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PHP1C
MCID: PSD117
MIFTS: 37

Pseudohypoparathyroidism, Type Ic (PHP1C)

Categories: Blood diseases, Bone diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases, Skin diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Pseudohypoparathyroidism, Type Ic

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MalaCards integrated aliases for Pseudohypoparathyroidism, Type Ic:

Name: Pseudohypoparathyroidism, Type Ic 57 40
Pseudohypoparathyroidism Type 1c 53 59 29 6 73
Php1c 57 53 75
Pseudohypoparathyroidism Ic 57 13
Pseudohypoparathyroidism 1c 75
Php Ic 57

Characteristics:

Orphanet epidemiological data:

59
pseudohypoparathyroidism type 1c
Inheritance: Autosomal dominant; Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
caused by inheritance of the mutation on the maternal allele (imprinting)
see also pseudohypoparathyroidism type ia


HPO:

32
pseudohypoparathyroidism, type ic:
Inheritance autosomal dominant inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases Metabolic diseases
Anatomical: Eye diseases Nephrological diseases Bone diseases Skin diseases Endocrine diseases Blood diseases
See all MalaCards categories (disease lists)
ICD10: 34
Orphanet: 59  
Rare eye diseases
Rare renal diseases
Rare bone diseases
Rare skin diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


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Summaries for Pseudohypoparathyroidism, Type Ic

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NIH Rare Diseases : 53 Pseudohypoparathyroidism type 1C is a genetic disorder that is very similar to hypoparathyroidism (parathyroid hormone levels are too low). However, pseudohypoparathyroidism is caused by no response to parathyroid hormone rather than having too little of the hormone itself. This causes low calcium and high phosphate levels in the blood. This condition is also associated with  a group of symptoms referred to as Albright's hereditary osteodystrophy, which includes short stature, a round face, obesity, and short hand bones. This disorder is different than pseudohypoparathyroidism type 1A because people with type 1C do not have abnormal activity of a particular protein (stimulatory protein G (Gs alpha)). Type 1C is inherited in an autosomal dominant fashion and is caused by a specific spelling mistake (mutation) in the GNAS gene.

MalaCards based summary : Pseudohypoparathyroidism, Type Ic, also known as pseudohypoparathyroidism type 1c, is related to pseudohypoparathyroidism and body mass index quantitative trait locus 11, and has symptoms including seizures An important gene associated with Pseudohypoparathyroidism, Type Ic is GNAS (GNAS Complex Locus), and among its related pathways/superpathways is G alpha (s) signalling events. The drugs Theophylline and Benzocaine have been mentioned in the context of this disorder. Affiliated tissues include bone, skin and eye, and related phenotypes are short neck and obesity

OMIM : 57 Pseudohypoparathyroidism type Ic (PHP1C) is characterized by resistance to parathyroid hormone (PTH; 168450) as well as to other hormones. It is associated with a constellation of physical features referred to as Albright hereditary osteodystrophy (AHO), which includes short stature, obesity, round facies, subcutaneous ossifications, brachydactyly, and other skeletal anomalies. Some patients have mental retardation. Laboratory studies in patients with PHP Ic show a decreased cellular cyclic AMP (cAMP) response to infused PTH, but no defect in activity of the erythrocyte Gs protein (Mantovani and Spada, 2006). (612462)

UniProtKB/Swiss-Prot : 75 Pseudohypoparathyroidism 1C: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification.

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Related Diseases for Pseudohypoparathyroidism, Type Ic

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Diseases in the Pseudohypoparathyroidism family:

Pseudohypoparathyroidism, Type Ia Pseudohypoparathyroidism, Type Ii
Pseudohypoparathyroidism, Type Ib Pseudohypoparathyroidism, Type Ic

Diseases related to Pseudohypoparathyroidism, Type Ic via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pseudohypoparathyroidism 10.3
2 body mass index quantitative trait locus 11 9.7 GNAS MC4R

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Symptoms & Phenotypes for Pseudohypoparathyroidism, Type Ic

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Symptoms via clinical synopsis from OMIM:

57
Head And Neck Neck:
short neck

Head And Neck Eyes:
nystagmus
cataract

Neurologic Central Nervous System:
seizures
hypocalcemic tetany
mental retardation
cognitive deficits
basal ganglion calcification
more
Skeletal:
osteoporosis

Skeletal Hands:
brachydactyly
short metacarpals (especially 4th and 5th)

Laboratory Abnormalities:
hypocalcemia
hyperphosphatemia
low urinary cyclic amp response to pth administration
elevated serum parathyroid hormone (pth) level
normal erythrocyte gs activity

Head And Neck Nose:
low nasal bridge

Skin Nails Hair Skin:
subcutaneous ossifications

Growth Weight:
obesity

Endocrine Features:
hypothyroidism
hypogonadism
pseudohypoparathyroidism

Growth Height:
short stature

Head And Neck Face:
full cheeks
round face

Skeletal Feet:
brachydactyly
short metatarsals (especially 4th and 5th)

Neurologic Peripheral Nervous System:
hypocalcemic tetany

Head And Neck Teeth:
delayed tooth eruption
enamel hypoplasia


Clinical features from OMIM:

612462

Human phenotypes related to Pseudohypoparathyroidism, Type Ic:

59 32 (show top 50) (show all 60)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short neck 59 32 frequent (33%) Frequent (79-30%) HP:0000470
2 obesity 59 32 frequent (33%) Frequent (79-30%) HP:0001513
3 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
4 depressivity 59 32 occasional (7.5%) Occasional (29-5%) HP:0000716
5 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
6 cataract 59 32 frequent (33%) Frequent (79-30%) HP:0000518
7 depressed nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0005280
8 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
9 dyspnea 59 32 occasional (7.5%) Occasional (29-5%) HP:0002094
10 full cheeks 59 32 frequent (33%) Frequent (79-30%) HP:0000293
11 irritability 59 32 occasional (7.5%) Occasional (29-5%) HP:0000737
12 delayed eruption of teeth 59 32 frequent (33%) Frequent (79-30%) HP:0000684
13 anxiety 59 32 occasional (7.5%) Occasional (29-5%) HP:0000739
14 short 4th metacarpal 59 32 frequent (33%) Frequent (79-30%) HP:0010044
15 short 5th metacarpal 59 32 frequent (33%) Frequent (79-30%) HP:0010047
16 prolonged qt interval 59 32 occasional (7.5%) Occasional (29-5%) HP:0001657
17 paresthesia 59 32 occasional (7.5%) Occasional (29-5%) HP:0003401
18 hypergonadotropic hypogonadism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000815
19 muscle cramps 59 32 occasional (7.5%) Occasional (29-5%) HP:0003394
20 brachydactyly 59 32 frequent (33%) Frequent (79-30%) HP:0001156
21 round face 59 32 frequent (33%) Frequent (79-30%) HP:0000311
22 chest pain 59 32 occasional (7.5%) Occasional (29-5%) HP:0100749
23 elevated circulating parathyroid hormone level 59 32 hallmark (90%) Very frequent (99-80%) HP:0003165
24 conjunctivitis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000509
25 increased bone mineral density 59 32 occasional (7.5%) Occasional (29-5%) HP:0011001
26 hyporeflexia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001265
27 myoclonic spasms 59 32 occasional (7.5%) Occasional (29-5%) HP:0003739
28 polyphagia 59 32 frequent (33%) Frequent (79-30%) HP:0002591
29 short metacarpal 59 32 Frequent (79-30%) HP:0010049
30 pseudohypoparathyroidism 59 32 obligate (100%) Obligate (100%) HP:0000852
31 confusion 59 32 occasional (7.5%) Occasional (29-5%) HP:0001289
32 hyperphosphatemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002905
33 prolactin deficiency 59 32 very rare (1%) Very rare (<4-1%) HP:0008202
34 short metatarsal 59 32 Frequent (79-30%) HP:0010743
35 growth hormone deficiency 59 32 frequent (33%) Frequent (79-30%) HP:0000824
36 hypoplasia of dental enamel 59 32 frequent (33%) Frequent (79-30%) HP:0006297
37 hypocalcemic seizures 59 32 very rare (1%) Very rare (<4-1%) HP:0002199
38 short fifth metatarsal 59 32 frequent (33%) Frequent (79-30%) HP:0004704
39 oligomenorrhea 59 32 occasional (7.5%) Occasional (29-5%) HP:0000876
40 abdominal symptom 59 32 occasional (7.5%) Occasional (29-5%) HP:0011458
41 ectopic ossification 59 32 frequent (33%) Frequent (79-30%) HP:0011986
42 laryngeal dystonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0012049
43 hypocalcemic tetany 59 32 occasional (7.5%) Occasional (29-5%) HP:0003472
44 low urinary cyclic amp response to pth administration 59 32 hallmark (90%) Very frequent (99-80%) HP:0003456
45 calcinosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0003761
46 basal ganglia calcification 59 32 frequent (33%) Frequent (79-30%) HP:0002135
47 pituitary resistance to thyroid hormone 59 32 hallmark (90%) Very frequent (99-80%) HP:0008227
48 choroid plexus calcification 59 32 frequent (33%) Frequent (79-30%) HP:0006960
49 constrictive median neuropathy 59 32 frequent (33%) Frequent (79-30%) HP:0012185
50 broad distal phalanx of the thumb 59 32 occasional (7.5%) Occasional (29-5%) HP:0009642

UMLS symptoms related to Pseudohypoparathyroidism, Type Ic:


seizures

GenomeRNAi Phenotypes related to Pseudohypoparathyroidism, Type Ic according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Negative genetic interaction between PTTG1-/- and PTTG1+/+ GR00255-A-4 8.62 GNAS MC4R

MGI Mouse Phenotypes related to Pseudohypoparathyroidism, Type Ic:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 8.62 GNAS MC4R
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Drugs & Therapeutics for Pseudohypoparathyroidism, Type Ic

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Drugs for Pseudohypoparathyroidism, Type Ic (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Theophylline Approved Phase 4 58-55-9 2153
2
Benzocaine Approved, Investigational Phase 4 94-09-7, 1994-09-7 2337
3 tannic acid Approved Phase 4
4 Neurotransmitter Agents Phase 4
5 Anti-Asthmatic Agents Phase 4
6 Vasodilator Agents Phase 4
7 Purinergic P1 Receptor Antagonists Phase 4
8 Phosphodiesterase Inhibitors Phase 4
9 Respiratory System Agents Phase 4
10 Peripheral Nervous System Agents Phase 4
11 Bronchodilator Agents Phase 4
12 Autonomic Agents Phase 4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Effect of Theophylline in Pseudohypoparathyroidism Not yet recruiting NCT03718403 Phase 4 Theophylline

Search NIH Clinical Center for Pseudohypoparathyroidism, Type Ic

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Genetic Tests for Pseudohypoparathyroidism, Type Ic

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Genetic tests related to Pseudohypoparathyroidism, Type Ic:

# Genetic test Affiliating Genes
1 Pseudohypoparathyroidism Type 1c 29 GNAS
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Anatomical Context for Pseudohypoparathyroidism, Type Ic

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MalaCards organs/tissues related to Pseudohypoparathyroidism, Type Ic:

41
Bone, Skin, Eye, Pituitary, Thyroid
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Publications for Pseudohypoparathyroidism, Type Ic

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Articles related to Pseudohypoparathyroidism, Type Ic:

# Title Authors Year
1
Different pattern of epigenetic changes of the GNAS gene locus in patients with pseudohypoparathyroidism type Ic confirm the heterogeneity of underlying pathomechanisms in this subgroup of pseudohypoparathyroidism and the demand for a new classification of GNAS-related disorders. ( 24878042 )
2014
2
Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsalpha-receptor interaction. ( 21488135 )
2011
3
Resistance to epinephrine and hypersensitivity (hyperresponsiveness) to CB1 antagonists in a patient with pseudohypoparathyroidism type Ic. ( 20075145 )
2010
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Variations for Pseudohypoparathyroidism, Type Ic

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UniProtKB/Swiss-Prot genetic disease variations for Pseudohypoparathyroidism, Type Ic:

75
# Symbol AA change Variation ID SNP ID
1 GNAS p.Leu388Arg VAR_066387 rs397514457
2 GNAS p.Glu392Lys VAR_066388 rs397514456

ClinVar genetic disease variations for Pseudohypoparathyroidism, Type Ic:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 GNAS GNAS, TYR391TER undetermined variant Pathogenic
2 GNAS NM_001077488.3(GNAS): c.1177G> T (p.Glu393Ter) single nucleotide variant Pathogenic rs397514456 GRCh37 Chromosome 20, 57485873: 57485873
3 GNAS NM_001077488.3(GNAS): c.1177G> T (p.Glu393Ter) single nucleotide variant Pathogenic rs397514456 GRCh38 Chromosome 20, 58910818: 58910818
4 GNAS NM_001077488.3(GNAS): c.1166T> G (p.Leu389Arg) single nucleotide variant Pathogenic rs397514457 GRCh37 Chromosome 20, 57485862: 57485862
5 GNAS NM_001077488.3(GNAS): c.1166T> G (p.Leu389Arg) single nucleotide variant Pathogenic rs397514457 GRCh38 Chromosome 20, 58910807: 58910807
6 GNAS NM_001077488.3(GNAS): c.1177G> A (p.Glu393Lys) single nucleotide variant Pathogenic rs397514456 GRCh37 Chromosome 20, 57485873: 57485873
7 GNAS NM_001077488.3(GNAS): c.1177G> A (p.Glu393Lys) single nucleotide variant Pathogenic rs397514456 GRCh38 Chromosome 20, 58910818: 58910818
8 GNAS NM_000516.5(GNAS): c.880C> T (p.Gln294Ter) single nucleotide variant Likely pathogenic rs863224876 GRCh37 Chromosome 20, 57485046: 57485046
9 GNAS NM_000516.5(GNAS): c.880C> T (p.Gln294Ter) single nucleotide variant Likely pathogenic rs863224876 GRCh38 Chromosome 20, 58909991: 58909991
10 GNAS NM_080425.3(GNAS): c.1200C> A (p.Ala400=) single nucleotide variant Uncertain significance rs908810796 GRCh37 Chromosome 20, 57429520: 57429520
11 GNAS NM_080425.3(GNAS): c.1200C> A (p.Ala400=) single nucleotide variant Uncertain significance rs908810796 GRCh38 Chromosome 20, 58854465: 58854465
12 GNAS NM_080425.3(GNAS): c.1455C> A (p.Ala485=) single nucleotide variant Uncertain significance rs55890501 GRCh37 Chromosome 20, 57429775: 57429775
13 GNAS NM_080425.3(GNAS): c.1455C> A (p.Ala485=) single nucleotide variant Uncertain significance rs55890501 GRCh38 Chromosome 20, 58854720: 58854720
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Expression for Pseudohypoparathyroidism, Type Ic

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Search GEO for disease gene expression data for Pseudohypoparathyroidism, Type Ic.
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Pathways for Pseudohypoparathyroidism, Type Ic

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Pathways related to Pseudohypoparathyroidism, Type Ic according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
G alpha (s) signalling events 66
10.79 GNAS MC4R
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GO Terms for Pseudohypoparathyroidism, Type Ic

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Biological processes related to Pseudohypoparathyroidism, Type Ic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.16 GNAS MC4R
2 adenylate cyclase-modulating G protein-coupled receptor signaling pathway GO:0007188 8.96 GNAS MC4R
3 energy reserve metabolic process GO:0006112 8.62 GNAS MC4R
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Sources for Pseudohypoparathyroidism, Type Ic

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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