Ovomucoid is a protein found in egg whites. Ovomucoid's main source are various avian species like chickens (Gallus gallus domesticus) and ducks (Anatidae). It makes up approximately 11% of proteins[2] found in egg whites.
Chicken ovomucoid, also known as Gal d 1, is a known allergen. It is the protein most often causing egg allergy. At least four IgEepitopes have been identified.[5] Three other egg white proteins are also identified as allergenic: ovalbumin (Gal d 2), ovotransferrin (Gal d 3) and lysozyme (Gal d 4).[6]
Structure
Primary
Ovocumoid consists of approximately 186 amino acids, which are composed of three protein domains, each containing about 60 amino acids.
Secondary
Ovomucoid is a glycoprotein with a secondary structure that makes up approximately 46% β-sheet, 10% β-turns, 26% α-helix, and 18% random coils.[2]
Tertiary
Each domain is attributed by five carbohydrate side chains on each domain, as well as a total of nine intra-domain disulfide bonds, also known as inter-chain disulfide bonds.[2] Every disulfide bond is formed between two cysteine amino acids located within the same polypeptide chain.[7]
Ovomucoid contains an isoelectric point of approximately 4.1[8] indicating an overall acidic protein, and containing a molecular weight of 28 kDa.[2] In contrast to other proteins found in egg whites, Ovomucoid is significantly resistant to heat, making it a thermo-resistant molecule.[9] As a result, individuals who are allergic to ovomucoid remain allergic to eggs after cooking, as the protein cannot be denatured through heat. As the main allergen in eggs, it contains trypsin inhibitor activity,[10] meaning it can block the enzyme trypsin, a crucial enzyme in that aids in digestion by breaking down proteins.
Variants
Ovomucoid is present in thousands of avian species that lay eggs, which can result in natural differences and variation. These differences are a result of genetic differences that occur across species such as chickens, quails, and ostriches. While the protein ovomucoid serves for the same overall purposes, the structures of ovomucoid can vary. The most common reason for variations is due to glycosylation, where different combinations of sugars are attached to the protein. As a result, these changes can drastically affect how an individual's immune system reacts when consumed or tested through IgE antibodies.[11]
Post-translational modifications
Glycolysation promotes the stability of ovomucoid by helping the protein maintain its structure and survive in extreme heat conditions, such as those when cooking. There are two recurring types of glycosylation, including O-linked and N-linked glycosylation. O-linked glycosylation occurs when sugars attach to the amino acid serine or threonine. N-linked glycosylation occurs when sugars attach to the amino acid asparagine. The A subunit of ovomucoid is primarily N-glycosylated, whereas the B subunit is primarily O-glycosylated. O-linked glycans contain sialic acid and are more complex than N-linked glycans, which play a role in maintaining stability in the protein. Sugar chains allow for variation in ovomucoid glycosylation patterns. Many of these differences can be observed through electrophoresis for laboratory research.[12][13]
Function
Ovomucoid carries out multiple important biological functions in egg whites, most importantly providing protection to an avian species embryo from enzymes that break proteins apart and from harmful bacterial growth. This occurs when enzymes, such as trypsin, prevent the breaking down of proteins in an egg, allowing the egg to remain undamaged. As the development process in the avian egg continues, Ovomucoid is then relocated to the yolk sac and continues to regulate the activity of enzymes[14]. However, once the chick is developed, it begins to make its own digestive enzymes and no longer requires ovomucoid. Ovomucoid is later broken down and eliminated through digestion as waste.[15]
The inhibitory activity of ovomucoid can be allocated to the structure of its three Kazal-type domains, which promotes its necessary functions and its stability. Each Kazal-type domain has inhibitory activity, however domain three is often the most well-known for having the highest inhibitory activity and is most effective at blocking the enzyme trypsin.[16] The inhibitory function of domain three is primarily controlled by the amino acid at the P1 position, and varies across avian species. When the amino acid at the P1 position is altered, domain three can block serine proteases that are inhibited.[17]
Allergenicity
Ovomucoid is the primary allergen in egg whites and the source of the majority of egg allergies in humans. The durable structural stability of this protein allows this protein to remain intact when eggs are boiled, scrambled, poached and when otherwise cooked or added as an ingredient in dishes. Allergies to eggs are most commonly seen in young children, with a rate of approximately 1.3-1.6%. Meanwhile, in adults, allergic reactions to eggs are seen in less than 0.25%.[18]
Worldwide, egg allergies are most commonly seen in more developed countries. A study conducted in Italy reported that 43.7% (20/46) of children between the ages of 0.7 to 15.1 years old with egg allergy demonstrated reactivity to Ovomucoid (Gal d 1) [19]. Egg allergy symptoms can range from mild reactions and most commonly occurring reactions such as hives and itching, to more severe reactions including anaphylaxis that may trigger symptoms such as tightening of airways, pain and cramping of the abdomen, and shock that may cause dizziness or fainting [20]. Most egg allergies are outgrown by age 16, however those who enter adulthood with persisting egg allergies may require dietary restrictions and medication management.[21]
Prevalence in the United States
A nationwide U.S population cross-sectional study was conducted from October 2015 to September 2016 which collected data reported by parents of 38,408 children. The study found that egg allergy was seen among 0.9% of children, 1.3% among children less than 5 years of age. Black children were more frequently affected, demonstrating 23.4% of egg allergy cases. Among those with egg allergies, 60.2% reported allergies to other foods, most commonly peanut allergies at 29.3%, while 64.2% had tolerance to baked goods containing eggs. Asthma was also more prevalent in children with egg allergies in comparison to those with eight other common food allergies. Children with egg allergies who can tolerate baked goods containing eggs reported having less emotional and social difficulties than those children who cannot consume baked goods.[22]
Deaths
While egg allergies can be fatal, deaths are often rare and believed to occur in about 1 out of 800,000 individuals per year. The risk of severe complications is increased in those with allergies, existing allergies, or other health conditions. Immediate treatment with an Epinephrine autoinjector is recommended in emergency life-threatening egg allergic reactions, as well as medical care to prevent fatalities.[23]
In foods
Ovomucoid is present in many foods and products for its binding and thickening agent. Those with egg allergies must avoid eggs from all avian species, including duck, quail, ostrich, and chicken eggs. Some commonly known food sources include baked goods such as cakes and pies, mayonnaise, pasta such as egg noodles, a variety of desserts, processed meats such as sausages, and foods containing breading or coated in batter. Traces of egg can also arise from cross-contamination, in which egg proteins and residues are transferred through surfaces and serving utensils, commonly in restaurants.[24] Additionally, egg proteins may appear as albumin or lysozyme under ingredient lists, although these proteins are not ovomucoid.[25]
Chemical properties
Ovomucoid demonstrates various chemical characteristics that promote its stability, bioreactivity, and allergenicity. The protein is highly soluble in water, however solubility is affected by other proteins present and temperature. It is also considered to be insoluble when combined and heated with wheat gluten [26].
Laboratory methods
Isolation of ovomucoid is performed using a variety of laboratory techniques, including precipitation, chromatography, centrifugation, and filtration methods[27].Through these methods, researchers are able to purify ovomucoid from samples of egg whites. Additionally, the most commonly used applications of ovomucoid are in a health laboratory setting, commonly used for allergy testing. Such procedures performed in a health laboratory are Enzyme-Linked Immunosorbent Assay (ELISA), a fluorecent enzyme immunoassay test (FEIA), and immunoglobulin E (IgE) blood tests[28].
Clinical applications
Blood tests are routinely used to quantify amounts of IgE antibodies present that may react to ovomucoid and trigger an allergic reaction. This test is commonly referred to as an OVMU or an ovomucoid IgE blood test, commonly performed using FEIA. During the testing process, a blood sample is collected at a clinic or medical laboratory, the sample is then separated, and the serum obtained is analyzed for how strongly the immune system reacts to ovomucoid [29]. The values are typically interpreted and reported in kU/L, where a value of 0.35 kU/L is considered positive. Higher levels of antibodies suggest stronger egg allergies. These tests are commonly performed to help diagnose, promote specific dietary recommendations, and reduce the risk of complications.[30]
Genetic engineering
Research laboratories have also created ovomucoid variants that have been genetically engineered and modified. Modified forms of ovomucoid are commonly used for studies and to allow researchers to understand and break down different components of the protein that may be responsible for causing egg allergies, and to produce genetically modified food products for those with special dietary needs. The genetically modified ovomucoid is produced through the study of genomics and genome editing tools such as CRISPR-Cas9[31]. A mother hen's DNA is edited so that her offspring contains little or no ovomucoid. The process is called a gene knockout, in which the gene controlling the production of ovomucoid is inactivated. Through targeting and deleting specific exons in a chicken's DNA, the production of ovomucoid is controlled. Implications regarding the safety and quality of genetically modified eggs have not allowed the product to be available on the market, however there are multiple egg alternatives available on the market for those with dietary restrictions [32].
Discovery
Ovomucoid was first identified as an allergen causing glycoprotein in egg whites in 1971 by the researchers Bleumink and Young. Their research primarily focused on studying parts of egg white that cause skin reactions through immunoelectrophoresis. Bleumink and Young's work was published in the International Archives of Allergy and Applied Immunology.[33]
During the 1980's to 1990's more studies were conducted that confirmed the major role of ovomucoid as an egg allergen. It was during this time that researchers discovered its resistance to heat and stability under a variety of environmental conditions.[34]
In 1983, an article in the Journal of Allergy and Clinical Immunology reported that ovomucoid and other egg white proteins can trigger allergic reactions. However, the study found no correlation between reactivity based on age, gender, or eczema. The study concluded that those who developed gastrointestinal symptoms such as bloating, cramping, and changes in bowel movements after consuming eggs experienced less reactivity to ovomucoid.[35]
In 1994, researchers Bernhisel-Broadbent, Dintzis, and Sampson compared the two main proteins found in egg whites, ovomucoid and ovalbumen, in their study titled Allergenicity and antigenicity of chicken egg ovomucoid (Gal d III) compared with ovalbumen (Gal d I) in children with egg allergy and in mice. For this study, liquid chromatography was utilized to analyze the two proteins, in which it was determined that ovomucoid is more likely to trigger immune reactions than ovalbumen.[36]
The study was conducted using a sample size of 18 children with egg allergies. Each child received a skin prick test with varying dilutions of egg white extract and proteins. The levels of IGe antibodies were determined to be greater against ovomucoid, specifically in children with continuous egg allergies, overall confirming previous research.[36]
Ongoing research
There are a multitude of scientific advances in recent years that are developing eggs without the main allergenic protein, ovomucoid. Allergen-free eggs were initially developed by researchers at Hiroshima University in Higashiroshima, Japan. Rather than using the CRISPR-Cas9 gene editing tool, researchers utilized a method not commonly utilized called Transcription Activator-Like Effector Nucleases (TALEN), which, similarly to CRISPR-Cas9, cuts and modifies DNA.[37]
Hens that underwent genetic modification were homozygous, both genes that encoded for ovomucoid were inactivated. The hens were in good physical condition and laid eggs free of ovomucoid with no complications. The hens were also analyzed for any adverse reactions and DNA mutations, however most changes were minor with little to no effect on protein-coding genes [38] There are ongoing efforts to create eggs that are safe for consumption for individuals with egg allergies. More studies across the globe are required to confirm the safety, long-term effects, and quality of genetically modified ovomucoid-free eggs before becoming freely available to consumers.
References
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1234Jalili-Firoozinezhad S, Filippi M, Mohabatpour F, Letourneur D, Scherberich A (November 2020). "Chicken egg white: Hatching of a new old biomaterial". Materials Today. 40: 193–214. doi:10.1016/j.mattod.2020.05.022.
↑Järvinen KM, Beyer K, Vila L, Bardina L, Mishoe M, Sampson HA (July 2007). "Specificity of IgE antibodies to sequential epitopes of hen's egg ovomucoid as a marker for persistence of egg allergy". Allergy. 62 (7): 758–765. doi:10.1111/j.1398-9995.2007.01332.x. PMID17573723. S2CID23540584.
↑Winiarska-Mieczan A, Kwiecień M, Krusiński R (2015-02-20). "The content of cadmium and lead in canned fish available in the Polish market". Journal für Verbraucherschutz und Lebensmittelsicherheit. 10 (2): 165–169. doi:10.1007/s00003-015-0933-0. ISSN1661-5751.
↑Urisu A, Ando H, Morita Y, Wada E, Yasaki T, Yamada K, etal. (August 1997). "Allergenic activity of heated and ovomucoid-depleted egg white". The Journal of Allergy and Clinical Immunology. 100 (2): 171–176. Bibcode:1997JACI..100..171U. doi:10.1016/S0091-6749(97)70220-3. PMID9275136.
↑Li C, Chen Q, Rong J, He H, Lu Y, Liu Y, etal. (November 2024). "LC-MS characterization of N/O-glycans of α- and β-subunits of chicken ovomucin separated by SDS-PAGE". Analytical Biochemistry. 694 115625. doi:10.1016/j.ab.2024.115625. PMID39038508.
↑Offengenden M, Fentabil MA, Wu J (May 2011). "N-glycosylation of ovomucin from hen egg white". Glycoconjugate Journal. 28 (3–4): 113–123. doi:10.1007/s10719-011-9328-3. PMID21484392.
↑"f233 Gal d 1". Thermo Fisher Scientific. Retrieved 2025-11-25.
↑Apostol I, Giletto A, Komiyama T, Zhang W, Laskowski M (August 1993). "Amino acid sequences of ovomucoid third domains from 27 additional species of birds". Journal of Protein Chemistry. 12 (4): 419–433. doi:10.1007/BF01025042. PMID8251062.
↑Asao T, Takahashi K, Tashiro M (September 1998). "Interaction of second and third domains of Japanese quail ovomucoid with ten mammalian trypsins". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1387 (1–2): 415–421. doi:10.1016/S0167-4838(98)00155-1. PMID9748658.
↑Kato Y, Watanabe H, Matsuda T (January 2000). "Ovomucoid rendered insoluble by heating with wheat gluten but not with milk casein". Bioscience, Biotechnology, and Biochemistry. 64 (1): 198–201. doi:10.1271/bbb.64.198. PMID10766508.
↑Tanabe S, Tesaki S, Watanabe M (September 2000). "Producing a low ovomucoid egg white preparation by precipitation with aqueous ethanol". Bioscience, Biotechnology, and Biochemistry. 64 (9): 2005–2007. doi:10.1271/bbb.64.2005. PMID11055414.
↑Bleumink E, Young E (1971). "Studies on the atopic allergen in hen's egg. II. Further characterization of the skin-reactive fraction in egg-white; immuno-electrophoretic studies". International Archives of Allergy and Applied Immunology. 40 (1): 72–88. doi:10.1159/000230396. PMID5546863.
↑Urisu A, Ando H, Morita Y, Wada E, Yasaki T, Yamada K, etal. (August 1997). "Allergenic activity of heated and ovomucoid-depleted egg white". The Journal of Allergy and Clinical Immunology. 100 (2): 171–6. Bibcode:1997JACI..100..171U. doi:10.1016/s0091-6749(97)70220-3. PMID9275136.
↑Hoffman DR (May 1983). "Immunochemical identification of the allergens in egg white". The Journal of Allergy and Clinical Immunology. 71 (5): 481–486. doi:10.1016/0091-6749(83)90465-7. PMID6601671.
12Bernhisel-Broadbent J, Dintzis HM, Dintzis RZ, Sampson HA (June 1994). "Allergenicity and antigenicity of chicken egg ovomucoid (Gal d III) compared with ovalbumin (Gal d I) in children with egg allergy and in mice". The Journal of Allergy and Clinical Immunology. 93 (6): 1047–1059. Bibcode:1994JACI...93.1047B. doi:10.1016/s0091-6749(94)70054-0. PMID8006309.
↑Ezaki R, Sakuma T, Kodama D, Sasahara R, Shiraogawa T, Ichikawa K, etal. (May 2023). "Transcription activator-like effector nuclease-mediated deletion safely eliminates the major egg allergen ovomucoid in chickens". Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association. 175 113703. doi:10.1016/j.fct.2023.113703. PMID36889429.
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