GPR135

protein-coding

G protein-coupled receptor 135, the group of G protein-coupled receptors, Class A orphans

Gene summary

Enables arrestin family protein binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in endosome and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_022571.6

Inheritance

—

ClinVar variants

U:107B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr14:59,429,022-59,465,380

External References & Databases

Ensembl (ENSG00000181619)

Transcript & Mutation Effects

hg38 • Region Span ~36.4 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 GPR135 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 110

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022571.6. 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						0
missense			107 clinvar	3 clinvar		110
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	107	3	0	110

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022571.6	RefSeq	NP_072093.2	1	MANE Select
ENST00000395116.2	Ensembl	ENSP00000378548.1	1	MANE Select
ENST00000481661.1	Ensembl	ENSP00000432696.1	1	Standard
XM_017021596.3	RefSeq	XP_016877085.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Other

Biological Process

G protein-coupled receptor signaling pathway

Molecular Function

G protein-coupled receptor activity
protein binding
arrestin family protein binding

Cellular Component

endosome
plasma membrane
endosome membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395116
Coding exons: 1
Length: 36321
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.235	275	264	1.04	0.0000150	2978
Missense (PolyPhen)		103	87.859	1.1723		966
Synonymous	0.192	121	124	0.978	0.00000702	1156
Loss of Function	0.475	7	8.49	0.824	4.33e-7	81

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. Has spontaneous activity for beta- arrestin recruitment (PubMed:28827538). Shows a reciprocal regulatory interaction with the melatonin receptor MTNR1B most likely through receptor heteromerization (PubMed:28827538). {ECO:0000269|PubMed:28827538}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.383

Gene Damage Prediction

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