Summary: A copy number variation that results in reduced GENE DOSAGE due to any loss-of-function mutation. The loss of heterozygosity is associated with abnormal phenotypes or diseased states because the remaining gene is insufficient.

Top Publications

  1. Afshari P, Yao W, Middleton F. Reduced Slc1a1 expression is associated with neuroinflammation and impaired sensorimotor gating and cognitive performance in mice: Implications for schizophrenia. PLoS ONE. 2017;12:e0183854 pubmed publisher
    ..magnitude of changes was approximately equivalent in the HET and KO mice suggesting a dominant effect of the haploinsufficiency. Behavioral changes in the HET mice were accompanied by reduced thickness of the dorsomedial prefrontal ..
  2. Lockyer P, Mao H, Fan Q, Li L, Yu Lee L, Eissa N, et al. LRP1-Dependent BMPER Signaling Regulates Lipopolysaccharide-Induced Vascular Inflammation. Arterioscler Thromb Vasc Biol. 2017;37:1524-1535 pubmed publisher
    ..The new signaling pathway initiated by BMPER/low-density lipoprotein receptor-related protein 1 axis broadens our understanding about BMPER's role in vascular homeostasis. ..
  3. Higashiyama H, Ozawa A, Sumitomo H, Uemura M, Fujino K, Igarashi H, et al. Embryonic cholecystitis and defective gallbladder contraction in the Sox17-haploinsufficient mouse model of biliary atresia. Development. 2017;144:1906-1917 pubmed publisher
    ..i>Sox17 haploinsufficiency causes biliary atresia-like phenotypes and hepatitis in late organogenesis mouse embryos, but the molecular ..
  4. Lelieveld S, Wiel L, Venselaar H, Pfundt R, Vriend G, Veltman J, et al. Spatial Clustering of de Novo Missense Mutations Identifies Candidate Neurodevelopmental Disorder-Associated Genes. Am J Hum Genet. 2017;101:478-484 pubmed publisher
    b>Haploinsufficiency (HI) is the best characterized mechanism through which dominant mutations exert their effect and cause disease...
  5. Feng W, Chen B, Xing D, Li X, Fatima H, Jaimes E, et al. Haploinsufficiency of the Transcription Factor Ets-1 Is Renoprotective in Dahl Salt-Sensitive Rats. J Am Soc Nephrol. 2017;28:3239-3250 pubmed publisher
    ..In conclusion, reduced renal expression of ETS-1 prevented hypertension-associated kidney injury in SS rats. ..
  6. Vandeweyer G, Helsmoortel C, Van Dijck A, Vulto van Silfhout A, Coe B, Bernier R, et al. The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism. Am J Med Genet C Semin Med Genet. 2014;166C:315-26 pubmed publisher
    ..It is concluded that detailed clinical and molecular studies on larger cohorts of patients are necessary to establish a better insight in the genotype phenotype correlation and in the mutational mechanism. ..
  7. Koemans T, Kleefstra T, Chubak M, Stone M, Reijnders M, de Munnik S, et al. Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder. PLoS Genet. 2017;13:e1006864 pubmed publisher
    Kleefstra syndrome, caused by haploinsufficiency of euchromatin histone methyltransferase 1 (EHMT1), is characterized by intellectual disability (ID), autism spectrum disorder (ASD), characteristic facial dysmorphisms, and other variable ..
  8. Kadmiel M, Matson B, Espenschied S, Lenhart P, Caron K. Loss of receptor activity-modifying protein 2 in mice causes placental dysfunction and alters PTH1R regulation. PLoS ONE. 2017;12:e0181597 pubmed publisher
  9. de Carcer G, Wachowicz P, Martínez Martínez S, Oller J, Méndez Barbero N, Escobar B, et al. Plk1 regulates contraction of postmitotic smooth muscle cells and is required for vascular homeostasis. Nat Med. 2017;23:964-974 pubmed publisher
    ..We report an unexpected function of Plk1 in sustaining cardiovascular homeostasis. Plk1 haploinsufficiency in mice did not induce obvious cell proliferation defects but did result in arterial structural alterations, ..

More Information


  1. Solowska J, Rao A, Baas P. Truncating mutations of SPAST associated with hereditary spastic paraplegia indicate greater accumulation and toxicity of the M1 isoform of spastin. Mol Biol Cell. 2017;28:1728-1737 pubmed publisher
    ..b>Haploinsufficiency is a popular explanation for the disease, in part because most of the >200 pathogenic mutations of the ..
  2. Novara F, Rinaldi B, Sisodiya S, Coppola A, Giglio S, Stanzial F, et al. Haploinsufficiency for ANKRD11-flanking genes makes the difference between KBG and 16q24.3 microdeletion syndromes: 12 new cases. Eur J Hum Genet. 2017;25:694-701 pubmed publisher
    ..To assess whether the haploinsufficiency of ANKRD11-flanking genes, such as ZFPM1, CDH15 and ZNF778, contributed to either the severity of the ..
  3. Dupuis A, Gaub M, Legrain M, Drenou B, Mauvieux L, Lutz P, et al. Biclonal and biallelic deletions occur in 20% of B-ALL cases with IKZF1 mutations. Leukemia. 2013;27:503-7 pubmed publisher
  4. Afzali B, Grönholm J, Vandrovcova J, O Brien C, Sun H, Vanderleyden I, et al. BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency. Nat Immunol. 2017;18:813-823 pubmed publisher
    ..we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency. Affected subjects had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal ..
  5. Gerull B. Skin-heart connection: what can the epidermis tell us about the myocardium in arrhythmogenic cardiomyopathy?. Circ Cardiovasc Genet. 2014;7:225-7 pubmed publisher
  6. Shibata A, Tanahashi K, Sugiura K, Akiyama M. TRPS1 Haploinsufficiency Results in Increased STAT3 and SOX9 mRNA Expression in Hair Follicles in Trichorhinophalangeal Syndrome. Acta Derm Venereol. 2015;95:620-1 pubmed publisher
  7. Hanish A, Butman J, Thomas F, Yao J, Han J. Pineal hypoplasia, reduced melatonin and sleep disturbance in patients with PAX6 haploinsufficiency. J Sleep Res. 2016;25:16-22 pubmed
    ..Pineal hypoplasia has been previously reported in patients with PAX6 haploinsufficiency (+/−); however, pineal measurement, melatonin concentrations and sleep quality have not been reported...
  8. Masilamani A, Ferrarese R, Kling E, Thudi N, Kim H, Scholtens D, et al. KLF6 depletion promotes NF-κB signaling in glioblastoma. Oncogene. 2017;36:3562-3575 pubmed publisher
    ..5% of the analyzed glioblastomas and predicts unfavorable patient prognosis suggesting that haploinsufficiency is a clinically relevant means of evading KLF6-dependent regulation of NF-κB...
  9. Yang A, Kim J, Ki C, Hong S, Cho S, Jin D. HDR syndrome with a novel mutation in GATA3 mimicking a congenital X-linked stapes gusher: a case report. BMC Med Genet. 2017;18:121 pubmed publisher
    ..also known as Barakat syndrome, is a rare genetic disorder with high phenotypic heterogeneity caused by haploinsufficiency of the GATA3 gene on chromosome 10p14-p15...
  10. Hammer M, Ishii A, Johnstone L, Tchourbanov A, Lau B, Sprissler R, et al. Rare variants of small effect size in neuronal excitability genes influence clinical outcome in Japanese cases of SCN1A truncation-positive Dravet syndrome. PLoS ONE. 2017;12:e0180485 pubmed publisher
    ..mutation types by limiting inclusion to individuals with a de novo truncation mutation resulting in SCN1A haploinsufficiency. We performed tests aimed at identifying 1) single common variants that are enriched in either phenotypic ..
  11. Katayama S, Suzuki M, Yamaoka A, Keleku Lukwete N, Katsuoka F, Otsuki A, et al. GATA2 haploinsufficiency accelerates EVI1-driven leukemogenesis. Blood. 2017;130:908-919 pubmed publisher
    ..Because GATA2 haploinsufficiency is strongly associated with MDS and AML, we asked whether EVI1 misexpression and GATA2 ..
  12. Stankiewicz P, Khan T, Szafranski P, Slattery L, Streff H, Vetrini F, et al. Haploinsufficiency of the Chromatin Remodeler BPTF Causes Syndromic Developmental and Speech Delay, Postnatal Microcephaly, and Dysmorphic Features. Am J Hum Genet. 2017;101:503-515 pubmed publisher
    ..Taken together, our data demonstrate the pathogenic role of BPTF haploinsufficiency in syndromic neurodevelopmental anomalies and extend the clinical spectrum of human disorders caused by ..
  13. She A, Kurtser I, Reis S, Hennig K, Lai J, Lang A, et al. Selectivity and Kinetic Requirements of HDAC Inhibitors as Progranulin Enhancers for Treating Frontotemporal Dementia. Cell Chem Biol. 2017;24:892-906.e5 pubmed publisher
    ..Autosomal dominant causes of FTD include heterozygous mutations in the GRN gene causing haploinsufficiency of progranulin (PGRN) protein...
  14. Jacob C, Yu N, Yoo D, Perez Zapata L, Barbu E, Kaplan M, et al. Haploinsufficiency of NADPH Oxidase Subunit Neutrophil Cytosolic Factor 2 Is Sufficient to Accelerate Full-Blown Lupus in NZM 2328 Mice. Arthritis Rheumatol. 2017;69:1647-1660 pubmed publisher
    ..In contrast, on a lupus-prone background, even haploinsufficiency of NCF-2 accelerated the development of full-blown lupus disease...
  15. Rieux Laucat F, Casanova J. Immunology. Autoimmunity by haploinsufficiency. Science. 2014;345:1560-1 pubmed publisher
  16. Badran Y, Dedeoglu F, Leyva Castillo J, Bainter W, Ohsumi T, Bousvaros A, et al. Human RELA haploinsufficiency results in autosomal-dominant chronic mucocutaneous ulceration. J Exp Med. 2017;214:1937-1947 pubmed publisher
    ..in RELA, encoding the NF-?B subunit RelA, segregated with the disease phenotype and resulted in RelA haploinsufficiency. The patients' fibroblasts exhibited increased apoptosis in response to TNF, impaired NF-?B activation, and ..
  17. Tan S, Chadha S, Liu Y, Gabasova E, Perera D, Ahmed K, et al. A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability. Cell. 2017;169:1105-1118.e15 pubmed publisher
    ..Heterozygous BRCA2 truncations, by lowering pre-existing BRCA2 expression, sensitize to BRCA2 haploinsufficiency induced by transient exposure to natural concentrations of formaldehyde...
  18. Sakurai M, Kasahara H, Yoshida K, Yoshimi A, Kunimoto H, Watanabe N, et al. Genetic basis of myeloid transformation in familial platelet disorder/acute myeloid leukemia patients with haploinsufficient RUNX1 allele. Blood Cancer J. 2016;6:e392 pubmed publisher
  19. Glazier V, Murante T, Murante D, Koselny K, Liu Y, Kim D, et al. Genetic analysis of the Candida albicans biofilm transcription factor network using simple and complex haploinsufficiency. PLoS Genet. 2017;13:e1006948 pubmed publisher
    ..genetic perturbation with the six network heterozygous mutants all showing alterations in biofilm formation (haploinsufficiency). In addition, many double heterozygous mutants are as severely affected as homozygous deletions...
  20. Tian X, Yan C, Liu M, Zhang Q, Liu D, Liu Y, et al. CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance. PLoS ONE. 2017;12:e0176873 pubmed publisher
    ..Creg1 haploinsufficiency also exacerbated HFD-induced liver steatosis, dyslipidemia and insulin resistance...
  21. De Langhe E, Cailotto F, De Vooght V, Aznar López C, Vanoirbeek J, Luyten F, et al. Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis. Respir Res. 2015;16:38 pubmed publisher
    ..Modulating the balance between BMP and TGF?, in particular increasing endogenous BMP signals, may therefore be a therapeutic target in fibrotic lung disease. ..
  22. Arthur R, An N, Khan S, McNerney M. The haploinsufficient tumor suppressor, CUX1, acts as an analog transcriptional regulator that controls target genes through distal enhancers that loop to target promoters. Nucleic Acids Res. 2017;45:6350-6361 pubmed publisher
    ..b>Haploinsufficiency of CUX1 altered the expression of a large number of genes, including cell cycle regulators, with concomitant ..
  23. Balasooriya G, Goschorska M, Piddini E, Rawlins E. FGFR2 is required for airway basal cell self-renewal and terminal differentiation. Development. 2017;144:1600-1606 pubmed publisher
    ..This heterozygous phenotype illustrates that subtle changes in receptor tyrosine kinase signalling can have significant effects, perhaps providing an explanation for the numerous changes seen in cancer. ..
  24. Cole C, Russler Germain D, Ketkar S, Verdoni A, Smith A, Bangert C, et al. Haploinsufficiency for DNA methyltransferase 3A predisposes hematopoietic cells to myeloid malignancies. J Clin Invest. 2017;127:3657-3674 pubmed publisher
    ..produce truncated proteins that could either have dominant negative activities or cause loss of function and haploinsufficiency. Here, we demonstrate that 3 of these mutants produce truncated, inactive proteins that do not dimerize with ..
  25. Sachdeva J, Mahajan A, Cheng J, Baeten J, Lilly B, Kuivaniemi H, et al. Smooth muscle cell-specific Notch1 haploinsufficiency restricts the progression of abdominal aortic aneurysm by modulating CTGF expression. PLoS ONE. 2017;12:e0178538 pubmed publisher
    ..Notch1 haploinsufficiency in myeloid cells (n = 9) prevented the formation of AAA attributed to decreased inflammation...
  26. Julian L, Delaney S, Wang Y, Goldberg A, Dore C, Yockell Lelièvre J, et al. Human Pluripotent Stem Cell-Derived TSC2-Haploinsufficient Smooth Muscle Cells Recapitulate Features of Lymphangioleiomyomatosis. Cancer Res. 2017;77:5491-5502 pubmed publisher
    ..Intriguingly, the LAM-like features of these cells suggest that haploinsufficiency at the TSC2 locus contributes to LAM pathology, and demonstrated that iPSC reprogramming and SMC ..
  27. Dong X, Majesky M. Restoring elastin with microRNA-29. Arterioscler Thromb Vasc Biol. 2012;32:548-51 pubmed publisher
  28. Ludwig D, Carter J, Smith J, Borsani G, Barlati S, Hafizi S. Functional characterisation of human cells harbouring a novel t(2p;7p) translocation involving TNS3 and EXOC6B genes. BMC Med Genet. 2013;14:65 pubmed publisher
    ..The phenotypic changes observed in proband cells may arise from TNS3 haploinsufficiency, causing partial loss of full-length Tensin3 protein...
  29. Shibata A, Sugiura K, Kimura U, Takamori K, Akiyama M. A novel ATP2C1 early truncation mutation suggests haploinsufficiency as a pathogenic mechanism in a patient with Hailey-Hailey disease. Acta Derm Venereol. 2013;93:719-20 pubmed publisher
  30. Potla U, Ni J, Vadaparampil J, Yang G, Leventhal J, Campbell K, et al. Podocyte-specific RAP1GAP expression contributes to focal segmental glomerulosclerosis-associated glomerular injury. J Clin Invest. 2014;124:1757-69 pubmed publisher
    ..Podocyte-specific Rap1a and Rap1b haploinsufficiency also resulted in severe podocyte damage, including features of podocyte detachment...
  31. Thangamani S, Maland M, Mohammad H, Pascuzzi P, Avramova L, Koehler C, et al. Repurposing Approach Identifies Auranofin with Broad Spectrum Antifungal Activity That Targets Mia40-Erv1 Pathway. Front Cell Infect Microbiol. 2017;7:4 pubmed publisher
  32. Skraban C, Wells C, Markose P, Cho M, Nesbitt A, Au P, et al. WDR26 Haploinsufficiency Causes a Recognizable Syndrome of Intellectual Disability, Seizures, Abnormal Gait, and Distinctive Facial Features. Am J Hum Genet. 2017;101:139-148 pubmed publisher
    ..contains WDR26, and noted that clinical features are consistent between the two subsets, suggesting that haploinsufficiency of WDR26 contributes to the pathology of 1q41q42 microdeletion syndrome...
  33. Gompers A, Su Feher L, Ellegood J, Copping N, Riyadh M, Stradleigh T, et al. Germline Chd8 haploinsufficiency alters brain development in mouse. Nat Neurosci. 2017;20:1062-1073 pubmed publisher
    ..This integrative analysis offers an initial picture of the consequences of Chd8 haploinsufficiency for brain development.
  34. Gabriele M, Vulto van Silfhout A, Germain P, Vitriolo A, Kumar R, Douglas E, et al. YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction. Am J Hum Genet. 2017;100:907-925 pubmed publisher
    ..Our combined clinical and molecular data define "YY1 syndrome" as a haploinsufficiency syndrome...
  35. Wang S, Peng J. Network-assisted target identification for haploinsufficiency and homozygous profiling screens. PLoS Comput Biol. 2017;13:e1005553 pubmed publisher
    ..Network-Assisted Target Identification), a network analysis method for drug target identification in haploinsufficiency profiling (HIP) and homozygous profiling (HOP) screens...
  36. Liu P, Ji Y, Yuen T, Rendina Ruedy E, DeMambro V, Dhawan S, et al. Blocking FSH induces thermogenic adipose tissue and reduces body fat. Nature. 2017;546:107-112 pubmed publisher
    ..Here, we report that this antibody sharply reduces adipose tissue in wild-type mice, phenocopying genetic haploinsufficiency for the Fsh receptor gene Fshr...
  37. Franken R, Teixido Tura G, Brion M, Forteza A, Rodríguez Palomares J, Gutierrez L, et al. Relationship between fibrillin-1 genotype and severity of cardiovascular involvement in Marfan syndrome. Heart. 2017;103:1795-1799 pubmed publisher
    ..negative (DN; incorporation of non-mutated and mutated fibrillin-1 in the extracellular matrix) or having haploinsufficiency (HI; only incorporation of non-mutated fibrillin-1, thus a decreased amount of fibrillin-1 protein)...
  38. Chen C, Ruiz Vega R, Vasudeva P, Espitia F, Krasieva T, de Feraudy S, et al. ATR Mutations Promote the Growth of Melanoma Tumors by Modulating the Immune Microenvironment. Cell Rep. 2017;18:2331-2342 pubmed publisher
    ..Taken together, these studies identify a mechanism by which melanoma cells modulate the immune microenvironment to promote continued growth. ..
  39. Enane F, Shuen W, Gu X, Quteba E, Przychodzen B, Makishima H, et al. GATA4 loss of function in liver cancer impedes precursor to hepatocyte transition. J Clin Invest. 2017;127:3527-3542 pubmed publisher
    ..In a murine model, liver-conditional deletion of 1 Gata4 allele to model the haploinsufficiency seen in HCC produced enlarged livers with a gene expression profile of persistent precursor proliferation ..
  40. Myers K, Warman Chardon J, Huang L, Boycott K. Deletion of AFG3L2 associated with spinocerebellar ataxia type 28 in the context of multiple genomic anomalies. Am J Med Genet A. 2014;164A:3209-12 pubmed publisher
  41. Ibn Salem J, Kohler S, Love M, Chung H, Huang N, Hurles M, et al. Deletions of chromosomal regulatory boundaries are associated with congenital disease. Genome Biol. 2014;15:423 pubmed publisher
    ..computationally with a gene-dosage pathomechanism that attempts to explain the deletion phenotype based on haploinsufficiency of genes located within the deletions. Up to 11...