HBA1

hemoglobin subunit alpha 1, the group of Hemoglobin subunits

Basic information

Region (hg38): 16:176680-177522

Links

ENSG00000206172 ∙ NCBI:3039 ∙ OMIM:141800 ∙ HGNC:4823 ∙ Uniprot:P69905 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• erythrocytosis, familial, 7 (Strong), mode of inheritance: AD
• alpha thalassemia (Definitive), mode of inheritance: Semidominant
• 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: AR
• methemoglobinemia, alpha type (Limited), mode of inheritance: AD
• alpha thalassemia (Strong), 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 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	980019; 8704193; 6199634; 2649166; 2831458; 4138824; 4311041; 7615401; 8416301; 9405682; 9516118; 10676771; 10215545; 10339580; 11283697; 12393486; 14184033; 15921161; 16138310; 18818920; 19205971; 20301608; 21381239; 22531344; 22631041; 24006930; 24081251; 24136020

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HBA1 gene.

• not provided (11 variants)
• alpha Thalassemia (7 variants)
• Alpha-thalassemia, Dutch type (1 variants)
• not specified (1 variants)
• HEMOGLOBIN M (SENDAI) (1 variants)
• HEMOGLOBIN M (KANKAKEE) (1 variants)
• HEMOGLOBIN M (OLDENBURG) (1 variants)
• Heinz body anemia;Methemoglobinemia, alpha type;Erythrocytosis, familial, 7;Hemoglobin H disease;alpha Thalassemia (1 variants)
• Hemoglobin H disease, nondeletional (1 variants)
• alpha Thalassemia;Hemoglobin H disease;Methemoglobinemia, alpha type;Erythrocytosis, familial, 7;Heinz body anemia (1 variants)
• Methemoglobinemia, alpha type (1 variants)
• HEMOGLOBIN M (IWATE) (1 variants)
• Erythrocytosis, familial, 7 (1 variants)
• HEMOGLOBIN ADANA (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HBA1 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	4		5
missense	4	8	29	14	1	56
nonsense	2					2
start loss	2	2				4
frameshift	3	4				7
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)	3	3				6
splice region	1		1			2
non coding			6	8	3	17
Total	14	17	40	27	4

Highest pathogenic variant AF is 0.0000394

Variants in HBA1

This is a list of pathogenic ClinVar variants found in the HBA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-176693-C-G		not specified • alpha Thalassemia	Benign (Aug 15, 2023)
16-176702-C-G			Likely benign (Mar 01, 2022)
16-176712-CCA-C		not specified	Uncertain significance (Oct 26, 2023)
16-176717-A-G			Pathogenic (Apr 21, 2022)
16-176717-AT-A		alpha Thalassemia	Likely pathogenic (Dec 30, 2019)
16-176718-T-A		alpha Thalassemia	Likely pathogenic (Jun 27, 2023)
16-176718-T-G		alpha Thalassemia	Pathogenic (May 03, 2020)
16-176721-T-A		HEMOGLOBIN THIONVILLE	other (Jul 20, 2016)
16-176724-T-G		HEMOGLOBIN CHONGQING	other (Jul 20, 2016)
16-176727-C-T		HEMOGLOBIN DOUALA	other (Jul 20, 2016)
16-176732-G-C		HEMOGLOBIN KARACHI	other (Aug 01, 1986)
16-176733-C-A		HEMOGLOBIN J (TORONTO) • alpha Thalassemia	Uncertain significance (May 27, 2023)
16-176733-CCGA-C		not specified	Uncertain significance (May 16, 2019)
16-176735-G-A		HEMOGLOBIN DUNN	other (Jul 20, 2016)
16-176735-G-C			Uncertain significance (Feb 21, 2020)
16-176735-G-T		HEMOGLOBIN WOODVILLE	other (Jul 20, 2016)
16-176736-A-C		HEMOGLOBIN SAWARA	other (May 10, 2018)
16-176736-A-G		HEMOGLOBIN SWAN RIVER • Erythrocytosis, familial, 7 • alpha Thalassemia	Uncertain significance (Apr 06, 2020)
16-176736-A-T		HEMOGLOBIN FERNDOWN	other (Jul 20, 2016)
16-176740-G-C		HEMOGLOBIN TATRAS	Likely benign (Jul 27, 2021)
16-176746-C-G		HEMOGLOBIN DELFZICHT	other (Jul 20, 2016)
16-176750-A-C		HEMOGLOBIN WUMING • HEMOGLOBIN J (WENCHANG-WUMING)	other (Jul 20, 2016)
16-176750-A-G		HEMOGLOBIN ANANTHARAJ	other (Jul 20, 2016)
16-176752-G-C		HEMOGLOBIN ALBANY-GEORGIA • HEMOGLOBIN ALBANY-SUMA	other (May 10, 2018)
16-176754-C-A		HEMOGLOBIN J (ALJEZUR) • HEMOGLOBIN J (PARIS 1)	other (Jul 20, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HBA1	protein_coding	protein_coding	ENST00000320868	3	843

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00673	0.537	109729	0	6	109735	0.0000273

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.53	41	79.4	0.516	0.00000383	899
Missense in Polyphen		10	25.305	0.39518		304
Synonymous	2.03	22	37.9	0.581	0.00000212	300
Loss of Function	0.0373	3	3.07	0.977	1.29e-7	40

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)	0.0000508	0.0000508
Middle Eastern	0.00	0.00
South Asian	0.0000341	0.0000341
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);Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;Effects of Nitric Oxide;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: 0.149

Haploinsufficiency Scores

• pHI: 0.129
• hipred: N
• hipred_score: 0.317
• ghis: 0.447

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	Low
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Low	Low	Low

Mouse Genome Informatics

• Gene name: Hba-a2

Gene ontology

• Biological process: receptor-mediated endocytosis;positive regulation of cell death;oxygen transport;bicarbonate transport;response to hydrogen peroxide;hydrogen peroxide catabolic process;protein heterooligomerization;cellular oxidant detoxification
• Cellular component: extracellular region;extracellular space;cytosol;hemoglobin complex;membrane;cytosolic small ribosomal subunit;haptoglobin-hemoglobin complex;extracellular exosome;endocytic vesicle lumen;blood microparticle
• Molecular function: peroxidase activity;oxygen carrier activity;iron ion binding;protein binding;oxygen binding;heme binding;haptoglobin binding;organic acid binding