GPR68

Chr 14q32.11

G protein-coupled receptor 68

Aliases:: OGR1
MANE:: ENST00000650645.1

OMIM: 601404 ↗NCBI: 8111 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

GPR68 · Q15743

v62025-08-01

Predicted Aligned Error matrix for GPR68 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

80.4/ 100

Confident

365 residues

Confidence breakdown

Very high(≥ 90)50%
Confident(70–90)27%
Low(50–70)6%
Very low(< 50)16%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Amelogenesis imperfecta
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

Hypomaturation amelogenesis imperfecta
0.65
amelogenesis imperfecta
0.57
neurodegenerative disease
0.37
neoplasm
0.11
breast cancer
0.11
familial idiopathic steroid-resistant nephrotic syndrome
0.10
nephronophthisis
0.10
focal segmental glomerulosclerosis
0.09
prostate carcinoma
0.09
breast carcinoma
0.09

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

G protein-coupled receptor 68

Proton-sensing G protein-coupled receptor activated by extracellular pH, which is required to monitor pH changes and generate adaptive reactions (PubMed:12955148, PubMed:29677517, PubMed:32865988, PubMed:33478938, PubMed:39753132, PubMed:40215959, PubMed:40215960). The receptor is almost silent at pH 7.8 but fully activated at pH 6.8 (PubMed:12955148, PubMed:39753132). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as phospholipase C (PubMed:29677517, PubMed:39753132). GPR68 is mainly coupled to G(q) G proteins and mediates production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) (PubMed:29677517, PubMed:39753132). Acts as a key mechanosensor of fluid shear stress and membrane stretch (PubMed:29677517, PubMed:30471999). Expressed in endothelial cells of small-diameter resistance arteries, where it mediates flow-induced dilation in response to shear stress (PubMed:29677517). May represents an osteoblastic pH sensor regulating cell-mediated responses to acidosis in bone (By similarity). Acts as a regulator of calcium-sensing receptor CASR in a seesaw manner: GPR68-mediated signaling inhibits CASR signaling in response to protons, while CASR inhibits GPR68 in presence of extracellular calcium (By similarity)