text Mining only
Hemoglobinopathies	Hemoglobinopathy	Pubtator	32576837	Inhibit	★☆☆☆☆ Found in Text Mining only
Hereditary gingival fibromatosis	Hereditary Gingival Fibromatosis	BEFREE	17075716		★☆☆☆☆ Found in Text Mining only
Hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome	Hereditary Persistence Of Fetal Hemoglobin-Beta-Thalassemia Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary persistence of fetal hemoglobin-sickle cell disease syndrome	Hereditary Persistence Of Fetal Hemoglobin-Sickle Cell Disease Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	26686224	Associate	★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	26686224		★☆☆☆☆ Found in Text Mining only
Hyperuricemia	Hyperuricemia	BEFREE	26686224		★☆☆☆☆ Found in Text Mining only
Hyperuricemia	Hyperuricemia	Pubtator	26686224	Associate	★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	19187226	Stimulate	★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	25885573, 33958780	Associate	★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	BEFREE	28190779		★☆☆☆☆ Found in Text Mining only
Iron-Refractory Iron Deficiency Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Juvenile Myelomonocytic Leukemia	Myelomonocytic Leukemia	BEFREE	16778141, 2456661, 28749240		★☆☆☆☆ Found in Text Mining only
LEOPARD Syndrome	Leopard syndrome	Pubtator	26686224	Associate	★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	15287957		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	25211130, 7795240, 7920413	Associate	★☆☆☆☆ Found in Text Mining only
Lymphedema	Lymphedema	Pubtator	26969357	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	CTD_human_DG	19208208		★☆☆☆☆ Found in Text Mining only
MELORHEOSTOSIS, ISOLATED	Melorheostosis	BEFREE	8630419, 9787182		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	26686224		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	26679864	Associate	★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	16292549		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia	Myeloid Leukemia	BEFREE	9133617		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	17097070, 7795240		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	CTD_human_DG	25475535		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic Neoplasms	CTD_human_DG	19208208		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sicca Syndrome	Sjogren`s Syndrome	BEFREE	1673815, 2039830		★☆☆☆☆ Found in Text Mining only
Stroke	Stroke	Pubtator	35138035	Associate	★☆☆☆☆ Found in Text Mining only
Sweet Syndrome	Sweet Syndrome	BEFREE	1673815, 2039830		★☆☆☆☆ Found in Text Mining only
synovial sarcoma	Synovial sarcoma	BEFREE	1673815, 2039830		★☆☆☆☆ Found in Text Mining only
Thalassemia	Thalassemia	Pubtator	11421306, 15536151, 1932755, 21725495, 21875313, 27591578, 28851297, 2997715, 33272312, 34690349, 36560719, 36888630, 40140352, 6306596, 7677966	Associate	★☆☆☆☆ Found in Text Mining only
Thalassemia Intermedia	Thalassemia	BEFREE	1725229, 18951049, 24112139, 30422819, 3207629		★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	29263092		★☆☆☆☆ Found in Text Mining only