RTN4IP1

Chr 6AR

reticulon 4 interacting protein 1

Also known as: NIMP, OPA10, Yim1

NCBI Gene: 84816ENSG00000130347UniProt: Q8WWV3

This gene encodes a mitochondrial protein that interacts with reticulon 4, which is a potent inhibitor of regeneration following spinal cord injury. This interaction may be important for reticulon-induced inhibition of neurite growth. Mutations in this gene can cause optic atrophy 10, with or without ataxia, cognitive disability, and seizures. There is a pseudogene for this gene on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Optic atrophy 10 with or without ataxia, impaired intellectual development and seizuresMIM #616732
AR
385
ClinVar variants
56
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RTN4IP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
56 Pathogenic / Likely Pathogenic· 173 VUS of 385 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.000
Z-score 1.78
OE 0.58 (0.37–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.73Z-score
OE missense 0.86 (0.77–0.97)
192 obs / 222.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.58 (0.37–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.77–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 12 / 20.8Missense obs/exp: 192 / 222.6Syn Z: -0.61

ClinVar Variant Classifications

385 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic12
VUS173
Likely Benign107
Benign42
Conflicting7
44
Pathogenic
12
Likely Pathogenic
173
VUS
107
Likely Benign
42
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
5
29
0
44
Likely Pathogenic
6
2
4
0
12
VUS
1
147
25
0
173
Likely Benign
0
6
41
60
107
Benign
0
1
36
5
42
Conflicting
—7
Total1716113565385

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

View 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.

Gene2Phenotype Curations

RTN4IP1-related optic atrophy with or without ataxia, intellectual developmental disorder, and seizures

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Optic atrophy 10 with or without ataxia, impaired intellectual development and seizures

MIM #616732

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RTN4IP1 is required for the final stages of mitochondrial complex I assembly and CoQ biosynthesis.
Oláhová M et al.·EMBO J
2025
The top 10 most frequently involved genes in hereditary optic neuropathies in 2186 probands.
Rocatcher A et al.·Brain
2023
Time-resolved mitochondrial screen identifies regulatory components of oxidative metabolism.
Zamora-Dorta M et al.·EMBO Rep
2025
A Novel Homozygous Founder Variant of RTN4IP1 in Two Consanguineous Saudi Families.
Aldosary M et al.·Cells
2022
Whole Exome Sequencing Identifies Two Novel Mutations in the Reticulon 4-Interacting Protein 1 Gene in a Chinese Family with Autosomal Recessive Optic Neuropathies.
Zou XH et al.·J Mol Neurosci
2019Case report
Exome sequencing identifies novel missense and deletion variants in RTN4IP1 associated with optic atrophy, global developmental delay, epilepsy, ataxia, and choreoathetosis.
D'Gama AM et al.·Am J Med Genet A
2021Case report
RTN4IP1 is down-regulated in thyroid cancer and has tumor-suppressive function.
Rahbari R et al.·J Clin Endocrinol Metab
2013
RTN4IP1-associated non-syndromic optic neuropathy and rod-cone dystrophy.
Gupta PR et al.·Ophthalmic Genet
2024Case report
Optic Atrophy and Generalized Chorea in a Patient Harboring an OPA10/RTN4IP1 Pathogenic Variant.
Giacomini T et al.·Neuropediatrics
2020Case report
Neurologic Phenotypes Associated With Mutations in RTN4IP1 (OPA10) in Children and Young Adults.
Charif M et al.·JAMA Neurol
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools