Tmem38b

Trimeric intracellular cation channel type B (TRIC-B) (TRICB) (Mitsugumin-33B) (Transmembrane protein 38B)

Spatial tier: REGION_BIASED · Class: ION_CHANNEL · Top region: DG-po (Dentate gyrus, polymorph layer) · Positive regions: 35/554

41.6Discovery Score
38.0Targetability Score
CEvidence grade C
What this means: Tmem38b: fine CCF profile is region-biased toward DG-po (top regions: DG-po, CA1sp, CA2sp, LSc, DG-sg); this is a discovery lead, not direct proof.

Function in DG-po: evidence, prediction, innovation

Gene function
TMEM38B encodes TRIC-B, a trimeric intracellular cation channel in the ER membrane. It conducts monovalent cations, mainly K+, into the ER lumen as counter-current while Ca2+ exits through IP3 or ryanodine receptors, dissipating the negative potential that would otherwise stall Ca2+ release. Biallelic TMEM38B mutations cause recessive osteogenesis imperfecta type XIV.
Region function
The dentate hilus contains mossy cells and GABAergic interneurons whose feedback onto granule cells controls dentate gain and enables pattern separation (Jinde 2012).
Published in this region
none No region-specific literature found. The nearest evidence is non-neural: TRIC-B knockout mice show defective IP3-receptor Ca2+ release, impaired alveolar epithelial Ca2+ handling and perinatal lethality (Yamazaki 2009), and disrupted osteoblast Ca2+ homeostasis and collagen synthesis (Zhao 2016, Cabral 2016). Allen ISH shows only weak Tmem38b signal in DG-po (energy 1.3), highest of the regions queried but near threshold.
Predicted function
Prediction: if TRIC-B is functional in hilar neurons it is the ER counter-ion pathway permitting full IP3-receptor Ca2+ release downstream of group I mGluR and muscarinic input, both prominent in mossy cells. Conditional deletion should shrink mGluR-evoked Ca2+ transients and Ca2+-activated afterhyperpolarisations, raising hilar excitability and degrading feedback inhibition. Compensation by the paralogue TRIC-A may make any single-gene phenotype weak.
Innovation
★★★★★ 5/5 No published work exists on TRIC-B in any brain region, despite a clear mechanistic role in ER Ca2+ release.
Tools
Tmem38b knockout and floxed mice (Yamazaki 2009, Zhao 2016); anti-TRIC-B antibodies from the osteogenesis imperfecta literature; no selective pharmacology, so AAV-shRNA or CRISPR with mossy-cell Cre drivers is the route.
References

Direct evidence located at the region

Tmem38b Allen ISH at the CCF centroid of DG-po

Allen ISH experiment 68301664, section image 68067843 (section 145): the section that contains the CCF centroid of Dentate gyrus, polymorph layer 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
DG-po MERFISH region locator
Real single-cell MERFISH coordinates for the DG-po (Dentate gyrus, polymorph layer) 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

Tmem38b regional expression profile

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

Spatial profile

DG-po
2.64
CA1sp
2.55
CA2sp
2.38
LSc
2.38
DG-sg
2.31
CA1so
2.22
CA3slm
2.16
CA2so
2.15
LRNp
2.08
CA1sr
2.06
CA3sp
2.06
VISp4
2.03
RO
2.01
CA3slu
2
APr
1.98
PG
1.96
ProS
1.96
CA3so
1.95
VTA
1.95
CLI
1.95

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.284
Top-region fraction
0.044
Filter status
PASS

Interpretation limits