ArticleThe Journal of clinical endocrinology and metabolism2014
Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.
Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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
43 citing papers in PubMed, 90 citations in OpenAlex.
- A calcium-sensing receptor dileucine motif directs internalization to spatially distinct endosomal signaling pathways.iScience · 2025Article
- Two novel rare variants in theOsteoporosis and sarcopenia · 2025Article
- An activating calcium-sensing receptor variant with biased signaling reveals a critical residue for Gα11 coupling.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Analysis of Calcium-Sensing Receptor Signaling Using Dual Luciferase Assays.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Capillary malformations.The Journal of clinical investigation · 2024Review
- Novel PTH Gene Mutations Causing Isolated Hypoparathyroidism.The Journal of clinical endocrinology and metabolism · 2022Article
- Review
- Pathogenic postzygotic mosaicism in the tyrosine receptor kinase pathway: potential unidentified human disease hidden away in a few cells.The FEBS journal · 2021Review
- Therapeutic Opportunities of Targeting Allosteric Binding Sites on the Calcium-Sensing Receptor.ACS pharmacology & translational science · 2021Review
- Rare diseases caused by abnormal calcium sensing and signalling.Endocrine · 2021Review
- Recombinant human parathyroid hormone (1-84) is effective in CASR-associated hypoparathyroidism.European journal of endocrinology · 2020Article
- International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function.Pharmacological reviews · 2020Review
- Hypoparathyroidism.The Journal of clinical endocrinology and metabolism · 2020Review
- Activating Mutations of the G-protein Subunit α 11 Interdomain Interface Cause Autosomal Dominant Hypocalcemia Type 2.The Journal of clinical endocrinology and metabolism · 2020Article
- The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.Nature reviews. Endocrinology · 2018Review
- Genetic Disorders of Parathyroid Development and Function.Endocrinology and metabolism clinics of North America · 2018Review
- Heterozygous Mutations in TBX1 as a Cause of Isolated Hypoparathyroidism.The Journal of clinical endocrinology and metabolism · 2018Article
- Calcium-sensing receptor residues with loss- and gain-of-function mutations are located in regions of conformational change and cause signalling bias.Human molecular genetics · 2018Article
- Successful pregnancies and reduced treatment requirement while breast feeding in a patient with congenital hypoparathyroidism due to homozygous c.68C>A null parathyroid hormone gene mutation.BMJ case reports · 2018Article
- CYP3A4 mutation causes vitamin D-dependent rickets type 3.The Journal of clinical investigation · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
contextMost cases of autosomal dominant hypoparathyroidism (ADH) are caused by gain-of-function mutations in CASR or dominant inhibitor mutations in GCM2 or PTH.
objectiveOur objectives were to identify the genetic basis for ADH in a multigenerational family and define the underlying disease mechanism. SUBJECTS: Here we evaluated a multigenerational family with ADH in which affected subjects had normal sequences in these genes and were shorter than unaffected family members.
methodsWe collected clinical and biochemical data from 6 of 11 affected subjects and performed whole-exome sequence analysis on DNA from two affected sisters and their affected father. Functional studies were performed after expression of wild-type and mutant Gα11 proteins in human embryonic kidney-293-CaR cells that stably express calcium-sensing receptors.
resultsWhole-exome-sequencing followed by Sanger sequencing revealed a heterozygous mutation, c.179G>T; p.R60L, in GNA11, which encodes the α-subunit of G11, the principal heterotrimeric G protein that couples calcium-sensing receptors to signal activation in parathyroid cells. Functional studies of Gα11 R60L showed increased accumulation of intracellular concentration of free calcium in response to extracellular concentration of free calcium with a significantly decreased EC50 compared with wild-type Gα11. By contrast, R60L was significantly less effective than the oncogenic Q209L form of Gα11 as an activator of the MAPK pathway. Compared to subjects with CASR mutations, patients with GNA11 mutations lacked hypercalciuria and had normal serum magnesium levels.
conclusionsOur findings indicate that the germline gain-of-function mutation of GNA11 is a cause of ADH and implicate a novel role for GNA11 in skeletal growth.
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.