{"gene":"GNG13","run_date":"2026-04-28T18:06:53","timeline":{"discoveries":[{"year":2003,"finding":"Gγ13 is expressed in rod bipolar cells and ON cone bipolar cells of the retina, where it co-localizes with Gαo in the dendrites. Single-cell PCR showed Gβ3, Gβ4, and Gγ13 are co-expressed selectively in ON bipolar cells but not OFF bipolar cells, implicating Gγ13 in ON bipolar cell signal transduction.","method":"Immunohistochemistry, single-cell RT-PCR, transgenic GFP reporter mouse, patch-clamp recordings","journal":"The Journal of comparative neurology","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (immunohistochemistry, single-cell PCR, electrophysiology) with functional validation; moderate evidence from single lab","pmids":["12454992"],"is_preprint":false},{"year":2001,"finding":"Gγ13 forms functional Gβγ dimers with all five Gβ subunits (Gβ1–5) as assessed by co-translation and channel modulation assays, but stable dimers detectable by co-immunoprecipitation under high-detergent conditions form selectively with Gβ1, Gβ3, and Gβ4. Multiple Gβ/Gγ13 pairings activate PLCβ2 and inhibit Gαq-stimulated PLCβ1 activity, and modulate Kir3.1/3.4 and N-type calcium channels. Gγ13 mRNA was detected in mouse and human brain and retina, beyond gustatory tissue.","method":"In vitro co-translation, co-immunoprecipitation, electrophysiology (channel modulation assays), cellular PLCβ activation assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal in vitro and cellular assays with mutagenesis-equivalent selectivity analysis in a single rigorous study","pmids":["11675383"],"is_preprint":false},{"year":2008,"finding":"Ric-8B, a guanine nucleotide exchange factor, physically interacts with Gγ13 as well as with Gαolf, and both proteins co-localize with Gbeta1 in the cilia of olfactory sensory neurons, implicating Gγ13 in olfactory signal transduction beyond its known role in taste.","method":"Co-immunoprecipitation (interaction assays), immunohistochemistry/co-localization in olfactory sensory neurons","journal":"Molecular and cellular neurosciences","confidence":"Medium","confidence_rationale":"Tier 2-3 — reciprocal co-IP and localization data, single lab, single study","pmids":["18462949"],"is_preprint":false}],"current_model":"GNG13 (Gγ13) is a divergent G protein γ subunit that selectively forms stable heterodimers with Gβ1, Gβ3, and Gβ4; these Gβγ13 complexes are functionally competent to modulate ion channels (Kir3/N-type Ca2+) and PLCβ isoforms, and are expressed in ON bipolar cells of the retina (co-localizing with Gαo) and in olfactory sensory neuron cilia (interacting with Gαolf via the GEF Ric-8B), consistent with roles in retinal ON-pathway and olfactory signal transduction."},"narrative":{"teleology":[{"year":2001,"claim":"Establishing that the divergent Gγ13 subunit can form functional Gβγ dimers — selectively stable with Gβ1, Gβ3, and Gβ4 — and that these dimers are competent to modulate ion channels (Kir3, N-type Ca²⁺) and PLCβ isoforms resolved the basic question of whether Gγ13 behaves as a canonical Gγ despite its sequence divergence.","evidence":"In vitro co-translation, co-immunoprecipitation under stringent detergent conditions, electrophysiology, and PLCβ activation assays","pmids":["11675383"],"confidence":"High","gaps":["No in vivo loss-of-function data to confirm physiological relevance of specific Gβγ13 effector coupling","Structural basis for selective stability with Gβ1/3/4 versus Gβ2/5 not determined","Upstream receptor(s) activating Gβγ13-containing heterotrimers not identified"]},{"year":2003,"claim":"Demonstrating that Gγ13 is selectively expressed in ON bipolar cells (but not OFF bipolar cells) and co-localizes with Gαo in their dendrites identified the specific retinal circuit in which Gγ13 operates, linking it to the mGluR6-Gαo signaling cascade.","evidence":"Immunohistochemistry, single-cell RT-PCR, and transgenic GFP reporter mouse lines in retinal sections","pmids":["12454992"],"confidence":"High","gaps":["No knockout or knockdown to demonstrate necessity of Gγ13 for ON bipolar cell light responses","Which specific Gβ partner (Gβ3 or Gβ4) predominates in vivo in ON bipolar cells is unresolved","Mechanism linking Gβγ13 release to downstream TRPM1 channel gating not addressed"]},{"year":2008,"claim":"Showing that Ric-8B physically interacts with Gγ13 and that both co-localize with Gβ1 and Gαolf in olfactory sensory neuron cilia extended Gγ13 function beyond retina and taste into olfactory signaling and identified a GEF that may regulate Gγ13-containing heterotrimers.","evidence":"Co-immunoprecipitation and immunohistochemical co-localization in olfactory sensory neurons","pmids":["18462949"],"confidence":"Medium","gaps":["Single-study co-IP without independent replication or reciprocal validation in a second system","Functional consequence of the Ric-8B–Gγ13 interaction on olfactory signal transduction not tested","Whether Gγ13 loss affects odorant-evoked responses in vivo is unknown"]},{"year":null,"claim":"In vivo loss-of-function studies are needed to establish the necessity of Gγ13 for retinal ON-pathway function, olfactory signaling, and taste transduction, and to determine whether its loss causes sensory deficits.","evidence":"","pmids":[],"confidence":"Low","gaps":["No Gng13 knockout phenotype reported in the primary literature captured here","No structural model of Gβγ13 heterodimer explaining selective Gβ pairing","Receptor specificity for Gγ13-containing heterotrimers remains undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[1]}],"localization":[{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[2]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,2]}],"pathway":[{"term_id":"R-HSA-9709957","term_label":"Sensory Perception","supporting_discovery_ids":[0,2]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,1,2]}],"complexes":[],"partners":["GNB1","GNB3","GNB4","GNAO1","GNAL","RIC8B"],"other_free_text":[]},"mechanistic_narrative":"GNG13 (Gγ13) is a G protein γ subunit that selectively forms stable heterodimers with Gβ1, Gβ3, and Gβ4, and these Gβγ13 complexes modulate Kir3.1/3.4 potassium channels, N-type calcium channels, and PLCβ isoforms [PMID:11675383]. In the retina, Gγ13 co-localizes with Gαo in the dendrites of rod and ON cone bipolar cells, where it participates in ON-pathway signal transduction together with Gβ3 and Gβ4 [PMID:12454992]. Gγ13 also localizes to olfactory sensory neuron cilia, where it physically interacts with the guanine nucleotide exchange factor Ric-8B and co-localizes with Gαolf and Gβ1, implicating it in olfactory signaling [PMID:18462949]."},"prefetch_data":{"uniprot":{"accession":"Q9P2W3","full_name":"Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13","aliases":[],"length_aa":67,"mass_kda":7.9,"function":"Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction","subcellular_location":"Cell membrane","url":"https://www.uniprot.org/uniprotkb/Q9P2W3/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GNG13","classification":"Not Classified","n_dependent_lines":21,"n_total_lines":1208,"dependency_fraction":0.0173841059602649},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/GNG13","total_profiled":1310},"omim":[{"mim_id":"610863","title":"GUANINE NUCLEOTIDE-BINDING PROTEIN, BETA-4; GNB4","url":"https://www.omim.org/entry/610863"},{"mim_id":"610142","title":"CENTROSOMAL PROTEIN, 290-KD; CEP290","url":"https://www.omim.org/entry/610142"},{"mim_id":"607298","title":"GUANINE NUCLEOTIDE-BINDING PROTEIN, GAMMA-13; GNG13","url":"https://www.omim.org/entry/607298"},{"mim_id":"602887","title":"DISCS LARGE MAGUK SCAFFOLD PROTEIN 4; DLG4","url":"https://www.omim.org/entry/602887"},{"mim_id":"139380","title":"GUANINE NUCLEOTIDE-BINDING PROTEIN, BETA-1; GNB1","url":"https://www.omim.org/entry/139380"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"brain","ntpm":58.3},{"tissue":"retina","ntpm":51.9}],"url":"https://www.proteinatlas.org/search/GNG13"},"hgnc":{"alias_symbol":["h2-35","G(gamma)13"],"prev_symbol":[]},"alphafold":{"accession":"Q9P2W3","domains":[{"cath_id":"-","chopping":"27-54","consensus_level":"medium","plddt":92.4511,"start":27,"end":54}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2W3","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2W3-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9P2W3-F1-predicted_aligned_error_v6.png","plddt_mean":88.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GNG13","jax_strain_url":"https://www.jax.org/strain/search?query=GNG13"},"sequence":{"accession":"Q9P2W3","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9P2W3.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9P2W3/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9P2W3"}},"corpus_meta":[{"pmid":"8097323","id":"PMC_8097323","title":"Interleukin 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Single-cell PCR showed Gβ3, Gβ4, and Gγ13 are co-expressed selectively in ON bipolar cells but not OFF bipolar cells, implicating Gγ13 in ON bipolar cell signal transduction.\",\n      \"method\": \"Immunohistochemistry, single-cell RT-PCR, transgenic GFP reporter mouse, patch-clamp recordings\",\n      \"journal\": \"The Journal of comparative neurology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (immunohistochemistry, single-cell PCR, electrophysiology) with functional validation; moderate evidence from single lab\",\n      \"pmids\": [\"12454992\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Gγ13 forms functional Gβγ dimers with all five Gβ subunits (Gβ1–5) as assessed by co-translation and channel modulation assays, but stable dimers detectable by co-immunoprecipitation under high-detergent conditions form selectively with Gβ1, Gβ3, and Gβ4. Multiple Gβ/Gγ13 pairings activate PLCβ2 and inhibit Gαq-stimulated PLCβ1 activity, and modulate Kir3.1/3.4 and N-type calcium channels. Gγ13 mRNA was detected in mouse and human brain and retina, beyond gustatory tissue.\",\n      \"method\": \"In vitro co-translation, co-immunoprecipitation, electrophysiology (channel modulation assays), cellular PLCβ activation assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal in vitro and cellular assays with mutagenesis-equivalent selectivity analysis in a single rigorous study\",\n      \"pmids\": [\"11675383\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Ric-8B, a guanine nucleotide exchange factor, physically interacts with Gγ13 as well as with Gαolf, and both proteins co-localize with Gbeta1 in the cilia of olfactory sensory neurons, implicating Gγ13 in olfactory signal transduction beyond its known role in taste.\",\n      \"method\": \"Co-immunoprecipitation (interaction assays), immunohistochemistry/co-localization in olfactory sensory neurons\",\n      \"journal\": \"Molecular and cellular neurosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — reciprocal co-IP and localization data, single lab, single study\",\n      \"pmids\": [\"18462949\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GNG13 (Gγ13) is a divergent G protein γ subunit that selectively forms stable heterodimers with Gβ1, Gβ3, and Gβ4; these Gβγ13 complexes are functionally competent to modulate ion channels (Kir3/N-type Ca2+) and PLCβ isoforms, and are expressed in ON bipolar cells of the retina (co-localizing with Gαo) and in olfactory sensory neuron cilia (interacting with Gαolf via the GEF Ric-8B), consistent with roles in retinal ON-pathway and olfactory signal transduction.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"GNG13 (Gγ13) is a G protein γ subunit that selectively forms stable heterodimers with Gβ1, Gβ3, and Gβ4, and these Gβγ13 complexes modulate Kir3.1/3.4 potassium channels, N-type calcium channels, and PLCβ isoforms [PMID:11675383]. In the retina, Gγ13 co-localizes with Gαo in the dendrites of rod and ON cone bipolar cells, where it participates in ON-pathway signal transduction together with Gβ3 and Gβ4 [PMID:12454992]. Gγ13 also localizes to olfactory sensory neuron cilia, where it physically interacts with the guanine nucleotide exchange factor Ric-8B and co-localizes with Gαolf and Gβ1, implicating it in olfactory signaling [PMID:18462949].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Establishing that the divergent Gγ13 subunit can form functional Gβγ dimers — selectively stable with Gβ1, Gβ3, and Gβ4 — and that these dimers are competent to modulate ion channels (Kir3, N-type Ca²⁺) and PLCβ isoforms resolved the basic question of whether Gγ13 behaves as a canonical Gγ despite its sequence divergence.\",\n      \"evidence\": \"In vitro co-translation, co-immunoprecipitation under stringent detergent conditions, electrophysiology, and PLCβ activation assays\",\n      \"pmids\": [\"11675383\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No in vivo loss-of-function data to confirm physiological relevance of specific Gβγ13 effector coupling\",\n        \"Structural basis for selective stability with Gβ1/3/4 versus Gβ2/5 not determined\",\n        \"Upstream receptor(s) activating Gβγ13-containing heterotrimers not identified\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstrating that Gγ13 is selectively expressed in ON bipolar cells (but not OFF bipolar cells) and co-localizes with Gαo in their dendrites identified the specific retinal circuit in which Gγ13 operates, linking it to the mGluR6-Gαo signaling cascade.\",\n      \"evidence\": \"Immunohistochemistry, single-cell RT-PCR, and transgenic GFP reporter mouse lines in retinal sections\",\n      \"pmids\": [\"12454992\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No knockout or knockdown to demonstrate necessity of Gγ13 for ON bipolar cell light responses\",\n        \"Which specific Gβ partner (Gβ3 or Gβ4) predominates in vivo in ON bipolar cells is unresolved\",\n        \"Mechanism linking Gβγ13 release to downstream TRPM1 channel gating not addressed\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Showing that Ric-8B physically interacts with Gγ13 and that both co-localize with Gβ1 and Gαolf in olfactory sensory neuron cilia extended Gγ13 function beyond retina and taste into olfactory signaling and identified a GEF that may regulate Gγ13-containing heterotrimers.\",\n      \"evidence\": \"Co-immunoprecipitation and immunohistochemical co-localization in olfactory sensory neurons\",\n      \"pmids\": [\"18462949\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-study co-IP without independent replication or reciprocal validation in a second system\",\n        \"Functional consequence of the Ric-8B–Gγ13 interaction on olfactory signal transduction not tested\",\n        \"Whether Gγ13 loss affects odorant-evoked responses in vivo is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"In vivo loss-of-function studies are needed to establish the necessity of Gγ13 for retinal ON-pathway function, olfactory signaling, and taste transduction, and to determine whether its loss causes sensory deficits.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No Gng13 knockout phenotype reported in the primary literature captured here\",\n        \"No structural model of Gβγ13 heterodimer explaining selective Gβ pairing\",\n        \"Receptor specificity for Gγ13-containing heterotrimers remains undefined\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0162582\", \"supporting_discovery_ids\": []},\n      {\"term_id\": \"R-HSA-9709957\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"GNB1\",\n      \"GNB3\",\n      \"GNB4\",\n      \"GNAO1\",\n      \"GNAL\",\n      \"RIC8B\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}