RTN3

protein-coding

reticulon 3

Gene summary

This gene belongs to the reticulon family of highly conserved genes that are preferentially expressed in neuroendocrine tissues. This family of proteins interact with, and modulate the activity of beta-amyloid converting enzyme 1 (BACE1), and the production of amyloid-beta. An increase in the expression of any reticulon protein substantially reduces the production of amyloid-beta, suggesting that reticulon proteins are negative modulators of BACE1 in cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, and pseudogenes of this gene are located on chromosomes 4 and 12. [provided by RefSeq, May 2012]

MANE transcript

NM_001265589.2

Inheritance

—

ClinVar variants

U:152B:16

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr11:63,681,446-63,759,891

External References & Databases

Ensembl (ENSG00000133318)

Transcript & Mutation Effects

hg38 • Region Span ~78.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RTN3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 159

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001265589.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar	2 clinvar	5
missense			151 clinvar	11 clinvar	1 clinvar	163
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	152	13	3	168

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 87 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001265589.2	RefSeq	NP_001252518.1	9	MANE Select
ENST00000377819.10	Ensembl	ENSP00000367050.5	9	MANE Select
NM_001265590.2	RefSeq	NP_001252519.1	8	Standard
NM_001265591.2	RefSeq	NP_001252520.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alzheimer,s disease - Homo sapiens (human)
Neuronal System
Synaptic adhesion-like molecules
Protein-protein interactions at synapses

Biological Process

apoptotic process
viral process
vesicle-mediated transport
endoplasmic reticulum tubular network organization
endoplasmic reticulum tubular network formation

Molecular Function

protein binding

Cellular Component

Golgi membrane
extracellular space
endoplasmic reticulum
endoplasmic reticulum membrane
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377819
Coding exons: 9
Length: 78446
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125748
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.239	546	530	1.03	0.0000254	6764
Missense (PolyPhen)		120	127.73	0.93948		1689
Synonymous	-0.0923	205	203	1.01	0.0000103	2062
Loss of Function	3.24	13	33.1	0.392	0.00000148	472

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0	0.0	absent
Finnish	0.000055	0.000046	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in membrane trafficking in the early secretory pathway. Inhibits BACE1 activity and amyloid precursor protein processing. May induce caspase-8 cascade and apoptosis. May favor BCL2 translocation to the mitochondria upon endoplasmic reticulum stress. In case of enteroviruses infection, RTN3 may be involved in the viral replication or pathogenesis. Induces the formation of endoplasmic reticulum tubules (PubMed:25612671). {ECO:0000269|PubMed:15286784, ECO:0000269|PubMed:16054885, ECO:0000269|PubMed:17031492, ECO:0000269|PubMed:17191123, ECO:0000269|PubMed:25612671}.;

Recessive Scores

pRec: 0.0968

Intolerance Scores

LoFtool: 0.847
RVIS EVS: -0.84
RVIS percentile EVS: 11.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.905

Gene Damage Prediction

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