HHC2
MCID: HYP753
MIFTS: 42

Hypocalciuric Hypercalcemia, Familial, Type Ii (HHC2)

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

Aliases & Classifications for Hypocalciuric Hypercalcemia, Familial, Type Ii

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

Name: Hypocalciuric Hypercalcemia, Familial, Type Ii 56 29 6 71
Hypocalciuric Hypercalcemia, Type Ii 56 29 13 39
Hhc2 56 12 52 73
Familial Hypocalciuric Hypercalcemia Type 2 12 52 58
Fbh2 56 52 73
Familial Hypocalciuric Hypercalcemia 2 12 15
Fhh Type 2 12 58
Hypocalciuric Hypercalcemia, Familial, Type 2 52
Familial Benign Hypercalcemia, Type Ii; Fbh2 56
Hypercalcemia, Familial Benign, Type Ii 56
Hypocalciuric Hypercalcemia, Familial 2 73
Familial Benign Hypercalcemia, Type Ii 56
Familial Benign Hypercalcemia, Type 2 52
Hypercalcemia, Familial Benign Type 2 52
Familial Benign Hypercalcemia Type Ii 73
Hypocalciuric Hypercalcemia Type Ii 12

Characteristics:

Orphanet epidemiological data:

58
familial hypocalciuric hypercalcemia type 2
Inheritance: Autosomal dominant;

OMIM:

56
Inheritance:
autosomal dominant with locus heterogeneity (19p13.3)


HPO:

31
hypocalciuric hypercalcemia, familial, type ii:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare respiratory diseases
Rare bone diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0060701
OMIM 56 145981
OMIM Phenotypic Series 56 PS145980
MeSH 43 D006934
ICD10 32 E83.5
MESH via Orphanet 44 C537146
ICD10 via Orphanet 33 E83.5
UMLS via Orphanet 72 C1840347 C2931427
Orphanet 58 ORPHA101049
MedGen 41 C1840347
UMLS 71 C1840347

Summaries for Hypocalciuric Hypercalcemia, Familial, Type Ii

UniProtKB/Swiss-Prot : 73 Hypocalciuric hypercalcemia, familial 2: 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.

MalaCards based summary : Hypocalciuric Hypercalcemia, Familial, Type Ii, also known as hypocalciuric hypercalcemia, type ii, is related to familial hypocalciuric hypercalcemia and hyperparathyroidism, neonatal severe. An important gene associated with Hypocalciuric Hypercalcemia, Familial, Type Ii is GNA11 (G Protein Subunit Alpha 11), and among its related pathways/superpathways are Signaling by GPCR and DAG and IP3 signaling. Affiliated tissues include bone, and related phenotypes are nephrolithiasis and peptic ulcer

Disease Ontology : 12 A familial hypocalciuric hypercalcemia that has material basis in heterozygous mutation in the GNA11 gene on chromosome 19p13.

OMIM : 56 Familial hypocalciuric hypercalcemia type II (HHC2) is an autosomal dominant disorder characterized by lifelong elevations of serum calcium concentrations with low urinary calcium excretion and normal circulating parathyroid hormone concentrations in most patients. Patients are generally asymptomatic, although pancreatitis or chondrocalcinosis may develop in some affected adults (summary by Nesbit et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of hypocalciuric hypercalcemia, see HHC1 (145980). (145981)

Related Diseases for Hypocalciuric Hypercalcemia, Familial, Type Ii

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 Ii via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 62)
# Related Disease Score Top Affiliating Genes
1 familial hypocalciuric hypercalcemia 30.5 PTH GNA11 CDC73 CASR AP2S1 ADH4
2 hyperparathyroidism, neonatal severe 11.3
3 water-clear cell adenoma 10.2 PTH AP2S1
4 alcohol-related birth defect 10.2 ADH4 ADH1B
5 hypercalcemia, infantile, 1 10.2 PTH CASR
6 phakomatosis cesioflammea 10.1 GNAQ GNA11
7 calciphylaxis 10.1 PTH CASR
8 malignant leptomeningeal tumor 10.1 GNAQ GNA11
9 meningeal melanoma 10.1 GNAQ GNA11
10 hyperparathyroidism 2 with jaw tumors 10.1 CDC73 CASR
11 metaphyseal chondrodysplasia, jansen type 10.1 PTH CASR
12 meningeal melanomatosis 10.1 GNAQ GNA11
13 melanomatosis 10.1 GNAQ GNA11
14 meningeal melanocytoma 10.1 GNAQ GNA11
15 malignant dermis tumor 10.1 GNAQ GNA11
16 malignant skin fibrous histiocytoma 10.1 GNAQ GNA11
17 chondrocalcinosis 10.1 GNA11 CASR AP2S1
18 vulvar melanoma 10.1 GNAQ GNA11
19 hypoparathyroidism, sensorineural deafness, and renal disease 10.1 PTH CASR
20 multiple endocrine neoplasia, type iv 10.1 CDC73 AP2S1
21 central nervous system melanocytic neoplasm 10.1 GNAQ GNA11
22 clear cell adenoma 10.1 PTH CDC73
23 chondrodysplasia, blomstrand type 10.1 PTH CASR
24 mongolian spot 10.1 GNAQ GNA11
25 malignant conjunctival melanoma 10.1 GNAQ GNA11
26 phosphorus metabolism disease 10.1 PTH CASR
27 spitzoid melanoma 10.0 GNAQ GNA11
28 hypomelanosis of ito 10.0 GNAQ GNA11
29 conjunctival cancer 10.0 GNAQ GNA11
30 malignant spindle cell melanoma 10.0 GNAQ GNA11
31 nodular malignant melanoma 10.0 GNAQ GNA11
32 renal tubular transport disease 10.0 PTH CASR
33 fetal alcohol spectrum disorder 10.0 ADH4 ADH1B
34 bone benign neoplasm 10.0 PTH CDC73
35 large congenital melanocytic nevus 9.9 GNAQ GNA11
36 epileptic encephalopathy, early infantile, 17 9.9 GNA15 GNA11
37 hypocalcemia, autosomal dominant 2 9.9 GNA15 GNA11
38 nephrocalcinosis 9.9 PTH GNA11 CASR
39 renal osteodystrophy 9.9 PTH CASR
40 ossifying fibroma 9.9 PTH CDC73
41 mucosal melanoma 9.9 GNAQ GNA11
42 basal ganglia disease 9.9 PTH CASR
43 charcot-marie-tooth disease, dominant intermediate f 9.8 GNA15 GNA11
44 osteitis fibrosa 9.8 PTH CDC73 CASR
45 parathyroid carcinoma 9.8 PTH CDC73 CASR
46 adenoma 9.8 PTH CDC73 CASR
47 parathyroid adenoma 9.8 PTH CDC73 CASR
48 primary hyperparathyroidism 9.8 PTH CDC73 CASR
49 hyperparathyroidism 9.8 PTH CDC73 CASR
50 hypoparathyroidism 9.8 PTH GNA11 CASR AP2S1

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



Diseases related to Hypocalciuric Hypercalcemia, Familial, Type Ii

Symptoms & Phenotypes for Hypocalciuric Hypercalcemia, Familial, Type Ii

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

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 nephrolithiasis 31 occasional (7.5%) HP:0000787
2 peptic ulcer 31 occasional (7.5%) HP:0004398
3 hypermagnesemia 31 very rare (1%) HP:0002918
4 chondrocalcinosis 31 HP:0000934
5 multiple lipomas 31 HP:0001012
6 hypercalcemia 31 HP:0003072
7 pancreatitis 31 HP:0001733
8 hypocalciuria 31 HP:0003127
9 primary hyperparathyroidism 31 HP:0008200
10 parathormone-independent increased renal tubular calcium reabsorption 31 HP:0003529

Symptoms via clinical synopsis from OMIM:

56
Radiology:
chondrocalcinosis

G I:
pancreatitis
peptic ulcer uncommon

G U:
nephrolithiasis uncommon

Lab:
hypercalcemia
hypocalciuria
hypermagnesemia
parathormone-independent renal tubular calcium reabsorption defect
ratio of renal calcium clearance to creatinine clearance usually below 0.01
more
Skin:
lipomas

Misc:
neonatal severe primary hyperparathyroidism in homozygotes
(e.g. hypocalciuric hypercalcemia, familial .0002)

Clinical features from OMIM:

145981

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.1 AP2S1 CASR CDC73 GNA11 GNAQ PTH

Drugs & Therapeutics for Hypocalciuric Hypercalcemia, Familial, Type Ii

Search Clinical Trials , NIH Clinical Center for Hypocalciuric Hypercalcemia, Familial, Type Ii

Genetic Tests for Hypocalciuric Hypercalcemia, Familial, Type Ii

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

# Genetic test Affiliating Genes
1 Hypocalciuric Hypercalcemia, Familial, Type Ii 29 GNA11
2 Hypocalciuric Hypercalcemia, Type Ii 29

Anatomical Context for Hypocalciuric Hypercalcemia, Familial, Type Ii

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

40
Bone

Publications for Hypocalciuric Hypercalcemia, Familial, Type Ii

Articles related to Hypocalciuric Hypercalcemia, Familial, Type Ii:

# Title Authors PMID Year
1
Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia. 6 56
23802516 2013
2
Genetic linkage analysis in familial benign hypercalcemia using a candidate gene strategy. I. Studies in four families. 56 6
1517376 1992
3
Identification and functional characterization of loss-of-function mutations of the calcium-sensing receptor in four Italian kindreds with familial hypocalciuric hypercalcemia. 6
19073830 2009
4
Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population. 6
17698911 2007
5
Identification and analysis of conserved cis-regulatory regions of the MEIS1 gene. 61
22448256 2012

Variations for Hypocalciuric Hypercalcemia, Familial, Type Ii

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

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GNA11 NM_002067.5(GNA11):c.595_597ATC[1] (p.Ile200del)short repeat Pathogenic 60661 rs672601249 19:3115059-3115061 19:3115061-3115063
2 GNA11 NM_002067.5(GNA11):c.404T>A (p.Leu135Gln)SNV Pathogenic 60662 rs587777019 19:3113410-3113410 19:3113412-3113412
3 GNA11 NM_002067.5(GNA11):c.95A>G (p.Asp32Gly)SNV Uncertain significance 695113 19:3094744-3094744 19:3094746-3094746

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

73
# Symbol AA change Variation ID SNP ID
1 GNA11 p.Leu135Gln VAR_070166 rs587777019

Expression for Hypocalciuric Hypercalcemia, Familial, Type Ii

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

Pathways for Hypocalciuric Hypercalcemia, Familial, Type Ii

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

(show all 36)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.91 PTH PLCB3 GNAQ GNA15 GNA11 CDC73
2
Show member pathways
12.88 PLCB3 GNAQ GNA15 GNA11
3
Show member pathways
12.84 PLCB3 GNAQ GNA15 GNA11
4
Show member pathways
12.69 PLCB3 GNAQ GNA15 GNA11
5
Show member pathways
12.47 PLCB3 GNAQ GNA15 GNA11
6
Show member pathways
12.3 PLCB3 GNAQ GNA11
7 12.23 PLCB3 GNA15 GNA11
8
Show member pathways
12.19 PLCB3 GNAQ GNA15 GNA11
9
Show member pathways
12.12 PLCB3 GNAQ GNA15 GNA11
10
Show member pathways
12.08 PLCB3 GNAQ GNA15 GNA11
11
Show member pathways
12.01 GNAQ GNA15 GNA11
12
Show member pathways
11.91 PLCB3 GNAQ GNA11
13
Show member pathways
11.87 PLCB3 GNAQ GNA11
14
Show member pathways
11.86 GNAQ GNA15 GNA11
15
Show member pathways
11.82 GNAQ GNA15 GNA11
16 11.81 PLCB3 GNAQ GNA11 CASR
17 11.74 PLCB3 GNA15 GNA11
18 11.69 PLCB3 GNAQ GNA11
19 11.68 PLCB3 GNAQ GNA15 GNA11
20 11.53 PLCB3 GNAQ GNA11
21 11.49 PLCB3 GNAQ GNA11
22 11.44 PLCB3 GNAQ GNA15 GNA11
23 11.41 PLCB3 GNAQ GNA11
24 11.39 GNAQ GNA15 GNA11
25 11.38 PTH PLCB3 GNAQ GNA11 CASR
26 11.34 GNA15 GNA11
27 11.3 PLCB3 CASR
28 11.28 PTH PLCB3 GNAQ AP2S1
29 11.21 PLCB3 GNAQ
30 11.18 PLCB3 GNAQ GNA11
31 11.14 GNAQ GNA15 GNA11
32
Show member pathways
11.13 ADH4 ADH1B
33 11.08 PLCB3 GNAQ
34 11.05 PTH PLCB3 GNAQ GNA11
35
Show member pathways
10.82 ADH4 ADH1B
36
Show member pathways
10.13 PLCB3 GNAQ GNA15 GNA11

GO Terms for Hypocalciuric Hypercalcemia, Familial, Type Ii

Cellular components related to Hypocalciuric Hypercalcemia, Familial, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 heterotrimeric G-protein complex GO:0005834 8.8 GNAQ GNA15 GNA11

Biological processes related to Hypocalciuric Hypercalcemia, Familial, Type Ii according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 G protein-coupled receptor signaling pathway GO:0007186 9.73 PTH PLCB3 GNAQ GNA15 GNA11 CASR
2 platelet activation GO:0030168 9.63 GNAQ GNA15 GNA11
3 retinol metabolic process GO:0042572 9.51 ADH4 ADH1B
4 adenylate cyclase-modulating G protein-coupled receptor signaling pathway GO:0007188 9.5 GNAQ GNA15 GNA11
5 G protein-coupled acetylcholine receptor signaling pathway GO:0007213 9.49 GNAQ GNA11
6 ethanol oxidation GO:0006069 9.48 ADH4 ADH1B
7 phototransduction, visible light GO:0007603 9.43 GNAQ GNA11
8 response to fibroblast growth factor GO:0071774 9.4 PTH CASR
9 entrainment of circadian clock GO:0009649 9.37 GNAQ GNA11
10 activation of phospholipase C activity GO:0007202 9.33 PTH GNAQ GNA15
11 action potential GO:0001508 9.13 GNAQ GNA15 GNA11
12 phospholipase C-activating dopamine receptor signaling pathway GO:0060158 8.8 GNAQ GNA15 GNA11

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

# Name GO ID Score Top Affiliating Genes
1 G protein-coupled receptor binding GO:0001664 9.43 GNAQ GNA15 GNA11
2 phosphatidylinositol phospholipase C activity GO:0004435 9.4 PLCB3 CASR
3 retinol dehydrogenase activity GO:0004745 9.37 ADH4 ADH1B
4 G-protein beta/gamma-subunit complex binding GO:0031683 9.33 GNAQ GNA15 GNA11
5 alcohol dehydrogenase activity, zinc-dependent GO:0004024 9.32 ADH4 ADH1B
6 guanyl nucleotide binding GO:0019001 9.13 GNAQ GNA15 GNA11
7 type 2A serotonin receptor binding GO:0031826 8.8 GNAQ GNA15 GNA11

Sources for Hypocalciuric Hypercalcemia, Familial, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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