Gpr149

Probable G protein-coupled receptor 149 (G protein-coupled receptor PGR10)

Spatial tier: RESTRICTED · Class: GPCR · Top region: OT (Olfactory tubercle) · Positive regions: 24/554

43.1Discovery Score
41.6Targetability Score
CEvidence grade C
What this means: Gpr149: fine CCF profile is restricted toward OT (top regions: OT, VMH, IPR, ACB, VPM; 24 positive regions); direct spatial validation is still required.

Function in OT: evidence, prediction, innovation

Gene function
GPR149 is an orphan class A G-protein-coupled receptor with no identified endogenous ligand. Its two functional studies both come from knockout phenotyping: Edson et al. 2010 found Gpr149 is oocyte-enriched and that deleting it increases female fertility, and Wyler et al. 2024 found that Gpr149-null male mice show altered energy homeostasis with changes in body weight and adiposity, pointing to a central metabolic role.
Region function
The olfactory tubercle is the ventral striatal region of the olfactory cortex: its D1 and D2 spiny neurons and islands of Calleja receive both piriform odour input and dense VTA dopamine, and they encode odour valence and odour-guided motivated behaviour.
Published in this region
inferred No region-specific literature found. Wyler et al. 2024 is the only study to implicate Gpr149 in central energy homeostasis in mouse and reports brain expression without resolving the olfactory tubercle, and Edson et al. 2010 characterised the gene in the ovary; no anatomical or functional study of GPR149 in ventral striatum exists.
Predicted function
Prediction: given that the olfactory tubercle links odour valence to reward and feeding, and that Gpr149-null mice have an energy-homeostasis phenotype, GPR149 in tubercle spiny neurons is predicted to be a Gs- or Gi-coupled modulator that sets how strongly food odours drive approach and consumption. Tubercle-restricted Gpr149 deletion or knockdown is predicted to leave basal odour detection intact but to shift odour-guided motivation - most plausibly increasing approach to palatable food odours and raising intake of a high-fat diet - while chemogenetic silencing of Gpr149-expressing tubercle neurons should abolish the odour-primed component of feeding without affecting chow intake in the dark.
Innovation
★★★★★ 5/5 An orphan receptor with a real but unexplained metabolic knockout phenotype mapped to the olfactory-reward interface, and nobody has connected the two.
Tools
Gpr149 knockout mice (Edson et al. 2010; Wyler et al. 2024) and IMPC alleles; no ligand or selective antibody - epitope-tagged knock-in and RNAscope are the practical entry points; Drd1-Cre and Drd2-Cre for tubercle cell types; AAV-shRNA for region-restricted knockdown combined with odour-guided operant assays.
References

Direct evidence located at the region

Gpr149 Allen ISH at the CCF centroid of OT

Allen ISH experiment 71283586, section image 71100749 (section 146): the section that contains the CCF centroid of Olfactory tubercle according to the Allen image-to-atlas alignment (reference_to_image), with a 2 mm window around that point. Left: whole section, red box = window. Middle: ISH signal. Right: Allen's expression-mask view of the same window. open this image in the Allen viewer

Direct spatial evidence

MERFISH REGION LOCATOR
OT MERFISH region locator
Real single-cell MERFISH coordinates for the OT (Olfactory tubercle) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.

Regional expression figure

Gpr149 regional expression profile

Predicted WMB × fine-CCF profile; not direct full-transcriptome spatial measurement.

Spatial profile

OT
4.81
VMH
3.35
IPR
3.31
ACB
2.96
VPM
2.29
LGd-ip
2.28
LGd-sh
1.98
IPC
1.87
LGd-co
1.86
RL
1.67
RT
1.65
MGd
1.64
MGv
1.62
B
1.6
SI
1.59
VAL
1.58
VPL
1.55
MGm
1.55
SGN
1.49
PBG
1.46

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.285
Top-region fraction
0.056
Filter status
PASS

Interpretation limits