| Name | shieldin complex subunit 2 |
| Description | Involved in negative regulation of double-strand break repair via homologous recombination; positive regulation of double-strand break repair via nonhomologous end joining; and positive regulation of isotype switching. Located in actin cytoskeleton; nucleoplasm; and site of double-strand break. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSHLD2, formerly known as FAM35A or RINN2, has emerged as a key effector in the repair of DNA double‐strand breaks. In this context, SHLD2 is recruited to sites of damage in a 53BP1-, RIF1- and REV7-dependent manner, where it promotes non-homologous end-joining by antagonizing homologous recombination through the limitation of DNA end resection. Loss or depletion of SHLD2 not only impairs efficient DSB repair but also compromises antibody diversification via class switch recombination and alters cellular sensitivity to DNA-damaging agents, particularly in BRCA1-mutant settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nInterestingly, beyond its established role in maintaining genomic stability, genetic studies have pointed to a possible connection between SHLD2 and metabolic traits. Genome‐wide association analyses have identified variants in SHLD2 associated with gout, and further investigations have linked a specific SNP (rs7903456) to elevated uric acid levels, suggesting that SHLD2 may exhibit pleiotropic functions that bridge DNA repair processes and metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Steven Findlay, John Heath, Vincent M Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SHLD2/FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.2018100158"}], "href": "https://doi.org/10.15252/embj.2018100158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30154076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30154076"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Junya Tomida, Kei-Ichi Takata, Sarita Bhetawal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201899543"}], "href": "https://doi.org/10.15252/embj.201899543"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29789392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29789392"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Akiyoshi Nakayama, Hirofumi Nakaoka, Ken Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Rheum Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/annrheumdis-2016-209632"}], "href": "https://doi.org/10.1136/annrheumdis-2016-209632"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27899376"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27899376"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Feng Yan, Peng Sun, Huishou Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic association and functional analysis of rs7903456 in FAM35A gene and hyperuricemia: a population based study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-27956-3"}], "href": "https://doi.org/10.1038/s41598-018-27956-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29942023"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29942023"}]}]}]}
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| NCBI Gene ID | 54537 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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SHLD2 has 2,269 functional associations with biological entities spanning 6 categories (functional term, phrase or reference, chemical, disease, phenotype or trait, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 38 datasets.
Click the + buttons to view associations for SHLD2 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SHLD2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with SHLD2 gene from the CellMarker Gene-Cell Type Associations dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of SHLD2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of SHLD2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing SHLD2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 | cellular components containing SHLD2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with SHLD2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| DeepCoverMOA Drug Mechanisms of Action | small molecule perturbations with high or low expression of SHLD2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by SHLD2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with SHLD2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with SHLD2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving SHLD2 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving SHLD2 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2023 | cellular components containing SHLD2 protein from the curated GO Cellular Component Annotations 2023 dataset. | |
| GO Cellular Component Annotations 2025 | cellular components containing SHLD2 protein from the curated GO Cellular Component Annotations 2025 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of SHLD2 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of SHLD2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue-Specific Aging Signatures | tissue samples with high or low expression of SHLD2 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with SHLD2 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of SHLD2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of SHLD2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of SHLD2 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of SHLD2 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset. | |
| NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of SHLD2 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving SHLD2 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving SHLD2 protein from the Wikipathways PFOCR 2024 dataset. | |
| Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of SHLD2 gene from the Replogle et al., Cell, 2022 K562 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of SHLD2 gene from the Replogle et al., Cell, 2022 K562 Genome-wide Perturb-seq Gene Perturbation Signatures dataset. | |
| Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures | gene perturbations changing expression of SHLD2 gene from the Replogle et al., Cell, 2022 RPE1 Essential Perturb-seq Gene Perturbation Signatures dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of SHLD2 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of SHLD2 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of SHLD2 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Sci-Plex Drug Perturbation Signatures | drug perturbations changing expression of SHLD2 gene from the Sci-Plex Drug Perturbation Signatures dataset. | |
| Tahoe Therapeutics Tahoe 100M Perturbation Atlas | drug perturbations changing expression of SHLD2 gene from the Tahoe Therapeutics Tahoe 100M Perturbation Atlas dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of SHLD2 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of SHLD2 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with SHLD2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2024 | pathways involving SHLD2 protein from the WikiPathways Pathways 2024 dataset. | |
