MRGPRX1

protein-coding

MAS related GPR family member X1, the group of G protein-coupled receptors, Class A orphans

Gene summary

Enables C-C chemokine receptor activity. Involved in several processes, including G protein-coupled receptor signaling pathway; negative regulation of sensory perception of pain; and sensory perception of itch. Predicted to be located in cell surface. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001393578.1

Inheritance

—

ClinVar variants

U:53B:22

Top phenotype

Gestational diabetes mellitus uncontrolled

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chr11:18,933,499-18,939,414

External References & Databases

Ensembl (ENSG00000170255)

Transcript & Mutation Effects

hg38 • Region Span ~5.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MRGPRX1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 11

Gestational diabetes mellitus uncontrolledTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001393578.1. 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				5 clinvar	1 clinvar	6
missense			52 clinvar	15 clinvar	1 clinvar	68
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	53	20	2	75

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001393578.1	RefSeq	NP_001380507.1	1	MANE Select
ENST00000526914.2	Ensembl	ENSP00000499076.2	1	MANE Select
NM_147199.4	RefSeq	NP_671732.3	1	Standard
ENST00000302797.4	Ensembl	ENSP00000305766.3	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

acute-phase response
signal transduction
cell surface receptor signaling pathway
G protein-coupled receptor signaling pathway
response to chloroquine

Molecular Function

transmembrane signaling receptor activity
G protein-coupled receptor activity

Cellular Component

plasma membrane
cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302797
Coding exons: 1
Length: 5695

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.918	219	184	1.19	0.0000116	2047
Missense (PolyPhen)		32	30.657	1.0438		443
Synonymous	-3.80	128	83.7	1.53	0.00000561	695
Loss of Function

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Orphan receptor. Probably involved in the function of nociceptive neurons. May regulate nociceptor function and/or development, including the sensation or modulation of pain. Potently activated by enkephalins including BAM22 (bovine adrenal medulla peptide 22) and BAM (8-22)(PubMed:26582731). BAM22 is the most potent compound and evoked a large and dose-dependent release of intracellular calcium in stably transfected cells. G(alpha)q proteins are involved in the calcium-signaling pathway. Activated by the antimalarial drug, chloroquine. May mediate chloroquine- induced itch, in a histamine-independent manner. {ECO:0000269|PubMed:11850634, ECO:0000269|PubMed:20004959, ECO:0000269|PubMed:26582731}.;

Recessive Scores

pRec: 0.0624

Intolerance Scores

LoFtool: 0.291
RVIS EVS: 0.69
RVIS percentile EVS: 85.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00421

Gene Damage Prediction

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