SMIM18 notes

2026-10-03 - initial review (MICROPROTEINS Tier 2)

Identity

• UniProt P0DKX4 (SIM18_HUMAN), 95 aa, PE1 (proteomics identification). HGNC:42973, chr 8p12.
• Single predicted helical TM segment, residues 35-55 [file:human/SMIM18/SMIM18-uniprot.txt "FT TRANSMEM 35..55"].
  Location annotation is by sequence analysis only [file:human/SMIM18/SMIM18-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane"].
• Gene lies inside an intron of GTF2E2, opposite strand [file:human/SMIM18/SMIM18-uniprot.txt "CC -!- CAUTION: Encoded in intron of the gene GTF2E2 (opposite strand)."].
  Ensembl REST overlap (8:30638559-30647260) confirms SMIM18 on + strand within GTF2E2 (- strand); a RNU5A-3P snRNA pseudogene also sits in the region.
• Sequence features from my own inspection (not experimentally tested): N-x-T sequon at N6 (NETT) in the
  ~34-residue N-terminal segment; a CCCC cluster (residues 61-64) immediately after the TM helix;
  basic/charged C-terminal tail. The juxtamembrane cysteine cluster is also a feature of its relative SMIM22/CASIMO1.

Family / conservation

• InterPro IPR031671 "SMIM5/18/22", Pfam PF15831 SMIM5_18_22, CDD cd20255 CASIMO1_SMIM22; PANTHER PTHR36982:SF1
  [file:human/SMIM18/SMIM18-uniprot.txt "DR InterPro; IPR031671; SMIM5/18/22."].
• So SMIM18 is a relative of SMIM22 (CASIMO1), the only member with functional data (SQLE binding, breast cancer cell
  proliferation) PMID:29765154. Family membership
  alone does not transfer this function: the shared region is essentially the TM helix plus juxtamembrane motif.
• Ensembl Compara (REST homology/id/human/ENSG00000253457, type=orthologues): 152 species with orthologues,
  including teleost fish (danio_rerio) and elephant shark (callorhinchus_milii) -> conserved across jawed vertebrates.
  Ensembl lists no human paralogues.
• PAN-GO: 0 IBA annotations.

Expression

• HPA: "Group enriched (brain, pituitary gland, retina)" [file:human/SMIM18/SMIM18-uniprot.txt "DR HPA; ENSG00000253457; Group enriched (brain, pituitary gland, retina)."];
  Bgee top: cortical plate. Original cDNA came from fetal brain [file:human/SMIM18/SMIM18-uniprot.txt "RC TISSUE=Fetal brain;"].

Literature

• PubMed esearch "SMIM18" (tiab and all fields): 0 hits (2026-10-03). No aliases in NCBI Gene (GeneID 100507341).
• NCBI Gene-linked PMIDs: 15885500 (cDNA discovery screen, CAP-Trapper; does not discuss this gene individually),
  20125193 (cognitive-test GWAS; gene-level association only), 8889548 (cDNA library method). None functional.
• PMID:15885500 - source of the mRNA sequence only.

Conclusion

• No functional literature. Only GOA row is IEA membrane (UniProt SubCell mapping) - correct, ACCEPT.
• No MF/BP can be supported; core_functions left empty. No NEW terms.
• Not in gocams/index.tsv.