MCID: HYP752
MIFTS: 38

Hypocalciuric Hypercalcemia, Familial, Type I

Categories: Genetic diseases, Rare diseases, Respiratory diseases, Bone diseases, Endocrine diseases, Fetal diseases, Metabolic diseases

Aliases & Classifications for Hypocalciuric Hypercalcemia, Familial, Type I

MalaCards integrated aliases for Hypocalciuric Hypercalcemia, Familial, Type I:

Name: Hypocalciuric Hypercalcemia, Familial, Type I 57
Hypocalciuric Hypercalcemia, Familial, Type 1 53 29 6 73
Hhc1 57 12 53 75
Hypocalciuric Hypercalcemia, Type I 57 13 40
Familial Benign Hypercalcemia 1 57 12 75
Fhh Type 1 12 53 59
Fhh1 57 53 75
Fbh1 57 53 75
Familial Hypocalciuric Hypercalcemia Type 1 53 59
Familial Hypocalciuric Hypercalcemia 1 12 15
Hypocalciuric Hypercalcemia Type I 12 75
Hypercalcemia, Familial Benign 57 55
Familial Benign Hypocalciuric Hypercalcemia 1 75
Familial Hypocalciuric Hypercalcemia Type I 12
Hypocalciuric Hypercalcemia, Familial 1 75
Familial Benign Hypercalcemia 1; Fbh1 57
Hypercalcemia, Familial Benign Type 1 53
Familial Benign Hypercalcemia Type 1 53
Fbhh1 75

Characteristics:

Orphanet epidemiological data:

59
familial hypocalciuric hypercalcemia type 1
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Worldwide),1-9/100000 (United Kingdom); Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
neonatal severe hyperparathyroidism in homozygotes


HPO:

32
hypocalciuric hypercalcemia, familial, type i:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 145980
Disease Ontology 12 DOID:0060700
ICD10 33 E83.5
Orphanet 59 ORPHA93372
MESH via Orphanet 45 C537145
UMLS via Orphanet 74 C0342637 C1809471
ICD10 via Orphanet 34 E83.5
MeSH 44 D006934
UMLS 73 C0342637

Summaries for Hypocalciuric Hypercalcemia, Familial, Type I

OMIM : 57 Familial hypocalciuric hypercalcemia (HHC) is a heritable disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. HHC is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone (PTH; 168450) level. Hypermagnesemia is typically present. Individuals with HHC are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults (summary by Hannan et al., 2010). (145980)

MalaCards based summary : Hypocalciuric Hypercalcemia, Familial, Type I, also known as hypocalciuric hypercalcemia, familial, type 1, is related to hypocalciuric hypercalcemia, familial, type iii and familial hypocalciuric hypercalcemia. An important gene associated with Hypocalciuric Hypercalcemia, Familial, Type I is CASR (Calcium Sensing Receptor), and among its related pathways/superpathways are Ca, cAMP and Lipid Signaling and Parathyroid hormone synthesis, secretion and action. The drugs Plasminogen and Arginine Vasopressin have been mentioned in the context of this disorder. Affiliated tissues include bone and liver, and related phenotypes are pancreatitis and nephrolithiasis

UniProtKB/Swiss-Prot : 75 Hypocalciuric hypercalcemia, familial 1: A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults.

Disease Ontology : 12 A familial hypocalciuric hypercalcemia that has material basis in heterozygous loss-of-function mutations in the CASR gene on chromosome 3q21.

Related Diseases for Hypocalciuric Hypercalcemia, Familial, Type I

Diseases in the Familial Hypocalciuric Hypercalcemia family:

Hypocalciuric Hypercalcemia, Familial, Type I Hypocalciuric Hypercalcemia, Familial, Type Ii
Hypocalciuric Hypercalcemia, Familial, Type Iii

Diseases related to Hypocalciuric Hypercalcemia, Familial, Type I via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hypocalciuric hypercalcemia, familial, type iii 30.2 AP2S1 CASR GNA11
2 familial hypocalciuric hypercalcemia 30.2 AP2S1 CASR GNA11
3 hypocalciuric hypercalcemia, familial, type ii 29.9 AP2S1 CASR GNA11
4 primary hyperparathyroidism 11.1
5 melanoma 10.0
6 hypocalcemia, autosomal dominant 1 9.2 CASR GNA11
7 chondrocalcinosis 8.5 AP2S1 CASR GNA11

Graphical network of the top 20 diseases related to Hypocalciuric Hypercalcemia, Familial, Type I:



Diseases related to Hypocalciuric Hypercalcemia, Familial, Type I

Symptoms & Phenotypes for Hypocalciuric Hypercalcemia, Familial, Type I

Symptoms via clinical synopsis from OMIM:

57
Abdomen Pancreas:
pancreatitis

Laboratory Abnormalities:
hypocalciuria
hypercalcemia
hypermagnesemia
urinary calcium-creatinine ratio < 0.01:1 supports diagnosis
normal concentration of parathyroid hormone

Genitourinary Kidneys:
nephrolithiasis (uncommon)


Clinical features from OMIM:

145980

Human phenotypes related to Hypocalciuric Hypercalcemia, Familial, Type I:

32 (show all 6)
# Description HPO Frequency HPO Source Accession
1 pancreatitis 32 HP:0001733
2 nephrolithiasis 32 HP:0000787
3 hyperparathyroidism 32 HP:0000843
4 hypercalcemia 32 HP:0003072
5 hypocalciuria 32 HP:0003127
6 hypermagnesemia 32 HP:0002918

GenomeRNAi Phenotypes related to Hypocalciuric Hypercalcemia, Familial, Type I according to GeneCards Suite gene sharing:

26 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.4 CASR
2 Increased shRNA abundance (Z-score > 2) GR00366-A-114 9.4 GNA11
3 Increased shRNA abundance (Z-score > 2) GR00366-A-115 9.4 GNA11
4 Increased shRNA abundance (Z-score > 2) GR00366-A-131 9.4 GNA11
5 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.4 CASR
6 Increased shRNA abundance (Z-score > 2) GR00366-A-146 9.4 GNA11 CASR
7 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.4 GNA11
8 Increased shRNA abundance (Z-score > 2) GR00366-A-174 9.4 CASR
9 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.4 GNA11
10 Increased shRNA abundance (Z-score > 2) GR00366-A-74 9.4 GNA11
11 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.4 CASR

MGI Mouse Phenotypes related to Hypocalciuric Hypercalcemia, Familial, Type I:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 pigmentation MP:0001186 8.62 CASR GNA11

Drugs & Therapeutics for Hypocalciuric Hypercalcemia, Familial, Type I

Drugs for Hypocalciuric Hypercalcemia, Familial, Type I (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Plasminogen Phase 2
2 Arginine Vasopressin
3 Calcium, Dietary
4 Liver Extracts

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 uPAR PET/CT for Staging Advanced and Localised Oral and Oropharyngeal Cancer Recruiting NCT02960724 Phase 2
2 Serum Calcium to Phosphorous Ratio (Ca/P) as a Simple, Inexpensive Screening Tool in the Diagnosis of Primary Hyperparathyroidism Completed NCT03027349
3 Studies of Inherited Diseases of Metabolism Recruiting NCT00001345

Search NIH Clinical Center for Hypocalciuric Hypercalcemia, Familial, Type I

Genetic Tests for Hypocalciuric Hypercalcemia, Familial, Type I

Genetic tests related to Hypocalciuric Hypercalcemia, Familial, Type I:

# Genetic test Affiliating Genes
1 Hypocalciuric Hypercalcemia, Familial, Type 1 29 CASR

Anatomical Context for Hypocalciuric Hypercalcemia, Familial, Type I

MalaCards organs/tissues related to Hypocalciuric Hypercalcemia, Familial, Type I:

41
Bone, Liver

Publications for Hypocalciuric Hypercalcemia, Familial, Type I

Articles related to Hypocalciuric Hypercalcemia, Familial, Type I:

# Title Authors Year
1
Increased trabecular volumetric bone mass density in Familial Hypocalciuric Hypercalcemia (FHH) type 1: a cross-sectional study. ( 24894639 )
2014

Variations for Hypocalciuric Hypercalcemia, Familial, Type I

UniProtKB/Swiss-Prot genetic disease variations for Hypocalciuric Hypercalcemia, Familial, Type I:

75 (show top 50) (show all 62)
# Symbol AA change Variation ID SNP ID
1 CASR p.Pro39Ala VAR_003585 rs121909262
2 CASR p.Arg62Met VAR_003586 rs121909265
3 CASR p.Arg66Cys VAR_003587 rs121909266
4 CASR p.Thr138Met VAR_003590 rs121909263
5 CASR p.Gly143Glu VAR_003591 rs121909264
6 CASR p.Leu174Arg VAR_003592
7 CASR p.Arg185Gln VAR_003593 rs104893689
8 CASR p.Arg227Gln VAR_003595 rs28936684
9 CASR p.Glu297Lys VAR_003596 rs121909259
10 CASR p.Cys582Tyr VAR_003597 rs104893690
11 CASR p.Arg795Trp VAR_003599 rs121909258
12 CASR p.Gly557Glu VAR_012649
13 CASR p.Leu11Ser VAR_058046 rs200673016
14 CASR p.Leu13Pro VAR_058047 rs104893717
15 CASR p.Gly21Arg VAR_058049
16 CASR p.Ser171Asn VAR_058056
17 CASR p.Phe180Cys VAR_058057 rs121909268
18 CASR p.Pro221Gln VAR_058059 rs397514728
19 CASR p.Lys225Thr VAR_058060
20 CASR p.Ser271Phe VAR_058062
21 CASR p.Gly397Arg VAR_058063
22 CASR p.Arg465Gln VAR_058064 rs104893716
23 CASR p.Gly509Arg VAR_058065 rs193922423
24 CASR p.Gly553Arg VAR_058066 rs104893719
25 CASR p.Ile555Val VAR_058067 rs777646067
26 CASR p.Cys562Tyr VAR_058068
27 CASR p.Cys582Phe VAR_058069 rs104893690
28 CASR p.Gly623Asp VAR_058072
29 CASR p.Gly670Arg VAR_058074
30 CASR p.Val728Phe VAR_058076
31 CASR p.Trp742Arg VAR_058077
32 CASR p.Arg886Trp VAR_058084
33 CASR p.Val697Met VAR_065494
34 CASR p.Phe42Ser VAR_078139
35 CASR p.Ser53Pro VAR_078140
36 CASR p.Pro55Leu VAR_078141 rs886041154
37 CASR p.Arg66His VAR_078142
38 CASR p.Ile81Met VAR_078143
39 CASR p.Ala110Thr VAR_078144
40 CASR p.Gly143Arg VAR_078149 rs769256610
41 CASR p.Gly158Arg VAR_078150
42 CASR p.Leu159Pro VAR_078151
43 CASR p.Ser166Gly VAR_078152 rs193922441
44 CASR p.Arg172Gly VAR_078153
45 CASR p.Asn178Asp VAR_078154
46 CASR p.Asp215Gly VAR_078155
47 CASR p.Arg220Trp VAR_078156
48 CASR p.Pro221Ser VAR_078158
49 CASR p.Gln459Arg VAR_078160
50 CASR p.Gly549Arg VAR_078161

ClinVar genetic disease variations for Hypocalciuric Hypercalcemia, Familial, Type I:

6
(show top 50) (show all 549)
# Gene Variation Type Significance SNP ID Assembly Location
1 CASR NM_000388.3(CASR): c.2383C> T (p.Arg795Trp) single nucleotide variant Pathogenic rs121909258 GRCh37 Chromosome 3, 122003184: 122003184
2 CASR NM_000388.3(CASR): c.2383C> T (p.Arg795Trp) single nucleotide variant Pathogenic rs121909258 GRCh38 Chromosome 3, 122284337: 122284337
3 CASR NM_000388.3(CASR): c.889G> A (p.Glu297Lys) single nucleotide variant Pathogenic rs121909259 GRCh37 Chromosome 3, 121980771: 121980771
4 CASR NM_000388.3(CASR): c.889G> A (p.Glu297Lys) single nucleotide variant Pathogenic rs121909259 GRCh38 Chromosome 3, 122261924: 122261924
5 CASR NM_000388.3(CASR): c.554G> A (p.Arg185Gln) single nucleotide variant Pathogenic rs104893689 GRCh37 Chromosome 3, 121980436: 121980436
6 CASR NM_000388.3(CASR): c.554G> A (p.Arg185Gln) single nucleotide variant Pathogenic rs104893689 GRCh38 Chromosome 3, 122261589: 122261589
7 CASR CASR, ALU INS, CODON 877 insertion Pathogenic
8 CASR NM_000388.3(CASR): c.115C> G (p.Pro39Ala) single nucleotide variant Pathogenic rs121909262 GRCh37 Chromosome 3, 121973151: 121973151
9 CASR NM_000388.3(CASR): c.115C> G (p.Pro39Ala) single nucleotide variant Pathogenic rs121909262 GRCh38 Chromosome 3, 122254304: 122254304
10 CASR NM_000388.3(CASR): c.680G> A (p.Arg227Gln) single nucleotide variant Pathogenic rs28936684 GRCh37 Chromosome 3, 121980562: 121980562
11 CASR NM_000388.3(CASR): c.680G> A (p.Arg227Gln) single nucleotide variant Pathogenic rs28936684 GRCh38 Chromosome 3, 122261715: 122261715
12 CASR NM_000388.3(CASR): c.413C> T (p.Thr138Met) single nucleotide variant Pathogenic rs121909263 GRCh37 Chromosome 3, 121976155: 121976155
13 CASR NM_000388.3(CASR): c.413C> T (p.Thr138Met) single nucleotide variant Pathogenic rs121909263 GRCh38 Chromosome 3, 122257308: 122257308
14 CASR NM_000388.3(CASR): c.428G> A (p.Gly143Glu) single nucleotide variant Pathogenic/Likely pathogenic rs121909264 GRCh37 Chromosome 3, 121976170: 121976170
15 CASR NM_000388.3(CASR): c.428G> A (p.Gly143Glu) single nucleotide variant Pathogenic/Likely pathogenic rs121909264 GRCh38 Chromosome 3, 122257323: 122257323
16 CASR NM_000388.3(CASR): c.185G> T (p.Arg62Met) single nucleotide variant Pathogenic rs121909265 GRCh37 Chromosome 3, 121973221: 121973221
17 CASR NM_000388.3(CASR): c.185G> T (p.Arg62Met) single nucleotide variant Pathogenic rs121909265 GRCh38 Chromosome 3, 122254374: 122254374
18 CASR NM_000388.3(CASR): c.196C> T (p.Arg66Cys) single nucleotide variant Likely pathogenic rs121909266 GRCh37 Chromosome 3, 121975938: 121975938
19 CASR NM_000388.3(CASR): c.196C> T (p.Arg66Cys) single nucleotide variant Likely pathogenic rs121909266 GRCh38 Chromosome 3, 122257091: 122257091
20 CASR NM_000388.3(CASR): c.1942C> T (p.Arg648Ter) single nucleotide variant Pathogenic rs104893705 GRCh37 Chromosome 3, 122002743: 122002743
21 CASR NM_000388.3(CASR): c.1942C> T (p.Arg648Ter) single nucleotide variant Pathogenic rs104893705 GRCh38 Chromosome 3, 122283896: 122283896
22 CASR NM_000388.3(CASR): c.186-1G> T single nucleotide variant Pathogenic rs797044441 GRCh37 Chromosome 3, 121975927: 121975927
23 CASR NM_000388.3(CASR): c.186-1G> T single nucleotide variant Pathogenic rs797044441 GRCh38 Chromosome 3, 122257080: 122257080
24 CASR NM_000388.3(CASR): c.38T> C (p.Leu13Pro) single nucleotide variant Pathogenic rs104893717 GRCh37 Chromosome 3, 121973074: 121973074
25 CASR NM_000388.3(CASR): c.38T> C (p.Leu13Pro) single nucleotide variant Pathogenic rs104893717 GRCh38 Chromosome 3, 122254227: 122254227
26 CASR NM_000388.3(CASR): c.539T> G (p.Phe180Cys) single nucleotide variant Pathogenic rs121909268 GRCh37 Chromosome 3, 121980421: 121980421
27 CASR NM_000388.3(CASR): c.539T> G (p.Phe180Cys) single nucleotide variant Pathogenic rs121909268 GRCh38 Chromosome 3, 122261574: 122261574
28 CASR NM_000388.3(CASR): c.1745G> T (p.Cys582Phe) single nucleotide variant Pathogenic rs104893690 GRCh37 Chromosome 3, 122002546: 122002546
29 CASR NM_000388.3(CASR): c.1745G> T (p.Cys582Phe) single nucleotide variant Pathogenic rs104893690 GRCh38 Chromosome 3, 122283699: 122283699
30 CASR NM_000388.3(CASR): c.1657G> A (p.Gly553Arg) single nucleotide variant Pathogenic rs104893719 GRCh37 Chromosome 3, 122001008: 122001008
31 CASR NM_000388.3(CASR): c.1657G> A (p.Gly553Arg) single nucleotide variant Pathogenic rs104893719 GRCh38 Chromosome 3, 122282161: 122282161
32 CASR NM_000388.3(CASR): c.662C> A (p.Pro221Gln) single nucleotide variant Pathogenic rs397514728 GRCh37 Chromosome 3, 121980544: 121980544
33 CASR NM_000388.3(CASR): c.662C> A (p.Pro221Gln) single nucleotide variant Pathogenic rs397514728 GRCh38 Chromosome 3, 122261697: 122261697
34 CASR NM_000388.3(CASR): c.114T> C (p.Phe38=) single nucleotide variant Conflicting interpretations of pathogenicity rs61733590 GRCh37 Chromosome 3, 121973150: 121973150
35 CASR NM_000388.3(CASR): c.114T> C (p.Phe38=) single nucleotide variant Conflicting interpretations of pathogenicity rs61733590 GRCh38 Chromosome 3, 122254303: 122254303
36 CASR NM_000388.3(CASR): c.78C> G (p.Ala26=) single nucleotide variant Benign rs77852524 GRCh37 Chromosome 3, 121973114: 121973114
37 CASR NM_000388.3(CASR): c.78C> G (p.Ala26=) single nucleotide variant Benign rs77852524 GRCh38 Chromosome 3, 122254267: 122254267
38 CASR NM_000388.3(CASR): c.748G> A (p.Glu250Lys) single nucleotide variant Benign/Likely benign rs62269092 GRCh37 Chromosome 3, 121980630: 121980630
39 CASR NM_000388.3(CASR): c.748G> A (p.Glu250Lys) single nucleotide variant Benign/Likely benign rs62269092 GRCh38 Chromosome 3, 122261783: 122261783
40 CASR NM_000388.3(CASR): c.2610G> A (p.Glu870=) single nucleotide variant Benign rs143738711 GRCh37 Chromosome 3, 122003411: 122003411
41 CASR NM_000388.3(CASR): c.2610G> A (p.Glu870=) single nucleotide variant Benign rs143738711 GRCh38 Chromosome 3, 122284564: 122284564
42 CASR NM_000388.3(CASR): c.2730C> A (p.Pro910=) single nucleotide variant Benign rs34200949 GRCh37 Chromosome 3, 122003531: 122003531
43 CASR NM_000388.3(CASR): c.2730C> A (p.Pro910=) single nucleotide variant Benign rs34200949 GRCh38 Chromosome 3, 122284684: 122284684
44 CASR NM_000388.3(CASR): c.2901C> A (p.Ile967=) single nucleotide variant Conflicting interpretations of pathogenicity rs199594582 GRCh37 Chromosome 3, 122003702: 122003702
45 CASR NM_000388.3(CASR): c.2901C> A (p.Ile967=) single nucleotide variant Conflicting interpretations of pathogenicity rs199594582 GRCh38 Chromosome 3, 122284855: 122284855
46 CASR NM_000388.3(CASR): c.294T> G (p.Phe98Leu) single nucleotide variant Uncertain significance rs878853976 GRCh37 Chromosome 3, 121976036: 121976036
47 CASR NM_000388.3(CASR): c.294T> G (p.Phe98Leu) single nucleotide variant Uncertain significance rs878853976 GRCh38 Chromosome 3, 122257189: 122257189
48 CASR NM_000388.3(CASR): c.427G> A (p.Gly143Arg) single nucleotide variant Uncertain significance rs769256610 GRCh37 Chromosome 3, 121976169: 121976169
49 CASR NM_000388.3(CASR): c.427G> A (p.Gly143Arg) single nucleotide variant Uncertain significance rs769256610 GRCh38 Chromosome 3, 122257322: 122257322
50 CASR NM_000388.3(CASR): c.573G> A (p.Glu191=) single nucleotide variant Benign/Likely benign rs141631116 GRCh37 Chromosome 3, 121980455: 121980455

Expression for Hypocalciuric Hypercalcemia, Familial, Type I

Search GEO for disease gene expression data for Hypocalciuric Hypercalcemia, Familial, Type I.

Pathways for Hypocalciuric Hypercalcemia, Familial, Type I

Pathways related to Hypocalciuric Hypercalcemia, Familial, Type I according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.06 CASR GNA11
2 10.65 CASR GNA11

GO Terms for Hypocalciuric Hypercalcemia, Familial, Type I

Molecular functions related to Hypocalciuric Hypercalcemia, Familial, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 obsolete signal transducer activity GO:0004871 8.62 CASR GNA11

Sources for Hypocalciuric Hypercalcemia, Familial, Type I

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7 CNVD
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74 UMLS via Orphanet
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