PHP1A
MCID: PSD108
MIFTS: 66

Pseudohypoparathyroidism, Type Ia (PHP1A)

Categories: Blood diseases, Bone diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases, Skin diseases

Aliases & Classifications for Pseudohypoparathyroidism, Type Ia

MalaCards integrated aliases for Pseudohypoparathyroidism, Type Ia:

Name: Pseudohypoparathyroidism, Type Ia 56 39 71
Albright's Hereditary Osteodystrophy 12 74 52 29 43 15 71
Albright Hereditary Osteodystrophy with Multiple Hormone Resistance 56 52 73
Albright Hereditary Osteodystrophy 12 52 73
Pseudohypoparathyroidism Type 1a 12 52 58
Php1a 56 52 73
Pseudohypoparathyroidism with Albright Hereditary Osteodystrophy 52 58
Pseudohypoparathyroidism Ia 56 13
Pseudohypoparathyroidism 43 71
Aho 52 73
Albright Hereditary Osteodystrophy-Php Syndrome Ia 58
Pseudohypoparathyroidism 1a 73
Aho-Php Syndrome Ia 58
Php Ia 56

Characteristics:

Orphanet epidemiological data:

58
pseudohypoparathyroidism with albright hereditary osteodystrophy
Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;
pseudohypoparathyroidism type 1a
Inheritance: Autosomal dominant; Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
caused by inheritance of the mutation on the maternal allele (imprinting)
see also pseudopseudohypoparathyroidism
see also pseudohypoparathyroidism type ib and ic


HPO:

31
pseudohypoparathyroidism, type ia:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Rare renal diseases
Rare bone diseases
Rare skin diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Pseudohypoparathyroidism, Type Ia

OMIM : 56 Pseudohypoparathyroidism is a term applied to a heterogeneous group of disorders whose common feature is end-organ resistance to parathyroid hormone (PTH; 168450). In addition to PTH resistance, PHP Ia is characterized by resistance to other hormones, including thyroid-stimulating hormone (TSH; see TSHB, 188540) and gonadotropins. PHP Ia is associated with a constellation of clinical 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 (Mantovani and Spada, 2006). In contrast, pseudopseudohypoparathyroidism (PPHP; 612463) is characterized by the physical findings of AHO but without hormone resistance (Kinard et al., 1979; Fitch, 1982; Mantovani and Spada, 2006). PHP1A occurs only after maternal inheritance of the molecular defect, whereas PPHP occurs only after paternal inheritance of the molecular defect (Davies and Hughes, 1993; Wilson et al., 1994). This is an example of imprinting, with differential gene expression depending on the parent of origin of the allele. See INHERITANCE and PATHOGENESIS sections. (103580)

MalaCards based summary : Pseudohypoparathyroidism, Type Ia, also known as albright's hereditary osteodystrophy, is related to chromosome 2q37 deletion syndrome and hyperphosphatemia, and has symptoms including seizures An important gene associated with Pseudohypoparathyroidism, Type Ia is GNAS (GNAS Complex Locus), and among its related pathways/superpathways are Signaling by GPCR and Activation of cAMP-Dependent PKA. The drugs Theophylline and tannic acid have been mentioned in the context of this disorder. Affiliated tissues include bone, skin and thyroid, and related phenotypes are pseudohypoparathyroidism and skeletal dysplasia

Disease Ontology : 12 An pseudohypoparathyroidism that has material basis in lack of responsiveness to parathyroid hormone which results in shortening and widening of long bones of the located in hand or located in foot along with short stature, obesity, and rounded face.

NIH Rare Diseases : 52 Albright's hereditary osteodystrophy (AHO) is a rare disorder with a wide range of signs and symptoms, including short stature , obesity, round face, subcutaneous ossifications (formation of bone under the skin), and short fingers and toes ( brachydactyly ). When the disorder is inherited from the mother, the features of AHO can be associated with resistance to certain hormones , in particular the parathyroid hormone (PTH). This is called pseudohypoparathyroidism type 1a (PHP1a) . When inherited from the father, an individual will have AHO without any hormone issues, which is called pseudopseudohypoparathyroidism (PPHP) . This condition is inherited in anautosomal dominant manner due to a mutation in the GNAS gene . Treatment consists of calcium and vitamin D supplements. If there are high levels of phosphate in the blood, it may be recommended to eat a low-phosphorous diet or take medications called phosphate binders to help lower the levels of phosphate.

UniProtKB/Swiss-Prot : 73 Albright hereditary osteodystrophy: A disorder characterized by short stature, obesity, round facies, brachydactyly and subcutaneous calcification. It is often associated with pseudohypoparathyoidism, hypocalcemia and elevated PTH levels.
Pseudohypoparathyroidism 1A: 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.

Wikipedia : 74 Albright's hereditary osteodystrophy is a form of osteodystrophy, and is classified as the phenotype of... more...

Related Diseases for Pseudohypoparathyroidism, Type Ia

Diseases in the Pseudohypoparathyroidism family:

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

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

(show top 50) (show all 385)
# Related Disease Score Top Affiliating Genes
1 chromosome 2q37 deletion syndrome 31.8 STX16 PTH HDAC4 GNAS-AS1 GNAS
2 hyperphosphatemia 31.2 STX16 PTH GNAS
3 disorders of gnas inactivation 31.1 STX16 GNAS-AS1 GNAS
4 pseudohypoparathyroidism, type ib 31.0 STX16 PTHLH PTH1R PTH GNAS-AS1 GNAS
5 pituitary tumors 30.8 PRL IGF1 GNAS GH1
6 congenital hypothyroidism 30.8 PRL IGF1 GNAS GH1
7 central precocious puberty 30.7 IGF1 GH1
8 turner syndrome 30.7 PRL IGF1 GHRH GH1
9 pseudohypoparathyroidism, type ic 30.4 MC4R GNAS
10 goiter 30.4 TRH PRL IGF1 GNAS
11 amenorrhea 30.3 TRH PRL IGF1
12 hypothyroidism 30.3 TRH PRL PDE4D IGF1 GNAS GHRH
13 hypothyroidism, congenital, nongoitrous, 4 30.2 PRL GH1
14 hypoglycemia 30.2 PRL IGF1 GHRH GH1
15 pseudopseudohypoparathyroidism 30.2 STX16 PTHLH PTH PRKAR1A PLPPR3 PDE4D
16 acrodysostosis with multiple hormone resistance 30.1 PRKAR1A PDE4D
17 bone disease 30.1 PTHLH PTH1R PTH IGF1
18 empty sella syndrome 30.0 TRH PRL IGF1 GH1
19 beckwith-wiedemann syndrome 30.0 PRKAR1A IGF1 GNAS-AS1 GNAS
20 prader-willi syndrome 29.9 TRH PRL MC4R IGF1 GH1
21 hypopituitarism 29.9 TRH PRL IGF1 GHRH GH1
22 hypocalcemia, autosomal dominant 1 29.8 PTHLH PTH PRKAR1A GNAS GNA11
23 hyperparathyroidism 29.8 PTHLH PTH1R PTH PRKAR1A IGF1
24 bone resorption disease 29.8 PTHLH PTH1R PTH IGF1
25 fibrous dysplasia 29.7 PTHLH PRL IGF1 GNAS GHRH GH1
26 acromegaly 29.6 TRH PRL PRKAR1A IGF1 GNAS GHRH
27 primary hyperparathyroidism 29.5 PTHLH PTH1R PTH PRL PRKAR1A IGF1
28 hyperthyroidism 29.5 TRH PTH PRL IGF1 GNAS GH1
29 pituitary adenoma, prolactin-secreting 29.5 TRH PTHLH PRL PRKAR1A IGF1 GNAS
30 adenoma 29.4 TRH PTH PRL PRKAR1A IGF1 GNAS
31 parathyroid adenoma 29.3 PTHLH PTH PRKAR1A IGF1 GNAS
32 hyperprolactinemia 29.3 TRH PTHLH PTH PRL IGF1 GNAS
33 hypoparathyroidism 29.2 PTHLH PTH1R PTH PRKAR1A IGF1 GNAS
34 osteogenic sarcoma 29.2 PTHLH PTH1R PTH IGF1
35 conn's syndrome 29.1 TRH PRL PRKAR1A IGF1 GNAS GHRH
36 osseous heteroplasia, progressive 29.0 STX16 PTH PRKAR1A PLPPR3 GNAS-AS1 GNAS
37 body mass index quantitative trait locus 11 28.9 TRH PTH PRL MC4R IGF1 GNAS
38 mccune-albright syndrome 28.9 PTHLH PRL PRKAR1A IGF1 GNAS GNA15
39 hypothyroidism, congenital, nongoitrous, 1 28.9 STX16 PTH PRKAR1A PLPPR3 PDE4D GNAS-AS1
40 brachydactyly 28.5 STX16 PTHLH PTH PRKAR1A PDE4D PDE3A
41 pseudohypoparathyroidism 28.2 TRH STX16 PTHLH PTH1R PTH PRL
42 osteoporosis 28.2 PTHLH PTH1R PTH PRL PRKAR1A IGF1
43 acrodysostosis 27.8 STX16 PTHLH PTH1R PTH PRKAR1A PLPPR3
44 pseudohypoparathyroidism without albright hereditary osteodystrophy 12.6
45 pseudohypoparathyroidism, type ii 11.2
46 basal ganglia calcification, idiopathic, childhood-onset 11.2
47 generalized resistance to thyroid hormone 10.5 TRH PRL
48 galactorrhea 10.5 PRL IGF1
49 hypocalciuric hypercalcemia, familial, type i 10.4 PTH GNA11
50 mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes 10.4 GHRH GH1

Graphical network of the top 20 diseases related to Pseudohypoparathyroidism, Type Ia:



Diseases related to Pseudohypoparathyroidism, Type Ia

Symptoms & Phenotypes for Pseudohypoparathyroidism, Type Ia

Human phenotypes related to Pseudohypoparathyroidism, Type Ia:

58 31 (show top 50) (show all 106)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 pseudohypoparathyroidism 58 31 obligate (100%) Obligate (100%) HP:0000852
2 skeletal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002652
3 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
4 joint dislocation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001373
5 obesity 58 31 hallmark (90%) Very frequent (99-80%),Frequent (79-30%) HP:0001513
6 multiple cafe-au-lait spots 58 31 hallmark (90%) Very frequent (99-80%) HP:0007565
7 hyperthyroidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000836
8 precocious puberty 58 31 hallmark (90%) Very frequent (99-80%) HP:0000826
9 gynecomastia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000771
10 round face 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000311
11 hyperphosphatemia 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002905
12 elevated circulating parathyroid hormone level 58 31 hallmark (90%) Very frequent (99-80%) HP:0003165
13 low urinary cyclic amp response to pth administration 58 31 hallmark (90%) Very frequent (99-80%) HP:0003456
14 pituitary resistance to thyroid hormone 58 31 hallmark (90%) Very frequent (99-80%) HP:0008227
15 abnormal calcium-phosphate regulating hormone level 31 hallmark (90%) HP:0100530
16 coarse facial features 58 31 frequent (33%) Frequent (79-30%) HP:0000280
17 cataract 58 31 frequent (33%) Frequent (79-30%) HP:0000518
18 intellectual disability 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0001249
19 depressed nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0005280
20 short neck 58 31 frequent (33%) Frequent (79-30%) HP:0000470
21 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
22 thickened calvaria 58 31 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0002684
23 cognitive impairment 58 31 frequent (33%) Frequent (79-30%) HP:0100543
24 full cheeks 58 31 frequent (33%) Frequent (79-30%) HP:0000293
25 dry skin 58 31 frequent (33%) Frequent (79-30%) HP:0000958
26 subcutaneous nodule 58 31 frequent (33%) Frequent (79-30%) HP:0001482
27 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
28 short 4th metacarpal 58 31 frequent (33%) Frequent (79-30%) HP:0010044
29 short 5th metacarpal 58 31 frequent (33%) Frequent (79-30%) HP:0010047
30 delayed eruption of teeth 58 31 frequent (33%) Frequent (79-30%) HP:0000684
31 brachydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001156
32 increased bone mineral density 58 31 frequent (33%) Frequent (79-30%) HP:0011001
33 abnormality of the penis 58 31 frequent (33%) Frequent (79-30%) HP:0000036
34 goiter 58 31 frequent (33%) Frequent (79-30%) HP:0000853
35 constrictive median neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0012185
36 thin skin 58 31 frequent (33%) Frequent (79-30%) HP:0000963
37 irregular menstruation 58 31 frequent (33%) Frequent (79-30%) HP:0000858
38 growth hormone deficiency 58 31 frequent (33%) Frequent (79-30%) HP:0000824
39 hypoplasia of dental enamel 58 31 frequent (33%) Frequent (79-30%) HP:0006297
40 polyphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002591
41 short fifth metatarsal 58 31 frequent (33%) Frequent (79-30%) HP:0004704
42 ectopic ossification 58 31 frequent (33%) Frequent (79-30%) HP:0011986
43 basal ganglia calcification 58 31 frequent (33%) Frequent (79-30%) HP:0002135
44 choroid plexus calcification 58 31 frequent (33%) Frequent (79-30%) HP:0006960
45 broad 1st metacarpal 58 31 frequent (33%) Frequent (79-30%) HP:0010027
46 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
47 sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000407
48 visual impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000505
49 dyspnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002094
50 irritability 58 31 occasional (7.5%) Occasional (29-5%) HP:0000737

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
cataract
nystagmus

Neurologic Central Nervous System:
seizures
hypocalcemic tetany
mental retardation
cognitive deficits
basal ganglion calcification
more
Endocrine Features:
hypothyroidism
pseudohypoparathyroidism
hypogonadism

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
reduced erythrocyte gs activity

Head And Neck Nose:
low nasal bridge

Skin Nails Hair Skin:
subcutaneous ossifications

Head And Neck Neck:
short neck

Growth Height:
short stature

Head And Neck Face:
full cheeks
round face

Growth Weight:
obesity

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:

103580

UMLS symptoms related to Pseudohypoparathyroidism, Type Ia:


seizures

MGI Mouse Phenotypes related to Pseudohypoparathyroidism, Type Ia:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.2 GHRH GNA11 GNAS HDAC4 MC4R PRKAR1A
2 growth/size/body region MP:0005378 10.15 GHRH GNA11 GNAS HDAC4 IGF1 MC4R
3 endocrine/exocrine gland MP:0005379 10.1 GHRH GNA11 GNAS IGF1 PRKAR1A PRL
4 adipose tissue MP:0005375 10.02 GHRH GNAS IGF1 MC4R PRKAR1A PTHLH
5 craniofacial MP:0005382 9.98 GNA11 GNAS HDAC4 PRKAR1A PTH PTH1R
6 liver/biliary system MP:0005370 9.92 GHRH GNA11 GNAS MC4R PRKAR1A PRL
7 normal MP:0002873 9.81 GNA11 GNA15 GNAS IGF1 MC4R PDE3A
8 neoplasm MP:0002006 9.8 GNAS IGF1 MC4R PRKAR1A PRL PTH1R
9 respiratory system MP:0005388 9.5 GNA11 GNAS IGF1 MC4R PRKAR1A PTH1R
10 skeleton MP:0005390 9.4 GHRH GNA11 GNAS HDAC4 IGF1 MC4R

Drugs & Therapeutics for Pseudohypoparathyroidism, Type Ia

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

(show all 32)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Theophylline Approved Phase 4 58-55-9 2153
2
tannic acid Approved Phase 4 1401-55-4
3
Benzocaine Approved, Investigational Phase 4 94-09-7, 1994-09-7 2337
4 Respiratory System Agents Phase 4
5 Phosphodiesterase Inhibitors Phase 4
6 Anti-Asthmatic Agents Phase 4
7 Vasodilator Agents Phase 4
8 Bronchodilator Agents Phase 4
9 Neurotransmitter Agents Phase 4
10
Methylprednisolone Approved, Vet_approved Phase 2 83-43-2 6741
11
Lidocaine Approved, Vet_approved Phase 2 137-58-6 3676
12
Methylprednisolone hemisuccinate Approved Phase 2 2921-57-5
13
Prednisolone phosphate Approved, Vet_approved Phase 2 302-25-0
14 Prednisolone acetate Approved, Vet_approved Phase 2 52-21-1
15
Prednisolone Approved, Vet_approved Phase 2 50-24-8 5755
16
Prednisolone hemisuccinate Experimental Phase 2 2920-86-7
17 Pharmaceutical Solutions Phase 2
18 Anti-Infective Agents Phase 2
19 Antitubercular Agents Phase 2
20 Antidotes Phase 2
21 Chelating Agents Phase 2
22 Antioxidants Phase 2
23 Methylprednisolone Acetate Phase 2
24 Anti-Bacterial Agents Phase 2
25 Protective Agents Phase 2
26 sodium thiosulfate Phase 2
27
Parathyroid hormone Approved, Investigational 9002-64-6
28
Vitamin D Approved, Nutraceutical, Vet_approved 1406-16-2
29 Mitogens
30 Hormones
31 Vitamins
32 Calciferol

Interventional clinical trials:

(show all 18)
# Name Status NCT ID Phase Drugs
1 Effect of Theophylline in Pseudohypoparathyroidism Not yet recruiting NCT03718403 Phase 4 Theophylline
2 Effects of Theophylline on cAMP Signaling in Children With Pseudohypoparathyroidism Type 1a Completed NCT02463409 Phase 2 Theophylline
3 Phase 2 Study of Theophylline Treatment for Pseudohypoparathyroidism Recruiting NCT03029429 Phase 2 Theophylline;Placebos
4 Efficacy of Sodium Thiosulfate in Shoulder Pain in Calcific Tendinitis of the Rotator Cuff Recruiting NCT04251832 Phase 2 Sodium Thiosulfate
5 Open-Label Extension Study of Theophylline for Treatment of Pseudohypoparathyroidism Enrolling by invitation NCT04240821 Phase 2 Theophylline ER
6 Subcutaneous Injection of Sodium Thiosulfate for Ectopic Calcifications or Ossifications. A Pilot Study Suspended NCT03582800 Phase 2 STS
7 Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia (PHP Ia) Unknown status NCT00497484 recombinant human somatotropin
8 Early-onset Obesity and Cognitive Impairment in Children With Pseudohypoparathyroidism Completed NCT02411461
9 Study of the Regulation of Parathyroid Hormone Secretion in Pseudohypoparathyroidism Completed NCT00004661
10 Hypoparathyroidism, Autosomal Dominant Hypocalcaemia and Pseudohypoparathyroidism in Denmark - Epidemiology, Causes, Symptoms and Prognoses Completed NCT01498341
11 Studies in Phosphorus Metabolism Completed NCT00066183
12 Physiologic Regulation of FGF-23 Completed NCT00356512
13 Natural History Study of Albright Hereditary Osteodystrophy: Includes Substudies on Effects of Growth Hormone in Patients With Pseudohypoparathyroidism Type 1a and Cognitive & Behavioral Studies in Albright Hereditary Osteodystrophy Recruiting NCT00209235
14 Studies of States With Resistance to Vitamin D and Parathyroid Hormone Recruiting NCT00001242
15 Family Studies in Metabolic Diseases and Mineral Metabolism Recruiting NCT00001345
16 Glucose Homeostasis and Beta Cell Function in Pseudohypoparathyroidism Active, not recruiting NCT03761290
17 Characterization of Patients With Idiopathic Hypoparathyroidism, Autosomal Dominant Hypocalcaemia and Pseudohypoparathyroidism Active, not recruiting NCT02551120
18 Altered Resting Energy Expenditure as a Cause of Obesity in Pseudohypoparathyroidism 1a: A Pilot Study Terminated NCT01398774

Search NIH Clinical Center for Pseudohypoparathyroidism, Type Ia

Cochrane evidence based reviews: pseudohypoparathyroidism

Genetic Tests for Pseudohypoparathyroidism, Type Ia

Genetic tests related to Pseudohypoparathyroidism, Type Ia:

# Genetic test Affiliating Genes
1 Albright's Hereditary Osteodystrophy 29

Anatomical Context for Pseudohypoparathyroidism, Type Ia

MalaCards organs/tissues related to Pseudohypoparathyroidism, Type Ia:

40
Bone, Skin, Thyroid, Spinal Cord, Pituitary, Eye, Breast

Publications for Pseudohypoparathyroidism, Type Ia

Articles related to Pseudohypoparathyroidism, Type Ia:

(show top 50) (show all 362)
# Title Authors PMID Year
1
Human G(salpha) mutant causes pseudohypoparathyroidism type Ia/neonatal diarrhea, a potential cell-specific role of the palmitoylation cycle. 61 56 6
17962410 2007
2
GNAS locus and pseudohypoparathyroidism. 6 56 61
15711092 2005
3
Mutational analysis of GNAS1 in patients with pseudohypoparathyroidism: identification of two novel mutations. 56 6 61
11095461 2000
4
Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy. 56 6 61
2109828 1990
5
Germline mosaicism for a GNAS1 mutation and Albright hereditary osteodystrophy. 6 56
11073544 2000
6
Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis. 56 6
2122458 1990
7
Pseudohypoparathyroidism: report on a family with four affected sisters. 56 6
219790 1979
8
The GNAS locus and pseudohypoparathyroidism. 56 61
18372789 2008
9
Epigenetic defects of GNAS in patients with pseudohypoparathyroidism and mild features of Albright's hereditary osteodystrophy. 61 56
17405843 2007
10
A disruptive mutation in exon 3 of the GNAS gene with albright hereditary osteodystrophy, normocalcemic pseudohypoparathyroidism, and selective long transcript variant Gsalpha-L deficiency. 61 6
17299070 2007
11
Brachydactyly in 14 genetically characterized pseudohypoparathyroidism type Ia patients. 61 56
15070926 2004
12
Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene. 61 56
12970263 2003
13
Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. 6 61
11784876 2002
14
Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy. 6 61
11600516 2001
15
Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia. 6 61
11450852 2001
16
Resistance to the lipolytic action of epinephrine: a new feature of protein Gs deficiency. 61 56
10566660 1999
17
Identification of two novel deletion mutations within the Gs alpha gene (GNAS1) in Albright hereditary osteodystrophy. 61 6
10487696 1999
18
GNAS1 mutational analysis in pseudohypoparathyroidism. 61 6
9876352 1998
19
An inherited mutation associated with functional deficiency of the alpha-subunit of the guanine nucleotide-binding protein Gs in pseudo- and pseudopseudohypoparathyroidism. 6 61
9506752 1998
20
A novel mutation adjacent to the switch III domain of G(S alpha) in a patient with pseudohypoparathyroidism. 6 61
9328353 1997
21
Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region of Gsalpha impairs receptor stimulation. 61 6
8702665 1996
22
Pseudohypoparathyroidism type Ia: two new heterozygous frameshift mutations in exons 5 and 10 of the Gs alpha gene. 61 6
8557265 1996
23
Parental origin of Gs alpha gene mutations in Albright's hereditary osteodystrophy. 61 56
7853365 1994
24
Parental origin of transcription from the human GNAS1 gene. 61 56
7815417 1994
25
Paternal and maternal transmission of pseudohypoparathyroidism type Ia in a family with Albright hereditary osteodystrophy: no evidence of genomic imprinting. 61 56
8151649 1994
26
Endocrine and molecular biological studies in a German family with Albright hereditary osteodystrophy. 56 61
8444241 1993
27
Imprinting in Albright's hereditary osteodystrophy. 61 56
8383205 1993
28
Pseudohypoparathyroidism type I and Albright's hereditary osteodystrophy with a proximal 15q chromosomal deletion in mother and daughter. 56 61
1356667 1992
29
Genetic deficiency of the alpha subunit of the guanine nucleotide-binding protein Gs as the molecular basis for Albright hereditary osteodystrophy. 56 61
2829196 1988
30
Activity of the stimulatory guanine nucleotide-binding protein is reduced in erythrocytes from patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism: biochemical, endocrine, and genetic analysis of Albright's hereditary osteodystrophy in six kindreds. 61 56
3003142 1986
31
Infantile hypothyroidism in two sibs: an unusual presentation of pseudohypoparathyroidism type Ia. 56 61
3934357 1985
32
Father to son transmission of decreased Ns activity in pseudohypoparathyroidism type Ia. 61 56
6090498 1984
33
Pseudohypoparathyroidism. 61 56
6344759 1983
34
Albright's hereditary osteodystrophy: a review. 56 61
6278930 1982
35
Probable autosomal recessive inheritance in a family with Albright's hereditary osteodystrophy and an evaluation of the genetics of the disorder. 61 56
4359274 1973
36
Autosomal dominant inheritance in Albright's hereditary osteodystrophy. 61 56
5125407 1971
37
PSEUDO-PSEUDOHYPOPARATHYROIDISM (ALBRIGHT'S HEREDITARY OSTEODYSTROPHY): A FAMILY STUDY. 56 61
14117275 1964
38
Albright's hereditary osteodystrophy comprising pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism. With a report of two cases representing the complete syndrome occurring in successive generations. 56 61
14469327 1962
39
Disorders of GNAS Inactivation 6
29072892 2017
40
Coexistence of two different pseudohypoparathyroidism subtypes (Ia and Ib) in the same kindred with independent Gs{alpha} coding mutations and GNAS imprinting defects. 56
19858129 2010
41
Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification. 6
18553568 2008
42
A maternal epimutation of GNAS leads to Albright osteodystrophy and parathyroid hormone resistance. 56
18182455 2008
43
Patients with mutations in Gsalpha have reduced activation of a downstream target in epithelial tissues due to haploinsufficiency. 56
17652219 2007
44
Mutations in the Gs alpha gene causing hormone resistance. 56
17161328 2006
45
The stimulatory G protein alpha-subunit Gs alpha is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and 1B. 56
12970307 2003
46
Growth hormone deficiency in pseudohypoparathyroidism type 1a: another manifestation of multihormone resistance. 56
12970262 2003
47
Constitutional deletion of chromosome 20q in two patients affected with albright hereditary osteodystrophy. 56
12407707 2002
48
GNAS1 mutations and progressive osseous heteroplasia. 6
12024004 2002
49
Imprinting of the G(s)alpha gene GNAS1 in the pathogenesis of acromegaly. 56
11254676 2001
50
The Role of Genomic Imprinting of Galpha in the Pathogenesis of Albright Hereditary Osteodystrophy. 56
10322399 1999

Variations for Pseudohypoparathyroidism, Type Ia

ClinVar genetic disease variations for Pseudohypoparathyroidism, Type Ia:

6 (show all 31) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GNAS NM_001077488.4(GNAS):c.842+1G>CSNV Pathogenic 15928 20:57484860-57484860 20:58909805-58909805
2 GNAS NM_001077488.4(GNAS):c.728del (p.Thr243fs)deletion Pathogenic 15929 20:57484745-57484745 20:58909690-58909690
3 GNAS GNAS, IVS3AS, A-G, -12SNV Pathogenic 15930
4 GNAS NM_001077488.4(GNAS):c.299T>C (p.Leu100Pro)SNV Pathogenic 15931 rs137854531 20:57478624-57478624 20:58903569-58903569
5 GNAS NM_001077488.4(GNAS):c.496C>T (p.Arg166Cys)SNV Pathogenic 15932 rs137854532 20:57480498-57480498 20:58905443-58905443
6 GNAS NM_001077488.4(GNAS):c.568_571del (p.Asp190fs)deletion Pathogenic 15938 rs587776829 20:57484249-57484252 20:58909194-58909197
7 GNAS NM_001077488.4(GNAS):c.753C>G (p.Ser251Arg)SNV Pathogenic 15939 rs137854534 20:57484770-57484770 20:58909715-58909715
8 GNAS GNAS, 38-BP DEL, EX1/IVS1 BOUNDARYdeletion Pathogenic 15940
9 GNAS NM_001077488.4(GNAS):c.695G>A (p.Arg232His)SNV Pathogenic 15946 rs137854538 20:57484608-57484608 20:58909553-58909553
10 GNAS GNAS, 2-BP DEL, GA, EXON 8deletion Pathogenic 15947
11 GNAS GNAS, 2-BP DEL, CT, EXON 4deletion Pathogenic 15948
12 GNAS GNAS, 1-BP DEL, 348Cdeletion Pathogenic 15949
13 GNAS GNAS, 1-BP DEL, C, EXON 1deletion Pathogenic 15950
14 GNAS GNAS, 2-BP DEL, TG, EXON 11deletion Pathogenic 15951
15 GNAS GNAS, 1-BP INS, A, EXON 3insertion Pathogenic 15957
16 GNAS GNAS, 12-BP INS, NT1107insertion Pathogenic 15958
17 GNAS NM_001077488.4(GNAS):c.280C>T (p.Gln94Ter)SNV Pathogenic 635558 20:57478605-57478605 20:58903550-58903550
18 GNAS NM_001077488.4(GNAS):c.85C>T (p.Gln29Ter)SNV Pathogenic 374113 rs1057518907 20:57466866-57466866 20:58891811-58891811
19 GNAS NM_001077488.4(GNAS):c.34C>T (p.Gln12Ter)SNV Pathogenic 209158 rs797045046 20:57466815-57466815 20:58891760-58891760
20 GNAS NM_001077488.4(GNAS):c.694C>T (p.Arg232Cys)SNV Pathogenic 816910 20:57484607-57484607 20:58909552-58909552
21 GNAS NM_001077488.4(GNAS):c.533+1G>TSNV Pathogenic 816649 20:57480536-57480536 20:58905481-58905481
22 GNAS NM_001077488.4(GNAS):c.274A>T (p.Lys92Ter)SNV Pathogenic 691981 20:57478599-57478599 20:58903544-58903544
23 GNAS NM_001077488.4(GNAS):c.1A>G (p.Met1Val)SNV Pathogenic/Likely pathogenic 15927 rs137854530 20:57466782-57466782 20:58891727-58891727
24 GNAS NM_001077488.4(GNAS):c.883C>T (p.Gln295Ter)SNV Likely pathogenic 216937 rs863224876 20:57485046-57485046 20:58909991-58909991
25 GNAS NM_080425.3(GNAS):c.475G>A (p.Glu159Lys)SNV Likely pathogenic 431104 rs1135401777 20:57428795-57428795 20:58853740-58853740
26 GNAS NM_001077488.4(GNAS):c.347C>T (p.Pro116Leu)SNV Likely pathogenic 15953 rs137854539 20:57478758-57478758 20:58903703-58903703
27 GNAS NM_080425.3(GNAS):c.1200C>A (p.Ala400=)SNV Uncertain significance 417934 rs908810796 20:57429520-57429520 20:58854465-58854465
28 GNAS NM_001077488.4(GNAS):c.137T>G (p.Leu46Arg)SNV Uncertain significance 689463 20:57466918-57466918 20:58891863-58891863
29 GNAS NM_001077488.4(GNAS):c.315+36C>TSNV Uncertain significance 816648 rs200066108 20:57478676-57478676 20:58903621-58903621
30 GNAS NM_001077488.4(GNAS):c.369C>T (p.Pro123=)SNV Benign 729218 rs35287986 20:57478780-57478780 20:58903725-58903725
31 GNAS NM_080425.3(GNAS):c.1455C>A (p.Ala485=)SNV Benign 417936 rs55890501 20:57429775-57429775 20:58854720-58854720

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

73 (show all 16)
# Symbol AA change Variation ID SNP ID
1 GNAS p.Leu99Pro VAR_003439 rs137854531
2 GNAS p.Arg165Cys VAR_003440 rs137854532
3 GNAS p.Arg385His VAR_003444
4 GNAS p.Arg258Trp VAR_015388 rs137854535
5 GNAS p.Pro115Leu VAR_017843 rs137854539
6 GNAS p.Arg231His VAR_017848 rs137854538
7 GNAS p.Ser250Arg VAR_017849 rs137854534
8 GNAS p.Ala366Ser VAR_017850 rs137854537
9 GNAS p.Asp156Asn VAR_031873
10 GNAS p.Val159Met VAR_031874
11 GNAS p.Thr242Ile VAR_031875
12 GNAS p.Phe246Ser VAR_031876
13 GNAS p.Glu259Val VAR_031877
14 GNAS p.Arg280Gly VAR_031878
15 GNAS p.Arg280Lys VAR_031879
16 GNAS p.Lys338Asn VAR_031881

Expression for Pseudohypoparathyroidism, Type Ia

Search GEO for disease gene expression data for Pseudohypoparathyroidism, Type Ia.

Pathways for Pseudohypoparathyroidism, Type Ia

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

(show all 34)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.94 TRH PTHLH PTH1R PTH PRKAR1A PLPPR3
2
Show member pathways
13.48 PRKAR1A PDE3A IGF1 GNAS GNA15 GNA11
3
Show member pathways
13.39 TRH PTHLH PTH1R PTH PRL PLPPR3
4
Show member pathways
13.21 PRKAR1A PDE3A IGF1 GNAS GNA15 GNA11
5
Show member pathways
12.99 IGF1 GNAS GNA15 GNA11 GHRH GH1
6
Show member pathways
12.99 PRKAR1A PDE4D PDE3A HDAC4 GNAS GNA15
7
Show member pathways
12.98 PRKAR1A PDE4D PDE3A GNAS GNA15 GNA11
8
Show member pathways
12.92 PRKAR1A IGF1 GNAS GNA15 GNA11 GHRH
9
Show member pathways
12.89 PRKAR1A PDE3A GNAS GNA15 GNA11 GHRH
10
Show member pathways
12.77 PRKAR1A IGF1 GNAS GNA15 GNA11
11
Show member pathways
12.51 IGF1 GNAS GNA15 GNA11 GHRH GH1
12
Show member pathways
12.47 PRKAR1A IGF1 GNAS GNA15 GNA11
13
Show member pathways
12.45 PRKAR1A PDE4D GNAS GNA11
14
Show member pathways
12.31 PTHLH PTH1R PTH GNAS GHRH
15
Show member pathways
12.29 PRKAR1A GNAS GNA15 GNA11
16
Show member pathways
12.12 PRKAR1A GNAS GNA15 GNA11
17 11.83 GNAS GNA15 GNA11
18 11.81 GNAS GNA15 GNA11
19
Show member pathways
11.77 PRKAR1A PDE4D GNAS
20 11.76 PTHLH PTH1R PTH PDE4D GNAS GNA11
21 11.7 PRKAR1A PDE4D PDE3A GNAS
22 11.56 IGF1 GNAS GNA11
23 11.56 PRKAR1A IGF1 GNAS GNA15 GNA11 GHRH
24 11.5 PTH1R PTH GNAS
25 11.48 GNAS GNA15 GNA11
26 11.45 PTHLH PTH1R PTH IGF1 HDAC4 GH1
27 11.43 GNAS GNA15 GNA11
28 11.4 PTH1R PTH IGF1
29 11.39 PTHLH PTH1R PTH PDE4D PDE3A MC4R
30 11.02 PTHLH PTH1R PTH PRKAR1A GNAS GNA11
31 10.94 IGF1 HDAC4
32 10.93 IGF1 GNAS GNA15 GNA11 GHRH GH1
33
Show member pathways
10.85 GNA15 GNA11
34 10.79 PTH1R PTH

GO Terms for Pseudohypoparathyroidism, Type Ia

Cellular components related to Pseudohypoparathyroidism, Type Ia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome lumen GO:0031904 8.96 PRL GH1
2 heterotrimeric G-protein complex GO:0005834 8.8 GNAS GNA15 GNA11

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

(show all 20)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.91 PTHLH PTH1R PRL IGF1 HDAC4 GHRH
2 G protein-coupled receptor signaling pathway GO:0007186 9.9 TRH PTHLH PTH1R PTH PDE4D PDE3A
3 response to drug GO:0042493 9.88 PTH PDE3A HDAC4 GNAS
4 cell-cell signaling GO:0007267 9.83 TRH PTHLH PTH GHRH
5 signal transduction GO:0007165 9.77 TRH PTHLH PTH1R PRL PLPPR3 PDE4D
6 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.73 PTHLH PTH1R PTH MC4R GNAS GHRH
7 adenylate cyclase-modulating G protein-coupled receptor signaling pathway GO:0007188 9.72 PTH1R MC4R GNAS GNA15 GNA11
8 female pregnancy GO:0007565 9.71 PTHLH PRL GNAS
9 response to nutrient levels GO:0031667 9.67 PTH PRL GH1
10 positive regulation of glycogen biosynthetic process GO:0045725 9.59 PTH IGF1
11 negative regulation of cAMP-mediated signaling GO:0043951 9.58 PDE4D PDE3A
12 osteoblast development GO:0002076 9.58 PTHLH PTH1R HDAC4
13 energy reserve metabolic process GO:0006112 9.57 MC4R GNAS
14 JAK-STAT cascade involved in growth hormone signaling pathway GO:0060397 9.56 PRL GH1
15 phospholipase C-activating dopamine receptor signaling pathway GO:0060158 9.55 GNA15 GNA11
16 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.54 IGF1 GHRH GH1
17 positive regulation of inositol phosphate biosynthetic process GO:0060732 9.51 PTH1R PTH
18 response to parathyroid hormone GO:0071107 9.48 PTH GNAS
19 cAMP metabolic process GO:0046058 9.46 PTHLH PTH
20 skeletal system development GO:0001501 9.17 PTHLH PTH1R PTH IGF1 HDAC4 GNAS

Molecular functions related to Pseudohypoparathyroidism, Type Ia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 G protein-coupled receptor binding GO:0001664 9.61 GNAS GNA15 GNA11
2 insulin-like growth factor receptor binding GO:0005159 9.48 IGF1 GNAS
3 3',5'-cyclic-AMP phosphodiesterase activity GO:0004115 9.46 PDE4D PDE3A
4 G-protein beta/gamma-subunit complex binding GO:0031683 9.43 GNAS GNA15 GNA11
5 type 2A serotonin receptor binding GO:0031826 9.4 GNA15 GNA11
6 beta-2 adrenergic receptor binding GO:0031698 9.37 PDE4D GNAS
7 guanyl nucleotide binding GO:0019001 9.33 GNAS GNA15 GNA11
8 prolactin receptor binding GO:0005148 9.32 PRL GH1
9 hormone activity GO:0005179 9.17 TRH PTHLH PTH PRL IGF1 GHRH
10 peptide hormone receptor binding GO:0051428 9.13 PTHLH PTH GHRH

Sources for Pseudohypoparathyroidism, Type Ia

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
Content
Loading form....