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TMEM69, also known as Transmembrane protein 69, is a protein that in humans is encoded by the TMEM69 gene.[5] A notable feature of the protein encoded by TMEM69 is the presence of five transmembrane segments.[6]

AliasesTMEM69, C1orf154, transmembrane protein 69
External IDsMGI: 3045357 HomoloGene: 9531 GeneCards: TMEM69
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for TMEM69
Genomic location for TMEM69
Band1p34.1Start45,688,181 bp[1]
End45,694,436 bp[1]
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 1: 45.69 – 45.69 MbChr 4: 116.55 – 116.56 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse


Background InformationEdit

Accession Numbers Location Identifiers M.W. pI
mRNA: NM_016486.3

protein: NP_057570.2 [5]

1p34.1 HSPC229, C1orf154, FLJ21029, LOC51249 27.6 kDa 10.3


The TMEM69 gene, located on chromosome 1p34.1, covers 7.24 kb.[7] It is on the plus strand in the genomic sequence from 46152886 to 46160121 and encodes a primary mRNA transcript that contains 3 exons and is 6262 bp in length. Three alternative transcripts are predicted to encode the TMEM69 gene.[8]

Gene NeighborhoodEdit

Name of Gene Location Orientation Function
GPBP1L1 (GC-rich promoter binding protein 1-like 1) 1p34.1 minus Functions in regulation of transcription[9]
CCDC17 (coiled-coil domain containing 17) 1p34.1 minus No functional information found
MAST2 (microtubule associated serine/threonine kinase 2) 1p34.1 plus Functions in a multi-protein

complex in spermatid maturation. Regulates lipopolysaccharide-induced IL-12 synthesis in macrophages[10]||

IPP (Intracisternal A particle-promoted polypeptide) 1p34-p32 minus interacts with actin[11]


The exact function of TMEM69 is not yet understood by the scientific community. It is, however, thought to play a role as a scaffolding protein in a G-coupled protein receptor complex in Xenopus tropicalis. It has been shown to form a cluster with the xtGPR54-2 gene IPP, and GPBP1 in scaffold_41.[12] This complex is part of a G-coupled protein receptor which acts as the receptor for a binding ligand, kisspeptin in the plasma membrane of brain cells.[12]


TMEM69 is 247 amino acids in length. Five transmembrane segments are present as well as a domain of unknown function, DUF3429, which spans amino acids 91-232.[13]


Predicted FeaturesEdit

Properties of TMEM69 that were predicted using Bioinformatics tools:

  • Molecular Weight: 27.6 KDa.[7]
  • Isoelectric Point: 10.3[14]
  • Post-translational modification: Multiple phosphorylation sites are predicted from the NetPhos program on ExPASy . NetPhos predicted 7 for the amino acid serine at position 12, 27, 33, 85, 93, 183, and 234; 1 for threonine at position 26; and 2 for tyrosine at position 57 and 159.[15] NetGlyc on ExPASy predicted 5 glycation sites at positions 7, 60, 73, 156, and 239.
  • Transmembrane Segments: TMEM69 contains 5 transmembrane regions occurring at positions 97-117, 122-142, 159-179, 185-205, and 216-236.[16]


TMEM69 is expressed ubiquitously at low levels throughout the human body, although EST Profile data reveal that TMEM69 is expressed particularly high in neuroendocrine tissues such as the liver, amygdala, hippocampus, and hypothalamus.[17] TMEM69 was found to be expressed in lower than normal values in patients suffering from atherosclerosis.[18]



The TMEM69 gene is deeply conserved in several life forms. Although it shows highest conservation among mammalian orthologs, along with other chordates such as fish, birds, and amphibians, there is some conservation in plants, insects, fungi, and bacteria.[13]

Genus/Species Organism Common Name Accession Number Sequence Identity Length (AAs)
Macaca fascicularis Crab-eating macaque EHH61428.1 89% 246
Callithrix jacchus Monkey XP_002750811.1 83% 249
Mus musculus House Mouse AAI06179.1 69% 245
Xenopus tropicalis Frog NP_001016103.1 49% 253
Rattus norvegicus Rat EDL90276.1 70% 247
Oryctolagus cuniculus Rabbit XP_002715715 74% 250
Anolis carolinensis Lizard XP_003220264.1 50% 257
Danio rerio Zebrafish XP_685684.1 49% 249
Salmo salar Salmon NP_001134056.1 50% 259
Daphia pulex Water flea EFX84634.1 35% 208
Ostreococcus tauri Green algae XP_003081614.1 34% 166
Pseudomonas putida W619 Soil bacterium YP_001748891.1 32% 152
Schizophyllum commune Fungus XP_003035659.1 27% 363


No paralogs were found for TMEM69.


TMEM69 is well conserved in a variety of organisms. Although most orthologs are found in placental mammals, some orthologs are found in bacteria and fungi. The most distant ortholog found to have sequence similarity with TMEM69 is Pseudomonas putida W619, which is a type of soil bacterium.[19] Particularly well conserved in even the most distant orthologs, including Pseudomonas putida W619, is most of the second transmembrane segment of TMEM69. In strict orthologs, all five transmembrane domains are conserved.[20] Conserved domains found within TMEM69 are part of DUF3429, which is a family of uncharacterized proteins found in bacteria and eukaryotes.[13]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000159596 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000055900 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ a b "Entrez Gene: TMEM69 Transmembrane Protein 69". Retrieved 22 April 2012.
  6. ^ "Expasy: SOSUI". Archived from the original on 15 May 2012. Retrieved 15 April 2012.
  7. ^ a b "TMEM69". Retrieved 2 February 2012.
  8. ^ "Transcript VariantsTMEM69". Retrieved 13 February 2012.
  9. ^ "NCBI:Gene". Retrieved 13 April 2012.
  10. ^ "NCBI:Gene". Retrieved 13 April 2012.
  11. ^ "NCBI:Gene". Retrieved 13 April 2012.
  12. ^ a b "Molecular Evolution of Multiple Forms of Kisspeptins and GPR54 Receptors in Vertebrates". Retrieved 22 April 2012.
  13. ^ a b c "BLAST". Retrieved 16 February 2012.
  14. ^ "Computer pI/Mw". Retrieved 11 April 2012.
  15. ^ "NetPhos". Retrieved 13 April 2012.
  16. ^ "UniProtKB". Retrieved 22 February 2012.
  17. ^ "GeneCards". Retrieved 18 April 2012.
  18. ^ "GEOProfiles". Retrieved 22 February 2012.
  19. ^ "Ensembl Genome Browser: TMEM69". Retrieved 22 April 2012.
  20. ^ "Biology Workbench: CLUSTALW". Retrieved 22 April 2012.[permanent dead link]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.