C19ORF12

Chr 19

chromosome 19 open reading frame 12

Also known as: MPAN, NBIA3, NBIA4, SPG43

NCBI Gene: 83636 ENSG00000131943 UniProt: Q9NSK7

This gene encodes a small transmembrane protein of unknown function. Mutations cause neurodegeneration with brain iron accumulation-4 (NBIA4) and spastic paraplegia 43, inherited in an autosomal recessive pattern. The mechanism of pathogenicity remains unclear given the unknown protein function.

GeneReviews ResearchSummary from RefSeq, OMIM

This gene encodes a small transmembrane protein. Mutations in this gene are a cause of neurodegeneration with brain iron accumulation-4 (NBIA4), but the specific function of the encoded protein is unknown. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodegeneration with brain iron accumulation 4

UniProtSpastic paraplegia 43, autosomal recessive

Clinical highlights

Gene-disease validity (ClinGen)

neurodegeneration with brain iron accumulation 4 · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

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GeneReview available — C19ORF12