RTN4IP1

reticulon 4 interacting protein 1

Basic information

Region (hg38): 6:106570770-106629498

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 (260 variants)
• Inborn genetic diseases (20 variants)
• Optic atrophy 10 with or without ataxia, intellectual disability, and seizures (13 variants)
• not specified (3 variants)
• Global developmental delay (2 variants)
• Macrocephaly;Global developmental delay;Chorea;Short stature (1 variants)
• Optic atrophy (1 variants)
• RTN4IP1-related condition (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	39	7	47
missense	1	2	119	4	2	128
nonsense	7		1			8
start loss	1					1
frameshift	6	1				7
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	5	1			7
splice region			9	7		16
non coding			2	25	30	57
Total	16	8	126	68	39

Highest pathogenic variant AF is 0.0000526

Variants in RTN4IP1

This is a list of pathogenic ClinVar variants found in the RTN4IP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-106571760-A-G			Benign (May 15, 2021)
6-106571786-T-C			Benign (May 15, 2021)
6-106571791-A-G			Benign (May 15, 2021)
6-106571999-A-G			Likely benign (May 08, 2022)
6-106572005-A-G			Benign (Jan 31, 2024)
6-106572014-A-C			Likely benign (Jun 01, 2023)
6-106572024-C-T		Inborn genetic diseases	Uncertain significance (Aug 31, 2022)
6-106572025-G-A			Pathogenic (Oct 29, 2022)
6-106572028-C-T			Uncertain significance (Oct 13, 2022)
6-106572029-G-A			Likely benign (Mar 09, 2022)
6-106572033-C-T			Uncertain significance (Sep 01, 2021)
6-106572067-T-C			Uncertain significance (Jul 06, 2022)
6-106572071-A-C		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
6-106572075-G-T			Uncertain significance (Jul 23, 2022)
6-106572092-A-T			Likely benign (May 07, 2021)
6-106572093-A-G		RTN4IP1-related disorder	Likely benign (Dec 07, 2023)
6-106572098-C-A			Likely benign (Jul 10, 2023)
6-106572099-C-T			Uncertain significance (Jul 14, 2022)
6-106572100-G-A			Uncertain significance (Sep 08, 2022)
6-106572101-G-A			Benign/Likely benign (Dec 16, 2023)
6-106572103-T-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jul 05, 2022)
6-106572113-A-G			Likely benign (Oct 18, 2022)
6-106572119-G-T			Benign (Jan 31, 2024)
6-106572122-T-G			Likely benign (Jan 12, 2023)
6-106572213-A-G			Benign (May 15, 2021)

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