Optic atrophy 10 with or without ataxia, intellectual disability, and seizures

Summary

Optic atrophy 10 with or without ataxia, intellectual disability, and seizures (MONDO:0020737) is a disease caused by RTN4IP1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: RTN4IP1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	optic atrophy 10 with or without ataxia, intellectual disability, and seizures
Mondo ID	MONDO:0020737
OMIM	616732
DOID	DOID:0111434
UMLS	C4225227
MedGen	905727
GARD	0018200
Is cancer (heuristic)	no

Also known as: OPA10 · optic atrophy 10 with or without ataxia, mental retardation, and seizures · RTN4IP1-optic atrophy 10 with or without ataxia, impaired intellectual development and seizures · RTN4IP1-related optic atrophy with or without neurological features

Data availability: 22 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › optic nerve disorder › optic atrophy › primary optic atrophy › hereditary optic atrophy › optic atrophy 10 with or without ataxia, intellectual disability, and seizures

Related subtypes (14): optic atrophy 13 with retinal and foveal abnormalities, optic atrophy 6, optic atrophy 2, Leber hereditary optic neuropathy, optic atrophy 4, autosomal recessive optic atrophy, OPA7 type, optic atrophy 11, osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome, autosomal dominant optic atrophy, optic atrophy 12, optic atrophy 14, optic atrophy 15, optic atrophy 16, ACO2-related optic atrophy with or without extraocular features

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

22 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 7 pathogenic, 2 conflicting classifications of pathogenicity, 2 benign, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1213927	NM_032730.5(RTN4IP1):c.2T>C (p.Met1Thr)	RTN4IP1	Pathogenic	criteria provided, single submitter
1405046	NM_032730.5(RTN4IP1):c.59G>A (p.Trp20Ter)	RTN4IP1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1686986	NM_032730.5(RTN4IP1):c.500C>T (p.Ser167Phe)	RTN4IP1	Pathogenic	no assertion criteria provided
1686987	NM_032730.5(RTN4IP1):c.432G>A (p.Trp144Ter)	RTN4IP1	Pathogenic	no assertion criteria provided
1686988	NM_032730.5(RTN4IP1):c.962G>A (p.Gly321Glu)	RTN4IP1	Pathogenic	no assertion criteria provided
218932	NM_032730.5(RTN4IP1):c.308G>A (p.Arg103His)	RTN4IP1	Pathogenic	criteria provided, multiple submitters, no conflicts
218933	NM_032730.5(RTN4IP1):c.601A>T (p.Lys201Ter)	RTN4IP1	Pathogenic	criteria provided, multiple submitters, no conflicts
997855	NM_032730.5(RTN4IP1):c.806+1G>A	RTN4IP1	Pathogenic	criteria provided, single submitter
2579180	GRCh38/hg38 6q21(chr6:106539306-106649299)x1	LOC129996911	Likely pathogenic	criteria provided, single submitter
807479	NM_032730.5(RTN4IP1):c.313C>T (p.Pro105Ser)	RTN4IP1	Likely pathogenic	criteria provided, single submitter
1034720	NM_032730.5(RTN4IP1):c.1162C>T (p.Arg388Ter)	RTN4IP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
983382	NM_032730.5(RTN4IP1):c.5A>C (p.Glu2Ala)	RTN4IP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030053	NM_032730.5(RTN4IP1):c.92G>C (p.Arg31Thr)	RTN4IP1	Uncertain significance	criteria provided, single submitter
1213928	NM_032730.5(RTN4IP1):c.508C>T (p.Pro170Ser)	RTN4IP1	Uncertain significance	criteria provided, single submitter
1334802	NM_032730.5(RTN4IP1):c.104_117delinsGAAGGATT (p.Thr35_Arg39delinsArgArgIle)	RTN4IP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431466	NM_032730.5(RTN4IP1):c.-328G>T	RTN4IP1	Uncertain significance	criteria provided, single submitter
2431550	NM_032730.5(RTN4IP1):c.275-1299T>C	RTN4IP1	Uncertain significance	criteria provided, single submitter
3064093	NM_032730.5(RTN4IP1):c.475G>T (p.Val159Phe)	RTN4IP1	Uncertain significance	criteria provided, single submitter
3367181	NM_032730.5(RTN4IP1):c.743G>T (p.Gly248Val)	RTN4IP1	Uncertain significance	criteria provided, single submitter
864721	NM_032730.5(RTN4IP1):c.254C>T (p.Pro85Leu)	RTN4IP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1170261	NM_032730.5(RTN4IP1):c.114T>A (p.Pro38=)	RTN4IP1	Benign	criteria provided, multiple submitters, no conflicts
1245120	NM_032730.5(RTN4IP1):c.495+27A>G	RTN4IP1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RTN4IP1	Definitive	Autosomal recessive	optic atrophy 10 with or without ataxia, intellectual disability, and seizures	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RTN4IP1	Orphanet:98676	Autosomal recessive isolated optic atrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RTN4IP1	HGNC:18647	ENSG00000130347	Q8WWV3	NAD(P)H oxidoreductase RTN4IP1, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RTN4IP1	NAD(P)H oxidoreductase RTN4IP1, mitochondrial	NAD(P)H oxidoreductase involved in the ubiquinone biosynthetic pathway.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RTN4IP1	Other/Unknown	no		Quin_OxRdtase/zeta-crystal_CS, GroES-like_sf, ADH-like_N

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
oocyte	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RTN4IP1	223	ubiquitous	yes	secondary oocyte, oocyte, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RTN4IP1	1,969

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RTN4IP1	Q8WWV3	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of dendrite development	1	991.3×	0.002	RTN4IP1
ubiquinone biosynthetic process	1	936.2×	0.002	RTN4IP1
nervous system development	1	45.9×	0.022	RTN4IP1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RTN4IP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RTN4IP1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
RTN4IP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.