Humanin: the 24-residue mitochondrial-derived peptide and its US status

Humanin is a 24-residue peptide, MAPRGFSCLLLLTSEIDLPVKRRA, made of coded L-amino acids with a free N-terminal amine and a free C-terminal acid. Its formula is C119H204N34O32S2 and its molecular weight 2687.2 (PubChem CID 16131438, CAS 330936-69-1, UniProt Q8IVG9). A Keio University group reported it in 2001 from a cDNA screen, and its coding sequence matches part of the mitochondrial 16S rRNA gene, MT-RNR2. As of November 7, 2026, no drug containing humanin is approved in the United States, and it is on none of FDA's compounding lists. The humanin sold here is research material, not an approved drug: ours is sold for laboratory research use only.

Who found it, and how

Yuichi Hashimoto, Ikuo Nishimoto and colleagues at Keio University School of Medicine, Tokyo, published the first report in PNAS on May 22, 2001: "Through functional expression screening, we identified a gene, designated Humanin (HN) cDNA, which encodes a short polypeptide." The library came from human occipital cortex, and the clone carried "a 75-base ORF that encodes a 24-residue peptide MAPRGFSCLLLLTSEIDLPVKRRA". The cDNA is GenBank AY029066, a 1,567-base mRNA submitted March 28, 2001.

The sequence, and what it means for testing

With five basic and three acidic groups, the net charge at neutral pH is about plus two. Without tryptophan or tyrosine, humanin absorbs weakly at 280 nm, so purity is read near 214 nm, where peptide bonds absorb (reading a chromatogram). An NMR study of synthetic humanin (Benaki and colleagues, 2005) found it "predominantly in an unstructured conformation" in water and helical from Gly5 to Leu18 in 30% trifluoroethanol.

The 16S rRNA question

The Keio group wrote in 2002 that the 1,567-base cDNA "is 99% identical to mitochondrial 16S ribosomal RNA as well as registered human mRNA", so "it was elusive whether HN is produced in vivo."

UniProt files humanin under MT-RNR2 (HGNC:7471), which HGNC names "mitochondrially encoded 16S rRNA", and adds a caution: translated inside mitochondria with the mitochondrial genetic code, the message would give a peptide "lacking the last three C-terminal residues", 21 residues ending at Lys21. UniProt says the mechanisms of production and secretion "remain unclear" and that a related gene in the nuclear genome may encode the peptide instead. Bodzioch and colleagues (2009) reported "13 MT-RNR2-like nuclear loci predicted to maintain the open reading frames of 15 distinct full-length HN-like peptides."

"Mitochondrial-derived" therefore describes where the sequence was first matched; which copy gives rise to the 24-residue chain is an open question. For testing research material, identity is the sequence and its mass either way.

Humanin and MOTS-c

UniProt records the gene location of both as the mitochondrion.

Lee and colleagues named MOTS-c in 2015 for "mitochondrial open reading frame of the 12S rRNA-c" and cited humanin as the earlier short open reading frame in mitochondrial DNA. Our SS-31 article compares MOTS-c with a synthetic peptide.

HNG, the S14G analogue

A second 2001 paper from the Keio group named "S14G HN (HNG)": serine 14 replaced by glycine, MAPRGFSCLLLLTGEIDLPVKRRA. We compute C118H202N34O31S2, monoisotopic mass 2655.47 and average mass 2657.2, which is 30.01 lighter than humanin.

Mass and charge states

We computed these from C119H204N34O32S2; the monoisotopic mass matches PubChem's, 2685.4822.

Five groups can carry a proton, so electrospray can show charge states up to 5+; 2687.2 is the average mass. See mass spectrometry and peptide identity and, for methionine and cysteine, freeze-thaw, aliquots and oxidation.

US status as of November 7, 2026

A UNII identifies a substance; it is not an approval or a listing. The lists are explained in Category 1, Category 2 and the 503A bulks list. Research humanin is not an approved drug; it is sold for laboratory research use only and is not for human or veterinary use.

What a certificate for research humanin should show

A humanin certificate should name the lot, laboratory and date, give purity by reversed-phase HPLC near 214 nm, and tie identity by mass spectrometry to 2685.48 or the charge states above. A main mass near 2655 indicates HNG; a peak 16 heavier, oxidized methionine.

Our 10 mg size has two certificates from Bioviridian Inc., the testing laboratory, both issued August 28, 2026:

Both report endotoxin below 0.05 EU/ml (USP <85>), heavy metals below 0.01 ppm (USP <232>) and sterility "Not Detected" (USP <71>). Certificate numbers can be checked on the laboratory's site (how to verify a lab report).

Common questions

Is humanin FDA approved?

No. Drugs@FDA lists no product containing it (checked November 7, 2026), and it is in none of FDA's 503A or 503B categories or bulks lists.

Sources

• PubChem CID 16131438, Humanin
• UniProt Q8IVG9, Humanin (human)
• UniProt A0A0C5B5G6, MOTS-c (human)
• FDA Global Substance Registration System, UNII H975EUX36G
• Hashimoto Y et al., Proc Natl Acad Sci USA 98:6336, 2001 (PMC33469)
• GenBank AY029066, NCBI
• Tajima H et al., Neurosci Lett 324:227, 2002
• Hashimoto Y et al., J Neurosci 21:9235, 2001
• Benaki D et al., Biochem Biophys Res Commun 329:152, 2005
• Bodzioch M et al., Genomics 94:247, 2009
• Lee C et al., Cell Metab 21:443, 2015
• HGNC:7471, MT-RNR2
• openFDA drugsfda endpoint, November 7, 2026
• 503A categories (PDF), FDA, updated May 14, 2026
• Category 2 page, FDA, April 22, 2026
• 21 CFR 216.23, eCFR
• 503B categories (PDF), FDA, updated March 21, 2025
• 503B Bulk Drug Substances List, FDA, updated August 21, 2023
• Federal Register search for "humanin", November 7, 2026