Hemoglobin Variants: Biochemical Properties and Clinical Correlates
Open accessAbstract
Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples.
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Analytical interference from hemoglobin variants or elevated fetal hemoglobin is a concern.
“An additional concern is analytical interference from hemoglobin variants or elevated fetal hemoglobin.”
From Comparison of point‑of‑care HbA1c devices with laboratory HPLC methods: A systematic review and meta‑analysis (2026) · cites this paper as [45]
The Identification of Hb Variants and Their Clinical Implications section says some variants can artificially elevate HbA1c measurements, and Laboratory Testing for Hb Variants says variants can produce misleading pulse-oximetry results. These passages support analytical interference from hemoglobin variants, but our copy does not say that elevated fetal hemoglobin causes analytical interference. (LLM, conf=0.86)
Experimental — accuracy not yet measuredClinically prevalent hemoglobin variants include HbS, HbC, HbE, and HbD, which occur at relatively high frequencies in individuals of African, Mediterranean, and Southeast Asian descent.
“These variants include clinically prevalent types such as HbS (sickle cell), HbC, HbE, and HbD, which occur at relatively high frequencies in individuals of African, Mediterranean, and Southeast Asian descent (45).”
From Comparison of point‑of‑care HbA1c devices with laboratory HPLC methods: A systematic review and meta‑analysis (2026) · cites this paper as [45]
The Abstract lists HbS, HbC, and HbE among the most common and medically important variants, and ‘Variants that Affect Multiple Hemoglobin Functions’ calls HbE common in Southeast Asia. The copy does not identify HbD as a prevalent variant or establish the claimed high frequencies among people of African or Mediterranean descent; no page numbers are provided for these passages. (LLM, conf=0.86)
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References 154 · Cited by 336
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- Authors
- Thom, C. S., Dickson, C. F., Gell, D. A., & Weiss, M. J.
- Affiliations
- Children's Hospital of Philadelphia (US)
- University of Tasmania (AU)
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-02-06
- Volume
- 3
- Issue
- 3
- Pages
- a011858-a011858
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC3579210
- OpenAlex
- W2132093600
- Cited by
- 336
- References
- 154
- Citations by year
- 2026: 19 · 2025: 18 · 2024: 25 · 2023: 27 · 2022: 33 · 2021: 45 · 2020: 36 · 2019: 36 · 2018: 20 · 2017: 23 · 2016: 23 · 2015: 16 · 2014: 10 · 2013: 4 · 2012: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL087427, HL087427)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK090969, DK061692, R01DK061692, R56DK061692)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- hemoglobin variants, hemoglobinopathies, single amino acid substitution, hemoglobin structure, hemoglobin synthesis
- MeSH terms
- Hemoglobinopathies, Hemoglobins, Hemoglobins, Abnormal, Humans, Methemoglobin, Mutation, Oxygen
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