ARR3

protein-coding

arrestin 3, the group of Classical arrestins

Gene summary

The protein encoded by this gene is a non-visual arrestin which binds to agonist-activated, phosphorylated G protein-coupled receptors. This binding uncouples the receptor from the heterotrimeric G protein, resulting in termination of the G protein-coupled receptor signaling. The encoded protein also is a part of the centrosome, interacting with gamma-tubulin to help regulate proper centrosome function. [provided by RefSeq, May 2016]

MANE transcript

NM_004312.3

Inheritance

ClinVar variants

P:16U:88B:38

Top phenotype

Myopia 26, X-linked, female-limited

gnomAD constraint

pLI —, LoF o/e 0.28

Max pathogenic AF

—

Genomic locus

chrX:70,268,305-70,281,840

External References & Databases

Ensembl (ENSG00000120500)

Transcript & Mutation Effects

hg38 • Region Span ~13.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

myopia 26, X-linked, female-limitedMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0049221

Submitter: Ambry Genetics

myopia 26, X-linked, female-limitedSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0049221

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Myopia 26, X-linked, female-limitedXL

Manifestation: 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: 27829781

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARR3 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 45

Inborn genetic diseasesTotal: 41

not providedTotal: 34

ARR3-related disorderTotal: 12

Myopia 26, X-linked, female-limitedTotal: 11

Anophthalmia-microphthalmia syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004312.3. 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			9 clinvar	22 clinvar		31
missense	2 clinvar		57 clinvar	15 clinvar	1 clinvar	75
nonsense	3 clinvar	3 clinvar	1 clinvar			7
start loss	1 clinvar					1
frameshift	1 clinvar	2 clinvar	1 clinvar			4
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	20 clinvar			24
Total	8	8	88	37	1	142

Highest pathogenic variant AF is 0.0000063750826

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004312.3	RefSeq	NP_004303.2	16	MANE Select
ENST00000307959.9	Ensembl	ENSP00000311538.8	16	MANE Select
ENST00000374495.7	Ensembl	ENSP00000363619.3	15	Standard
ENST00000480877.6	Ensembl	ENSP00000425505.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
arr3a	Danio rerio	Structure: visual perception Quality: disrupted abnormal

Gene / Model

Organism

Observed Phenotype

arr3a

Danio rerio

Structure: visual perception

Quality: disrupted

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

CXCR4-mediated signaling events
Thromboxane A2 receptor signaling
Visual signal transduction: Cones

Biological Process

regulation of protein phosphorylation
endocytosis
signal transduction
visual perception

Molecular Function

opsin binding
protein binding
phosphoprotein binding

Cellular Component

photoreceptor outer segment
photoreceptor inner segment
cytoplasm
synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307959
Coding exons: 16
Length: 13536
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125690
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.572	131	151	0.869	0.0000119	2507
Missense (PolyPhen)		37	48.239	0.76701		876
Synonymous	0.411	55	59.0	0.932	0.00000453	774
Loss of Function	2.82	5	17.8	0.280	0.00000141	288

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000036	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000013	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in an as yet undefined retina-specific signal transduction. Could binds to photoactivated-phosphorylated red/green opsins.;

Recessive Scores

pRec: 0.192

Intolerance Scores

LoFtool: 0.502
RVIS EVS: -0.23
RVIS percentile EVS: 37.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.712

Gene Damage Prediction

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