C19ORF12

Chr 19ARAD

chromosome 19 open reading frame 12

Also known as: MPAN, NBIA3, NBIA4, SPG43

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.

OMIMResearchSummary from RefSeq, OMIM
LOFmechanismAR/ADLOEUF 1.062 OMIM phenotypes
Clinical SummaryC19ORF12
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Gene-Disease Validity (ClinGen)
neurodegeneration with brain iron accumulation 4 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.06LOEUF
pLI 0.344
Z-score 1.52
OE 0.22 (0.081.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.39Z-score
OE missense 0.89 (0.741.06)
84 obs / 94.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.081.06)
00.351.4
Missense OE0.89 (0.741.06)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 1 / 4.5Missense obs/exp: 84 / 94.7Syn Z: -0.78

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

C19ORF12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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