OPTA1
MCID: OST125
MIFTS: 44

Osteopetrosis, Autosomal Dominant 1 (OPTA1)

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Aliases & Classifications for Osteopetrosis, Autosomal Dominant 1

MalaCards integrated aliases for Osteopetrosis, Autosomal Dominant 1:

Name: Osteopetrosis, Autosomal Dominant 1 57 73 71
Autosomal Dominant Osteopetrosis 1 11 28 5 14
Opta1 57 11 19 73
Autosomal Dominant Osteopetrosis Type 1 11 19 58
Osteopetrosis Autosomal Dominant Type 1 19 43
Osteopetrosis, Autosomal Dominant, Type I 57
Osteopetrosis, Autosomal Dominant, Type 1 38

Characteristics:


Inheritance:

Osteopetrosis, Autosomal Dominant 1: Autosomal dominant 57
Autosomal Dominant Osteopetrosis Type 1: Autosomal dominant 58

Prevelance:

Autosomal Dominant Osteopetrosis Type 1: <1/1000000 (Worldwide) 58

Age Of Onset:

Autosomal Dominant Osteopetrosis Type 1: Adolescent,Childhood 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
genetic heterogeneity (see )
progressive sclerosis with age
allelic to osteoporosis-pseudoglioma syndrome , van buchem type 2 , high bone mass , autosomal dominant endosteal hyperostosis


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 11 DOID:0110937
OMIM® 57 607634
OMIM Phenotypic Series 57 PS607634
MESH via Orphanet 44 C536056
ICD10 via Orphanet 32 Q78.2
UMLS via Orphanet 72 C1843330 C2931097
Orphanet 58 ORPHA2783
MedGen 40 C1843330
UMLS 71 C1843330

Summaries for Osteopetrosis, Autosomal Dominant 1

GARD: 19 Osteopetrosis refers to a group of rare, inherited skeletal disorders characterized by increased bone density and abnormal bone growth. Symptoms and severity can vary greatly, ranging from neonatal onset with serious complications (such as bone marrow failure) to the incidental finding of osteopetrosis on X-ray. Depending on severity and age of onset, symptoms may include fractures, short stature, compressive neuropathies (pressure on the nerves), hypocalcemia with attendant tetanic seizures, and pancytopenia. In rare cases, there may be neurological impairment or involvement of other body systems. Osteopetrosis may be caused by genetic changes in at least 10 genes. Inheritance can be autosomal recessive, autosomal dominant, or X-linked recessive with the most severe forms being autosomal recessive.

MalaCards based summary: Osteopetrosis, Autosomal Dominant 1, also known as autosomal dominant osteopetrosis 1, is related to osteopetrosis, autosomal dominant 2 and osteopetrosis, autosomal dominant 3, and has symptoms including headache An important gene associated with Osteopetrosis, Autosomal Dominant 1 is LRP5 (LDL Receptor Related Protein 5), and among its related pathways/superpathways are Alzheimer's disease and miRNA effects and ncRNAs involved in Wnt signaling in hepatocellular carcinoma. Affiliated tissues include bone, bone marrow and cortex, and related phenotypes are headache and torus palatinus

UniProtKB/Swiss-Prot: 73 A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. OPTA1 is an autosomal dominant form characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate.

OMIM®: 57 The osteopetroses are a heterogeneous group of genetic disorders characterized by increased bone density due to impaired bone resorption by osteoclasts. Autosomal dominant osteopetrosis-1 is characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate (summary by Van Hul et al., 2002). (607634) (Updated 08-Dec-2022)

Disease Ontology: 11 An osteopetrosis characterized by autosomal dominant inheritance of generalized osteosclerosis that is most pronounced in the cranial vault, absence of increased fractures and has material basis in heterozygous mutation in the LRP5 gene on chromosome 11q13.

Orphanet: 58 A rare sclerosing bone disorder characterized by skeletal densification that predominantly involves the cranial vault.

Related Diseases for Osteopetrosis, Autosomal Dominant 1

Diseases in the Osteopetrosis family:

Osteopetrosis, Autosomal Dominant 2 Osteopetrosis, Autosomal Recessive 1
Osteopetrosis, Autosomal Recessive 2 Osteopetrosis, Autosomal Recessive 5
Osteopetrosis, Autosomal Recessive 3 Osteopetrosis, Autosomal Dominant 1
Osteopetrosis, Autosomal Recessive 4 Osteopetrosis, Autosomal Recessive 6
Osteopetrosis, Autosomal Recessive 7 Osteopetrosis, Autosomal Recessive 8
Osteopetrosis, Autosomal Dominant 3 Clcn7-Related Osteopetrosis
Autosomal Recessive Malignant Osteopetrosis

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

(show all 29)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis, autosomal dominant 2 31.0 TRAPPC10 LRP5 CLCN7
2 osteopetrosis, autosomal dominant 3 11.0
3 osteogenesis imperfecta, type xv 10.0 RBM27 LRP5
4 glucocorticoid-induced osteoporosis 10.0 LRP5 DKK1
5 osteopetrosis, autosomal recessive 7 10.0 TNFRSF11A CLCN7
6 craniodiaphyseal dysplasia, autosomal dominant 10.0 LRP6 LRP5
7 osteopetrosis, autosomal recessive 2 10.0 TNFRSF11A CLCN7
8 ectodermal dysplasia 13, hair/tooth type 10.0 LRP6 LRP5
9 osteoporosis, juvenile 10.0 LRP5 DKK1
10 osteopathia striata with cranial sclerosis 9.9 LRP6 LRP5
11 cenani-lenz syndactyly syndrome 9.9 LRP6 LRP5
12 craniometaphyseal dysplasia, autosomal dominant 9.9 TNFRSF11A CLCN7
13 osteopetrosis 9.9 TNFRSF11A LRP5 CLCN7
14 norrie disease 9.9 LRP6 LRP5
15 osteopetrosis, autosomal recessive 5 9.8 TRAPPC10 CLCN7
16 endosteal hyperostosis, autosomal dominant 9.8 LRP5 DKK1 CLCN7
17 exudative vitreoretinopathy 9.8 LRP6 LRP5
18 polycystic liver disease 9.8 LRP6 LRP5
19 osteoporosis-pseudoglioma syndrome 9.7 LRP6 LRP5 DKK1
20 van buchem disease 9.7 LRP6 LRP5 DKK1
21 sclerosteosis 9.7 LRP6 LRP5 DKK1
22 bone resorption disease 9.7 LRP5 DKK1
23 focal segmental glomerulosclerosis 9.6 LRP6 LRP5 DKK1
24 bone remodeling disease 9.6 TNFRSF11A LRP5 DKK1 CLCN7
25 bone disease 9.6 TNFRSF11A LRP5 DKK1 CLCN7
26 tooth agenesis 9.5 LRP6 LRP5 DKK1 CLCN7
27 osteochondrodysplasia 9.5 LRP6 LRP5 DKK1 CLCN7
28 brittle bone disorder 9.3 TNFRSF11A LRP6 LRP5 DKK1 CLCN7
29 osteoporosis 9.3 TNFRSF11A LRP6 LRP5 DKK1 CLCN7

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



Diseases related to Osteopetrosis, Autosomal Dominant 1

Symptoms & Phenotypes for Osteopetrosis, Autosomal Dominant 1

Human phenotypes related to Osteopetrosis, Autosomal Dominant 1:

30 (show all 11)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 headache 30 Very rare (1%) HP:0002315
2 torus palatinus 30 Very rare (1%) HP:0100789
3 thickened cortex of long bones 30 Very rare (1%) HP:0000935
4 mandibular pain 30 Very rare (1%) HP:0200025
5 calvarial osteosclerosis 30 Very rare (1%) HP:0005450
6 thickened calvaria 30 HP:0002684
7 conductive hearing impairment 30 HP:0000405
8 abnormality of the vertebral column 30 HP:0000925
9 generalized osteosclerosis 30 HP:0005789
10 osteopetrosis 30 HP:0011002
11 abnormal pelvic girdle bone morphology 30 HP:0002644

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
headache

Skeletal Skull:
thickened cranial vault
pronounced calvarial sclerosis

Skeletal Spine:
no 'rugger-jersey spine'
variable sclerosis

Laboratory Abnormalities:
normal serum acid phosphatase

Head And Neck Ears:
conductive hearing loss

Skeletal:
diffuse, symmetrical osteosclerosis
no increased fracture rate

Skeletal Pelvis:
no endobones

Clinical features from OMIM®:

607634 (Updated 08-Dec-2022)

UMLS symptoms related to Osteopetrosis, Autosomal Dominant 1:


headache

MGI Mouse Phenotypes related to Osteopetrosis, Autosomal Dominant 1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 9.55 CLCN7 DKK1 LRP5 LRP6 TNFRSF11A
2 craniofacial MP:0005382 9.43 CLCN7 DKK1 LRP5 LRP6 TNFRSF11A TRAPPC10
3 skeleton MP:0005390 9.1 CLCN7 DKK1 LRP5 LRP6 TNFRSF11A TRAPPC10

Drugs & Therapeutics for Osteopetrosis, Autosomal Dominant 1

Search Clinical Trials, NIH Clinical Center for Osteopetrosis, Autosomal Dominant 1

Cochrane evidence based reviews: osteopetrosis autosomal dominant type 1

Genetic Tests for Osteopetrosis, Autosomal Dominant 1

Genetic tests related to Osteopetrosis, Autosomal Dominant 1:

# Genetic test Affiliating Genes
1 Autosomal Dominant Osteopetrosis 1 28 LRP5

Anatomical Context for Osteopetrosis, Autosomal Dominant 1

Organs/tissues related to Osteopetrosis, Autosomal Dominant 1:

MalaCards : Bone, Bone Marrow, Cortex

Publications for Osteopetrosis, Autosomal Dominant 1

Articles related to Osteopetrosis, Autosomal Dominant 1:

(show all 20)
# Title Authors PMID Year
1
Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. 57 5
12579474 2003
2
Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13. 57 5
12054167 2002
3
Molecular genetics of too much bone. 57
12351574 2002
4
High bone density due to a mutation in LDL-receptor-related protein 5. 5
12015390 2002
5
A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. 5
11741193 2002
6
Dominant endosteal hyperostosis. Skeletal characteristics and review of the literature. 5
11701785 2001
7
[Van Buchem disease. Maxillofacial changes, diagnostic classification and general principles of treatment]. 5
10434540 1999
8
Autosomal dominant osteopetrosis. 57
8358946 1993
9
Radiological, biochemical and hereditary evidence of two types of autosomal dominant osteopetrosis. 57
3377922 1988
10
Heterogeneity of autosomal dominant osteopetrosis. 57
3588909 1987
11
Endosteal hyperostosis. 5
1002767 1976
12
Suppressors of dGTP Starvation in Escherichia coli. 62
28373271 2017
13
Transcriptome Analysis of Escherichia coli during dGTP Starvation. 62
27002130 2016
14
[Autosomal dominant osteopetrosis: a presentation of 3 cases and a new gene mutation]. 62
24882046 2015
15
Structure and regulation of the gene for dGTP triphosphohydrolase from Escherichia coli. 62
2157212 1990
16
Escherichia coli dGTP triphosphohydrolase is inhibited by gene 1.2 protein of bacteriophage T7. 62
2843524 1988
17
A unique deoxyguanosine triphosphatase is responsible for the optA1 phenotype of Escherichia coli. 62
2833745 1988
18
Gene 1.2 protein of bacteriophage T7. Effect on deoxyribonucleotide pools. 62
3549718 1987
19
Purification and characterization of the gene 1.2 protein of bacteriophage T7. 62
3494013 1987
20
Genetic analysis of gene 1.2 of bacteriophage T7: isolation of a mutant of Escherichia coli unable to support the growth of T7 gene 1.2 mutants. 62
7012382 1981

Variations for Osteopetrosis, Autosomal Dominant 1

ClinVar genetic disease variations for Osteopetrosis, Autosomal Dominant 1:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LRP5 NM_002335.4(LRP5):c.511G>C (p.Gly171Arg) SNV Pathogenic
6281 rs121908669 GRCh37: 11:68125140-68125140
GRCh38: 11:68357672-68357672
2 LRP5 NM_002335.4(LRP5):c.724G>A (p.Ala242Thr) SNV Pathogenic
6282 rs121908670 GRCh37: 11:68131252-68131252
GRCh38: 11:68363784-68363784
3 LRP5 NM_002335.4(LRP5):c.758C>T (p.Thr253Ile) SNV Pathogenic
6285 rs121908673 GRCh37: 11:68131286-68131286
GRCh38: 11:68363818-68363818
4 LRP5 NM_002335.4(LRP5):c.640G>A (p.Ala214Thr) SNV Pathogenic
6283 rs121908671 GRCh37: 11:68125269-68125269
GRCh38: 11:68357801-68357801
5 LRP5 NM_002335.4(LRP5):c.2555C>T (p.Thr852Met) SNV Likely Pathogenic
1179140 GRCh37: 11:68181208-68181208
GRCh38: 11:68413740-68413740
6 LRP5 NM_002335.4(LRP5):c.3107G>A (p.Arg1036Gln) SNV Uncertain Significance
Uncertain Significance
183255 rs61889560 GRCh37: 11:68191036-68191036
GRCh38: 11:68423568-68423568
7 LRP5 NM_002335.4(LRP5):c.1199C>T (p.Ala400Val) SNV Uncertain Significance
520692 rs201320326 GRCh37: 11:68153967-68153967
GRCh38: 11:68386499-68386499
8 LRP5 NM_002335.4(LRP5):c.3162C>A (p.Ser1054Arg) SNV Uncertain Significance
1683591 GRCh37: 11:68191091-68191091
GRCh38: 11:68423623-68423623
9 LRP5 NM_002335.4(LRP5):c.4583A>C (p.Tyr1528Ser) SNV Not Provided
1019709 rs1182722973 GRCh37: 11:68213998-68213998
GRCh38: 11:68446530-68446530
10 LRP5 NM_002335.4(LRP5):c.4349-8C>A SNV Not Provided
1339809 GRCh37: 11:68207237-68207237
GRCh38: 11:68439769-68439769

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

73
# Symbol AA change Variation ID SNP ID
1 LRP5 p.Asp111Tyr VAR_021807
2 LRP5 p.Gly171Arg VAR_021808 rs121908669
3 LRP5 p.Ala242Thr VAR_021812 rs121908670
4 LRP5 p.Thr253Ile VAR_021813 rs121908673

Expression for Osteopetrosis, Autosomal Dominant 1

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

Pathways for Osteopetrosis, Autosomal Dominant 1

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

(show all 17)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.47 LRP6 LRP5 DKK1
2
Show member pathways
12.44 LRP6 LRP5 DKK1
3 12.34 LRP6 LRP5 DKK1
4
Show member pathways
12.11 LRP6 LRP5 DKK1
5 12.08 LRP6 LRP5 DKK1
6 11.89 DKK1 LRP5 LRP6
7 11.61 LRP6 LRP5 DKK1
8
Show member pathways
11.61 LRP6 LRP5 DKK1
9 11.4 TNFRSF11A LRP5 DKK1
11 11.29 LRP6 LRP5 DKK1
12 11.19 LRP6 DKK1
13
Show member pathways
10.94 LRP6 LRP5
14 10.85 TNFRSF11A LRP6 LRP5
15 10.51 LRP6 LRP5 DKK1
16 10.45 TNFRSF11A CLCN7
17
Show member pathways
10.12 LRP6 LRP5 DKK1

GO Terms for Osteopetrosis, Autosomal Dominant 1

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

# Name GO ID Score Top Affiliating Genes
1 Wnt signalosome GO:1990909 9.26 LRP6 LRP5
2 Wnt-Frizzled-LRP5/6 complex GO:1990851 8.92 LRP6 LRP5

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

# Name GO ID Score Top Affiliating Genes
1 positive regulation of JUN kinase activity GO:0043507 9.67 TNFRSF11A DKK1
2 positive regulation of DNA-binding transcription factor activity GO:0051091 9.63 TNFRSF11A LRP6 LRP5
3 Wnt signaling pathway GO:0016055 9.62 LRP6 LRP5 DKK1
4 negative regulation of protein serine/threonine kinase activity GO:0071901 9.56 LRP6 LRP5
5 canonical Wnt signaling pathway GO:0060070 9.43 LRP6 LRP5 DKK1
6 Wnt signaling pathway involved in somitogenesis GO:0090244 8.92 LRP6 DKK1

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

# Name GO ID Score Top Affiliating Genes
1 Wnt-protein binding GO:0017147 9.62 LRP6 LRP5
2 Wnt receptor activity GO:0042813 9.56 LRP6 LRP5
3 toxin transmembrane transporter activity GO:0019534 9.33 LRP6 LRP5
4 coreceptor activity involved in canonical Wnt signaling pathway GO:1904928 9.26 LRP6 LRP5
5 coreceptor activity involved in Wnt signaling pathway GO:0071936 8.92 LRP6 LRP5

Sources for Osteopetrosis, Autosomal Dominant 1

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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