GPRASP2

protein-coding

G protein-coupled receptor associated sorting protein 2, the group of Armadillo repeat containing

Gene summary

The protein encoded by this gene is a member of a family that regulates the activity of G protein-coupled receptors (GPCRs). The encoded protein has been shown to be capable of interacting with several GPCRs, including the M1 muscarinic acetylcholine receptor and the calcitonin receptor. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

MANE transcript

NM_001004051.4

Inheritance

ClinVar variants

P:2U:79B:27

Top phenotype

Deafness, X-linked, 7

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chrX:102,712,445-102,717,733

External References & Databases

Ensembl (ENSG00000158301)

Transcript & Mutation Effects

hg38 • Region Span ~5.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndromeSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0044702

Submitter: Orphanet

X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0044702

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Deafness, X-linked, 7XL

Manifestation: Audiologic/Otolaryngologic; Craniofacial

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 28096187

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPRASP2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 77

GPRASP2-related disorderTotal: 34

not providedTotal: 12

X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndromeTotal: 5

ARMCX5-GPRASP2-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001004051.4. 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				13 clinvar	1 clinvar	14
missense	1 clinvar	1 clinvar	79 clinvar	10 clinvar	3 clinvar	94
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	1	79	23	4	108

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001004051.4	RefSeq	NP_001004051.1	1	MANE Select
ENST00000483720.7	Ensembl	ENSP00000507692.1	1	MANE Select
NM_001184874.3	RefSeq	NP_001171803.1	1	Standard
NM_001184875.3	RefSeq	NP_001171804.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

amyloid-beta binding
protein binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000543253
Coding exons: 1
Length: 6504
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125742
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.713	270	305	0.885	0.0000217	5552
Missense (PolyPhen)		43	68.962	0.62353		1392
Synonymous	1.17	99	115	0.861	0.00000859	1642
Loss of Function	3.67	1	17.6	0.0567	0.00000138	309

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000076	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.000061	0.000044	rare
South Asian	0	0.0	absent
Other	0.00022	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in regulation of a variety of G-protein coupled receptors. {ECO:0000269|PubMed:15086532}.;

Recessive Scores

pRec: 0.0850

Intolerance Scores

LoFtool: 0.656
RVIS EVS: 0.29
RVIS percentile EVS: 71.5

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.000130

Gene Damage Prediction

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