{"doi":"10.1002/9780470015902.a0005489.pub2","title":"Haploinsufficiency","abstract":"Abstract\n \n \n Diploid organisms such as humans have two copies of each autosomal gene. Loss of both copies often has serious consequences – but what happens if just one copy is lost? For some genes, it matters; for others, it does not. Haploinsufficiency describes the situation where having only a single functioning copy of a gene is not enough for normal function, so that loss‐of‐function mutations cause a dominant phenotype. The reasons why some genes, but not others, show haploinsufficiency are interesting. In a few cases, the gene product is required in such large amounts that a single gene copy cannot satisfy the need. But more often, the reason is that the gene product interacts with something else in the cell in a way that requires the correct relative amounts of the interacting partners: a ligand interacting with its receptor or a transcription factor interacting with its target sequence, for example.\n \n \n Key Concepts\n \n \n \n DNA sequence variants in a protein‐coding gene may cause monogenic conditions either by causing a loss of function of the gene product or by causing a gain of function.\n \n \n Conditions caused by a gain of function are normally dominant (a single copy of the variant gene is sufficient to cause the condition). Usually, they are caused by a very limited set of variants.\n \n \n Conditions caused by a loss of function usually show extensive allelic heterogeneity.\n \n \n Loss‐of‐function conditions may be either dominant or recessive, depending whether the 50% overall level of function in a heterozygote is sufficient for a normal phenotype. Haploinsufficiency describes the situation where a 50% level of function is not sufficient. In these cases, loss‐of‐function mutations cause a dominant condition.\n \n \n Haploinsufficiency is sometimes caused due to inability of a single functional copy of a gene to produce a sufficient quantity of an abundant protein, but more often, it is because the gene product is interacting with something else in the cell, and the correct relative amounts are important. Examples would include interaction of a ligand with its receptor or a transcription factor with its target sequence.\n \n \n Haploinsufficiency may be suspected when databases of genome sequences of healthy individuals show a significant deficiency of heterozygous loss‐of‐function mutations in a particular gene.\n \n \n \n ","journal":"Encyclopedia of Life Sciences","year":2017,"id":610116,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1568513,"name":"Andrew P Read","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Haploinsufficiency","abstract":"Abstract\n \n \n Diploid organisms such as humans have two copies of each autosomal gene. Loss of both copies often has serious consequences – but what happens if just one copy is lost? For some genes, it matters; for others, it does not. Haploinsufficiency describes the situation where having only a single functioning copy of a gene is not enough for normal function, so that loss‐of‐function mutations cause a dominant phenotype. The reasons why some genes, but not others, show haploinsufficiency are interesting. In a few cases, the gene product is required in such large amounts that a single gene copy cannot satisfy the need. But more often, the reason is that the gene product interacts with something else in the cell in a way that requires the correct relative amounts of the interacting partners: a ligand interacting with its receptor or a transcription factor interacting with its target sequence, for example.\n \n \n Key Concepts\n \n \n \n DNA sequence variants in a protein‐coding gene may cause monogenic conditions either by causing a loss of function of the gene product or by causing a gain of function.\n \n \n Conditions caused by a gain of function are normally dominant (a single copy of the variant gene is sufficient to cause the condition). Usually, they are caused by a very limited set of variants.\n \n \n Conditions caused by a loss of function usually show extensive allelic heterogeneity.\n \n \n Loss‐of‐function conditions may be either dominant or recessive, depending whether the 50% overall level of function in a heterozygote is sufficient for a normal phenotype. Haploinsufficiency describes the situation where a 50% level of function is not sufficient. In these cases, loss‐of‐function mutations cause a dominant condition.\n \n \n Haploinsufficiency is sometimes caused due to inability of a single functional copy of a gene to produce a sufficient quantity of an abundant protein, but more often, it is because the gene product is interacting with something else in the cell, and the correct relative amounts are important. Examples would include interaction of a ligand with its receptor or a transcription factor with its target sequence.\n \n \n Haploinsufficiency may be suspected when databases of genome sequences of healthy individuals show a significant deficiency of heterozygous loss‐of‐function mutations in a particular gene.\n \n \n \n ","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21097893","pmcid":null,"openalex_id":"https://openalex.org/W4234813344","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2023,"count":1}],"oa_status":"closed","license":"http://doi.wiley.com/10.1002/tdm_license_1.1","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2F9780470015902.a0005489.pub2","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/9780470015902.a0005489.pub2","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1002/9780470015902.a0005489.pub2","host_type":"publisher"},{"url":"https://doi.org/10.1002/9780470015902.a0005489.pub2","host_type":"journal"}],"fields_of_study":["Genomic variations and chromosomal abnormalities","Genomics and Rare Diseases","Genetics and Neurodevelopmental Disorders"],"mesh_terms":[],"keywords":["Haploinsufficiency","Loss function","Genetics","Gene","Biology","Phenotype","Gene product","Function (biology)","Allele","Coding region","Mutation","Gene expression"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T19:35:17.270316Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}