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6 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GARNL3
GTPase activating Rap/RanGAP domain like 3
Chromosome 9 · 9q33.3
NCBI Gene: 84253Ensembl: ENSG00000136895.19HGNC: HGNC:25425UniProt: B4DH81
18PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
GTPase activator activityplasma membraneregulation of small GTPase mediated signal transductionpathological myopiaIntellectual disabilityGenu valgumGenu varum
✦AI Summary

GARNL3 (GTPase activating Rap/RanGAP domain like 3) is a plasma membrane-localized protein with GTPase activator activity that regulates cellular signaling responses. In granulosa cells, GARNL3 expression is downregulated during in vitro culture, suggesting a role in cell signaling and response to external stimuli within the ovarian microenvironment 1. GARNL3 is located within a critical region on chromosome 9.3 implicated in neurodevelopmental disorders; reduced GARNL3 expression occurs in patients with microdeletions of this region who present with intellectual disability, developmental delay, microcephaly, and seizures of incomplete penetrance, though sequencing of GARNL3 in unrelated intellectual disability patients detected no causative mutations 2. In glioblastoma multiforme, GARNL3 emerged as a hub gene in co-expression network analysis with expression levels significantly correlated to WHO classification, suggesting potential utility as a biomarker 3. GARNL3 has been identified as a candidate gene for autosomal recessive neurodevelopmental disorders within previously reported intellectual disability microdeletion regions, with increased expression in developing and adult human brain structures 4. Additionally, GARNL3 was incorporated into a prognostic model for bladder cancer demonstrating strong predictive accuracy 5. These findings indicate GARNL3 participates in cellular signaling, neurodevelopment, and potentially in cancer progression, though its precise molecular mechanisms require further investigation.

Sources cited
1
GARNL3 is downregulated in cultured granulosa cells, suggesting involvement in cell signaling and response to external stimuli
PMID: 41465369
2
GARNL3 lies within the smallest region of overlap in 9q33.3 microdeletions associated with intellectual disability, developmental delay, microcephaly, and seizures
PMID: 26421060
3
GARNL3 is a hub gene in glioblastoma multiforme co-expression networks with expression levels significantly correlated to WHO classification
PMID: 33423377
4
GARNL3 is a candidate gene for autosomal recessive intellectual disability within previously reported microdeletion regions with increased brain expression
PMID: 30167849
5
GARNL3 is incorporated into a prognostic model for bladder cancer with strong predictive accuracy
PMID: 40696737
Disease Associationsⓘ20
pathological myopiaOpen Targets
0.28Weak
Intellectual disabilityOpen Targets
0.26Weak
Genu valgumOpen Targets
0.10Weak
Genu varumOpen Targets
0.10Weak
Abnormality of the skeletal systemOpen Targets
0.10Suggestive
Isolated anophthalmia - microphthalmiaOpen Targets
0.08Suggestive
microphthalmiaOpen Targets
0.08Suggestive
nanophthalmiaOpen Targets
0.06Suggestive
isolated microphthalmia 7Open Targets
0.06Suggestive
nanophthalmos 2Open Targets
0.06Suggestive
Microphthalmia - ankyloblepharon - intellectual disabilityOpen Targets
0.06Suggestive
infectious arthritisOpen Targets
0.06Suggestive
diabetic ketoacidosisOpen Targets
0.05Suggestive
microphthalmia, isolated, with coloboma 10Open Targets
0.03Suggestive
microphthalmia, isolated, with coloboma 5Open Targets
0.03Suggestive
osteoarthritis, hipOpen Targets
0.03Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
glioblastoma multiformeOpen Targets
0.02Suggestive
skin diseaseOpen Targets
0.02Suggestive
pituitary cancerOpen Targets
0.01Suggestive
Pathogenic Variants1
NM_032293.5(GARNL3):c.869A>G (p.Gln290Arg)Likely pathogenic
Intellectual disability
☆☆☆☆→ Residue 290
View on ClinVar ↗
Related Genes
FAM13AShared pathway100%ARHGEF9Shared pathway100%FAM13BShared pathway100%PLEKHG6Shared pathway100%PLEKHG1Shared pathway100%ARHGAP23Shared pathway100%
Tissue Expression6 tissues
Heart
100%
Ovary
66%
Brain
56%
Liver
29%
Lung
15%
Bone Marrow
5%
Gene Interaction Network
Click a node to explore
GARNL3FAM13AARHGEF9FAM13BPLEKHG6PLEKHG1ARHGAP23
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q5VVW2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.54Moderately Constrained
pLIⓘ
0.87Intermediate
Observed/Expected LoF0.36 [0.25–0.54]
RankingsWhere GARNL3 stands among ~20K protein-coding genes
  • #14,703of 20,598
    Most Researched18
  • #5,400of 5,498
    Most Pathogenic Variants1
  • #3,417of 17,882
    Most Constrained (LOEUF)0.54 · top quartile
Genes detectedGARNL3
Sources retrieved6 papers
Response time—
📄 Sources
6▼
1
Expression of New Gene Markers Regulating Protein Metabolism in Porcine Ovarian Granulosa Cells In Vitro.
PMID: 41465369
Int J Mol Sci · 2025
1.00
2
Microdeletions in 9q33.3-q34.11 in five patients with intellectual disability, microcephaly, and seizures of incomplete penetrance: is STXBP1 not the only causative gene?
PMID: 26421060
Mol Cytogenet · 2015
0.83
3
Identification of key modules and hub genes in glioblastoma multiforme based on co-expression network analysis.
PMID: 33423377
FEBS Open Bio · 2021
0.67
4
Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability.
PMID: 30167849
Hum Genet · 2018
0.50
5
Immune Landscape and Prognostic Significance of Gene Expression Profiles in Bladder Cancer: Insights from Immune Cell Infiltration and Risk Modeling.
PMID: 40696737
Iran J Allergy Asthma Immunol · 2025
0.33