HBA2

hemoglobin subunit alpha 2, the group of Hemoglobin subunits

Basic information

Region (hg38): 16:172876-173710

Links

ENSG00000188536 ∙ NCBI:3040 ∙ OMIM:141850 ∙ HGNC:4824 ∙ Uniprot:P69905 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the HBA2 gene.

• not provided (27 variants)
• alpha Thalassemia (18 variants)
• Hemoglobin H disease, nondeletional (5 variants)
• Hemoglobin H disease;alpha Thalassemia;Heinz body anemia;Erythrocytosis, familial, 7 (2 variants)
• Heinz body anemia (2 variants)
• Alpha-thalassemia, Dutch type (1 variants)
• not specified (1 variants)
• Splenomegaly;Anemia (1 variants)
• Hemoglobin Quong Sze (1 variants)
• HEMOGLOBIN H HYDROPS FETALIS SYNDROME (1 variants)
• Hemoglobin constant spring (1 variants)
• HEMOGLOBIN TARRANT (1 variants)
• Non-immune hydrops fetalis (1 variants)
• alpha Thalassemia;Hemoglobin H disease;Heinz body anemia;Erythrocytosis, familial, 7 (1 variants)
• HEMOGLOBIN PLASENCIA (1 variants)
• HBA2-related disorder (1 variants)
• HEMOGLOBIN AGRINIO (1 variants)
• Alpha-thalassemia, Hmong type (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	3	5		9
missense	12	9	41	16	1	79
nonsense	2	2				4
start loss	4	1				5
frameshift	8		2			10
inframe indel		2				2
splice donor/acceptor (+/-2bp)	4	1				5
splice region			1	1		2
non coding		2	10	13	3	28
Total	30	18	56	34	4

Highest pathogenic variant AF is 0.000106

Variants in HBA2

This is a list of pathogenic ClinVar variants found in the HBA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-172889-C-G		not specified • alpha Thalassemia	Benign (Aug 15, 2023)
16-172898-C-G			Uncertain significance (Jun 19, 2018)
16-172908-CCA-C		not specified	Uncertain significance (Oct 26, 2023)
16-172909-C-T		HBA2-related disorder	Uncertain significance (Mar 17, 2023)
16-172912-CA-C		Alpha-thalassemia, Hmong type • alpha Thalassemia	Pathogenic (Jan 30, 2020)
16-172913-A-G		Hemoglobin H disease, nondeletional • alpha Thalassemia	Pathogenic (Aug 04, 2020)
16-172913-AT-A		Hemoglobin H disease, nondeletional • alpha Thalassemia	Pathogenic (Mar 26, 2021)
16-172914-T-C		alpha Thalassemia	Pathogenic (Apr 06, 2023)
16-172914-T-G		alpha Thalassemia	Likely pathogenic (Feb 02, 2023)
16-172917-T-G		HEMOGLOBIN ANTANANARIVO	other (Sep 12, 2014)
16-172920-T-G			Likely benign (Jun 24, 2022)
16-172929-CCGA-C		HEMOGLOBIN BOYLE HEIGHTS	other (Sep 12, 2022)
16-172930-C-G			Uncertain significance (Jan 30, 2018)
16-172934-A-G		HEMOGLOBIN KUROSAKI	Likely benign (Apr 02, 2022)
16-172936-G-T		not specified • alpha Thalassemia	Uncertain significance (Feb 20, 2019)
16-172942-C-G		HEMOGLOBIN PARK RIDGE • alpha Thalassemia	Uncertain significance (Aug 27, 2020)
16-172944-T-A			Uncertain significance (Jun 18, 2021)
16-172950-C-A			Conflicting classifications of pathogenicity (Nov 24, 2021)
16-172952-G-C			Conflicting classifications of pathogenicity (Aug 10, 2021)
16-172955-T-C		not specified	Uncertain significance (Jan 18, 2024)
16-172957-G-A			Pathogenic (Nov 07, 2022)
16-172957-G-C		alpha Thalassemia	Conflicting classifications of pathogenicity (Apr 14, 2023)
16-172958-G-A		not specified	Uncertain significance (May 09, 2023)
16-172958-G-C			Uncertain significance (Jul 23, 2021)
16-172958-G-T		alpha Thalassemia	Likely pathogenic (-)

GnomAD

Source: gnomAD

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: dbNSFP

• 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_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