RIC3

protein-coding

RIC3 acetylcholine receptor chaperone

Gene summary

This gene encodes a member of the resistance to inhibitors of cholinesterase 3-like family which functions as a chaperone of specific 5-hydroxytryptamine type 3 receptor and nicotinic acetylcholine receptor subtypes. The encoded protein influences the folding and assembly of these receptor subunits in the endoplasmic reticulum and expression on the cell surface. This protein contains an N-terminal transmembrane domain, a proline-rich spacer, and a cytosolic C-terminal coiled-coil domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

MANE transcript

NM_001206671.4

Inheritance

AD, AR

ClinVar variants

U:58B:8

Top phenotype

RIC3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr11:8,106,056-8,169,055

External References & Databases

Ensembl (ENSG00000166405)

Transcript & Mutation Effects

hg38 • Region Span ~63.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Parkinson diseaseLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005180

Submitter: Ambry Genetics

movement disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005395

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RIC3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 6

RIC3-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001206671.4. 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				1 clinvar		1
missense			56 clinvar	4 clinvar	3 clinvar	63
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	58	5	3	66

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001206671.4	RefSeq	NP_001193600.1	6	MANE Select
ENST00000309737.11	Ensembl	ENSP00000308820.6	6	MANE Select
NM_001135109.4	RefSeq	NP_001128581.1	2	Standard
NM_001206672.4	RefSeq	NP_001193601.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein folding
positive regulation of cytosolic calcium ion concentration
synaptic transmission, cholinergic
protein localization to cell surface
cellular protein-containing complex assembly

Molecular Function

acetylcholine receptor binding
protein folding chaperone

Cellular Component

Golgi membrane
endoplasmic reticulum membrane
integral component of membrane
neuron projection
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309737
Coding exons: 6
Length: 63006
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 39
Defined: 125748
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.640	220	195	1.13	0.00000954	2397
Missense (PolyPhen)		71	71.182	0.99744		897
Synonymous	-1.74	90	71.3	1.26	0.00000363	712
Loss of Function	1.16	11	16.0	0.687	8.50e-7	200

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00033	0.00033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes functional expression of homomeric alpha-7 and alpha-8 nicotinic acetylcholine receptors at the cell surface. May also promote functional expression of homomeric serotoninergic 5- HT3 receptors, and of heteromeric acetylcholine receptors alpha- 3/beta-2, alpha-3/beta-4, alpha-4/beta-2 and alpha-4/beta-4. {ECO:0000269|PubMed:12821669, ECO:0000269|PubMed:15504725, ECO:0000269|PubMed:15809299, ECO:0000269|PubMed:15927954, ECO:0000269|PubMed:16120769, ECO:0000269|PubMed:17609200, ECO:0000269|PubMed:18691158}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.385
RVIS EVS: 1.62
RVIS percentile EVS: 96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.275

Gene Damage Prediction

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