GRM7

Chr 3AR

glutamate metabotropic receptor 7

Also known as: GLUR7, GPRC1G, MGLU7, MGLUR7, NEDSHBA, PPP1R87

NCBI Gene: 2917 ENSG00000196277 UniProt: Q14831 OMIM: 604101

This protein is a Group III metabotropic glutamate receptor that inhibits adenylate cyclase and regulates axon outgrowth through MAPK-cAMP-PKA signaling during neuronal development. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with seizures, hypotonia, and brain abnormalities. The gene is highly constrained against loss-of-function variation (pLI = 1.0, LOEUF = 0.24), indicating that haploinsufficiency is likely not tolerated.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it 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 three 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.241 OMIM phenotype

Clinical Summary— GRM7

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

12 unique Pathogenic / Likely Pathogenic· 150 VUS of 318 total submissions

Explore recent and relevant literature in Research Assistant →

📖

GeneReview available — GRM7

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 0.999

Z-score 5.07

OE 0.11 (0.05–0.24)

Highly constrained

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

Missense Constraint?

2.05Z-score

OE missense 0.75 (0.69–0.81)

402 obs / 535.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.11 (0.05–0.24)

0≤0.351.4

Missense OE?0.75 (0.69–0.81)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 4 / 37.6Missense obs/exp: 402 / 535.8Syn Z: -1.39

ClinVar Variant Classifications

318 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic5

VUS150

Likely Benign121

Benign23

Conflicting3

Pathogenic

Likely Pathogenic

150

VUS

121

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	3	0	0	7
Likely Pathogenic	1	3	1	0	5
VUS	1	145	4	0	150
Likely Benign	0	6	19	96	121
Benign	0	2	4	17	23
Conflicting	—				3
Total	6	159	28	113	309

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

69 pathogenic / likely-pathogenic (of 102) ClinVar copy-number / structural variants overlap GRM7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →