HBA2
hemoglobin subunit alpha 2, the group of Hemoglobin subunits
Basic information
Region (hg38): 16:172876-173710
Links
Phenotypes
GenCC
Source:
- erythrocytosis, familial, 7 (Strong), mode of inheritance: AD
- hemoglobin H disease (Supportive), mode of inheritance: AR
- Hb Bart's hydrops fetalis (Supportive), mode of inheritance: AR
- hemoglobin M disease (Supportive), mode of inheritance: AD
- Heinz body anemia (Limited), mode of inheritance: AD
- erythrocytosis, familial, 7 (Limited), mode of inheritance: AD
- alpha thalassemia spectrum (Strong), mode of inheritance: AR
- methemoglobinemia, alpha type (Limited), mode of inheritance: AD
- alpha thalassemia spectrum (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Heinz body anemias; Erythrocytosis, familial, 7; Alpha-thalassemia (Hemoglobin Bart syndrome); Alpha-thalassemia (Hemoglobin H disease) | AD/AR/Digenic | Hematologic; Pharmacogenomic | RBC transfusions may be effective for individuals with alpha-thalassemia or HbH disease during hemolytic/aplastic crises; Individuals with HbH disease should be monitored for hemolytic/aplastic crisis during febrile episodes; Monitoring should be performed in order to assess iron overload; For Erythrocytosis, phlebotomy has been described as beneficial in some individuals; Individuals with HbH should avoid inappropriate iron therapy, oxidant drugs (eg sulphonamides), some antimalarials; Variants may also result in a variety of hematologic disease (eg, hemolytic anemia), and genetic diagnosis may aid early recognition and treatment, as well as avoid uneccesary treatments (eg, splenectomy in Heinz body anemia) | Hematologic | 8704193; 9516118; 2831458; 4138824; 10676771; 14184033; 15266345; 12393486; 15921161; 16461765; 18818920; 20301608; 22631041 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (147 variants)
- alpha_Thalassemia (102 variants)
- not_specified (34 variants)
- Heinz_body_anemia (33 variants)
- Erythrocytosis,_familial,_7 (31 variants)
- Hemoglobin_H_disease (27 variants)
- Hemoglobin_H_disease,_nondeletional (8 variants)
- HBA2-related_disorder (7 variants)
- Alpha-thalassemia,_Dutch_type (3 variants)
- HEMOGLOBIN_H_HYDROPS_FETALIS_SYNDROME (3 variants)
- Inborn_genetic_diseases (2 variants)
- HEMOGLOBIN_G_(AZAKUOLI) (2 variants)
- HEMOGLOBIN_G_(PHILADELPHIA) (2 variants)
- HEMOGLOBIN_D_(WASHINGTON) (2 variants)
- HEMOGLOBIN_STANLEYVILLE-I (2 variants)
- HEMOGLOBIN_KNOXVILLE-1 (2 variants)
- Abnormal_hemoglobin (2 variants)
- HEMOGLOBIN_G_(KNOXVILLE) (2 variants)
- HEMOGLOBIN_D_(BALTIMORE) (2 variants)
- HEMOGLOBIN_CLINICO-MADRID (2 variants)
- HEMOGLOBIN_G_(BRISTOL) (2 variants)
- HEMOGLOBIN_D_(ST._LOUIS) (2 variants)
- Thalassemia (2 variants)
- HEMOGLOBIN_NATAL (1 variants)
- HEMOGLOBIN_EVANS (1 variants)
- HEMOGLOBIN_L_(FERRARA) (1 variants)
- HEMOGLOBIN_ICARIA (1 variants)
- HEMOGLOBIN_TOULON (1 variants)
- HEMOGLOBIN_G_(SINGAPORE) (1 variants)
- HEMOGLOBIN_SAVARIA (1 variants)
- beta_Thalassemia (1 variants)
- HEMOGLOBIN_SEAL_ROCK (1 variants)
- HEMOGLOBIN_I_(BURLINGTON) (1 variants)
- HEMOGLOBIN_GOUDA (1 variants)
- HEMOGLOBIN_LOMBARD (1 variants)
- HEMOGLOBIN_KANAGAWA (1 variants)
- HEMOGLOBIN_WESTMEAD (1 variants)
- HEMOGLOBIN_DARTMOUTH (1 variants)
- HEMOGLOBIN_SPANISH_TOWN (1 variants)
- HEMOGLOBIN_SAN_ANTONIO (1 variants)
- HEMOGLOBIN_DECINES-CHARPIEU (1 variants)
- HEMOGLOBIN_AL-HAMMADI_RIYADH (1 variants)
- HEMOGLOBIN_AGRINIO (1 variants)
- HEMOGLOBIN_I_(TEXAS) (1 variants)
- HEMOGLOBIN_SEALY (1 variants)
- HEMOGLOBIN_PLASENCIA (1 variants)
- HEMOGLOBIN_ZURICH_ALBISRIEDEN (1 variants)
- HEMOGLOBIN_KURDISTAN (1 variants)
- HEMOGLOBIN_MANITOBA (1 variants)
- HEMOGLOBIN_HANAMAKI (1 variants)
- HEMOGLOBIN_PARK_RIDGE (1 variants)
- Non-immune_hydrops_fetalis (1 variants)
- HEMOGLOBIN_BIRMINGHAM_(USA) (1 variants)
- Hemoglobin_Quong_Sze (1 variants)
- HEMOGLOBIN_SINAI (1 variants)
- HEMOGLOBIN_G_(HONG_KONG) (1 variants)
- HEMOGLOBIN_BOYLE_HEIGHTS (1 variants)
- HEMOGLOBIN_J_(BUDA) (1 variants)
- HEMOGLOBIN_MONTGOMERY (1 variants)
- HEMOGLOBIN_J_(OXFORD) (1 variants)
- HEMOGLOBIN_NORTON (1 variants)
- HEMOGLOBIN_SUAN-DOK (1 variants)
- HEMOGLOBIN_J_(SARDEGNA) (1 variants)
- HEMOGLOBIN_ANAMOSA (1 variants)
- HEMOGLOBIN_G_(CHINESE) (1 variants)
- HEMOGLOBIN_I_(PHILADELPHIA) (1 variants)
- Anemia (1 variants)
- HEMOGLOBIN_DAVENPORT (1 variants)
- HEMOGLOBIN_TARRANT (1 variants)
- HEMOGLOBIN_ANTANANARIVO (1 variants)
- HEMOGLOBIN_PART-DIEU (1 variants)
- HEMOGLOBIN_WAYNE (1 variants)
- HEMOGLOBIN_GERLAND (1 variants)
- HEMOGLOBIN_CHARTRES (1 variants)
- HEMOGLOBIN_WATTS (1 variants)
- HEMOGLOBIN_CAMPINAS (1 variants)
- Hemoglobin_Val_de_Marne (1 variants)
- HEMOGLOBIN_I (1 variants)
- Alpha-thalassemia,_Hmong_type (1 variants)
- HEMOGLOBIN_CONAKRY (1 variants)
- Hemoglobin_constant_spring (1 variants)
- HEMOGLOBIN_I_(INTERLAKEN) (1 variants)
- HEMOGLOBIN_SUN_PRAIRIE (1 variants)
- Splenomegaly (1 variants)
- Alpha_trait_thalassemia (1 variants)
- HEMOGLOBIN_HASHARON (1 variants)
- Alpha-thalassemia_and_related_diseases (1 variants)
- HEMOGLOBIN_RAMPA (1 variants)
- HEMOGLOBIN_N_(COSENZA) (1 variants)
- HEMOGLOBIN_BOGHE (1 variants)
- HEMOGLOBIN_KOYA_DORA (1 variants)
- HEMOGLOBIN_LE_LAMENTIN (1 variants)
- HEMOGLOBIN_PASSY (1 variants)
- HEMOGLOBIN_HIROSAKI (1 variants)
- HEMOGLOBIN_NIKAIA (1 variants)
- HEMOGLOBIN_INKSTER (1 variants)
- HEMOGLOBIN_KUROSAKI (1 variants)
- HEMOGLOBIN_FUKUI (1 variants)
- HEMOGLOBIN_G_(HONOLULU) (1 variants)
- HEMOGLOBIN_I_(SKAMANIA) (1 variants)
- HEMOGLOBIN_COLUMBIA_MISSOURI (1 variants)
- HEMOGLOBIN_SALLANCHES (1 variants)
- HEMOGLOBIN_MANAWATU (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HBA2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000517.6. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 18 | |||||
| missense | 21 | 21 | 93 | 35 | 172 | |
| nonsense | 7 | |||||
| start loss | 4 | 1 | 5 | |||
| frameshift | 12 | 22 | ||||
| splice donor/acceptor (+/-2bp) | 6 | |||||
| Total | 44 | 39 | 102 | 43 | 2 |
Highest pathogenic variant AF is 0.00028767672
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HBA2 | protein_coding | protein_coding | ENST00000251595 | 3 | 864 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00306 | 0.382 | 111577 | 0 | 1 | 111578 | 0.00000448 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.18 | 36 | 62.1 | 0.580 | 0.00000302 | 909 |
| Missense in Polyphen | 11 | 21.109 | 0.52111 | 308 | ||
| Synonymous | 1.14 | 23 | 31.1 | 0.741 | 0.00000175 | 313 |
| Loss of Function | -0.759 | 3 | 1.88 | 1.60 | 7.86e-8 | 42 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000981 | 0.00000981 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in oxygen transport from the lung to the various peripheral tissues.;
- Disease
- DISEASE: Heinz body anemias (HEIBAN) [MIM:140700]: Form of non- spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency. {ECO:0000269|PubMed:2833478}. Note=The disease may be caused by mutations affecting the gene represented in this entry.; DISEASE: Alpha-thalassemia (A-THAL) [MIM:604131]: A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of alpha-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. The level of alpha chain production can range from none to very nearly normal levels. Deletion of both copies of each of the two alpha-globin genes causes alpha(0)-thalassemia, also known as homozygous alpha thalassemia. Due to the complete absence of alpha chains, the predominant fetal hemoglobin is a tetramer of gamma-chains (Bart hemoglobin) that has essentially no oxygen carrying capacity. This causes oxygen starvation in the fetal tissues leading to prenatal lethality or early neonatal death. The loss of two alpha genes results in mild alpha-thalassemia, also known as heterozygous alpha-thalassemia. Affected individuals have small red cells and a mild anemia (microcytosis). If three of the four alpha-globin genes are functional, individuals are completely asymptomatic. Some rare forms of alpha-thalassemia are due to point mutations (non-deletional alpha-thalassemia). Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Alpha(0)-thalassemia is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non- immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders.; DISEASE: Hemoglobin H disease (HBH) [MIM:613978]: A form of alpha- thalassemia due to the loss of three alpha genes. This results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia. Untreated, most patients die in childhood or early adolescence. {ECO:0000269|PubMed:10569720}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- African trypanosomiasis - Homo sapiens (human);Malaria - Homo sapiens (human);Vesicle-mediated transport;hemoglobins chaperone;O2/CO2 exchange in erythrocytes;Transport of small molecules;Erythrocytes take up oxygen and release carbon dioxide;Erythrocytes take up carbon dioxide and release oxygen;Scavenging of heme from plasma;Binding and Uptake of Ligands by Scavenger Receptors
(Consensus)
Recessive Scores
- pRec
- 0.203
Haploinsufficiency Scores
- pHI
- 0.0810
- hipred
- N
- hipred_score
- 0.238
- ghis
- 0.583
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.539
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hba-a2
- Phenotype