GPS2

Chr 17

G protein pathway suppressor 2

Also known as: AMF-1

NCBI Gene: 2874ENSG00000132522UniProt: Q13227

This gene encodes a protein involved in G protein-mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function. [provided by RefSeq, Jul 2008]

67
ClinVar variants
29
Pathogenic / LP
0.05
pLI score
1
Active trials
Clinical Summary— GPS2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 36 VUS of 67 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.58LOEUF
pLI 0.053
Z-score 2.94
OE 0.30 (0.16–0.58)
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.
1.16Z-score
OE missense 0.76 (0.66–0.87)
136 obs / 179.7 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.0.30 (0.16–0.58)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.66–0.87)
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.1.71
0≤1.21.6
LoF obs/exp: 6 / 20.3Missense obs/exp: 136 / 179.7Syn Z: -4.48

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic3
VUS36
Benign2
26
Pathogenic
3
Likely Pathogenic
36
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
3
0
3
VUS
0
29
7
0
36
Likely Benign
0
0
0
0
0
Benign
0
0
2
0
2
Total02938067

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

View in ClinVar →

Protein Context — Lollipop Plot

GPS2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Inherited Thrombocytopenia Related Genes: GPS2 Mediates the Interplay Between ANKRD26 and ETV6.
Capaci V et al.·Cells
2024
GPS2 promotes erythroid differentiation in K562 erythroleukemia cells primarily via NCOR1.
Lu Y et al.·Int J Hematol
2024
G-protein pathway suppressor 2 (GPS2) interacts with the regulatory factor X4 variant 3 (RFX4_v3) and functions as a transcriptional co-activator.
Zhang D et al.·J Biol Chem
2008
GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation.
Drareni K et al.·Cell Rep
2018
Pseudogene-gene functional networks are prognostic of patient survival in breast cancer.
Smerekanych S et al.·BMC Med Genomics
2020Functional
Prognostic factors in patients who received end-of-life chemotherapy for advanced cancer.
Hiramoto S et al.·Int J Clin Oncol
2019Cohort
Nanosilicate-reinforced GelMA-PEGDA hydrogel promotes angiogenesis for bone regeneration.
Long J et al.·Int J Biol Macromol
2024
Genomic analysis reveals molecular characterization of CD30(+) and CD30(-) extranodal natural killer/T-cell lymphomas (ENKTLs).
Zhang X et al.·Hum Pathol
2024
Persistence of the clinical effect of grass allergen peptide immunotherapy after the second and third grass pollen seasons.
Ellis AK et al.·J Allergy Clin Immunol
2020Clinical trial
Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.
Pugh TJ et al.·Nature
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Gastrointestinal CancerUrologic CancerGynecologic Cancer

Palliative Radiotherapy in Symptomatic Pelvic Soft Tissue Tumors

RECRUITING
NCT06398314Phase NASykehuset TelemarkStarted 2024-12-10
Palliative radiotherapy

External Resources

Links to major genomics databases and tools