C19ORF12

Chr 19ARAD

chromosome 19 open reading frame 12

Also known as: MPAN, NBIA3, NBIA4, SPG43

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]

GeneReviewsOMIMResearchGenerating clinical summary…
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.
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ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 174 VUS of 346 total submissions
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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

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 OE?0.22 (0.081.06)
00.351.4
Missense OE?0.89 (0.741.06)
00.61.4
Synonymous OE?1.15
01.21.6
LoF obs/exp: 1 / 4.5Missense obs/exp: 84 / 94.7Syn Z: -0.78

ClinVar Variant Classifications

346 submitted variants in ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic20
VUS174
Likely Benign75
Benign42
Conflicting13
13
Pathogenic
20
Likely Pathogenic
174
VUS
75
Likely Benign
42
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
2
1
0
13
Likely Pathogenic
12
7
1
0
20
VUS
15
74
85
0
174
Likely Benign
0
1
34
40
75
Benign
0
1
40
1
42
Conflicting
13
Total378516141337

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap C19ORF12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

C19ORF12 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →