{"gene":"PIH1D2","run_date":"2026-04-28T19:45:44","timeline":{"discoveries":[{"year":2018,"finding":"PIH1D2 binds SPAG1 and RUVBL1/RUVBL2 to form an R2TP-like complex termed R2SP, which functions as a quaternary chaperone enriched in testis. R2SP is required for liprin-α2 expression and assembly of liprin-α2 complexes, demonstrating a role in quaternary protein folding.","method":"Systematic interaction analyses (Co-IP, pulldown), functional knockdown with client protein expression as readout, temperature-sensitivity experiments","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 — reciprocal interaction analyses plus functional client assembly assay, replicated with multiple clients and temperature conditions","pmids":["29844425"],"is_preprint":false},{"year":2018,"finding":"PIH1D2 is specifically required for the assembly of distinct axonemal dynein subtypes in motile cilia/flagella, as demonstrated by loss of specific dynein subtypes in pih1d2 zebrafish mutant spermatozoa, correlating with abnormal sperm motility.","method":"Zebrafish genetic mutant analysis with cryo-electron tomography of axonemal dynein structures and sperm motility assays","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 — clean genetic KO with defined ultrastructural phenotype (cryo-ET) and functional readout (motility), ortholog in vertebrate model system","pmids":["29741156"],"is_preprint":false},{"year":2019,"finding":"Within the R2SP complex, SPAG1 recruits HSP70 and HSP90 chaperones via its TPR domains, and SPAG1 regulates nucleotide hydrolysis activity of HSP and RUVBL1/2 partners rather than acting as a GTPase itself, while PIH1D2 participates as a component of the R2SP assembly.","method":"Biochemical assays, ITC, NMR spectroscopy, molecular dynamics simulations, in vitro GTP hydrolysis assay","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 1 for SPAG1 mechanism within the R2SP complex; PIH1D2 role inferred as complex member rather than directly assayed","pmids":["31118266"],"is_preprint":false},{"year":2025,"finding":"The human R2SP complex (RUVBL1, RUVBL2, SPAG1, PIH1D2) has a three-dimensional structure similar to the canonical R2TP complex but with differences in RUVBL1/2 ATPase activity and in the mode of binding of its adaptors SPAG1 and PIH1D2, as resolved by combined structural approaches.","method":"NMR, structural mass spectrometry, cryo-EM, biochemical ATPase assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 1 structural methods but preprint, not yet peer-reviewed","pmids":["bio_10.1101_2025.01.27.635100"],"is_preprint":true}],"current_model":"PIH1D2 is an adaptor subunit of the R2SP quaternary chaperone complex (together with SPAG1 and RUVBL1/RUVBL2 ATPases), which promotes the assembly of specific protein clients including axonemal dynein subtypes and liprin-α2 complexes, particularly in testis and motile cilia, with SPAG1 recruiting HSP70/HSP90 and the complex adopting an architecture related to but distinct from canonical R2TP."},"narrative":{"teleology":[{"year":2018,"claim":"Two independent studies established that PIH1D2 functions within a novel R2TP-like chaperone complex (R2SP) and is required for assembly of specific multi-subunit clients — liprin-α2 complexes and axonemal dynein subtypes — resolving its molecular context and biological roles in quaternary protein folding and motile cilia function.","evidence":"Co-IP/pulldown interaction mapping and client expression assays in human cells (PMID:29844425); zebrafish pih1d2 genetic knockout with cryo-electron tomography and sperm motility assays (PMID:29741156)","pmids":["29844425","29741156"],"confidence":"High","gaps":["How PIH1D2 selects or recognizes specific dynein subtypes versus other potential clients is unknown","Whether PIH1D2 loss causes motile ciliopathy phenotypes beyond spermatozoa (e.g. airway cilia) has not been tested in mammals","The direct contacts between PIH1D2 and client proteins have not been mapped"]},{"year":2019,"claim":"Biochemical dissection of the R2SP complex revealed that the co-chaperone recruitment and ATPase regulatory activities reside in SPAG1 rather than PIH1D2, clarifying the division of labor within the complex.","evidence":"ITC, NMR spectroscopy, molecular dynamics simulations, and in vitro hydrolysis assays on SPAG1 TPR domains and RUVBL1/2","pmids":["31118266"],"confidence":"Medium","gaps":["PIH1D2's specific biochemical contribution to R2SP function (beyond scaffold membership) was not directly assayed","Whether PIH1D2 modulates HSP70/HSP90 recruitment or RUVBL ATPase activity allosterically is untested"]},{"year":2025,"claim":"Structural analysis of the intact human R2SP complex showed an architecture related to but distinct from canonical R2TP, with differences in RUVBL1/2 ATPase activity and in how SPAG1 and PIH1D2 bind the RUVBL ring, providing the first three-dimensional model of the holocomplex.","evidence":"NMR, structural mass spectrometry, cryo-EM, and ATPase assays (preprint)","pmids":["bio_10.1101_2025.01.27.635100"],"confidence":"Medium","gaps":["Preprint not yet peer-reviewed","Structure of R2SP bound to a client protein has not been determined","Functional consequences of the distinct ATPase properties relative to R2TP are not established"]},{"year":null,"claim":"The mechanism by which PIH1D2 directly recognizes and delivers specific protein clients to the RUVBL1/2 ATPase machinery, and whether PIH1D2 has roles beyond testis and motile cilia, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No client-binding interface on PIH1D2 has been defined","PIH1D2 function in somatic tissues outside testis is unexplored","Whether PIH1D2 mutations cause human disease (e.g. primary ciliary dyskinesia or male infertility) has not been investigated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[0,2]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"GO:0044183","term_label":"protein folding chaperone","supporting_discovery_ids":[0]}],"complexes":["R2SP"],"partners":["SPAG1","RUVBL1","RUVBL2"],"other_free_text":[]},"mechanistic_narrative":"PIH1D2 is an adaptor subunit of the R2SP quaternary chaperone complex, in which it associates with SPAG1 and the AAA+ ATPases RUVBL1/RUVBL2 to promote the assembly of multi-subunit protein clients [PMID:29844425]. R2SP is enriched in testis and is required for the stability and assembly of liprin-α2 complexes, functioning as a temperature-sensitive quaternary protein folding machine [PMID:29844425]. PIH1D2 is also specifically required for the assembly of distinct axonemal dynein subtypes in motile cilia and flagella; loss of pih1d2 in zebrafish results in absence of specific dynein arms and defective sperm motility [PMID:29741156]."},"prefetch_data":{"uniprot":{"accession":"Q8WWB5","full_name":"PIH1 domain-containing protein 2","aliases":[],"length_aa":315,"mass_kda":36.0,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q8WWB5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/PIH1D2","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/PIH1D2","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Vesicles","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"testis","ntpm":62.1}],"url":"https://www.proteinatlas.org/search/PIH1D2"},"hgnc":{"alias_symbol":["DNAAF15"],"prev_symbol":[]},"alphafold":{"accession":"Q8WWB5","domains":[{"cath_id":"-","chopping":"11-46","consensus_level":"medium","plddt":81.0678,"start":11,"end":46},{"cath_id":"-","chopping":"50-165","consensus_level":"high","plddt":91.5414,"start":50,"end":165},{"cath_id":"2.60.40.790","chopping":"236-314","consensus_level":"high","plddt":86.7822,"start":236,"end":314}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WWB5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WWB5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WWB5-F1-predicted_aligned_error_v6.png","plddt_mean":77.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=PIH1D2","jax_strain_url":"https://www.jax.org/strain/search?query=PIH1D2"},"sequence":{"accession":"Q8WWB5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WWB5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WWB5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WWB5"}},"corpus_meta":[{"pmid":"29844425","id":"PMC_29844425","title":"The RPAP3-Cterminal domain identifies R2TP-like quaternary chaperones.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/29844425","citation_count":60,"is_preprint":false},{"pmid":"29741156","id":"PMC_29741156","title":"Systematic studies of all PIH proteins in zebrafish reveal their distinct roles in axonemal dynein assembly.","date":"2018","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/29741156","citation_count":53,"is_preprint":false},{"pmid":"35207567","id":"PMC_35207567","title":"Omics and Male Infertility: Highlighting the Application of Transcriptomic Data.","date":"2022","source":"Life (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/35207567","citation_count":29,"is_preprint":false},{"pmid":"32251302","id":"PMC_32251302","title":"Transcriptomic analysis of female and male gonads in juvenile snakeskin gourami (Trichopodus pectoralis).","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/32251302","citation_count":14,"is_preprint":false},{"pmid":"31118266","id":"PMC_31118266","title":"Binding properties of the quaternary assembly protein SPAG1.","date":"2019","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/31118266","citation_count":12,"is_preprint":false},{"pmid":"20310044","id":"PMC_20310044","title":"Novel germline SDHD deletion associated with an unusual sympathetic head and neck paraganglioma.","date":"2010","source":"Head & neck","url":"https://pubmed.ncbi.nlm.nih.gov/20310044","citation_count":4,"is_preprint":false},{"pmid":"39857704","id":"PMC_39857704","title":"Genetic Nurture Effects on Type 2 Diabetes Among Chinese Han Adults: A Family-Based Design.","date":"2025","source":"Biomedicines","url":"https://pubmed.ncbi.nlm.nih.gov/39857704","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.01.27.635100","title":"R2TP-like Quaternary Chaperones: a comprehensive overview to understand the dynamic R2SP complex","date":"2025-01-28","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.27.635100","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5740,"output_tokens":1028,"usd":0.01632},"stage2":{"model":"claude-opus-4-6","input_tokens":4229,"output_tokens":2692,"usd":0.132667},"total_usd":0.148987,"stage1_batch_id":"msgbatch_01SUR8NDzVrNmyszWyJeCct7","stage2_batch_id":"msgbatch_01G7Yfutko3cDWzejrwH5AMx","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"PIH1D2 binds SPAG1 and RUVBL1/RUVBL2 to form an R2TP-like complex termed R2SP, which functions as a quaternary chaperone enriched in testis. R2SP is required for liprin-α2 expression and assembly of liprin-α2 complexes, demonstrating a role in quaternary protein folding.\",\n      \"method\": \"Systematic interaction analyses (Co-IP, pulldown), functional knockdown with client protein expression as readout, temperature-sensitivity experiments\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal interaction analyses plus functional client assembly assay, replicated with multiple clients and temperature conditions\",\n      \"pmids\": [\"29844425\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PIH1D2 is specifically required for the assembly of distinct axonemal dynein subtypes in motile cilia/flagella, as demonstrated by loss of specific dynein subtypes in pih1d2 zebrafish mutant spermatozoa, correlating with abnormal sperm motility.\",\n      \"method\": \"Zebrafish genetic mutant analysis with cryo-electron tomography of axonemal dynein structures and sperm motility assays\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean genetic KO with defined ultrastructural phenotype (cryo-ET) and functional readout (motility), ortholog in vertebrate model system\",\n      \"pmids\": [\"29741156\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Within the R2SP complex, SPAG1 recruits HSP70 and HSP90 chaperones via its TPR domains, and SPAG1 regulates nucleotide hydrolysis activity of HSP and RUVBL1/2 partners rather than acting as a GTPase itself, while PIH1D2 participates as a component of the R2SP assembly.\",\n      \"method\": \"Biochemical assays, ITC, NMR spectroscopy, molecular dynamics simulations, in vitro GTP hydrolysis assay\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 for SPAG1 mechanism within the R2SP complex; PIH1D2 role inferred as complex member rather than directly assayed\",\n      \"pmids\": [\"31118266\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The human R2SP complex (RUVBL1, RUVBL2, SPAG1, PIH1D2) has a three-dimensional structure similar to the canonical R2TP complex but with differences in RUVBL1/2 ATPase activity and in the mode of binding of its adaptors SPAG1 and PIH1D2, as resolved by combined structural approaches.\",\n      \"method\": \"NMR, structural mass spectrometry, cryo-EM, biochemical ATPase assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 structural methods but preprint, not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2025.01.27.635100\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"PIH1D2 is an adaptor subunit of the R2SP quaternary chaperone complex (together with SPAG1 and RUVBL1/RUVBL2 ATPases), which promotes the assembly of specific protein clients including axonemal dynein subtypes and liprin-α2 complexes, particularly in testis and motile cilia, with SPAG1 recruiting HSP70/HSP90 and the complex adopting an architecture related to but distinct from canonical R2TP.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PIH1D2 is an adaptor subunit of the R2SP quaternary chaperone complex, in which it associates with SPAG1 and the AAA+ ATPases RUVBL1/RUVBL2 to promote the assembly of multi-subunit protein clients [PMID:29844425]. R2SP is enriched in testis and is required for the stability and assembly of liprin-α2 complexes, functioning as a temperature-sensitive quaternary protein folding machine [PMID:29844425]. PIH1D2 is also specifically required for the assembly of distinct axonemal dynein subtypes in motile cilia and flagella; loss of pih1d2 in zebrafish results in absence of specific dynein arms and defective sperm motility [PMID:29741156].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Two independent studies established that PIH1D2 functions within a novel R2TP-like chaperone complex (R2SP) and is required for assembly of specific multi-subunit clients — liprin-α2 complexes and axonemal dynein subtypes — resolving its molecular context and biological roles in quaternary protein folding and motile cilia function.\",\n      \"evidence\": \"Co-IP/pulldown interaction mapping and client expression assays in human cells (PMID:29844425); zebrafish pih1d2 genetic knockout with cryo-electron tomography and sperm motility assays (PMID:29741156)\",\n      \"pmids\": [\"29844425\", \"29741156\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How PIH1D2 selects or recognizes specific dynein subtypes versus other potential clients is unknown\",\n        \"Whether PIH1D2 loss causes motile ciliopathy phenotypes beyond spermatozoa (e.g. airway cilia) has not been tested in mammals\",\n        \"The direct contacts between PIH1D2 and client proteins have not been mapped\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Biochemical dissection of the R2SP complex revealed that the co-chaperone recruitment and ATPase regulatory activities reside in SPAG1 rather than PIH1D2, clarifying the division of labor within the complex.\",\n      \"evidence\": \"ITC, NMR spectroscopy, molecular dynamics simulations, and in vitro hydrolysis assays on SPAG1 TPR domains and RUVBL1/2\",\n      \"pmids\": [\"31118266\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"PIH1D2's specific biochemical contribution to R2SP function (beyond scaffold membership) was not directly assayed\",\n        \"Whether PIH1D2 modulates HSP70/HSP90 recruitment or RUVBL ATPase activity allosterically is untested\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Structural analysis of the intact human R2SP complex showed an architecture related to but distinct from canonical R2TP, with differences in RUVBL1/2 ATPase activity and in how SPAG1 and PIH1D2 bind the RUVBL ring, providing the first three-dimensional model of the holocomplex.\",\n      \"evidence\": \"NMR, structural mass spectrometry, cryo-EM, and ATPase assays (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.01.27.635100\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint not yet peer-reviewed\",\n        \"Structure of R2SP bound to a client protein has not been determined\",\n        \"Functional consequences of the distinct ATPase properties relative to R2TP are not established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The mechanism by which PIH1D2 directly recognizes and delivers specific protein clients to the RUVBL1/2 ATPase machinery, and whether PIH1D2 has roles beyond testis and motile cilia, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No client-binding interface on PIH1D2 has been defined\",\n        \"PIH1D2 function in somatic tissues outside testis is unexplored\",\n        \"Whether PIH1D2 mutations cause human disease (e.g. primary ciliary dyskinesia or male infertility) has not been investigated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"R2SP\"],\n    \"partners\": [\"SPAG1\", \"RUVBL1\", \"RUVBL2\"],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I need to fix the pathway — it should use Reactome IDs, not GO terms. Let me correct:\n\n```json\n{\n  \"mechanistic_narrative\": \"PIH1D2 is an adaptor subunit of the R2SP quaternary chaperone complex, in which it associates with SPAG1 and the AAA+ ATPases RUVBL1/RUVBL2 to promote the assembly of multi-subunit protein clients [PMID:29844425]. R2SP is enriched in testis and is required for the stability and assembly of liprin-α2 complexes, functioning as a temperature-sensitive quaternary protein folding machine [PMID:29844425]. PIH1D2 is also specifically required for the assembly of distinct axonemal dynein subtypes in motile cilia and flagella; loss of pih1d2 in zebrafish results in absence of specific dynein arms and defective sperm motility [PMID:29741156].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Two independent studies established that PIH1D2 functions within a novel R2TP-like chaperone complex (R2SP) and is required for assembly of specific multi-subunit clients — liprin-α2 complexes and axonemal dynein subtypes — resolving its molecular context and biological roles in quaternary protein folding and motile cilia function.\",\n      \"evidence\": \"Co-IP/pulldown interaction mapping and client expression assays in human cells (PMID:29844425); zebrafish pih1d2 genetic knockout with cryo-electron tomography and sperm motility assays (PMID:29741156)\",\n      \"pmids\": [\"29844425\", \"29741156\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How PIH1D2 selects or recognizes specific dynein subtypes versus other potential clients is unknown\",\n        \"Whether PIH1D2 loss causes motile ciliopathy phenotypes beyond spermatozoa (e.g. airway cilia) has not been tested in mammals\",\n        \"The direct contacts between PIH1D2 and client proteins have not been mapped\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Biochemical dissection of the R2SP complex revealed that the co-chaperone recruitment and ATPase regulatory activities reside in SPAG1 rather than PIH1D2, clarifying the division of labor within the complex.\",\n      \"evidence\": \"ITC, NMR spectroscopy, molecular dynamics simulations, and in vitro hydrolysis assays on SPAG1 TPR domains and RUVBL1/2\",\n      \"pmids\": [\"31118266\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"PIH1D2's specific biochemical contribution to R2SP function (beyond scaffold membership) was not directly assayed\",\n        \"Whether PIH1D2 modulates HSP70/HSP90 recruitment or RUVBL ATPase activity allosterically is untested\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Structural analysis of the intact human R2SP complex showed an architecture related to but distinct from canonical R2TP, with differences in RUVBL1/2 ATPase activity and in how SPAG1 and PIH1D2 bind the RUVBL ring, providing the first three-dimensional model of the holocomplex.\",\n      \"evidence\": \"NMR, structural mass spectrometry, cryo-EM, and ATPase assays (preprint)\",\n      \"pmids\": [\"bio_10.1101_2025.01.27.635100\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Preprint not yet peer-reviewed\",\n        \"Structure of R2SP bound to a client protein has not been determined\",\n        \"Functional consequences of the distinct ATPase properties relative to R2TP are not established\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The mechanism by which PIH1D2 directly recognizes and delivers specific protein clients to the RUVBL1/2 ATPase machinery, and whether PIH1D2 has roles beyond testis and motile cilia, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No client-binding interface on PIH1D2 has been defined\",\n        \"PIH1D2 function in somatic tissues outside testis is unexplored\",\n        \"Whether PIH1D2 mutations cause human disease (e.g. primary ciliary dyskinesia or male infertility) has not been investigated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0044183\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"R2SP\"],\n    \"partners\": [\"SPAG1\", \"RUVBL1\", \"RUVBL2\"],\n    \"other_free_text\": []\n  }\n}\n```"}