F2rl1

Proteinase-activated receptor 2 (PAR-2) (Coagulation factor II receptor-like 1) (G protein-coupled receptor 11) (Thrombin receptor-like 1)

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: SCO (Subcommissural organ) · Positive regions: 1/554

53.6Discovery Score
45.5Targetability Score
CEvidence grade C
What this means: F2rl1: predicted fine-region profile is strict-exclusive, with 1 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in SCO: evidence, prediction, innovation

Gene function
F2rl1 encodes protease-activated receptor 2 (PAR2), a class-A GPCR activated irreversibly when trypsin, tryptase, kallikreins or factor Xa cleave its N-terminus to expose a tethered ligand (SLIGRL in mouse). Via Gq/Ca2+, Gi and beta-arrestin/ERK it senses extracellular proteolysis, driving secretion, inflammation and pain.
Region function
The subcommissural organ is a secretory ependymal gland under the posterior commissure at the third-ventricle/aqueduct junction, releasing SCO-spondin into CSF to form Reissner's fibre and shaping aqueduct patency, CSF flow and axial morphogenesis.
Published in this region
inferred No region-specific literature found. Closest: PAR2 is functional in CNS glia and neurons and its blockade reduces EAE neuroinflammation (Eftekhari et al. 2024), while choroid plexus mast cells, a tryptase source and PAR2 activator, cause tumour-associated hydrocephalus (Li et al. 2023).
Predicted function
Prediction: PAR2 would make SCO ependymal cells CSF proteolysis sensors, coupling tryptase, kallikrein or coagulation activity after haemorrhage to Ca2+ rises, altered ciliary beating and SCO-spondin exocytosis. Sspo-CreER x F2rl1-flox deletion should protect Reissner's fibre and aqueduct patency after intraventricular blood; intracerebroventricular SLIGRL-NH2 should trigger degranulation and ventriculomegaly.
Innovation
★★★★★ 5/5 PAR2 is unstudied in the SCO although CSF protease signalling is a leading mechanism of post-haemorrhagic hydrocephalus.
Tools
F2rl1-null (F2rl1tm1Mslb) and F2rl1-flox mice; Sspo-Cre, Sspo-CreER (Zhang et al. 2024); agonists SLIGRL-NH2, 2-furoyl-LIGRLO-NH2, AC-264613; antagonists GB88, I-191, biased C781; anti-PAR2 antibody SAM11.
References

Direct evidence located at the region

F2rl1 Allen ISH at the CCF centroid of SCO

Allen ISH experiment 199391, section image 101750876 (section 227): the section that contains the CCF centroid of Subcommissural organ 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
SCO MERFISH region locator
Real single-cell MERFISH coordinates for the SCO (Subcommissural organ) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.
DIRECT ALLEN ISH
Allen ISH experiment 199391, image 100096522 -- target region: SCO (Subcommissural organ)
Allen ISH experiment 199391, image 100096522 -- target region: SCO (Subcommissural organ)
DIRECT ALLEN ISH
Allen ISH experiment 199391, image 100115430 -- target region: SCO (Subcommissural organ)
Allen ISH experiment 199391, image 100115430 -- target region: SCO (Subcommissural organ)

Regional expression figure

F2rl1 regional expression profile

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

Spatial profile

SCO
0.283
NPC
0.0275
OP
0.0241
AIp5
0.0226
PERI6a
0.021
EPv
0.0205
ENTl5
0.0183
EPd
0.0173
AIp6a
0.0169
PVa
0.0162
BLAv
0.0158
ENTl3
0.0158
AVP
0.0136
TR
0.0133
AUDpo1
0.0122
SPFm
0.0121
PIR
0.0116
VMPO
0.0116
VISrl1
0.0111
CLA
0.0109

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.440
Top-region fraction
0.359
Filter status
PASS

Interpretation limits