HYPOC1
MCID: HYP802
MIFTS: 67

Hypocalcemia, Autosomal Dominant 1 (HYPOC1)

Categories: Blood diseases, Endocrine diseases, Eye diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hypocalcemia, Autosomal Dominant 1

MalaCards integrated aliases for Hypocalcemia, Autosomal Dominant 1:

Name: Hypocalcemia, Autosomal Dominant 1 57 75 29 6 40 73
Autosomal Dominant Hypocalcemia 12 25 59 29 15 73
Hypocalcemia, Autosomal Dominant 57 53 13 55 40
Hypocalcemia, Autosomal Dominant, with Bartter Syndrome 57 29 40
Hypoc1 57 12 75
Hypercalciuric Hypocalcemia 57 75
Familial Hypocalcemia 25 75
Hypocalcemia 44 73
Autosomal Dominant Hypocalcemia with Bartter Syndrome 75
Hypoparathyroidism - Autosomal Dominant 73
Autosomal Dominant Hypoparathyroidism 25
Familial Hypercalciuric Hypocalcemia 25
Bartter Syndrome with Hypocalcemia 59
Autosomal Dominant Hypocalcemia 1 12
Bartter Syndrome Type 5 59
Bartter Syndrome Type V 59
Hypocalcemia, Familial 57
Ad Hypocalcemia 59
Hypoc 12
Adh 25

Characteristics:

Orphanet epidemiological data:

59
bartter syndrome with hypocalcemia
Inheritance: Autosomal dominant; Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: normal life expectancy;
autosomal dominant hypocalcemia
Inheritance: Autosomal dominant; Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
some patients have asymptomatic hypocalcemia


HPO:

32
hypocalcemia, autosomal dominant 1:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Hypocalcemia, Autosomal Dominant 1

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 428Disease definitionAutosomal dominant hypocalcemia (AD hypocalcemia) is a disorder of calcium homeostasis characterized by variable degrees of hypocalcemia with abnormally low levels of parathyroid hormone (PTH) and persistant normal or elevated calciuria.EpidemiologyPrevalence is unknown, but the disease is likely to be underdiagnosed as the hypocalcemia may remain asymptomatic.Clinical descriptionClinical expression and age of onset are extremely variable (depending on the degree of hypocalcemia), ranging from completely asymptomatic patients (in whom the diagnosis is made by chance during a routine exam) to patients with limited symptoms (cramps, asthenia, paresthesias) and patients with severe symptoms (i.e. recurrent seizures). In addition to hypocalcemia, hypercalciuria or relative hypercalciuria (hypercalciuria within the normal range, but relatively high in the presence of hypocalcemia) is present. Hyperphosphatemia, hypomagnesemia and hypermagnesuria are also common. Nephrocalcinosis and impaired renal function have been reported and cases of AD hypocalcemia with classical features of Bartter syndrome (BS; see this term) have been described (referred to as BS with hypocalcemia; see this term). Serum levels of PTH are normal or low. In addition to regulation by PTH, environmental factors also influence calcium homeostasis and may explain why an initially well-controlled hypocalcemia may become symptomatic at various stages of life.EtiologyAD hypocalcemia is caused by activating mutations of the geneCASR (3q21.1), encoding the calcium-sensing receptor (CaSR). CaSR plays a key role in the regulation of calcium-phosphate metabolism by controlling PTH secretion and urinary calcium excretion in response to variations in serum calcium levels. Gain-of-function CASR mutations result in increased sensitivity of parathyroid and renal cells to calcium levels, leading to hypocalcemia being perceived as normal. Activating mutations in GNA11 (19p13.3) have also been described.Diagnostic methodsDiagnosis is made through analysis of calcium levels in the serum and urine and PTH levels, Molecular analysis of CaSR followed by GNA11 confirms diagnosis.Differential diagnosisDifferential diagnosis includes all other causes of hypoparathyroidism as well as BS in patients with renal salt wasting.Antenatal diagnosisAntenatal diagnosis is possible.Genetic counselingGenetic counseling may be proposed but patients should be informed about the wide variability in clinical presentation.Management and treatmentTreatment to normalize calcemia levels should be considered with caution, as any increase in calcium levels (even within the normal range) will be perceived by renal cells as hypercalcemia and lead to increased urinary calcium excretion, and possibly to nephrocalcinosis and renal failure. Treatment should aim towards finding a balance between the clinical signs of hypocalcemia and maintenance of calcium homeostasis, without being iatrogenic. Urine calcium levels should be monitored in order to avoid hypercalciuria rather than adapting treatment towards hypocalcemia. In asymptomatic and mildly symptomatic patients, treatment may not be necessary. Special care must be given to children as chronic hypocalcemia has deleterious effects on intellectual development. Treatment is based on administration of 1-alpha hydroxylated vitamin D (doses ranging from 0.5 to 1.5 micrograms/day in adults; higher doses are sometimes required in children). Careful monitoring of calciuria and regular kidney ultrasound are required. In cases where calcium homeostasis is difficult to achieve, exogenous PTH administered by infusion pump can be proposed.PrognosisThe prognosis is variable, depending on the severity of the hypocalcemia and the possible consequences of inadequate treatment.Visit the Orphanet disease page for more resources.

MalaCards based summary : Hypocalcemia, Autosomal Dominant 1, also known as autosomal dominant hypocalcemia, is related to hypomagnesemia 1, intestinal and hypoparathyroidism, familial isolated, and has symptoms including seizures, carpopedal spasm and muscle cramp. An important gene associated with Hypocalcemia, Autosomal Dominant 1 is CASR (Calcium Sensing Receptor), and among its related pathways/superpathways are CREB Pathway and Neuroscience. Affiliated tissues include kidney, bone and liver, and related phenotypes are emotional lability and depressivity

Disease Ontology : 12 A metal metabolism disorder characterized by autosomal dominant inheritance of variable degrees of hypocalcemia with normal to low levels of parathyroid hormone.

Genetics Home Reference : 25 Autosomal dominant hypocalcemia is characterized by low levels of calcium in the blood (hypocalcemia). Affected individuals can have an imbalance of other molecules in the blood as well, including too much phosphate (hyperphosphatemia) or too little magnesium (hypomagnesemia). Some people with autosomal dominant hypocalcemia also have low levels of a hormone called parathyroid hormone (hypoparathyroidism). This hormone is involved in the regulation of calcium levels in the blood. Abnormal levels of calcium and other molecules in the body can lead to a variety of signs and symptoms, although about half of affected individuals have no associated health problems.

OMIM : 57 Autosomal dominant hypocalcemia-1 is associated with low or normal serum parathyroid hormone concentrations (PTH). Approximately 50% of patients have mild or asymptomatic hypocalcemia; about 50% have paresthesias, carpopedal spasm, and seizures; about 10% have hypercalciuria with nephrocalcinosis or kidney stones; and more than 35% have ectopic and basal ganglia calcifications (summary by Nesbit et al., 2013). Thakker (2001) noted that patients with gain-of-function mutations in the CASR gene, resulting in generally asymptomatic hypocalcemia with hypercalciuria, have low-normal serum PTH concentrations and have often been diagnosed with hypoparathyroidism because of the insensitivity of earlier PTH assays. Because treatment with vitamin D to correct the hypocalcemia in these patients causes hypercalciuria, nephrocalcinosis, and renal impairment, these patients need to be distinguished from those with other forms of hypoparathyroidism (see 146200). Thakker (2001) suggested the designation 'autosomal dominant hypocalcemic hypercalciuria' for this CASR-related disorder. (601198)

UniProtKB/Swiss-Prot : 75 Hypocalcemia, autosomal dominant 1: A disorder of mineral homeostasis characterized by blood calcium levels below normal, and low or normal serum parathyroid hormone concentrations. Disease manifestations include mild or asymptomatic hypocalcemia, paresthesias, carpopedal spasm, seizures, hypercalciuria with nephrocalcinosis or kidney stones, and ectopic and basal ganglia calcifications. Few patients manifest hypocalcemia and features of Bartter syndrome, including hypomagnesemia, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronemia.

Related Diseases for Hypocalcemia, Autosomal Dominant 1

Diseases in the Hypocalcemia, Autosomal Dominant 1 family:

Hypocalcemia, Autosomal Dominant 2

Diseases related to Hypocalcemia, Autosomal Dominant 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 279)
# Related Disease Score Top Affiliating Genes
1 hypomagnesemia 1, intestinal 33.0 CLDN16 PTH TRPM6
2 hypoparathyroidism, familial isolated 32.2 CASR GCM2 PTH
3 primary hypomagnesemia 31.3 CLDN16 PTH TRPM6
4 familial hypocalciuric hypercalcemia 30.4 CASR GNA11 PTH
5 hyperparathyroidism, neonatal severe 30.3 CASR CXADR PRKAR1A
6 hyperphosphatemia 30.1 CASR FGF23 GCM2 GNAS PTH VDR
7 rickets 29.9 FGF23 PTH VDR
8 thyroid crisis 29.8 ALB PTH
9 hypoparathyroidism 29.8 CASR FGF23 GCM2 PTH
10 uremia 29.6 ALB CASR PTH VDR
11 parathyroid carcinoma 29.6 CALCA CASR PTH
12 idiopathic hypercalciuria 29.6 CASR PRKAR1A VDR
13 multiple endocrine neoplasia, type i 29.6 CASR GNAS PRKAR1A PTH
14 secondary hyperparathyroidism of renal origin 29.5 ALB CALCA CASR FGF23 PTH VDR
15 osteitis fibrosa 29.5 CALCA CASR GNAS PTH
16 bone resorption disease 29.4 CALCA PTH VDR
17 parathyroid adenoma 29.4 CALCA CASR GCM2 PTH VDR
18 osteomalacia 29.4 CALCA CASR FGF23 PTH VDR
19 hypervitaminosis d 29.4 FGF23 PTH VDR
20 hyperparathyroidism 29.4 CALCA CASR FGF23 GCM2 PRKAR1A PTH
21 osteoporosis 29.1 ALB CALCA CASR FGF23 PRKAR1A PTH
22 renal osteodystrophy 29.0 CALCA CASR FGF23 PTH VDR
23 bone disease 29.0 CALCA CASR FGF23 PTH VDR
24 calciphylaxis 29.0 ALB CASR FGF23 PTH VDR
25 kidney disease 28.9 ALB CASR FGF23 PTH VDR
26 primary hyperparathyroidism 28.9 ALB CALCA CASR CXADR FGF23 GCM2
27 chronic kidney failure 28.3 ALB CALCA CASR CLDN16 FGF23 PTH
28 hypocalcemia, autosomal dominant 2 12.6
29 inappropriate adh syndrome 12.6
30 bartter syndrome, type 5, antenatal, transient 12.3
31 diabetes insipidus, nephrogenic, autosomal 12.2
32 kenny-caffey syndrome, type 2 11.8
33 syndrome of inappropriate antidiuretic hormone 11.6
34 pseudohypoparathyroidism, type ib 11.5
35 digeorge syndrome 11.4
36 osteopetrosis, autosomal recessive 1 11.4
37 diabetes insipidus, nephrogenic, x-linked 11.3
38 osteopetrosis 11.3
39 diabetes insipidus, neurohypophyseal 11.2
40 pseudohypoparathyroidism, type ii 11.2
41 kenny-caffey syndrome 11.2
42 pseudohypoparathyroidism, type ia 11.0
43 hypoparathyroidism, sensorineural deafness, and renal disease 11.0
44 vitamin d hydroxylation-deficient rickets, type 1a 11.0
45 familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis 11.0
46 osteopetrosis, autosomal dominant 2 10.9
47 hypoparathyroidism-retardation-dysmorphism syndrome 10.9
48 kenny-caffey syndrome, type 1 10.9
49 hypomagnesemia 3, renal 10.9
50 osteopetrosis, autosomal recessive 2 10.9

Graphical network of the top 20 diseases related to Hypocalcemia, Autosomal Dominant 1:



Diseases related to Hypocalcemia, Autosomal Dominant 1

Symptoms & Phenotypes for Hypocalcemia, Autosomal Dominant 1

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
paresthesias
calcification of the basal ganglia

Muscle Soft Tissue:
muscle cramps
tetany
carpopedal spasm

Growth Height:
short stature (rare)

Skeletal:
osteoarthritis, premature (rare)

Genitourinary Kidneys:
hypercalciuria
nephrocalcinosis
nephrolithiasis
decreased renal function

Endocrine Features:
hypomagnesemia
hypocalcemia, mild or severe
parathyroid hormone concentration low or low-normal
normal or mildly elevated serum phosphate
hypokalemia (rare)
more
Respiratory Larynx:
laryngospasm (rare)

Skeletal Spine:
increased bone mineral density of lumbar spine (rare)


Clinical features from OMIM:

601198

Human phenotypes related to Hypocalcemia, Autosomal Dominant 1:

59 32 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 emotional lability 59 32 hallmark (90%) Very frequent (99-80%) HP:0000712
2 depressivity 59 32 hallmark (90%) Very frequent (99-80%) HP:0000716
3 hypotension 59 32 frequent (33%) Frequent (79-30%) HP:0002615
4 increased intracranial pressure 59 32 occasional (7.5%) Occasional (29-5%) HP:0002516
5 optic atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000648
6 reduced consciousness/confusion 59 32 occasional (7.5%) Occasional (29-5%) HP:0004372
7 emg abnormality 59 32 hallmark (90%) Very frequent (99-80%) HP:0003457
8 arrhythmia 59 32 frequent (33%) Frequent (79-30%) HP:0011675
9 abdominal pain 59 32 frequent (33%) Frequent (79-30%) HP:0002027
10 congestive heart failure 59 32 occasional (7.5%) Occasional (29-5%) HP:0001635
11 reduced bone mineral density 59 32 occasional (7.5%) Occasional (29-5%) HP:0004349
12 dry skin 59 32 frequent (33%) Frequent (79-30%) HP:0000958
13 anxiety 59 32 hallmark (90%) Very frequent (99-80%) HP:0000739
14 abnormality of the fingernails 59 32 frequent (33%) Frequent (79-30%) HP:0001231
15 alopecia 59 32 frequent (33%) Frequent (79-30%) HP:0001596
16 hypercalciuria 59 32 hallmark (90%) Very frequent (99-80%) HP:0002150
17 paresthesia 59 32 hallmark (90%) Very frequent (99-80%) HP:0003401
18 irregular hyperpigmentation 59 32 occasional (7.5%) Occasional (29-5%) HP:0007400
19 hypocalcemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002901
20 nephrocalcinosis 59 32 frequent (33%) Frequent (79-30%) HP:0000121
21 eczema 59 32 occasional (7.5%) Occasional (29-5%) HP:0000964
22 writer's cramp 59 32 hallmark (90%) Very frequent (99-80%) HP:0002356
23 fatigable weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0003473
24 abnormal pattern of respiration 59 32 frequent (33%) Frequent (79-30%) HP:0002793
25 hyperphosphatemia 59 32 frequent (33%) Frequent (79-30%) HP:0002905
26 hypomagnesemia 59 32 frequent (33%) Frequent (79-30%) HP:0002917
27 hypermagnesiuria 59 32 frequent (33%) Frequent (79-30%) HP:0012608
28 cortical myoclonus 59 32 hallmark (90%) Very frequent (99-80%) HP:0040148
29 seizures 32 HP:0001250
30 behavioral abnormality 59 Very frequent (99-80%)
31 short stature 32 occasional (7.5%) HP:0004322
32 hypokalemia 32 occasional (7.5%) HP:0002900
33 abnormality of the nail 59 Frequent (79-30%)
34 abnormal renal physiology 32 HP:0012211
35 muscle cramps 32 HP:0003394
36 laryngospasm 32 occasional (7.5%) HP:0025425
37 tetany 32 HP:0001281
38 nephrolithiasis 32 HP:0000787
39 increased circulating renin level 32 occasional (7.5%) HP:0000848
40 basal ganglia calcification 32 HP:0002135

UMLS symptoms related to Hypocalcemia, Autosomal Dominant 1:


seizures, carpopedal spasm, muscle cramp

MGI Mouse Phenotypes related to Hypocalcemia, Autosomal Dominant 1:

46 (show all 14)
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.25 ALB CASR CLDN16 CXADR FGF23 GCM2
2 cellular MP:0005384 10.19 ALB CASR CXADR GCM2 GNAS GRM1
3 endocrine/exocrine gland MP:0005379 10.19 ALB CASR CXADR FGF23 GCM2 GNA11
4 growth/size/body region MP:0005378 10.13 CASR FGF23 GNA11 GNAS GRM1 PRKAR1A
5 mortality/aging MP:0010768 10.1 ALB CASR CXADR FGF23 GCM2 GNA11
6 craniofacial MP:0005382 10.07 GCM2 GNA11 GNAS PRKAR1A PTH TRPM6
7 hematopoietic system MP:0005397 10.06 CASR CXADR FGF23 GNA11 GNAS PRKAR1A
8 immune system MP:0005387 10.01 CASR CXADR FGF23 GNA11 GNAS PRKAR1A
9 digestive/alimentary MP:0005381 9.99 ALB CASR CXADR FGF23 PRKAR1A VDR
10 integument MP:0010771 9.91 CASR FGF23 GNA11 GNAS GRM1 PRKAR1A
11 muscle MP:0005369 9.86 ALB CASR CXADR GNA11 GNAS GRM1
12 renal/urinary system MP:0005367 9.61 ALB CASR CLDN16 FGF23 GCM2 GNA11
13 pigmentation MP:0001186 9.46 CASR GNA11 GRM1 PRKAR1A
14 skeleton MP:0005390 9.32 CASR FGF23 GCM2 GNA11 GNAS GRM1

Drugs & Therapeutics for Hypocalcemia, Autosomal Dominant 1

Genetic Tests for Hypocalcemia, Autosomal Dominant 1

Genetic tests related to Hypocalcemia, Autosomal Dominant 1:

# Genetic test Affiliating Genes
1 Hypocalcemia, Autosomal Dominant 1 29 CASR
2 Autosomal Dominant Hypocalcemia 29
3 Hypocalcemia, Autosomal Dominant, with Bartter Syndrome 29

Anatomical Context for Hypocalcemia, Autosomal Dominant 1

MalaCards organs/tissues related to Hypocalcemia, Autosomal Dominant 1:

41
Kidney, Bone, Liver, Heart, Brain, Eye, Thyroid

Publications for Hypocalcemia, Autosomal Dominant 1

Articles related to Hypocalcemia, Autosomal Dominant 1:

(show all 36)
# Title Authors Year
1
Identification and Functional Characterization of a Novel Mutation in the Human Calcium-Sensing Receptor That Co-Segregates With Autosomal-Dominant Hypocalcemia. ( 29743878 )
2018
2
Autosomal dominant hypocalcemia due to a truncation in the C-tail of the calcium-sensing receptor. ( 27561204 )
2017
3
Clinical characterization of a novel calcium sensing receptor genetic alteration in a Greek patient with autosomal dominant hypocalcemia type 1. ( 28742508 )
2017
4
Identification of a G-Protein Subunit-I+11 Gain-of-Function Mutation, Val340Met, in a Family With Autosomal Dominant Hypocalcemia Type 2 (ADH2). ( 26818911 )
2016
5
Novel calcium-sensing receptor cytoplasmic tail deletion mutation causing autosomal dominant hypocalcemia: molecular and clinical study. ( 26764418 )
2016
6
Impaired growth and intracranial calcifications in autosomal dominant hypocalcemia caused by a GNA11 mutation. ( 27334330 )
2016
7
Autosomal Dominant Hypocalcemia (Hypoparathyroidism) Types 1 and 2. ( 27803672 )
2016
8
Pathogenesis of hypokalemia in autosomal dominant hypocalcemia type 1. ( 26323216 )
2015
9
Autosomal dominant hypocalcemia with Bartter syndrome due to a novel activating mutation of calcium sensing receptor, Y829C. ( 25932037 )
2015
10
Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH). ( 25967373 )
2015
11
The Calcilytic Agent NPS 2143 Rectifies Hypocalcemia in a Mouse Model With an Activating Calcium-Sensing Receptor (CaSR) Mutation: Relevance to Autosomal Dominant Hypocalcemia Type 1 (ADH1). ( 26052899 )
2015
12
Novel Mutation in the CASR Gene (p.Leu123Ser) in a Case of Autosomal Dominant Hypocalcemia. ( 27617113 )
2015
13
Functional activities of mutant calcium-sensing receptors determine clinical presentations in patients with autosomal dominant hypocalcemia. ( 24297799 )
2014
14
Mutational analysis of the adaptor protein 2 sigma subunit (AP2S1) gene: search for autosomal dominant hypocalcemia type 3 (ADH3). ( 24708097 )
2014
15
Amino alcohol- (NPS-2143) and quinazolinone-derived calcilytics (ATF936 and AXT914) differentially mitigate excessive signalling of calcium-sensing receptor mutants causing Bartter syndrome Type 5 and autosomal dominant hypocalcemia. ( 25506941 )
2014
16
Identification and characterization of D410E, a novel mutation in the loop 3 domain of CASR, in autosomal dominant hypocalcemia and a therapeutic approach using a novel calcilytic, AXT914. ( 23009664 )
2013
17
Extrapyramidal symptoms and advanced calcification of the basal ganglia in a patient with autosomal dominant hypocalcemia. ( 24042516 )
2013
18
CASR gene activating mutations in two families with autosomal dominant hypocalcemia. ( 22789683 )
2012
19
A novel mutation of the primary protein kinase C phosphorylation site in the calcium-sensing receptor causes autosomal dominant hypocalcemia. ( 21135065 )
2011
20
Autosomal dominant hypocalcemia caused by an activating mutation of the calcium-sensing receptor gene: the first case report in Korea. ( 20119591 )
2010
21
Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome. ( 17048213 )
2006
22
A novel mutation (E767K) in the second extracellular loop of the calcium sensing receptor in a family with autosomal dominant hypocalcemia. ( 15551332 )
2005
23
Autosomal dominant hypocalcemia in monozygotic twins caused by a de novo germline mutation near the amino-terminus of the human calcium receptor. ( 15005845 )
2004
24
CASRdb: calcium-sensing receptor locus-specific database for mutations causing familial (benign) hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. ( 15241791 )
2004
25
A novel mutation in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia in a family with two uncommon parathyroid hormone polymorphisms. ( 14519094 )
2003
26
Autosomal dominant hypocalcemia: a novel activating mutation (E604K) in the cysteine-rich domain of the calcium-sensing receptor. ( 12574188 )
2003
27
A family of autosomal dominant hypocalcemia with an activating mutation of calcium-sensing receptor gene. ( 12733714 )
2003
28
Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia. ( 11889203 )
2002
29
Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome. ( 12191970 )
2002
30
A family of autosomal dominant hypocalcemia with a positive correlation between serum calcium and magnesium: identification of a novel gain of function mutation (Ser(820)Phe) in the calcium-sensing receptor. ( 12050233 )
2002
31
Autosomal dominant hypocalcemia caused by a novel mutation in the loop 2 region of the human calcium receptor extracellular domain. ( 12162500 )
2002
32
A novel activating mutation (C129S) in the calcium-sensing receptor gene in a Japanese family with autosomal dominant hypocalcemia. ( 11289719 )
2001
33
Three novel activating mutations in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia. ( 11136551 )
2000
34
Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. ( 11013439 )
2000
35
A large homozygous or heterozygous in-frame deletion within the calcium-sensing receptor's carboxylterminal cytoplasmic tail that causes autosomal dominant hypocalcemia. ( 10770217 )
2000
36
A novel activating mutation in calcium-sensing receptor gene associated with a family of autosomal dominant hypocalcemia. ( 9920108 )
1999

Variations for Hypocalcemia, Autosomal Dominant 1

UniProtKB/Swiss-Prot genetic disease variations for Hypocalcemia, Autosomal Dominant 1:

75 (show all 34)
# Symbol AA change Variation ID SNP ID
1 CASR p.Ala116Thr VAR_003588 rs104893691
2 CASR p.Glu127Ala VAR_003589 rs121909260
3 CASR p.Gln681His VAR_003598 rs121909261
4 CASR p.Phe806Ser VAR_003600 rs104893693
5 CASR p.Leu616Val VAR_015414 rs104893703
6 CASR p.Glu767Lys VAR_021019
7 CASR p.Lys47Asn VAR_058050 rs104893702
8 CASR p.Asn118Lys VAR_058051 rs104893695
9 CASR p.Leu125Pro VAR_058052 rs104893708
10 CASR p.Phe128Leu VAR_058053 rs104893696
11 CASR p.Cys131Trp VAR_058054 rs121909267
12 CASR p.Thr151Met VAR_058055 rs104893694
13 CASR p.Glu191Lys VAR_058058 rs104893697
14 CASR p.Glu604Lys VAR_058070 rs104893712
15 CASR p.Phe612Ser VAR_058071 rs104893698
16 CASR p.Leu727Gln VAR_058075 rs104893718
17 CASR p.Leu773Arg VAR_058078 rs104893699
18 CASR p.Phe788Cys VAR_058079 rs104893701
19 CASR p.Phe788Leu VAR_058080 rs886041537
20 CASR p.Ser820Phe VAR_058081 rs104893710
21 CASR p.Ala843Glu VAR_058082 rs104893706
22 CASR p.Ser122Cys VAR_078145
23 CASR p.Leu125Phe VAR_078146
24 CASR p.Cys129Arg VAR_078147
25 CASR p.Pro136Leu VAR_078148
26 CASR p.Pro221Leu VAR_078157 rs397514728
27 CASR p.Glu228Lys VAR_078159
28 CASR p.Pro569His VAR_078165
29 CASR p.Gln681Arg VAR_078171
30 CASR p.Asn802Ile VAR_078176
31 CASR p.Gly830Ser VAR_078179
32 CASR p.Phe832Leu VAR_078180
33 CASR p.Phe832Ser VAR_078181
34 CASR p.Ile839Thr VAR_078182

ClinVar genetic disease variations for Hypocalcemia, Autosomal Dominant 1:

6 (show top 50) (show all 782)
# Gene Variation Type Significance SNP ID Assembly Location
1 CASR NM_000388.3(CASR): c.889G> A (p.Glu297Lys) single nucleotide variant Pathogenic rs121909259 GRCh37 Chromosome 3, 121980771: 121980771
2 CASR NM_000388.3(CASR): c.889G> A (p.Glu297Lys) single nucleotide variant Pathogenic rs121909259 GRCh38 Chromosome 3, 122261924: 122261924
3 CASR NM_000388.3(CASR): c.554G> A (p.Arg185Gln) single nucleotide variant Pathogenic rs104893689 GRCh37 Chromosome 3, 121980436: 121980436
4 CASR NM_000388.3(CASR): c.554G> A (p.Arg185Gln) single nucleotide variant Pathogenic rs104893689 GRCh38 Chromosome 3, 122261589: 122261589
5 CASR NM_000388.3(CASR): c.380A> C (p.Glu127Ala) single nucleotide variant Pathogenic rs121909260 GRCh37 Chromosome 3, 121976122: 121976122
6 CASR NM_000388.3(CASR): c.380A> C (p.Glu127Ala) single nucleotide variant Pathogenic rs121909260 GRCh38 Chromosome 3, 122257275: 122257275
7 CASR NM_000388.3(CASR): c.1745G> A (p.Cys582Tyr) single nucleotide variant Uncertain significance rs104893690 GRCh37 Chromosome 3, 122002546: 122002546
8 CASR NM_000388.3(CASR): c.1745G> A (p.Cys582Tyr) single nucleotide variant Uncertain significance rs104893690 GRCh38 Chromosome 3, 122283699: 122283699
9 CASR NM_000388.3(CASR): c.2043G> T (p.Gln681His) single nucleotide variant Pathogenic rs121909261 GRCh37 Chromosome 3, 122002844: 122002844
10 CASR NM_000388.3(CASR): c.2043G> T (p.Gln681His) single nucleotide variant Pathogenic rs121909261 GRCh38 Chromosome 3, 122283997: 122283997
11 CASR NM_000388.3(CASR): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic rs104893691 GRCh37 Chromosome 3, 121976088: 121976088
12 CASR NM_000388.3(CASR): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic rs104893691 GRCh38 Chromosome 3, 122257241: 122257241
13 CASR NM_000388.3(CASR): c.2417T> C (p.Phe806Ser) single nucleotide variant Pathogenic rs104893693 GRCh37 Chromosome 3, 122003218: 122003218
14 CASR NM_000388.3(CASR): c.2417T> C (p.Phe806Ser) single nucleotide variant Pathogenic rs104893693 GRCh38 Chromosome 3, 122284371: 122284371
15 CASR NM_000388.3(CASR): c.452C> T (p.Thr151Met) single nucleotide variant Pathogenic rs104893694 GRCh37 Chromosome 3, 121976194: 121976194
16 CASR NM_000388.3(CASR): c.452C> T (p.Thr151Met) single nucleotide variant Pathogenic rs104893694 GRCh38 Chromosome 3, 122257347: 122257347
17 CASR NM_000388.3(CASR): c.354C> A (p.Asn118Lys) single nucleotide variant Pathogenic rs104893695 GRCh37 Chromosome 3, 121976096: 121976096
18 CASR NM_000388.3(CASR): c.354C> A (p.Asn118Lys) single nucleotide variant Pathogenic rs104893695 GRCh38 Chromosome 3, 122257249: 122257249
19 CASR NM_000388.3(CASR): c.382T> C (p.Phe128Leu) single nucleotide variant Pathogenic rs104893696 GRCh37 Chromosome 3, 121976124: 121976124
20 CASR NM_000388.3(CASR): c.382T> C (p.Phe128Leu) single nucleotide variant Pathogenic rs104893696 GRCh38 Chromosome 3, 122257277: 122257277
21 CASR NM_000388.3(CASR): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic rs104893697 GRCh37 Chromosome 3, 121980453: 121980453
22 CASR NM_000388.3(CASR): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic rs104893697 GRCh38 Chromosome 3, 122261606: 122261606
23 CASR NM_000388.3(CASR): c.1835T> C (p.Phe612Ser) single nucleotide variant Pathogenic rs104893698 GRCh37 Chromosome 3, 122002636: 122002636
24 CASR NM_000388.3(CASR): c.1835T> C (p.Phe612Ser) single nucleotide variant Pathogenic rs104893698 GRCh38 Chromosome 3, 122283789: 122283789
25 CASR NM_000388.3(CASR): c.2318T> G (p.Leu773Arg) single nucleotide variant Pathogenic rs104893699 GRCh37 Chromosome 3, 122003119: 122003119
26 CASR NM_000388.3(CASR): c.2318T> G (p.Leu773Arg) single nucleotide variant Pathogenic rs104893699 GRCh38 Chromosome 3, 122284272: 122284272
27 CASR NM_000388.3(CASR): c.680G> A (p.Arg227Gln) single nucleotide variant Pathogenic rs28936684 GRCh37 Chromosome 3, 121980562: 121980562
28 CASR NM_000388.3(CASR): c.680G> A (p.Arg227Gln) single nucleotide variant Pathogenic rs28936684 GRCh38 Chromosome 3, 122261715: 122261715
29 CASR NM_000388.3(CASR): c.413C> T (p.Thr138Met) single nucleotide variant Likely pathogenic rs121909263 GRCh37 Chromosome 3, 121976155: 121976155
30 CASR NM_000388.3(CASR): c.413C> T (p.Thr138Met) single nucleotide variant Likely pathogenic rs121909263 GRCh38 Chromosome 3, 122257308: 122257308
31 CASR NM_000388.3(CASR): c.428G> A (p.Gly143Glu) single nucleotide variant Pathogenic/Likely pathogenic rs121909264 GRCh37 Chromosome 3, 121976170: 121976170
32 CASR NM_000388.3(CASR): c.428G> A (p.Gly143Glu) single nucleotide variant Pathogenic/Likely pathogenic rs121909264 GRCh38 Chromosome 3, 122257323: 122257323
33 CASR NM_000388.3(CASR): c.2363T> G (p.Phe788Cys) single nucleotide variant Pathogenic rs104893701 GRCh37 Chromosome 3, 122003164: 122003164
34 CASR NM_000388.3(CASR): c.2363T> G (p.Phe788Cys) single nucleotide variant Pathogenic rs104893701 GRCh38 Chromosome 3, 122284317: 122284317
35 CASR NM_000388.3(CASR): c.141A> C (p.Lys47Asn) single nucleotide variant Pathogenic rs104893702 GRCh37 Chromosome 3, 121973177: 121973177
36 CASR NM_000388.3(CASR): c.141A> C (p.Lys47Asn) single nucleotide variant Pathogenic rs104893702 GRCh38 Chromosome 3, 122254330: 122254330
37 CASR NM_000388.3(CASR): c.1846C> G (p.Leu616Val) single nucleotide variant Pathogenic rs104893703 GRCh37 Chromosome 3, 122002647: 122002647
38 CASR NM_000388.3(CASR): c.1846C> G (p.Leu616Val) single nucleotide variant Pathogenic rs104893703 GRCh38 Chromosome 3, 122283800: 122283800
39 CASR NM_000388.3(CASR): c.2682_3224del543 (p.Ser895_Val1075del) deletion Pathogenic GRCh38 Chromosome 3, 122284636: 122285178
40 CASR NM_000388.3(CASR): c.2682_3224del543 (p.Ser895_Val1075del) deletion Pathogenic GRCh37 Chromosome 3, 122003483: 122004025
41 CASR NM_000388.3(CASR): c.2641T> C (p.Phe881Leu) single nucleotide variant Uncertain significance rs104893704 GRCh37 Chromosome 3, 122003442: 122003442
42 CASR NM_000388.3(CASR): c.2641T> C (p.Phe881Leu) single nucleotide variant Uncertain significance rs104893704 GRCh38 Chromosome 3, 122284595: 122284595
43 CASR NM_000388.3(CASR): c.2528C> A (p.Ala843Glu) single nucleotide variant Pathogenic rs104893706 GRCh37 Chromosome 3, 122003329: 122003329
44 CASR NM_000388.3(CASR): c.2528C> A (p.Ala843Glu) single nucleotide variant Pathogenic rs104893706 GRCh38 Chromosome 3, 122284482: 122284482
45 CASR NM_000388.3(CASR): c.393C> G (p.Cys131Trp) single nucleotide variant Pathogenic rs121909267 GRCh37 Chromosome 3, 121976135: 121976135
46 CASR NM_000388.3(CASR): c.393C> G (p.Cys131Trp) single nucleotide variant Pathogenic rs121909267 GRCh38 Chromosome 3, 122257288: 122257288
47 CASR NM_000388.3(CASR): c.374T> C (p.Leu125Pro) single nucleotide variant Pathogenic rs104893708 GRCh37 Chromosome 3, 121976116: 121976116
48 CASR NM_000388.3(CASR): c.374T> C (p.Leu125Pro) single nucleotide variant Pathogenic rs104893708 GRCh38 Chromosome 3, 122257269: 122257269
49 CASR NM_000388.3(CASR): c.2459C> T (p.Ser820Phe) single nucleotide variant Pathogenic rs104893710 GRCh37 Chromosome 3, 122003260: 122003260
50 CASR NM_000388.3(CASR): c.2459C> T (p.Ser820Phe) single nucleotide variant Pathogenic rs104893710 GRCh38 Chromosome 3, 122284413: 122284413

Expression for Hypocalcemia, Autosomal Dominant 1

Search GEO for disease gene expression data for Hypocalcemia, Autosomal Dominant 1.

Pathways for Hypocalcemia, Autosomal Dominant 1

Pathways related to Hypocalcemia, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

(show all 19)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.06 FGF23 GNA11 GNAS GRM1 PRKAR1A TRPM6
2 12.36 CALCA GNA11 GRM1 PRKAR1A
3
Show member pathways
12.27 CALCA GNA11 GNAS PRKAR1A
4
Show member pathways
12.03 GNA11 GNAS GRM1
5
Show member pathways
11.99 GNA11 GNAS PRKAR1A
6 11.9 CALCA GNAS PTH
7
Show member pathways
11.82 GNA11 GNAS PRKAR1A
8 11.66 ALB CASR GNA11 PRKAR1A VDR
9
Show member pathways
11.57 GNAS GRM1 PRKAR1A
10 11.52 GNA11 GNAS GRM1
11 11.45 FGF23 GNA11 GNAS PRKAR1A
12 11.28 GNA11 GNAS GRM1
13 11.19 CASR FGF23 GCM2 GNA11 GNAS PTH
14 11.09 CALCA PTH VDR
15 10.94 GNA11 GNAS PRKAR1A PTH VDR
16 10.93 GNAS PRKAR1A
17 10.74 CASR GRM1
18 10.66 FGF23 PTH
19 10.37 PTH VDR

GO Terms for Hypocalcemia, Autosomal Dominant 1

Cellular components related to Hypocalcemia, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 heterotrimeric G-protein complex GO:0005834 8.96 GNA11 GNAS
2 neuron projection GO:0043005 8.92 CALCA CASR CXADR GRM1

Biological processes related to Hypocalcemia, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 G protein-coupled receptor signaling pathway GO:0007186 9.93 CALCA CASR GNA11 GNAS GRM1 PTH
2 calcium ion transport GO:0006816 9.7 PTH TRPM6 VDR
3 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.67 CALCA GNAS PTH
4 activation of adenylate cyclase activity GO:0007190 9.57 CALCA GNAS
5 renal water homeostasis GO:0003091 9.56 GNAS PRKAR1A
6 positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway GO:0051482 9.55 CALCA GRM1
7 cellular response to glucagon stimulus GO:0071377 9.54 GNAS PRKAR1A
8 vasodilation GO:0042311 9.51 CALCA CASR
9 vitamin D metabolic process GO:0042359 9.48 FGF23 VDR
10 cellular response to vitamin D GO:0071305 9.43 CASR FGF23
11 cellular phosphate ion homeostasis GO:0030643 9.4 FGF23 GCM2
12 phosphate ion homeostasis GO:0055062 9.37 FGF23 PTH
13 response to fibroblast growth factor GO:0071774 9.32 CASR PTH
14 response to parathyroid hormone GO:0071107 9.26 GNAS PTH
15 skeletal system development GO:0001501 9.26 GNA11 GNAS PTH VDR
16 positive regulation of vitamin D 24-hydroxylase activity GO:0010980 9.16 FGF23 VDR
17 cellular calcium ion homeostasis GO:0006874 9.02 CALCA CASR GCM2 PTH VDR

Molecular functions related to Hypocalcemia, Autosomal Dominant 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 G-protein beta/gamma-subunit complex binding GO:0031683 8.96 GNA11 GNAS
2 guanyl nucleotide binding GO:0019001 8.62 GNA11 GNAS

Sources for Hypocalcemia, Autosomal Dominant 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
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69 SNOMED-CT via HPO
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