RTN4IP1

reticulon 4 interacting protein 1

Basic information

Region (hg38): 6:106570771-106629498

Links

ENSG00000130347 ∙ NCBI:84816 ∙ OMIM:610502 ∙ HGNC:18647 ∙ Uniprot:Q8WWV3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• optic atrophy 10 with or without ataxia, intellectual disability, and seizures (Strong), mode of inheritance: AR
• autosomal recessive optic atrophy (Supportive), mode of inheritance: AR
• optic atrophy 10 with or without ataxia, intellectual disability, and seizures (Moderate), mode of inheritance: AR
• optic atrophy 10 with or without ataxia, intellectual disability, and seizures (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Optic atrophy 10 with or without ataxia, impaired intellectual development, and seizures	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic; Ophthalmologic	26593267

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RTN4IP1 gene.

• not_provided (258 variants)
• Inborn_genetic_diseases (49 variants)
• Optic_atrophy_10_with_or_without_ataxia,_intellectual_disability,_and_seizures (18 variants)
• Retinal_dystrophy (3 variants)
• not_specified (3 variants)
• Optic_atrophy (3 variants)
• RTN4IP1-related_disorder (3 variants)
• Short_stature (1 variants)
• Chorea (1 variants)
• Global_developmental_delay (1 variants)
• See_cases (1 variants)
• Macrocephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RTN4IP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032730.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				54	3	57
missense	4	4	139	10	1	158
nonsense	9	2	1			12
start loss	1					1
frameshift	7	1				8
splice donor/acceptor (+/-2bp)	3	5				8
Total	24	12	140	64	4

Highest pathogenic variant AF is 0.0000458482

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RTN4IP1	protein_coding	protein_coding	ENST00000369063	9	58471

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000314	0.939	125662	0	86	125748	0.000342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.728	192	223	0.863	0.0000114	2582
Missense in Polyphen		69	88.35	0.78099		983
Synonymous	-0.614	82	75.2	1.09	0.00000400	783
Loss of Function	1.78	12	20.8	0.578	0.00000111	239

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000275	0.000275
Ashkenazi Jewish	0.00	0.00
East Asian	0.000166	0.000163
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000424	0.000413
Middle Eastern	0.000166	0.000163
South Asian	0.000688	0.000686
Other	0.000654	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the regulation of retinal ganglion cell (RGC) neurite outgrowth, and hence in the development of the inner retina and optic nerve. Appears to be a potent inhibitor of regeneration following spinal cord injury. {ECO:0000250|UniProtKB:Q924D0}.

Recessive Scores

• pRec: 0.0926

Intolerance Scores

• loftool: 0.811
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.51

Haploinsufficiency Scores

• pHI: 0.0598
• hipred: N
• hipred_score: 0.204
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.600

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rtn4ip1

Zebrafish Information Network

• Gene name: rtn4ip1
• Affected structure: retinal outer plexiform layer
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: regulation of dendrite development;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial outer membrane
• Molecular function: zinc ion binding;oxidoreductase activity