C19ORF12

Chr 19ARAD

chromosome 19 open reading frame 12

Also known as: MPAN, NBIA3, NBIA4, SPG43

NCBI Gene: 83636ENSG00000131943UniProt: Q9NSK7OMIM: 614297

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM
LOFmechanismAR/ADLOEUF 1.062 OMIM phenotypes
Clinical Summary— C19ORF12
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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

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
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ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 178 VUS of 364 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — C19ORF12
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.06LOEUF
pLI 0.344
Z-score 1.52
OE 0.22 (0.08–1.06)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.39Z-score
OE missense 0.89 (0.74–1.06)
84 obs / 94.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.08–1.06)
0≤0.351.4
Missense OE0.89 (0.74–1.06)
0≤0.61.4
Synonymous OE1.15
0≤1.21.6
LoF obs/exp: 1 / 4.5Missense obs/exp: 84 / 94.7Syn Z: -0.78

ClinVar Variant Classifications

364 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic22
VUS178
Likely Benign76
Benign42
Conflicting13
24
Pathogenic
22
Likely Pathogenic
178
VUS
76
Likely Benign
42
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
2
11
0
24
Likely Pathogenic
11
7
4
0
22
VUS
15
74
89
0
178
Likely Benign
0
1
35
40
76
Benign
0
1
40
1
42
Conflicting
—13
Total378517941355

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Phase separation of C19orf12 regulates BNIP3 protein quality control and maintains neuronal mitophagy.
Shao C et al.·Autophagy
2026
Autophagy-related proteomics reveals lysosomal alterations linked to C19orf12 mutations and candidate biomarkers in MPAN patients' fibroblasts.
Pakula B et al.·Neurobiol Dis
2026Cohort
Inflammation and oligoclonal bands in cerebrospinal fluid in neurodegeneration associated with C19orf12 mutations.
Skowrońska M et al.·Parkinsonism Relat Disord
2026
Distinct Neurodegenerative Pathways in Two NBIA Subtypes: Inflammatory Activation in C19orf12 but Not in PANK2 Mutation Carriers.
Skowrońska M et al.·Cells
2025Open Access
Loss of mouse C19orf12 homolog disturbs tubular ER homeostasis and leads to neuroaxonal dystrophy.
Wu F et al.·Acta Neuropathol Commun
2025Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients