RTN4IP1

Chr 6AR

reticulon 4 interacting protein 1

Also known as: NIMP, OPA10, Yim1

RTN4IP1 encodes a mitochondrial NAD(P)H oxidoreductase required for ubiquinone biosynthesis and COQ3 O-methyltransferase activity, and may regulate retinal ganglion cell neurite outgrowth. Biallelic mutations cause autosomal recessive optic atrophy 10 with or without ataxia, intellectual disability, and seizures. This gene is extremely intolerant to loss-of-function variants (pLI ~1.0), indicating that heterozygous loss-of-function mutations are likely pathogenic in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.941 OMIM phenotype
Clinical SummaryRTN4IP1
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Gene-Disease Validity (ClinGen)
optic atrophy 10 with or without ataxia, intellectual disability, and seizures · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.78
OE 0.58 (0.370.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.73Z-score
OE missense 0.86 (0.770.97)
192 obs / 222.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.58 (0.370.94)
00.351.4
Missense OE0.86 (0.770.97)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 12 / 20.8Missense obs/exp: 192 / 222.6Syn Z: -0.61
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveRTN4IP1-related optic atrophy with or without ataxia, intellectual developmental disorder, and seizuresLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.79top 25%
GOF
0.6637th %ile
LOF
0.2680th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

RTN4IP1 · 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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