HBG2
protein-codinghemoglobin subunit gamma 2, the group of Hemoglobin subunits
Gene 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 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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~252.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0018749
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0013511
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0016672
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0017238
Submitter: Orphanet
Inheritance Pattern: Unknown
Disease ID:MONDO:0013511
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0018749
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Hematologic
Intervention: Hematologic
Rationale: Though a range of severity has been described, some individuals have been reported as requiring supplemental oxygen and/or RBC transfusions
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HBG2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000184.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 3 | 3 | 49 | 5 | 1 | 61 |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 3 | 49 | 6 | 1 | 62 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000175.1 | 3 | MANE Select | |
| Ensembl | ENSP00000338082.4 | 3 | MANE Select | |
| Ensembl | ENSP00000369602.2 | 2 | Standard | |
| Ensembl | ENSP00000369602.2 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- ATF-2 transcription factor network
Biological Process
- blood coagulation
- oxygen transport
- hydrogen peroxide catabolic process
- protein heterooligomerization
- cellular oxidant detoxification
Molecular Function
- peroxidase activity
- oxygen carrier activity
- protein binding
- oxygen binding
- heme binding
Cellular Component
- cytosol
- hemoglobin complex
- haptoglobin-hemoglobin complex
- blood microparticle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000380259
- Coding exons
- 3
- Length
- 392600
- Individuals with no LoFs
- 124730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124731
- p
- 0.00000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.35 | 35 | 65.8 | 0.532 | 0.00000303 | 930 |
| Missense (PolyPhen) | 3 | 22.137 | 0.13552 | 348 | ||
| Synonymous | 0.905 | 21 | 27.0 | 0.778 | 0.00000134 | 280 |
| Loss of Function | 1.76 | 0 | 3.61 | 0.00 | 1.53e-7 | 49 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.;
- Disease
- DISEASE: 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.;
Recessive Scores
- pRec
- 0.0956
Intolerance Scores
- LoFtool
- 0.188
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 52.85
Essentials
- Essential (CRISPR)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.101
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |