SelenocysteineSec · U

In brief

The molecule

Selenocysteine is cysteine with one atom changed. Selenium, the element directly below sulfur in the periodic table, sits where cysteine’s sulfur would, so the side chain is a selenol, –SeH, rather than a thiol ¹.

The selenol gives up its hydrogen far more easily. Its pKa was measured at about 5.2 in 1967 ¹³, and later estimates put it near 5.7, against 8.2 to 8.5 for cysteine’s thiol ¹⁴. At the pH inside a cell a selenol is almost entirely ionized into the reactive selenolate; a thiol mostly is not ¹⁴.

The bigger difference is what happens after it reacts. Selenium forms only weak double bonds to oxygen, so an oxidized selenium is readily reduced back, and a selenium enzyme resists the permanent overoxidation that would end a sulfur one ¹. When mice were given a GPX4 with cysteine in place of selenocysteine, the enzyme was irreversibly overoxidized and the cells became highly sensitive to ferroptosis ¹⁵.

StereochemistryLike cysteine, L-selenocysteine is R rather than S. Nothing about its shape differs from the other L-amino acids: selenium outranks the oxygens of the carboxyl group under the Cahn–Ingold–Prelog rules, which flips the letter.

Where it comes from

Selenocysteine is the only amino acid in humans that is made on its own transfer RNA ²⁵. Seryl-tRNA synthetase loads serine onto tRNA[Ser]Sec; a kinase, PSTK, phosphorylates it; and selenocysteine synthase, SEPSECS, a vitamin B6 enzyme, replaces the phosphate with selenium, delivered as selenophosphate that selenophosphate synthetase 2 makes from selenide ¹⁶.

The selenium comes from food in several forms and is pooled. The liver is the central organ: it secretes selenoprotein P, which carries one selenocysteine in its larger domain and nine in its smaller one, and the rest of the body takes its selenium from that ^7,26.

Free selenocysteine released when selenoproteins are broken down is not reused as such. Selenocysteine lyase splits it into alanine and selenide, and the selenide goes back to be made into selenophosphate ²⁷.

Made on its own tRNANot taken from the diet as an amino acid: the body builds it from serine on its own tRNA, with selenium supplied as selenophosphate ¹⁶. What the diet must supply is selenium, for which the US recommended allowance for adults is 55 µg a day ¹².

In the bottle · not sold as itselfSupplements labeled selenium contain selenomethionine, selenite or Se-methylselenocysteine, which is a different molecule despite the name ^11,29. The body makes its own selenocysteine from whatever selenium arrives ¹⁶.

What the body does with it

In 2003 Kryukov and colleagues counted 25 selenoprotein genes in the human genome, many of them misannotated until then because their UGA had been read as a stop ⁴. Most are oxidoreductases, enzymes that move electrons, and in most the selenocysteine sits at the active site ².

The glutathione peroxidases dismantle peroxides, and one of them, GPX4, repairs oxidized fats in membranes and is the main brake on ferroptosis ¹⁵. The thioredoxin reductases reduce thioredoxin through a selenocysteine near their tail, and are targeted by drugs including auranofin, the old gold-based arthritis treatment ^5,30. The three deiodinases are the selenoproteins of thyroid hormone metabolism, converting T4, the main circulating form, into active T3 ⁶. Two of those families turn out to pull against each other. Thioredoxin reductase 1 PROMOTES ferroptosis rather than preventing it, and its selenocysteine is required for the effect: TrxR1 stabilizes KEAP1 by blocking CRL4A-E3-mediated KEAP1 ubiquitination, which drives NRF2 degradation and lowers GPX4 expression, sensitizing cells to ferroptosis. High TrxR1 sensitized cancer cells to ferroptosis in living animals, and combining the CRBN inhibitor thalidomide with a ferroptosis inducer markedly slowed tumor growth ³¹. The two selenoproteins this page lists as parallel protectors of the same membrane are, in this mechanism, one suppressing the other.

Selenoprotein P is the courier. Made mostly in the liver, it delivers selenium to the testis and brain through the receptor ApoER2 and is reclaimed by the kidney through megalin ²⁶. In rats about a quarter of the body’s selenium passes through it each day, and mice without it have very little selenium in the brain, the testis and the fetus ³².

Under shortage the body ranks its selenoproteins. Cells make the ones most important to them first, and tissues are supplied in order of their selenoprotein P receptors ⁷. In rats fed graded selenium, testis GPX4 activity held at the lowest intakes while GPX1 fell to 28% of normal ⁸.

Not every selenoprotein is an oxidoreductase, and the clearest counter-example arrived in 2026. SELENOO — SelO — hydrolyzes mitochondrial NAD⁺ to nicotinamide mononucleotide and AMP using manganese as cofactor, and the catalysis depends on the enzyme's selenocysteine-serine-serine C-terminal residues, particularly SELENOCYSTEINE 667. The reaction associates directly with fatty acid oxidation enzymes, responds to a rise in matrix pH — the signal that respiration has stepped up — and protects mitochondria from sustained metabolic overactivation; it is conserved in mammalian cells and in bacteria ³³. An amino acid whose whole reputation is redox chemistry turns out to be doing hydrolysis at the center of NAD⁺ regulation.

The current framing of the whole family has also moved. A 2026 overview of selenoprotein genetics names an entirely new field centered on the biosynthesis of ethanolamine phospholipids; describes the deiodinases as modulators of a growing list of specific developmental decisions in organs where they set local thyroid hormone concentrations rather than simply as the enzymes of circulating T3; and identifies skeletal muscle, the endocrine system, the immune system and in particular the BRAIN as the tissues sensitive to selenoprotein deficiency ³⁴. It also reviews the patients described with inborn errors of selenoprotein biosynthesis and of individual selenoprotein genes, which is the part of this page's clinical list that keeps growing.

A licensed cancer drug turns out to work partly by switching the recoding off. In a drug screen built around a selenoprotein translation reporter, FLT3 inhibitors were found to suppress selenoprotein translation by disrupting the recoding of UGA as selenocysteine through the SECIS element and its binding proteins, which induces ferroptosis in FLT3-mutant acute myeloid leukemia. The antileukemic efficacy of gilteritinib was MARKEDLY REDUCED by dietary vitamin E, which blunted the ferroptosis — so the authors suggest high vitamin E intake may compromise tyrosine kinase inhibitor efficacy partly by suppressing it ³⁵. An over-the-counter antioxidant interfering with a leukemia drug is the sharpest version of this page's argument about selenium supplements, and it is in mice and cells, not in a trial.

How it is made, moved and broken down

Its lifecycle is a loop. Serine goes onto the tRNA, the finished selenocysteine goes into a selenoprotein, and when that protein is broken down selenocysteine lyase returns the selenium to the start ^16,27.

Carbon skeleton · not applicableThe point of breaking it down is the selenium, not the carbon: selenocysteine lyase splits free selenocysteine into alanine and selenide, and the selenide is reused to make new selenoproteins ²⁷.

Where it matters most

Thyroid and the tissues that use its hormone

The deiodinases are selenoproteins, and the thyroid’s own antioxidant defense depends on glutathione peroxidases ⁶.

Liver

The central organ of selenium regulation: it makes most plasma selenoprotein P and, in deficiency, cuts excretion and keeps exporting it at the expense of its own selenoproteins ⁷.

Brain

Holds its selenium in deficiency through ApoER2; GPX4 with selenocysteine is required for the survival of a class of interneurons in mice ^15,26.

Testis and sperm

Protected first in deficiency; loss of testis selenoproteins causes azoospermia in people with SECISBP2 defects ^8,36.

Muscle

Selenoprotein N defects cause a myopathy, and people with SECISBP2 defects develop a similar axial muscular dystrophy ³⁶.

When it goes wrong

How it is measured

Nobody measures selenocysteine itself in clinical practice. Selenium status is judged by what the selenoproteins do, selenoprotein P concentration and glutathione peroxidase activity, within the range of intake where their synthesis is regulated, and by total selenium, which reflects intake over a wider range but not function ¹⁰.

What the selenoprotein P assay predicts has now been measured at scale, and the answer is specific rather than general. In the German ESTHER cohort — 6,600 adults free of cardiovascular disease and 1,729 who already had it, followed for 17 years — those in the lowest quartile of serum selenoprotein P had a 1.58-fold higher risk of STROKE than the highest quartile, and patients with existing cardiovascular disease in the lowest quartile had nearly double the cardiovascular mortality (HR 1.85, 95% CI 1.31 to 2.60). There was NO association with coronary heart disease incidence, and the association with overall cardiovascular incidence appeared only in participants with hypertension or diabetes ⁴⁵. A second endpoint has a cut-off attached: among 320 patients hospitalized for acute heart failure — 58% of them selenium-deficient — higher selenoprotein P went with lower odds of selective glomerular hypofiltration syndrome (OR 0.69) and lower risk of later kidney hospitalization (HR 0.60), especially acute kidney injury (HR 0.42), and selenoprotein P below 3.23 mg/L predicted that admission (HR 4.02) ⁴⁶. The authors of the cohort study are explicit that trials are still needed before any of this becomes a reason to supplement.

And in the disease that made selenium famous, the biomarkers do not behave linearly. A study pairing 6,987 adults from 29 Chinese provinces with a rat selenite intervention found saturation kinetics throughout: serum selenium rose then FELL against hair selenium in non-endemic areas while rising and saturating in endemic ones; myocardial selenium correlated increasingly with erythrocyte and hair selenium after prolonged supplementation; and myocardial selenium plateaued against serum glutathione peroxidase activity while staying inversely correlated with selenoprotein P. The authors conclude that erythrocyte selenium is what reflects myocardial status, that selenoprotein P and glutathione peroxidase activity are respectively long- and short-term indicators, and that Keshan disease is threshold-saturation-driven systemic selenium DYSREGULATION rather than mere deficiency — which argues for continuous moderate rather than short-term high-dose supplementation ⁴³.

• Selenoprotein PThe selenium transport protein, made by the liver; in a repletion trial it was the last plasma marker to plateau, so it is the best single readout of whether all selenoproteins are being made ⁹.Informative within the range where selenoprotein synthesis is regulated, roughly intakes below 55 µg a day ¹⁰.Once selenoproteins are full it stops rising, so it cannot show excess; with selenomethionine supplements, part of the measured rise is selenomethionine built nonspecifically into the protein ¹¹.
• Plasma or serum seleniumTotal selenium, in selenoproteins and in selenomethionine-containing proteins such as albumin ^10,11.Tracks intake over a wide range, including from food, and confirms poisoning: serum averaged 751 µg/L in a supplement outbreak, against a reference limit of 125 ^10,12.Says nothing directly about function; in the Chinese repletion trial it kept rising with dose and never plateaued ⁹.
• Glutathione peroxidase activityThe activity of a selenoenzyme, in plasma, platelets or red cells ^9,29.A direct functional measure in deficiency ¹⁰.It plateaus at a lower intake than selenoprotein P, so it calls marginal intakes adequate; platelet activity did not change at all with supplementation in UK adults ^9,29.

Food, supplements and the evidence

What is strange about it

UGA means stop in almost every human gene. In twenty-five of them, a fold of RNA further down the same message turns it into an instruction to insert selenium ^4,19.

The enzyme that makes selenocysteine was known to medicine before anyone knew what it did: it is the soluble liver antigen, a target of autoantibodies in autoimmune hepatitis ^16,44.

Land plants and fungi have lost selenoproteins entirely, and several groups of land animals, insects and nematodes among them, have replaced most of theirs with cysteine; aquatic organisms keep the largest selenoproteomes ^3,57. A 2025 review puts a census behind that. Metazoan selenoproteomes are strikingly diverse: many animals including mammals depend on selenoproteins for redox homeostasis and signaling, thyroid hormone metabolism and stress responses, while other lineages have lost the entire selenocysteine pathway outright — and the review catalogues the gene duplications, the losses, and the substitutions of selenocysteine to cysteine across the known selenoprotein families with their phylogenetic distribution ⁵⁸.

Mice whose GPX4 has cysteine instead of selenocysteine develop normally as embryos, then lose a specific class of interneurons and die of seizures. It took two hundred years after selenium’s discovery to find a role in mammals that sulfur could not fill ¹⁵.

Where it connects

Sources

58 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1. 1
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   Review: selenium against sulfur, and why selenium enzymes resist permanent oxidation.

2. 2
   Labunskyy VM, Hatfield DL, Gladyshev VN. Selenoproteins: molecular pathways and physiological roles.Physiol Rev · 2014 · 94(3):739–777doi:10.1152/physrev.00039.2013 · PMID 24987004

   Review of selenoprotein function and the SECIS insertion machinery.

3. 3
   Lobanov AV, Hatfield DL, Gladyshev VN. Eukaryotic selenoproteins and selenoproteomes.Biochim Biophys Acta · 2009 · 1790(11):1424–1428doi:10.1016/j.bbagen.2009.05.014 · PMID 19477234

   Selenium’s dietary importance is mainly as selenocysteine; plants and fungi lost selenoproteins.

4. 4
   Kryukov GV, Castellano S, Novoselov SV, et al. Characterization of mammalian selenoproteomes.Science · 2003 · 300(5624):1439–1443doi:10.1126/science.1083516 · PMID 12775843

   The human selenoproteome: 25 selenoproteins, many previously misannotated.

5. 5
   Arnér ES. Focus on mammalian thioredoxin reductases: important selenoproteins with versatile functions.Biochim Biophys Acta · 2009 · 1790(6):495–526doi:10.1016/j.bbagen.2009.01.014 · PMID 19364476

   Review: TXNRD1–3, their selenocysteine, and the drugs that target them.

6. 6
   Souza LSL, Campos RO, Braga JS, et al. Selenium nutritional status and thyroid dysfunction.Arch Endocrinol Metab · 2025 · 69(1):e230348doi:10.20945/2359-4292-2023-0348 · PMID 39992731

   Narrative review: deiodinases, glutathione peroxidases, Keshan and Kashin–Beck disease.

7. 7
   Burk RF, Hill KE. Regulation of selenium metabolism and transport.Annu Rev Nutr · 2015 · 35:109–134doi:10.1146/annurev-nutr-071714-034250 · PMID 25974694

   The selenoprotein hierarchy, the liver’s role, and the ApoER2 and megalin receptors.

8. 8
   Schriever SC, Barnes KM, Evenson JK, et al. Selenium requirements are higher for glutathione peroxidase-1 mRNA than gpx1 activity in rat testis.Exp Biol Med (Maywood) · 2009 · 234(5):513–521doi:10.3181/0812-RM-369 · PMID 19234057

   Rats: GPX4 held at the lowest selenium intakes, GPX1 fell to 28%. Animal study.

9. 9
   Xia Y, Hill KE, Li P, et al. Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects.Am J Clin Nutr · 2010 · 92(3):525–531doi:10.3945/ajcn.2010.29642 · PMID 20573787

   98 selenium-deficient adults, 40 weeks: selenoprotein P optimized near 49 µg/day, GPX earlier; plasma selenium never plateaued.

10. 10
    Combs GF. Biomarkers of selenium status.Nutrients · 2015 · 7(4):2209–2236doi:10.3390/nu7042209 · PMID 25835046

    Review: functional markers below about 55 µg/day; total selenium over wider ranges.

11. 11
    Del Castillo Busto ME, Ward-Deitrich C, Evans SO, et al. Selenium speciation studies in cancer patients to evaluate the responses of biomarkers of selenium status to different selenium compounds.Anal Bioanal Chem · 2024 · 416(11):2835–2848doi:10.1007/s00216-024-05141-y · PMID 38286852

    Selenite, selenomethionine or Se-methylselenocysteine at 400 µg/day: about 45% of the selenoprotein P rise with selenomethionine was nonspecific incorporation.

12. 12
    MacFarquhar JK, Broussard DL, Melstrom P, et al. Acute selenium toxicity associated with a dietary supplement.Arch Intern Med · 2010 · 170(3):256–261doi:10.1001/archinternmed.2009.495 · PMID 20142570

    201 cases in ten states from a supplement with 200 times its labeled selenium.

13. 13
    Huber RE, Criddle RS. Comparison of the chemical properties of selenocysteine and selenocystine with their sulfur analogs.Arch Biochem Biophys · 1967 · 122(1):164–173doi:10.1016/0003-9861(67)90136-1 · PMID 6076213

    The original measurement of selenocysteine’s chemistry against cysteine’s, including the selenol pKa.

14. 14
    McGrath NA, Raines RT. Chemoselectivity in chemical biology: acyl transfer reactions with sulfur and selenium.Acc Chem Res · 2011 · 44(9):752–761doi:10.1021/ar200081s · PMID 21639109

    Gives pKa 8.5 for the cysteine thiol and 5.7 for the selenocysteine selenol.

15. 15
    Ingold I, Berndt C, Schmitt S, et al. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis.Cell · 2018 · 172(3):409–422.e21doi:10.1016/j.cell.2017.11.048 · PMID 29290465

    Mice: cysteine-GPX4 is overoxidized; interneurons die and seizures follow. Animal and cell study.

16. 16
    Xu XM, Carlson BA, Mix H, et al. Biosynthesis of selenocysteine on its tRNA in eukaryotes.PLoS Biol · 2007 · 5(1):e4doi:10.1371/journal.pbio.0050004 · PMID 17194211

    Identified mammalian selenocysteine synthase and the full pathway from serine and selenide.

17. 17
    Gaston MA, Zhang L, Green-Church KB, Krzycki JA. The complete biosynthesis of the genetically encoded amino acid pyrrolysine from lysine.Nature · 2011 · 471(7340):647–650doi:10.1038/nature09918 · PMID 21455182

    PylB, PylC and PylD make pyrrolysine from two lysines; required for methane from methylamines.

18. 18
    Blight SK, Larue RC, Mahapatra A, et al. Direct charging of tRNA(CUA) with pyrrolysine in vitro and in vivo.Nature · 2004 · 431(7006):333–335doi:10.1038/nature02895 · PMID 15329732

    Synthetic pyrrolysine attached as a free molecule by PylS, with ATP.

19. 19
    Chavatte L, Lange L, Schweizer U, et al. Understanding the role of tRNA modifications in UGA recoding as selenocysteine in eukaryotes.J Mol Biol · 2025 · 437(16):169017doi:10.1016/j.jmb.2025.169017 · PMID 39988117

    Review of SECIS, SECISBP2, EEFSEC and the tRNA modifications that tune recoding.

20. 20
    Peiter N, Rother M, Krzycki JA. Recent developments in (archaeal) pyrrolysine and selenocysteine specification and metabolism.Cold Spring Harb Perspect Biol · 2026doi:10.1101/cshperspect.a041979 · PMID 41997725

    Review contrasting how the two recoded amino acids are made and read.

21. 21
    Longstaff DG, Blight SK, Zhang L, et al. In vivo contextual requirements for UAG translation as pyrrolysine.Mol Microbiol · 2007 · 63(1):229–241doi:10.1111/j.1365-2958.2006.05500.x · PMID 17140411

    A downstream PYLIS enhances UAG translation; a UAG with no evolved context was still read at 20%.

22. 22
    Zhang Y, Baranov PV, Atkins JF, Gladyshev VN. Pyrrolysine and selenocysteine use dissimilar decoding strategies.J Biol Chem · 2005 · 280(21):20740–20751doi:10.1074/jbc.M501458200 · PMID 15788401

    The pyrrolysine trait in a few microbes; one organism with both; four protein families.

23. 23
    Srinivasan G, James CM, Krzycki JA. Pyrrolysine encoded by UAG in Archaea: charging of a UAG-decoding specialized tRNA.Science · 2002 · 296(5572):1459–1462doi:10.1126/science.1069588 · PMID 12029131

    The pylT tRNA with a CUA anticodon and the pylS synthetase; homologs in a Gram-positive bacterium.

24. 24
    Kivenson V, Peters SL, Borrel G, et al. An archaeal genetic code with all TAG codons as pyrrolysine.Science · 2025 · 390(6775):eadu2404doi:10.1126/science.adu2404 · PMID 41264687

    The Pyl code: 62 sense codons, 21 amino acids; more than 1,800 pyrrolysine proteins.

25. 25
    Agamy O, Ben Zeev B, Lev D, et al. Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy.Am J Hum Genet · 2010 · 87(4):538–544doi:10.1016/j.ajhg.2010.09.007 · PMID 20920667

    SEPSECS founder mutations in families of Iraqi and Moroccan Jewish ancestry.

26. 26
    Burk RF, Hill KE. Selenoprotein P: expression, functions, and roles in mammals.Biochim Biophys Acta · 2009 · 1790(11):1441–1447doi:10.1016/j.bbagen.2009.03.026 · PMID 19345254

    Ten selenocysteines; ApoER2 uptake in testis and brain, megalin in kidney.

27. 27
    Seale LA, Khadka VS, Menor M, et al. Combined omics reveals that disruption of the selenocysteine lyase gene affects amino acid pathways in mice.Nutrients · 2019 · 11(11):2584doi:10.3390/nu11112584 · PMID 31717805

    Selenocysteine lyase splits selenocysteine into selenide and alanine for reuse. Mouse study.

28. 28
    Rayman MP. Food-chain selenium and human health: emphasis on intake.Br J Nutr · 2008 · 100(2):254–268doi:10.1017/S0007114508939830 · PMID 18346308

    Review: how selenium enters the food chain and how much intakes vary.

29. 29
    Hurst R, Armah CN, Dainty JR, et al. Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial.Am J Clin Nutr · 2010 · 91(4):923–931doi:10.3945/ajcn.2009.28169 · PMID 20181815

    119 UK adults, 12 weeks of selenium yeast or selenium-enriched onion: selenoprotein P rose, platelet GPx did not.

30. 30
    Bak DW, Gao J, Wang C, Weerapana E. A quantitative chemoproteomic platform to monitor selenocysteine reactivity within a complex proteome.Cell Chem Biol · 2018 · 25(9):1157–1167.e4doi:10.1016/j.chembiol.2018.05.017 · PMID 29983274

    Uses selenocysteine’s low pKa to profile selenoproteins; auranofin as a thioredoxin reductase inhibitor.

31. 31
    Luan J, He J, Wu D, et al. Selenoprotein thioredoxin reductase 1 promotes cancer cells ferroptosis by suppressing GPX4 expression.Cell Death Differ · 2026 · 33(9):1829–1845doi:10.1038/s41418-026-01691-z · PMID 41748901

    One selenoprotein suppressing another, with the selenocysteine required for it. The opposite of the parallel-protectors picture.

32. 32
    Burk RF, Hill KE. Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis.Annu Rev Nutr · 2005 · 25:215–235doi:10.1146/annurev.nutr.24.012003.132120 · PMID 16011466

    About a quarter of whole-body selenium passes through it daily in rats; knockout mice lose brain and testis selenium.

33. 33
    Jia X, Zhang T, Yang C, et al. NAD+ hydrolysis catalyzed by SelO is required for mitochondrial homeostasis.Cell · 2026 · 189(9):2633–2647.e24doi:10.1016/j.cell.2026.01.033 · PMID 41806834

    A human selenoprotein doing something that is not redox chemistry, and one residue — selenocysteine 667 — carrying it.

34. 34
    Schweizer U, Fabiano M. Genetics of selenoproteins and selenoprotein metabolism — an overview of current concepts and emerging aspects.Redox Biol · 2026 · 91:104083doi:10.1016/j.redox.2026.104083 · PMID 41719757

    The current authoritative framing, written by people who treat the patients with inborn errors.

35. 35
    Li M, Zhu Y, Kageyama Y, et al. Targeting oncogenic FLT3 uncovers a ferroptosis vulnerability through selenocysteine recoding in acute myeloid leukaemia.Nat Cell Biol · 2026 · 28(8):1715–1727doi:10.1038/s41556-026-02016-5 · PMID 42576015

    A drug screen built on a selenoprotein translation reporter, and a licensed leukemia drug found to work partly by switching the recoding off.

36. 36
    Schoenmakers E, Agostini M, Mitchell C, et al. Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans.J Clin Invest · 2010 · 120(12):4220–4235doi:10.1172/JCI43653 · PMID 21084748

    Multisystem disorder from reduced synthesis of most selenoproteins.

37. 37
    Dumitrescu AM, Liao XH, Abdullah MS, et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism.Nat Genet · 2005 · 37(11):1247–1252doi:10.1038/ng1654 · PMID 16228000

    The first inherited selenocysteine incorporation defect in humans.

38. 38
    Schoenmakers E, Carlson B, Agostini M, et al. Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis.J Clin Invest · 2016 · 126(3):992–996doi:10.1172/JCI84747 · PMID 26854926

    One proband; stress-related selenoproteins fall, housekeeping ones are kept.

39. 39
    Killam BY, Knol MJ, Fradejas-Villar N, et al. Disease characteristics of SEPSECS deficiency: an international, retrospective, multicenter cohort study.Genet Med · 2026 · 28(11):102684doi:10.1016/j.gim.2026.102684 · PMID 42603098

    27 people; three clinical courses; proposes renaming from PCH2D.

40. 40
    Smith AC, Mears AJ, Bunker R, et al. Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type spondylometaphyseal dysplasia.J Med Genet · 2014 · 51(7):470–474doi:10.1136/jmedgenet-2013-102218 · PMID 24706940

    Truncating GPX4 mutations in two families with this neonatal-lethal dysplasia.

41. 41
    Pierce WG, Mackrill JJ. Selenium in aging and longevity.Biochimie · 2026doi:10.1016/j.biochi.2026.09.002 · PMID 42710827

    Review: deficiency and excess, including Keshan disease and selenosis.

42. 42
    Wang P, Chen B, Huang Y, et al. Selenium intake and multiple health-related outcomes: an umbrella review of meta-analyses.Front Nutr · 2023 · 10:1263853doi:10.3389/fnut.2023.1263853 · PMID 37781125

    Umbrella review: mostly low-quality evidence; possible higher type 2 diabetes risk; no general supplementation.

43. 43
    Hao S, Li G, Wang R, et al. Linear and nonlinear modeling of selenium biomarker dynamics in Keshan disease: insights for precision prevention from rats and human populations.Ecotoxicol Environ Saf · 2026 · 320:120376doi:10.1016/j.ecoenv.2026.120376 · PMID 42296709

    6,987 adults across 29 Chinese provinces plus 100 rats, with the heart muscle itself measured. The conclusion is about dysregulation rather than shortage.

44. 44
    Kramer M, Mele F, Jovic S, et al. Clonal analysis of SepSecS-specific B and T cells in autoimmune hepatitis.J Clin Invest · 2025 · 135(2):e183776doi:10.1172/JCI183776 · PMID 39817450

    SEPSECS is the soluble liver antigen; anti-SepSecS antibodies go with a more severe phenotype.

45. 45
    Cui Z, Schomburg L, Holleczek B, Hybsier S, Köhrle J, Brenner H, Schöttker B. Serum selenoprotein P concentrations and cardiovascular disease: results from a large, prospective cohort study of older German adults.Free Radic Biol Med · 2025 · 239:270–279doi:10.1016/j.freeradbiomed.2025.07.039 · PMID 40738180

    6,600 people free of cardiovascular disease plus 1,729 who already had it, 17 years of follow-up. The signal is specific rather than general.

46. 46
    Ohlsson MA, Molvin J, Holm Isholth H, et al. Selenoprotein P deficiency is associated with early signs of kidney disease and hospitalization risk in heart failure.Nutrients · 2026 · 18(5):721doi:10.3390/nu18050721 · PMID 41829892

    320 patients with the assay done, a 43-month follow-up, and a concrete cut-off. 58% of them were selenium-deficient.

47. 47
    Linn YH, Aziz S, Mok SL. Selenium status and supplementation in thyroid disorders: a narrative review of current evidence.J Trace Elem Med Biol · 2025 · 92:127799doi:10.1016/j.jtemb.2025.127799 · PMID 41206976

    Antibodies fall in autoimmune thyroiditis; effects on hypothyroidism inconsistent.

48. 48
    Zhang H, Yang Y, Liu S, Yang Y, Liu Z. Clinical efficacy of selenium supplementation in patients with Hashimoto thyroiditis: a systematic review and meta-analysis.Medicine (Baltimore) · 2025 · 104(35):e44043doi:10.1097/MD.0000000000044043 · PMID 40898469

    21 trials, 1,610 people. Note which antibody effect does not survive to six months.

49. 49
    Acik H, Aydin Y. The impact of selenium deficiency and supplementation on Hashimoto's thyroiditis: a clinical evaluation.Endocr Metab Immune Disord Drug Targets · 2026 · 26:e18715303424962doi:10.2174/0118715303424962251204064911 · PMID 42083539

    Retrospective, 270 patients and 350 controls, with the antibodies going the wrong way after six months of supplementation. The authors say so against the prior trials.

50. 50
    Berisha-Muharremi V, Tahirbegolli B, Humolli A, Hanna R. Comparative effects of photobiomodulation therapy versus conventional antioxidant supplementation on serum glutathione levels in euthyroid chronic autoimmune thyroiditis: a prospective open-label interventional clinical trial.Antioxidants (Basel) · 2026 · 15(9):1105doi:10.3390/antiox15091105 · PMID 42792144

    Not randomized and open-label, which limits it; the selenium arm is still a measured null on its own proposed mechanism.

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    Rayman MP. Selenium and human health.Lancet · 2012 · 379(9822):1256–1268doi:10.1016/S0140-6736(11)61452-9 · PMID 22381456

    Review: the U-shaped relationship with status; supplementation may harm the replete.

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    Vinceti M, Till C, Goodman PJ, Filippini T, Rothman KJ, Thompson IM. The selenium and vitamin E cancer prevention trial (SELECT): a secondary, post-intervention analysis on potential excess chronic disease incidence induced by selenium administration.Am J Epidemiol · 2026 · kwag189doi:10.1093/aje/kwag189 · PMID 42581651

    34,887 men, Medicare data to 2019 and the National Death Index to 2024, 341,697 person-years. The trial that was supposed to show prevention, followed up long enough to show the other thing.

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    Bahari P, Mobasseri M, Ranjbari S, et al. Impact of organic selenium supplementation on glycaemic control and quality of life in patients with diabetic neuropathy: a randomized placebo-controlled trial.Eur J Nutr · 2026 · 65(6):04091doi:10.1007/s00394-026-04091-8 · PMID 42631762

    Triple-blind, placebo-controlled, 50 patients, eight weeks. A positive result whose own authors list its limits.

54. 54
    Apalowo OE, Adewole TS, Yusuf IF, Schilling MW. Selenium and selenoproteins in age-related metabolic diseases: mechanistic insights and translational perspectives.Front Nutr · 2026 · 13:1908597doi:10.3389/fnut.2026.1908597 · PMID 42713210

    A review that ends by recommending against the product it reviews, except in diagnosed deficiency.

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    Donner K, Seifert R. Selenium containing dietary supplements: market-, efficacy- and risk analysis.J Trace Elem Med Biol · 2026 · 95:127903doi:10.1016/j.jtemb.2026.127903 · PMID 42241865

    70 products from two countries, read against what a national risk authority actually advises, with poison-center data attached.

56. 56
    Sun Q, Dong M, Wang Z, et al. Retraction: Selenium-enriched polysaccharides from (Se-PFPs) inhibit the growth and invasive potential of ovarian cancer cells through inhibiting β-catenin signaling.Oncotarget · 2025 · 16(1):886–887doi:10.18632/oncotarget.28816 · PMID 42664429

    The source organism is missing from the indexed title. PubMed types this as a retraction notice, and the notice states no reason.

57. 57
    Lobanov AV, Fomenko DE, Zhang Y, et al. Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life.Genome Biol · 2007 · 8(9):R198doi:10.1186/gb-2007-8-9-r198 · PMID 17880704

    Independent selenoprotein losses on land; replacement of selenocysteine by cysteine.

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    Ticó M, Mariotti M. The metazoan selenoproteome.Annu Rev Anim Biosci · 2025 · 14(1):107–135doi:10.1146/annurev-animal-030424-072943 · PMID 41212935

    An updated census of selenoprotein families across animals, with the losses and the cysteine substitutions counted.