GRIP1

Chr 12

glutamate receptor interacting protein 1

ENSG00000155974UniProt: Q9Y3R0

May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (PubMed:10197531). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity)

Primary Disease Associations & Inheritance

UniProtFraser syndrome 3
471
ClinVar variants
28
Pathogenic / LP
0.51
pLI score
0
Active trials
Clinical Summary— GRIP1
🧬
Gene-Disease Validity (ClinGen)
Fraser syndrome 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.51) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 126 VUS of 471 total submissions
Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.36LOEUF
pLI 0.508
Z-score 5.34
OE 0.22 (0.14–0.36)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.58Z-score
OE missense 0.82 (0.76–0.88)
478 obs / 585.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.14–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.76–0.88)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 12 / 54.6Missense obs/exp: 478 / 585.7Syn Z: -0.50

ClinVar Variant Classifications

471 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic7
VUS126
Likely Benign275
Benign19
Conflicting23
21
Pathogenic
7
Likely Pathogenic
126
VUS
275
Likely Benign
19
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
15
0
21
Likely Pathogenic
5
1
1
0
7
VUS
0
88
35
3
126
Likely Benign
2
2
118
153
275
Benign
0
3
16
0
19
Conflicting
—23
Total1394185156471

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

View in ClinVar →

Protein Context — Lollipop Plot

GRIP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GRIP1-related Fraser syndrome

strong
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Fraser Syndrome.
Saleem AA et al.·J Coll Physicians Surg Pak
2015Case report
Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype.
Crayle JI et al.·Neurology
2024
Anti-interferon alpha treatment in SLE.
Kirou KA et al.·Clin Immunol
2013Review
Fraser syndrome without cryptophthalmos: Two cases.
Boussion S et al.·Eur J Med Genet
2020Case report
Supramodular nature of GRIP1 revealed by the structure of its PDZ12 tandem in complex with the carboxyl tail of Fras1.
Long J et al.·J Mol Biol
2008
12q14 microdeletion syndrome: A family with short stature and Silver-Russell syndrome (SRS)-like phenotype and review of the literature.
Heldt F et al.·Eur J Med Genet
2018Review
The first adolescent case of Fraser syndrome 3, with a novel nonsense variant in GRIP1.
Koprulu M et al.·Am J Med Genet A
2021Case report
Identification of new fusion genes and their clinical significance in endometrial cancer.
Yao T et al.·Chin Med J (Engl)
2019
AKT regulation of estrogen receptor beta transcriptional activity in breast cancer.
Duong BN et al.·Cancer Res
2006
The function of TIF2/GRIP1 in mouse reproduction is distinct from those of SRC-1 and p/CIP.
Gehin M et al.·Mol Cell Biol
2002Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Dysregulated GluA2-Y876 phosphorylation contributes to loss of synaptic upscaling in GRIP1 mutant mice with reduced sociability and increased repetitive behavior.
Han M et al.·Mol Psychiatry
2025
LncRNA MSTRG.13,871/miR155-5p/Grip1 network involved in the post-cardiac arrest brain injury.
Li Y et al.·Sci Rep
2024🔓 Open Access
[GRIP1 is Involved in the Interaction of Vimentin Filaments with Focal Adhesions in Endothelial Cells].
Gyoeva FK.·Mol Biol (Mosk)
2024
A Class I HDAC Inhibitor Rescues Synaptic Damage and Neuron Loss in APP-Transfected Cells and APP/PS1 Mice through the GRIP1/AMPA Pathway.
Han Y et al.·Molecules
2022🔓 Open Access
GLCCI1 Deficiency Induces Glucocorticoid Resistance via the Competitive Binding of IRF1:GRIP1 and IRF3:GRIP1 in Asthma.
Hu X et al.·Front Med (Lausanne)
2021🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools