Kcnj5

G protein-activated inward rectifier potassium channel 4 (GIRK-4) (Cardiac inward rectifier) (CIR) (Heart KATP channel) (Inward rectifier K(+) channel Kir3.4) (KATP-1) (Potassium channel, inwardly rec

Spatial tier: RESTRICTED · Class: ION_CHANNEL · Top region: PVT (Paraventricular nucleus of the thalamus) · Positive regions: 14/554

45.0Discovery Score
40.4Targetability Score
CEvidence grade C
What this means: Kcnj5: fine CCF profile is restricted toward PVT (top regions: PVT, PT, PF, VMH, Xi; 14 positive regions); direct spatial validation is still required.

Function in PVT: evidence, prediction, innovation

Gene function
Kcnj5 encodes GIRK4 (Kir3.4), a subunit of G protein-gated inwardly rectifying potassium channels. GIRK subunits assemble as tetramers opened directly by Gbeta-gamma released from Gi/Go-coupled receptors such as GABA-B, mu-opioid, D2 and alpha2, producing slow hyperpolarising inhibitory postsynaptic currents. Gain-of-function KCNJ5 mutations cause human primary aldosteronism.
Region function
The paraventricular nucleus of the thalamus (PVT) is a midline thalamic hub that integrates arousal, stress and homeostatic signals and routes salience and threat information to nucleus accumbens, prefrontal cortex and amygdala.
Published in this region
expression only Expression is directly documented but function is not. Wickman et al. 2000 used GIRK4-null mice as a negative background to map Kcnj5 mRNA and found it in only a handful of brain regions, explicitly including the parafascicular and paraventricular thalamic nuclei (plus deep cortical pyramidal neurons, claustrum/endopiriform, globus pallidus, VMH and some brainstem nuclei); the same study found GIRK4-null mice grossly normal in locomotion, vision, nociception and passive avoidance. Karschin et al. 1996 similarly showed GIRK1-4 are differentially distributed across the adult rodent brain. No study has tested GIRK4 function in PVT.
Predicted function
Prediction: GIRK4 co-assembles with GIRK1/GIRK2 in PVT neurons to provide the postsynaptic effector for GABA-B, mu-opioid and other Gi signalling, setting how strongly PVT cells can be silenced during satiety, sedation and opioid exposure. Conditional Kcnj5 deletion or intra-PVT tertiapin-Q should reduce baclofen- and opioid-evoked outward currents, leaving PVT neurons hyperexcitable and predicting exaggerated arousal, stress reactivity and cue-driven salience responses; the mild whole-body knockout phenotype suggests the deficit appears only under challenge.
Innovation
★★★★★ 5/5 GIRK4 is one of the few genes with confirmed PVT expression yet no functional study there, while PVT has become a major salience and arousal target.
Tools
Kcnj5/GIRK4 knockout mice (Wickman et al. 2000) and Kcnj5 floxed alleles; GIRK blocker tertiapin-Q; GIRK activator ML297 and related VU compounds; anti-GIRK4 antibodies; baclofen and DAMGO as physiological probes. No validated Kcnj5-Cre driver - PVT is instead accessed with Drd2-Cre, Gal-Cre or retro-AAV from nucleus accumbens.
References

Direct evidence located at the region

Kcnj5 Allen ISH at the CCF centroid of PVT

Allen ISH experiment 72119660, section image 72040840 (section 269): the section that contains the CCF centroid of Paraventricular nucleus of the thalamus 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

Look it up yourself: Allen Mouse Brain ISH for Kcnj5Allen reference atlas: PVT (structure 149)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Kcnj5" or by parcellation_substructure "PVT")All genes confined to PVT + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
PVT MERFISH region locator
Real single-cell MERFISH coordinates for the PVT (Paraventricular nucleus of the thalamus) 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

Kcnj5 regional expression profile

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

Spatial profile

PVT
2.28
PT
1.46
PF
1.39
VMH
1.32
Xi
1.07
MEPO
0.784
PMv
0.705
RE
0.699
DTN
0.683
ARH
0.648
SPA
0.647
AVPV
0.645
IAM
0.633
SBPV
0.608
PRC
0.548
TMd
0.533
IMD
0.526
PVi
0.52
MPN
0.497
DMH
0.485

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.314
Top-region fraction
0.078
Filter status
PASS

Interpretation limits