ArticleHuman genetics2012
Missense substitutions in the GAS1 protein present in holoprosencephaly patients reduce the affinity for its ligand, SHH.
Article in Human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Molecular testing in holoprosencephaly.American journal of medical genetics. Part C, Seminars in medical genetics · 2018Pooled it
- Recent advances in the diagnosis and molecular pathogenesis of holoprosencephaly: a review.Journal of applied genetics · 2025Article
- Gas1 regulates embryonic tongue muscle proliferation, differentiation and maturation via alternative pathways to Hedgehog signaling.Development (Cambridge, England) · 2025Article
- The hidden hedgehog of the pituitary: hedgehog signaling in development, adulthood and disease of the hypothalamic-pituitary axis.Frontiers in endocrinology · 2023Review
- Brain Organization and Human Diseases.Cells · 2022Review
- Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex.Developmental cell · 2022Article
- GAS1 is required for NOTCH-dependent facilitation of SHH signaling in the ventral forebrain neuroepithelium.Development (Cambridge, England) · 2021Article
- The hedgehog pathway and ocular developmental anomalies.Human genetics · 2019Review
- Hedgehog Signal and Genetic Disorders.Frontiers in genetics · 2019Review
- Multiple roles of Sonic Hedgehog in the developing human cortex are suggested by its widespread distribution.Brain structure & function · 2018Article
- Modeling the complex etiology of holoprosencephaly in mice.American journal of medical genetics. Part C, Seminars in medical genetics · 2018Review
- Extracephalic manifestations of nonchromosomal, nonsyndromic holoprosencephaly.American journal of medical genetics. Part C, Seminars in medical genetics · 2018Review
- BOC is a modifier gene in holoprosencephaly.Human mutation · 2017Article
- Distinct structural requirements for CDON and BOC in the promotion of Hedgehog signaling.Developmental biology · 2015Article
- Overweight in mice and enhanced adipogenesis in vitro are associated with lack of the hedgehog coreceptor boc.Diabetes · 2015Article
- Solution structure and biophysical characterization of the multifaceted signalling effector protein growth arrest specific-1.BMC biochemistry · 2015Article
- Induction of autophagy and apoptosis by miR-148a through the sonic hedgehog signaling pathway in hepatic stellate cells.American journal of cancer research · 2015Article
- Article
- The ubiquitin E3 ligase NOSIP modulates protein phosphatase 2A activity in craniofacial development.PloS one · 2014Article
- The teratogenic effects of prenatal ethanol exposure are exacerbated by Sonic Hedgehog or GLI2 haploinsufficiency in the mouse.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Holprosencephaly (HPE) is the most common disorder of the developing forebrain in humans, and is characterized by varying degrees of abnormal union of the cerebral hemispheres. These defects are typically co-associated with midline craniofacial anomalies. The combination of forebrain and craniofacial defects that comprise HPE can present along a broad and variable phenotypic spectrum. Both the SHH and NODAL signaling pathways play important roles in the pathogenesis of this disorder. Disruption of these pathways by chromosomal rearrangements, mutations in pathway-related genes and/or biochemical alterations are proposed to contribute to HPE in a large number of patients. Additional factors that are not yet fully delineated are also very likely to be involved in the pathogenesis and phenotypic heterogeneity of the disorder. Genetic loss of GAS1, a cell membrane receptor and positive regulator of SHH, has been demonstrated to contribute to the HPE phenotypic spectrum in animal models. We have evaluated the coding and flanking sequence of GAS1 in 394 patients who have clinical findings within the HPE phenotypic spectrum, and now report five novel missense sequence variants among five unrelated HPE probands. Finally, we tested the effect of these variants (as well as previously reported GAS1 variants) on the ability of GAS1 to bind to SHH. Here, we demonstrate that sequence variants in GAS1 can impair its physical interaction with SHH, suggesting a decrease in the SHH downstream signaling cascade as a pathogenic mechanism of disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.