RTN4IP1

Chr 6AR

reticulon 4 interacting protein 1

Also known as: NIMP, OPA10, Yim1

NCBI Gene: 84816 ENSG00000130347 UniProt: Q8WWV3 OMIM: 610502

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.941 OMIM phenotype

Clinical Summary— RTN4IP1

🧬

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.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.000

Z-score 1.78

OE 0.58 (0.37–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.73Z-score

OE missense 0.86 (0.77–0.97)

192 obs / 222.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.37–0.94)

0≤0.351.4

Missense OE?0.86 (0.77–0.97)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

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

This gene — mechanism propensity

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

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.