RNF170

protein-coding

ring finger protein 170, the group of MicroRNA protein coding host genes|Ring finger proteins

Gene summary

This gene encodes a RING domain-containing protein that resides in the endoplasmic reticulum (ER) membrane. This protein functions as an E3 ubiquitin ligase and mediates ubiquitination and processing of inositol 1,4,5-trisphosphate (IP3) receptors via the ER-associated protein degradation pathway. It is recruited to the activated IP3 receptors by the ERLIN1/ERLIN2 complex to which it is constitutively bound. Mutations in this gene are associated with autosomal dominant sensory ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

Previous symbols:

SNAX1

MANE transcript

NM_030954.4

Inheritance

AR, AD

ClinVar variants

P:10U:36B:6

Top phenotype

Ataxia, sensory, 1, autosomal dominant; Spastic paraplegia 85, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr8:42,849,637-42,897,290

External References & Databases

Ensembl (ENSG00000120925)

Transcript & Mutation Effects

hg38 • Region Span ~47.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spastic paraplegia 85, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030512

Submitter: Labcorp Genetics (formerly Invitae)

autosomal dominant sensory ataxia 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012166

Submitter: Labcorp Genetics (formerly Invitae)

autosomal dominant sensory ataxia 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012166

Submitter: PanelApp Australia

spastic paraplegia 85, autosomal recessiveSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030512

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ataxia, sensory, 1, autosomal dominant; Spastic paraplegia 85, autosomal recessiveAD/AR

Manifestation: Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 17190954; 21115467; 31636353

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RNF170 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 23

not providedTotal: 19

Spastic paraplegia 85, autosomal recessiveTotal: 9

Autosomal dominant sensory ataxia 1Total: 8

not specifiedTotal: 5

RNF170-related disorderTotal: 5

Spastic paraplegiaTotal: 2

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030954.4. 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			2 clinvar	2 clinvar	1 clinvar	5
missense	1 clinvar	4 clinvar	33 clinvar	2 clinvar	1 clinvar	41
nonsense	2 clinvar	1 clinvar				3
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	4	6	36	4	2	52

Highest pathogenic variant AF is 0.00012478918

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030954.4	RefSeq	NP_112216.3	6	MANE Select
ENST00000527424.6	Ensembl	ENSP00000434797.1	6	MANE Select
NM_001160223.2	RefSeq	NP_001153695.1	6	Standard
NM_001160224.2	RefSeq	NP_001153696.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
rnf170	Danio rerio	Structure: whole organism Quality: dead abnormal

Gene / Model

Organism

Observed Phenotype

rnf170

Danio rerio

Structure: whole organism

Quality: dead

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein ubiquitination

Molecular Function

protein binding
metal ion binding
ubiquitin protein ligase activity

Cellular Component

endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000534961
Coding exons: 6
Length: 47654
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.42	93	140	0.663	0.00000701	1686
Missense (PolyPhen)		20	37.733	0.53004		477
Synonymous	0.810	40	47.1	0.850	0.00000224	496
Loss of Function	2.86	3	14.9	0.201	8.48e-7	157

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000091	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway. Also involved in ITPR1 turnover in resting cells. {ECO:0000269|PubMed:21610068}.;

Recessive Scores

pRec: 0.0928

Intolerance Scores

LoFtool: 0.174
RVIS EVS: 0.17
RVIS percentile EVS: 65.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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