GRM4

Chr 6

glutamate metabotropic receptor 4

Also known as: GPRC1D, MGLUR4, mGlu4

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
11
Pubs (1 yr)
P/LP submissions
P/LP missense
0.28
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.28LOEUF
pLI 0.993
Z-score 4.86
OE 0.14 (0.070.28)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
2.68Z-score
OE missense 0.70 (0.650.76)
447 obs / 637.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.14 (0.070.28)
00.351.4
Missense OE?0.70 (0.650.76)
00.61.4
Synonymous OE?0.92
01.21.6
LoF obs/exp: 5 / 36.9Missense obs/exp: 447 / 637.7Syn Z: 1.03

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GRM4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →