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 some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains ... See more...

Aliases for HBG2 Gene

Aliases for HBG2 Gene

  • Hemoglobin Subunit Gamma 2 2 3 5
  • Hemoglobin Subunit Gamma-2 3 4
  • Hemoglobin Gamma-2 Chain 3 4
  • Hemoglobin Gamma-G Chain 3 4
  • Hemoglobin, Gamma G 2 3
  • Gamma-2-Globin 3 4
  • Hb F Ggamma 3 4
  • HBG-T1 2 3
  • G-Gamma Globin Paulinia 3
  • Abnormal Hemoglobin 3
  • Gamma-Globin Chain 3
  • Methemoglobin 3
  • Gamma Globin 3
  • TNCY 3
  • HBG2 5

External Ids for HBG2 Gene

Previous GeneCards Identifiers for HBG2 Gene

  • GC11M006018
  • GC11M005572
  • GC11M005229
  • GC11M005216
  • GC11M005235
  • GC11M005230
  • GC11M005274
  • GC11M004934
  • GC11M005256
  • GC11M005280
  • GC11M005299
  • GC11M005349

Summaries for HBG2 Gene

Entrez Gene Summary for HBG2 Gene

  • 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 some beta-thalassemias and related conditions, gamma chain production continues into adulthood. The two types of gamma chains differ at residue 136 where glycine is found in the G-gamma product (HBG2) and alanine is found in the A-gamma product (HBG1). The former is predominant at birth. The order of the genes in the beta-globin cluster is: 5'- epsilon -- gamma-G -- gamma-A -- delta -- beta--3'. [provided by RefSeq, Jul 2008]

GeneCards Summary for HBG2 Gene

HBG2 (Hemoglobin Subunit Gamma 2) is a Protein Coding gene. Diseases associated with HBG2 include Cyanosis, Transient Neonatal and Fetal Hemoglobin Quantitative Trait Locus 1. Among its related pathways are p70S6K Signaling and IL-2 Pathway. Gene Ontology (GO) annotations related to this gene include iron ion binding and oxygen binding. An important paralog of this gene is ENSG00000284931.

UniProtKB/Swiss-Prot Summary for HBG2 Gene

  • Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.

Gene Wiki entry for HBG2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HBG2 Gene

Genomics for HBG2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for HBG2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J005504 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE 600.7 +0.6 574 2.5 ARHGAP35 IKZF1 JUND DDX20 PKNOX1 DPF2 HDAC1 SOX6 TCF12 GTF2E2 HBE1 HBG2 OR51B5 lnc-HBE1-1 DNHD1 UBQLNL FAM160A2 OR52D1 ENSG00000239920
GH11J005254 Promoter/Enhancer 1.2 EPDnew Ensembl dbSUPER 615.7 +249.8 249819 2 CREB1 IKZF1 PKNOX1 ZNF24 ATF7 POLR2A TAF9B EHMT2 NFIC ARNT HBG2 ENSG00000284931 HBB ENSG00000221031 HBG1 lnc-OR51B4-3 OR51B4 ENSG00000239920
GH11J005255 Promoter/Enhancer 0.8 EPDnew dbSUPER 600.1 +251.2 251197 0.1 NKRF POLR2A THRAP3 HDAC1 ENSG00000284931 HBG2 HBB ENSG00000221031 HBG1 ENSG00000239920
GH11J005253 Promoter/Enhancer 0.5 EPDnew dbSUPER 600.1 +252.2 252244 0.1 ENSG00000284931 HBG2 HBG1
GH11J005272 Enhancer 1.6 FANTOM5 Ensembl ENCODE dbSUPER 79 +223.0 223004 21.6 CTCF ATF7 RFX1 LEF1 IKZF1 BACH1 JUND ETV6 DDX20 MTA2 lnc-OR51B4-3 HBD HBG2 HBG1 HBB HBBP1 ENSG00000224091 ENSG00000221031 OR51V1 OR52A4P
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HBG2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HBG2

Top Transcription factor binding sites by QIAGEN in the HBG2 gene promoter:
  • c-Myb
  • GATA-1
  • HNF-4alpha1
  • TBP

Genomic Locations for HBG2 Gene

Genomic Locations for HBG2 Gene
252,418 bases
Minus strand
392,600 bases
Minus strand

Genomic View for HBG2 Gene

Genes around HBG2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HBG2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HBG2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HBG2 Gene

Proteins for HBG2 Gene

  • Protein details for HBG2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Hemoglobin subunit gamma-2
    Protein Accession:
    Secondary Accessions:
    • A8MZE0
    • P02096
    • P62027
    • Q14491
    • Q68NH9
    • Q96FH6
    • Q96FH7

    Protein attributes for HBG2 Gene

    147 amino acids
    Molecular mass:
    16126 Da
    Quaternary structure:
    • Heterotetramer of two alpha chains and two gamma chains in fetal hemoglobin (Hb F).
    • Sequence=AAB50159.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for HBG2 Gene

neXtProt entry for HBG2 Gene

Post-translational modifications for HBG2 Gene

  • Acetylation of Gly-2 converts Hb F to the minor Hb F1.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for HBG2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for HBG2 Gene

Domains & Families for HBG2 Gene

Gene Families for HBG2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for HBG2 Gene

  • Leghaemoglobin
  • Beta haemoglobin signature

Suggested Antigen Peptide Sequences for HBG2 Gene

GenScript: Design optimal peptide antigens:
  • Gamma globin (A1EGU3_HUMAN)
  • Gamma-globin chain (B7UCU6_HUMAN)
  • G-gamma globin Paulinia variant (D3GKD9_HUMAN)
  • Hemoglobin, gamma G (D9YZU9_HUMAN)
  • G gamma globin chain (E7CYP2_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the globin family.
  • Belongs to the globin family.
genes like me logo Genes that share domains with HBG2: view

Function for HBG2 Gene

Molecular function for HBG2 Gene

UniProtKB/Swiss-Prot Function:
Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
GENATLAS Biochemistry:
globin,gamma G,fetal (G 136)

Phenotypes From GWAS Catalog for HBG2 Gene

Gene Ontology (GO) - Molecular Function for HBG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004601 contributes_to peroxidase activity IBA 21873635
GO:0005344 oxygen carrier activity IEA,IBA 21873635
GO:0005515 protein binding IPI --
GO:0019825 oxygen binding IEA,IBA 21873635
GO:0020037 heme binding IEA,IBA 21873635
genes like me logo Genes that share ontologies with HBG2: view
genes like me logo Genes that share phenotypes with HBG2: view

Human Phenotype Ontology for HBG2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HBG2 Gene

MGI Knock Outs for HBG2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HBG2

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targets and HOMER Transcription for HBG2 Gene

Localization for HBG2 Gene

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HBG2 gene
Compartment Confidence
cytosol 5
extracellular 4
nucleus 3
plasma membrane 1
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1

Gene Ontology (GO) - Cellular Components for HBG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0005833 hemoglobin complex IEA,IBA 21873635
GO:0031838 haptoglobin-hemoglobin complex IBA 21873635
GO:0072562 blood microparticle HDA 22516433
genes like me logo Genes that share ontologies with HBG2: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot and Subcellular locations from the Human Protein Atlas (HPA) for HBG2 Gene

Pathways & Interactions for HBG2 Gene

genes like me logo Genes that share pathways with HBG2: view

Pathways by source for HBG2 Gene

2 Qiagen pathways for HBG2 Gene
  • IL-4 Pathway
  • p70S6K Signaling

SIGNOR curated interactions for HBG2 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for HBG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007596 blood coagulation TAS --
GO:0015671 oxygen transport IEA --
GO:0042744 hydrogen peroxide catabolic process IBA 21873635
GO:0098869 cellular oxidant detoxification IEA --
genes like me logo Genes that share ontologies with HBG2: view

Drugs & Compounds for HBG2 Gene

(47) Drugs for HBG2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Oxygen Approved, Vet_approved Pharma 0
heme Pharma Agonist 0

(57) Additional Compounds for HBG2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with HBG2: view

Transcripts for HBG2 Gene

mRNA/cDNA for HBG2 Gene

10 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for HBG2

Alternative Splicing Database (ASD) splice patterns (SP) for HBG2 Gene

No ASD Table

Relevant External Links for HBG2 Gene

GeneLoc Exon Structure for

Expression for HBG2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HBG2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for HBG2 Gene

This gene is overexpressed in Whole Blood (x49.1).

Protein differential expression in normal tissues from HIPED for HBG2 Gene

This gene is overexpressed in Fetal Liver (15.1), Placenta (14.5), Fetal heart (9.6), Fetal gut (8.8), and Fetal testis (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for HBG2 Gene

Protein tissue co-expression partners for HBG2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HBG2

SOURCE GeneReport for Unigene cluster for HBG2 Gene:


mRNA Expression by UniProt/SwissProt for HBG2 Gene:

Tissue specificity: Red blood cells.

Evidence on tissue expression from TISSUES for HBG2 Gene

  • Spleen(5)
  • Nervous system(4.9)
  • Lung(4.9)
  • Liver(4.8)
  • Bone marrow(4.6)
  • Pancreas(4.5)
  • Blood(4.4)
  • Heart(4.1)
  • Skin(2.6)
  • Eye(2.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for HBG2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • skeleton
  • thymus
  • liver
  • spleen
  • blood
  • blood vessel
  • bone marrow
  • coagulation system
  • red blood cell
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with HBG2: view

Orthologs for HBG2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for HBG2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HBG2 30 31
  • 99.32 (n)
(Canis familiaris)
Mammalia HBE1 30
  • 84.35 (n)
-- 31
  • 75 (a)
(Bos Taurus)
Mammalia HBE1 30
  • 84.13 (n)
HBE4 31
  • 74 (a)
HBE2 31
  • 71 (a)
(Mus musculus)
Mammalia Hbb-y 30 17
  • 80.73 (n)
Hbb-bh1 31
  • 76 (a)
(Rattus norvegicus)
Mammalia Hbe1 30
  • 80.05 (n)
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 76 (a)
(Monodelphis domestica)
Mammalia -- 31
  • 62 (a)
(Gallus gallus)
Aves HBB 31
  • 70 (a)
HBE1 31
  • 69 (a)
HBG1 31
  • 67 (a)
HBE 31
  • 66 (a)
(Anolis carolinensis)
Reptilia -- 31
  • 62 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100037901 30
  • 63.27 (n)
(Danio rerio)
Actinopterygii hbaa1 31 31
  • 42 (a)
hbae3 31
  • 41 (a)
hbz 31
  • 41 (a)
si:ch211-5k11.6 31
  • 40 (a)
hbae1 31 31
  • 38 (a)
si:ch211-5k11.2 31
  • 38 (a)
Species where no ortholog for HBG2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for HBG2 Gene

Gene Tree for HBG2 (if available)
Gene Tree for HBG2 (if available)
Evolutionary constrained regions (ECRs) for HBG2: view image

Paralogs for HBG2 Gene

Paralogs for HBG2 Gene

(13) SIMAP similar genes for HBG2 Gene using alignment to 9 proteins:

  • F8WB96_HUMAN
  • Q9UNL6_HUMAN Pseudogenes for HBG2 Gene

genes like me logo Genes that share paralogs with HBG2: view

Variants for HBG2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HBG2 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
800493 Pathogenic: Cyanosis, transient neonatal 5,254,644(-) G/T MISSENSE_VARIANT
rs1554922455 Likely Pathogenic: not provided 5,254,444(-) T/TGGCAGA INFRAME_INSERTION
rs281860594 Other: HEMOGLOBIN F (MINOO). - 5,254,390(-) C/Gp.Gly73Arg MISSENSE_VARIANT
rs281864890 Other: HEMOGLOBIN F (HEATHER). - 5,254,691(-) G/Cp.Thr13Arg MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for HBG2 Gene

Structural Variations from Database of Genomic Variants (DGV) for HBG2 Gene

Variant ID Type Subtype PubMed ID
dgv1597n54 CNV loss 21841781
dgv194n67 CNV gain 20364138
esv2648523 CNV deletion 19546169
esv2671356 CNV deletion 23128226
esv2744059 CNV deletion 23290073
esv3547249 CNV deletion 23714750
esv3625218 CNV loss 21293372
esv3625219 CNV loss 21293372
esv3625220 CNV gain 21293372
esv5471 CNV loss 19470904
nsv1036997 CNV gain 25217958
nsv553229 CNV gain 21841781
nsv982977 CNV duplication 23825009
nsv983203 CNV duplication 23825009

Variation tolerance for HBG2 Gene

Residual Variation Intolerance Score: 62.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.42; 9.27% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HBG2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HBG2 Gene

Disorders for HBG2 Gene

MalaCards: The human disease database

(36) MalaCards diseases for HBG2 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
cyanosis, transient neonatal
  • tncy
fetal hemoglobin quantitative trait locus 1
  • hbfqtl1
hemoglobinopathy toms river
  • transient neonatal cyanosis and anemia due to toms river hemoglobin
hereditary persistence of fetal hemoglobin-sickle cell disease syndrome
  • hpfh-sickle cell disease syndrome
hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome
  • hpfh-beta-thalassemia syndrome
- elite association - COSMIC cancer census association via MalaCards
Search HBG2 in MalaCards View complete list of genes associated with diseases


  • Cyanosis transient neonatal (TNCY) [MIM:613977]: A disorder characterized by cyanosis in the fetus and neonate, due to a defect in the fetal hemoglobin chain which has reduced affinity for oxygen. Some patients develop anemia resulting from increased destruction of red cells containing abnormal or unstable hemoglobin. The cyanosis resolves spontaneously by 5 to 6 months of age or earlier, as the adult beta-globin chain is produced and replaces the fetal gamma-globin chain. {ECO:0000269 PubMed:19065339, ECO:0000269 PubMed:21561349, ECO:0000269 PubMed:24502349, ECO:0000269 PubMed:2470017, ECO:0000269 PubMed:2483933, ECO:0000269 PubMed:7741137}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for HBG2

Genetic Association Database
Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with HBG2: view

No data available for Genatlas for HBG2 Gene

Publications for HBG2 Gene

  1. A new (G)γ-globin variant causing low oxygen affinity: Hb F-Brugine/Feldkirch [(G)γ105(G7)Leu→His; HBG2: c.317T>A]. (PMID: 24502349) Saller E … Frischknecht H (Hemoglobin 2014) 3 4
  2. A hemoglobin variant associated with neonatal cyanosis and anemia. (PMID: 21561349) Crowley MA … Weiss MJ (The New England journal of medicine 2011) 3 4
  3. The XmnI (G)gamma polymorphism influences hemoglobin F synthesis contrary to BCL11A and HBS1L-MYB SNPs in a cohort of 57 beta-thalassemia intermedia patients. (PMID: 20472475) Nguyen TK … Francina A (Blood cells, molecules & diseases 2010) 3 41
  4. The Hellenic type of nondeletional hereditary persistence of fetal hemoglobin results from a novel mutation (g.-109G>T) in the HBG2 gene promoter. (PMID: 19050890) Chassanidis C … Kollia P (Annals of hematology 2009) 3 23
  5. Molecular, hematological and clinical aspects of thalassemia major and thalassemia intermedia associated with Hb E-beta-thalassemia in Northeast Thailand. (PMID: 18951049) Nuntakarn L … Wiangnon S (Blood cells, molecules & diseases 2009) 3 41

Products for HBG2 Gene

  • Signalway ELISA kits for HBG2

Sources for HBG2 Gene