RTN4

reticulon 4

Basic information

Region (hg38): 2:54972187-55112621

Links

ENSG00000115310 ∙ NCBI:57142 ∙ OMIM:604475 ∙ HGNC:14085 ∙ Uniprot:Q9NQC3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RTN4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RTN4 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				4	2	6
missense			75	7	4	86
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	76	11	6

Variants in RTN4

This is a list of pathogenic ClinVar variants found in the RTN4 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-54973169-C-T		not specified	Uncertain significance (May 09, 2023)
2-54973170-G-A		not specified	Uncertain significance (Apr 18, 2023)
2-54973569-A-G		not specified	Uncertain significance (Dec 03, 2021)
2-54973570-T-C		not specified	Uncertain significance (Mar 07, 2024)
2-54973590-T-C		not specified	Uncertain significance (Sep 29, 2023)
2-54973828-C-T		not specified	Uncertain significance (Jan 05, 2022)
2-54973837-A-G		not specified	Uncertain significance (Nov 14, 2023)
2-54973865-G-A		not specified	Uncertain significance (Mar 01, 2023)
2-54974710-T-G		not specified	Uncertain significance (Mar 17, 2023)
2-54974736-T-C		not specified	Uncertain significance (Mar 16, 2022)
2-54982570-G-A		not specified	Uncertain significance (Mar 29, 2023)
2-54982573-C-T		not specified	Uncertain significance (Apr 17, 2023)
2-54982589-G-A		not specified	Uncertain significance (Jun 06, 2023)
2-54982628-T-C		not specified	Uncertain significance (Sep 17, 2021)
2-54982646-G-C		not specified	Uncertain significance (Aug 17, 2022)
2-54987503-C-G			Likely benign (Mar 01, 2023)
2-54987537-C-A		not specified	Uncertain significance (Jan 03, 2024)
2-55025104-C-G		not specified	Uncertain significance (Mar 04, 2024)
2-55025123-T-C			Benign (Apr 16, 2018)
2-55025158-G-A		not specified	Uncertain significance (Jan 26, 2022)
2-55025166-T-C		not specified	Uncertain significance (Aug 04, 2023)
2-55025218-G-C			Likely benign (May 14, 2018)
2-55025265-G-A		not specified	Likely benign (Jan 20, 2023)
2-55025278-T-G			Likely benign (May 14, 2018)
2-55025295-G-A		not specified	Uncertain significance (Aug 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RTN4	protein_coding	protein_coding	ENST00000337526	9	140433

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.453	0.547	125735	0	12	125747	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.12	634	560	1.13	0.0000264	7698
Missense in Polyphen		154	143.5	1.0732		1924
Synonymous	-0.118	220	218	1.01	0.0000112	2377
Loss of Function	4.35	8	36.3	0.220	0.00000162	578

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.000164	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000443	0.0000439
Middle Eastern	0.000164	0.000163
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS. Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Isoform 2 reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. Isoform 2 and isoform 3 inhibit BACE1 activity and amyloid precursor protein processing. Induces the formation and stabilization of endoplasmic reticulum (ER) tubules (PubMed:25612671, PubMed:24262037, PubMed:27619977). Regulates membrane morphogenesis in the ER by promoting tubular ER production (PubMed:27619977). Influences NE expansion, nuclear pore complex formation and proper localization of inner nuclear membrane proteins (PubMed:26906412). {ECO:0000250|UniProtKB:Q99P72, ECO:0000269|PubMed:10667797, ECO:0000269|PubMed:11201742, ECO:0000269|PubMed:16965550, ECO:0000269|PubMed:24262037, ECO:0000269|PubMed:25612671, ECO:0000269|PubMed:26906412, ECO:0000269|PubMed:27619977}.
• Pathway: Alzheimer,s disease - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Spinal Cord Injury;Signal Transduction;Death Receptor Signalling;Axonal growth inhibition (RHOA activation);p75NTR regulates axonogenesis;p75 NTR receptor-mediated signalling;p75(NTR)-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.235

Intolerance Scores

• loftool: 0.805
• rvis_EVS: 1.85
• rvis_percentile_EVS: 97.13

Haploinsufficiency Scores

• pHI: 0.407
• hipred: N
• hipred_score: 0.289
• ghis: 0.435

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.836

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rtn4
• Phenotype: normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Zebrafish Information Network

• Gene name: rtn4b
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: immature

Gene ontology

• Biological process: blastocyst formation;apoptotic process;axonal fasciculation;positive regulation of epithelial cell migration;cerebral cortex radial glia guided migration;negative regulation of cell growth;negative regulation of axon extension;positive regulation of mammary gland epithelial cell proliferation;regulation of apoptotic process;negative regulation of axonogenesis;protein stabilization;nuclear pore complex assembly;positive regulation of protein kinase B signaling;cardiac epithelial to mesenchymal transition;endoplasmic reticulum tubular network organization;endoplasmic reticulum tubular network formation;positive regulation of protein localization to endoplasmic reticulum;positive regulation of ERBB3 signaling pathway;endoplasmic reticulum tubular network membrane organization;regulation of branching morphogenesis of a nerve
• Cellular component: nuclear envelope;endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;postsynaptic density;integral component of endoplasmic reticulum membrane;cell projection;neuronal cell body;endoplasmic reticulum tubular network;endoplasmic reticulum tubular network membrane
• Molecular function: RNA binding;protein binding;ubiquitin protein ligase binding;cadherin binding