GPRASP1

protein-coding

G protein-coupled receptor associated sorting protein 1, the group of Armadillo repeat containing

Gene summary

This gene encodes a member of the GPRASP (G protein-coupled receptor associated sorting protein) family. The protein may modulate lysosomal sorting and functional down-regulation of a variety of G-protein coupled receptors. It targets receptors for degradation in lysosomes. The receptors interacting with this sorting protein include D2 dopamine receptor (DRD2), delta opioid receptor (OPRD1), beta-2 adrenergic receptor (ADRB2), D4 dopamine receptor (DRD4) and cannabinoid 1 receptor (CB1R). Multiple alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, May 2010]

MANE transcript

NM_001184727.2

Inheritance

ClinVar variants

U:125B:21

Top phenotype

Intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chrX:102,651,092-102,659,083

External References & Databases

Ensembl (ENSG00000198932)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

arteriovenous hemangioma/malformationMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0001256

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GPRASP1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 131

not providedTotal: 12

Intellectual disabilityTotal: 3

GPRASP1-related disorderTotal: 2

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001184727.2. 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				4 clinvar	1 clinvar	5
missense			124 clinvar	16 clinvar		140
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	125	20	1	146

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001184727.2	RefSeq	NP_001171656.1	1	MANE Select
ENST00000537097.2	Ensembl	ENSP00000445683.1	1	MANE Select
NM_001099410.2	RefSeq	NP_001092880.1	1	Standard
NM_001099411.2	RefSeq	NP_001092881.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

endosome to lysosome transport
G protein-coupled receptor catabolic process

Molecular Function

protein binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000537097
Coding exons: 1
Length: 7718
Individuals with no LoFs: 125707
Homozygous LoFs: 12
Heterozygous LoFs: 27
Defined: 125746
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.728	454	500	0.908	0.0000347	9323
Missense (PolyPhen)		70	85.828	0.81559		1778
Synonymous	1.72	147	176	0.835	0.0000127	2611
Loss of Function	4.20	8	34.7	0.231	0.00000271	567

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00015	0.00012	rare
Latino/Admixed American	0.00018	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00051	0.00038	rare
Finnish	0.000062	0.000046	rare
European (Non-Finnish)	0.00027	0.00019	rare
South Asian	0.00010	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Modulates lysosomal sorting and functional down- regulation of a variety of G-protein coupled receptors. Targets receptors for degradation in lysosomes via its interaction with BECN2. {ECO:0000269|PubMed:12142540, ECO:0000269|PubMed:15452121, ECO:0000269|PubMed:23954414}.;

Intolerance Scores

LoFtool: 0.810
RVIS EVS: -0.24
RVIS percentile EVS: 36.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.611

Gene Damage Prediction

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