SMIM12 review notes

Identity

SMIM12 (previous symbol C1orf212; UniProt Q96EX1, SIM12_HUMAN) is a 92-residue (10.8 kDa)
protein with one predicted helical transmembrane segment at residues 15-34 (UniProt,
ECO:0000255) followed by a ~58-residue hydrophilic, charge-rich C-terminal tail. UniProt
protein existence level 1. Pfam PF15990 (UPF0767), PANTHER PTHR28599 (SMIM12 family).
UniProt subcellular location is "Membrane; Single-pass membrane protein" by curator
inference only (ECO:0000305). UniProt records many cDNA clones translated in the wrong frame.

Literature search (2026-10-03)

PubMed SMIM12[tiab] OR C1orf212[tiab]: 2 hits, both epigenome-wide DNA methylation
association studies (physical activity in pregnancy; air pollution) in which the locus
appears only as a CpG-associated gene. No study of SMIM12 protein function exists.

Localisation evidence

• MitoCoP high-confidence mitochondrial proteome (HTP, PMID:34800366) placed SMIM12 in
  mitochondrial preparations: PMID:34800366. The SMIM12-specific data are in supplementary tables, not the text.
• Human Protein Atlas (ENSG00000163866, JSON inspected 2026-10-03): antibody
  immunofluorescence, reliability "Approved", main location "Mitochondria". This is an
  independent method that agrees with MitoCoP.
• Which mitochondrial membrane (outer vs inner) is not known. The N-terminal TM helix with a
  long C-terminal tail would fit an N-terminally anchored outer-membrane protein, but this is
  speculation from sequence alone.

Expression

HPA: low tissue specificity, detected in all tissues; single-cell enhanced in oesophageal
apical cells and pericytes.

Interactions

Three binary Y2H interactions from the neurodegeneration interactome (PMID:32814053,
abstract-only in cache): LAMP2 isoform B (P13473-2), PRPF40A isoform 2 (O75400-2) and
SH3GLB1/endophilin-B1 (Q9Y371). PMID:32814053. None is validated in a second assay;
LAMP2 (lysosome) and PRPF40A (nuclear splicing factor) are not compartment-compatible with a
mitochondrial membrane protein. SH3GLB1 can associate with mitochondria, but a single Y2H hit
is not evidence of function.

Decisions

• protein binding x3 (IPI): REMOVE (no informative MF supportable; single-TM Y2H hits).
• mitochondrion (HTP): ACCEPT (corroborated by HPA IF).
• membrane (IEA): ACCEPT (correct, uninformative).
• No MF or BP can be assigned. No NEW terms.