HBA2

Chr 16AD

hemoglobin subunit alpha 2

The alpha-2 globin protein combines with beta globin chains to form hemoglobin A, the primary oxygen-carrying protein that comprises 97% of normal adult hemoglobin. Mutations cause alpha thalassemia (ranging from mild anemia to severe hemoglobin H disease), familial erythrocytosis, and Heinz body anemia with autosomal dominant inheritance. The gene has low constraint against loss-of-function variants, reflecting the functional redundancy with the nearly identical HBA1 gene.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismADLOEUF 1.934 OMIM phenotypes
Clinical SummaryHBA2
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Gene-Disease Validity (ClinGen)
methemoglobinemia, alpha type · ADLimited

Limited evidence — not for standalone diagnostic reporting

4 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.93LOEUF
pLI 0.003
Z-score -0.76
OE 1.60 (0.591.93)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.18Z-score
OE missense 0.58 (0.440.77)
36 obs / 62.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.60 (0.591.93)
00.351.4
Missense OE0.58 (0.440.77)
00.61.4
Synonymous OE0.74
01.21.6
LoF obs/exp: 3 / 1.9Missense obs/exp: 36 / 62.1Syn Z: 1.14
DN
0.5280th %ile
GOF
0.5562th %ile
LOF
0.2581th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOF1 literature citation

Literature Evidence

GOFAfter resequencing and using a combination of chromatin immunoprecipitation and expression analysis on a tiled oligonucleotide array, De Gobbi et al. (2006) identified a gain-of-function regulatory single-nucleotide polymorphism (rSNP) (141800.0218) in a nongenic region between the alpha-globin genePMID:16728641

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HBA2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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