OPTB6
MCID: OST134
MIFTS: 46

Osteopetrosis, Autosomal Recessive 6 (OPTB6)

Categories: Blood diseases, Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Liver diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Osteopetrosis, Autosomal Recessive 6

MalaCards integrated aliases for Osteopetrosis, Autosomal Recessive 6:

Name: Osteopetrosis, Autosomal Recessive 6 56 73 13 71
Autosomal Recessive Osteopetrosis 6 12 29 6 15
Optb6 56 12 52 73
Autosomal Recessive Osteopetrosis Intermediate Form 12 73
Osteopetrosis, Autosomal Recessive, Intermediate Form 56
Osteopetrosis Autosomal Recessive Intermediate Form 52
Autosomal Recessive Intermediate Osteopetrosis 58
Osteopetrosis, Autosomal Recessive, Type 6 39
Autosomal Recessive Osteopetrosis Type 6 52
Osteopetrosis Autosomal Recessive 6 52
Intermediate Osteopetrosis 58

Characteristics:

Orphanet epidemiological data:

58
intermediate osteopetrosis
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: any age;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
based on report of 1 patient (last curated august 2018)
younger homozygous sib showed only dense metaphyseal bands in femur


HPO:

31
osteopetrosis, autosomal recessive 6:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0110945
OMIM 56 611497
OMIM Phenotypic Series 56 PS259700
MeSH 43 D010022
ICD10 via Orphanet 33 Q78.2
UMLS via Orphanet 72 C0432261 C1969093
Orphanet 58 ORPHA210110
MedGen 41 C1969093
UMLS 71 C1969093

Summaries for Osteopetrosis, Autosomal Recessive 6

NIH Rare Diseases : 52 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 life-threatening complications (such as bone marrow failure) to the incidental finding of osteopetrosis on X-ray . Depending on severity and age of onset, features may include fractures, short stature , compressive neuropathies (pressure on the nerves), hypocalcemia with attendant tetanic seizures , and life-threatening pancytopenia . In rare cases, there may be neurological impairment or involvement of other body systems. Osteopetrosis may be caused by mutations in at least 10 genes . Inheritance can be autosomal recessive , autosomal dominant , or X-linked recessive with the most severe forms being autosomal recessive. Management depends on the specific symptoms and severity and may include vitamin D supplements, various medications, and/or surgery. Adult osteopetrosis requires no treatment by itself, but complications may require intervention.

MalaCards based summary : Osteopetrosis, Autosomal Recessive 6, also known as autosomal recessive osteopetrosis 6, is related to osteopetrosis and pycnodysostosis. An important gene associated with Osteopetrosis, Autosomal Recessive 6 is PLEKHM1 (Pleckstrin Homology And RUN Domain Containing M1), and among its related pathways/superpathways are Metabolism and Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. The drugs Interferon-gamma and interferons have been mentioned in the context of this disorder. Affiliated tissues include bone and bone marrow, and related phenotypes are back pain and recurrent fractures

Disease Ontology : 12 An osteopetrosis characterized by autosomal recessive inheritance of that has material basis in mutation in the PLEKHM1 gene on chromosome 17q21.31.

UniProtKB/Swiss-Prot : 73 Osteopetrosis, autosomal recessive 6: 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. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves.

More information from OMIM: 611497 PS259700

Related Diseases for Osteopetrosis, Autosomal Recessive 6

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 Recessive 6 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 44)
# Related Disease Score Top Affiliating Genes
1 osteopetrosis 30.0 TNFSF11 TCIRG1 PLEKHM1 CLCN7 ATP6V0A2
2 pycnodysostosis 29.8 TNFSF11 TCIRG1 PLEKHM1 CLCN7
3 axial osteomalacia 10.4 TCIRG1 CLCN7
4 fibrogenesis imperfecta ossium 10.4 TCIRG1 CLCN7
5 medullary sponge kidney 10.4 ATP6V1B1 ATP6V0A4
6 osteopetrosis, autosomal recessive 8 10.4 TCIRG1 CLCN7
7 craniodiaphyseal dysplasia 10.3 TCIRG1 PLEKHM1 CLCN7
8 osteopetrosis, autosomal recessive 5 10.3 TCIRG1 CLCN7 ATP6V1B1
9 hereditary distal renal tubular acidosis 10.2 SLC4A1 ATP6V1B1 ATP6V0A4
10 distal renal tubular acidosis 10.2 SLC4A1 ATP6V1B1 ATP6V0A4
11 renal tubular acidosis, distal, autosomal recessive 10.2 SLC4A1 ATP6V1B1 ATP6V0A4
12 autosomal recessive malignant osteopetrosis 10.1 TNFSF11 TCIRG1 CLCN7
13 clcn7-related osteopetrosis 10.1
14 osteopetrosis, autosomal dominant 2 10.1 TNFSF11 TCIRG1 CLCN7
15 craniometaphyseal dysplasia, autosomal dominant 10.0 TNFSF11 TCIRG1 CLCN7
16 renal tubular transport disease 10.0 SLC4A4 SLC4A1 ATP6V1B1 ATP6V0A4
17 retinitis pigmentosa 17 10.0 SLC4A4 IMPDH1
18 bone remodeling disease 10.0 TNFSF11 TCIRG1 CLCN7
19 metabolic acidosis 10.0 SLC4A4 SLC4A1 ATP6V1B1 ATP6V0A4
20 osteopetrosis, autosomal recessive 2 10.0 TNFSF11 TCIRG1 PLEKHM1 CLCN7
21 disseminated chorioretinitis 9.9 TNFSF11 GFER
22 nephrolithiasis 9.9 SLC4A1 CA8 ATP6V1B1 ATP6V0A4
23 endosteal hyperostosis, autosomal dominant 9.9 TNFSF11 TCIRG1 PLEKHM1 CLCN7
24 poikiloderma with neutropenia 9.9
25 bone resorption disease 9.9
26 overgrowth syndrome 9.9
27 west nile fever 9.8 CD40LG ATP5F1A
28 hereditary elliptocytosis 9.8 SLC4A1 HBB ATP6V1B1 ATP6V0A4
29 corneal dystrophy and perceptive deafness 9.8 SLC4A4 SLC4A1
30 osteopetrosis, autosomal recessive 1 9.8 TCIRG1 IMPDH1 CLCN7 ATP6V1B1 ATP6V0A4 ATP6V0A2
31 corneal degeneration 9.8 TGFBI SLC4A4
32 auditory system disease 9.8 CD40LG ATP6V1B1 ATP6V0A4
33 hydrops of gallbladder 9.7 CD40LG CA8
34 scarlet fever 9.7 CD40LG CA8
35 nephrocalcinosis 9.7 SLC4A1 HBB CLCN7 ATP6V1B1 ATP6V0A4
36 splenic infarction 9.6 HBB CD40LG
37 sporotrichosis 9.6 CD40LG CBSL
38 splenic sequestration 9.6 HBB CD40LG
39 interstitial keratitis 9.6 TGFBI CD40LG
40 osteopetrosis, autosomal recessive 3 9.5 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
41 renal tubular acidosis 9.5 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
42 plasmodium falciparum malaria 9.5 SLC4A1 HBB CD40LG
43 osteopetrosis, autosomal recessive 7 5.7 TNFSF11 TGFBI TCIRG1 STX8 SLC4A4 SLC4A1
44 osteopetrosis, autosomal recessive 4 5.7 TNFSF11 TGFBI TCIRG1 STX8 SLC4A4 SLC4A1

Graphical network of the top 20 diseases related to Osteopetrosis, Autosomal Recessive 6:



Diseases related to Osteopetrosis, Autosomal Recessive 6

Symptoms & Phenotypes for Osteopetrosis, Autosomal Recessive 6

Human phenotypes related to Osteopetrosis, Autosomal Recessive 6:

58 31 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 back pain 58 31 frequent (33%) Frequent (79-30%) HP:0003418
2 recurrent fractures 58 31 frequent (33%) Frequent (79-30%) HP:0002757
3 generalized osteosclerosis 58 31 frequent (33%) Frequent (79-30%) HP:0005789
4 sandwich appearance of vertebral bodies 58 31 frequent (33%) Frequent (79-30%) HP:0004618
5 erlenmeyer flask deformity of the femurs 58 31 frequent (33%) Frequent (79-30%) HP:0004975
6 cortical sclerosis 58 31 frequent (33%) Frequent (79-30%) HP:0005652
7 osteosclerosis of the base of the skull 58 31 frequent (33%) Frequent (79-30%) HP:0005746
8 anemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001903
9 elevated alkaline phosphatase 58 31 occasional (7.5%) Occasional (29-5%) HP:0003155
10 dental malocclusion 58 31 very rare (1%) Very rare (<4-1%) HP:0000689
11 visual impairment 58 31 very rare (1%) Very rare (<4-1%) HP:0000505
12 osteomyelitis 58 31 very rare (1%) Very rare (<4-1%) HP:0002754
13 abnormality of dental morphology 58 31 very rare (1%) Very rare (<4-1%) HP:0006482
14 hepatosplenomegaly 58 31 very rare (1%) Very rare (<4-1%) HP:0001433
15 chronic infection 58 31 very rare (1%) Very rare (<4-1%) HP:0031035
16 optic atrophy from cranial nerve compression 58 31 very rare (1%) Very rare (<4-1%) HP:0007958
17 abnormality of the dentition 58 Very rare (<4-1%)
18 thrombocytopenia 58 Excluded (0%)
19 abnormality of bone mineral density 58 Very frequent (99-80%)
20 hypocalcemia 58 Excluded (0%)
21 abnormality of the nervous system 58 Occasional (29-5%)
22 osteopetrosis 31 HP:0011002
23 increased susceptibility to fractures 58 Frequent (79-30%)
24 dense metaphyseal bands 31 HP:0100959
25 cranial nerve compression 58 Very rare (<4-1%)

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
band-like sclerosis of vertebral endplates ('rugger-jersey' spine)

Skeletal Limbs:
nonhomogeneous sclerosis of metadiaphyses (distal femora, tibiae, and fibulae, and proximal fibulae and tibiae)
'erlenmeyer flask' deformity of distal femora and proximal tibiae

Skeletal Pelvis:
cortical sclerosis of pelvic bones

Clinical features from OMIM:

611497

MGI Mouse Phenotypes related to Osteopetrosis, Autosomal Recessive 6:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 10.18 ABCB6 ATP6V0A2 CBSL CD40LG CLCN7 IMPDH1
2 homeostasis/metabolism MP:0005376 10.17 ABCB6 ATP6V0A4 ATP6V1B1 CBSL CD40LG CLCN7
3 immune system MP:0005387 10.07 ATP6V0A2 CBSL CD40LG CLCN7 GFER IMPDH1
4 integument MP:0010771 9.76 ABCB6 ATP6V0A2 CBSL CD40LG CLCN7 SLC4A1
5 renal/urinary system MP:0005367 9.56 ATP6V0A4 ATP6V1B1 CBSL CD40LG CLCN7 PLEKHM1
6 skeleton MP:0005390 9.28 ATP6V0A4 ATP6V1B1 CD40LG CLCN7 PLEKHM1 SLC4A4

Drugs & Therapeutics for Osteopetrosis, Autosomal Recessive 6

Drugs for Osteopetrosis, Autosomal Recessive 6 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Interferon-gamma Phase 2
2 interferons Phase 2
3 Antiviral Agents Phase 2
4 Anti-Infective Agents Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Open-label Early Phase 2 Study With a Single Arm of Interferon Gamma-1b Treatment of Osteopetrosis Completed NCT02666768 Phase 2 Interferon gamma-1b

Search NIH Clinical Center for Osteopetrosis, Autosomal Recessive 6

Genetic Tests for Osteopetrosis, Autosomal Recessive 6

Genetic tests related to Osteopetrosis, Autosomal Recessive 6:

# Genetic test Affiliating Genes
1 Autosomal Recessive Osteopetrosis 6 29 PLEKHM1

Anatomical Context for Osteopetrosis, Autosomal Recessive 6

MalaCards organs/tissues related to Osteopetrosis, Autosomal Recessive 6:

40
Bone, Bone Marrow

Publications for Osteopetrosis, Autosomal Recessive 6

Articles related to Osteopetrosis, Autosomal Recessive 6:

(show all 11)
# Title Authors PMID Year
1
Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. 6 56
17404618 2007
2
Localization of the gene causing the osteopetrotic phenotype in the incisors absent (ia) rat on chromosome 10q32.1. 56
14969387 2004
3
Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation. 61
32119750 2020
4
Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis. 61
24269275 2014
5
Clinical considerations for prosthodontic rehabilitation of intermediate form of osteopetrosis: A report of two cases. 61
25737849 2012
6
Dental management in autosomal recessive (intermediate) osteopetrosis: a case report. 61
21462770 2010
7
Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations. 61
19953639 2010
8
[Osteopetrosis. Classification, etiology, treatment options and implications for oral health]. 61
16385937 2005
9
Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. 61
14584882 2003
10
Cranial MR imaging of osteopetrosis. 61
10871023 2000
11
Association of intermediate osteopetrosis with poikiloderma. 61
10320533 1999

Variations for Osteopetrosis, Autosomal Recessive 6

ClinVar genetic disease variations for Osteopetrosis, Autosomal Recessive 6:

6 ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PLEKHM1 NM_014798.3(PLEKHM1):c.296+1G>ASNV Pathogenic 922 rs786205055 17:43555265-43555265 17:45477899-45477899

Expression for Osteopetrosis, Autosomal Recessive 6

Search GEO for disease gene expression data for Osteopetrosis, Autosomal Recessive 6.

Pathways for Osteopetrosis, Autosomal Recessive 6

Pathways related to Osteopetrosis, Autosomal Recessive 6 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.82 TCIRG1 SLC4A1 PRKAG2 IMPDH1 HBB CBSL
2
Show member pathways
13.05 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
3
Show member pathways
13 TCIRG1 PRKAG2 ATP6V1B1 ATP6V0A4 ATP6V0A2 ATP5F1A
4
Show member pathways
12.15 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4 ATP6V0A2
5 11.85 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
6
Show member pathways
11.8 TCIRG1 SLC4A1 ATP6V1B1 ATP6V0A4 ATP6V0A2
7 11.69 TCIRG1 ATP6V0A4 ATP6V0A2
8
Show member pathways
11.57 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
9 10.99 TNFSF11 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

GO Terms for Osteopetrosis, Autosomal Recessive 6

Cellular components related to Osteopetrosis, Autosomal Recessive 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 10.03 TGFBI SLC4A4 SLC4A1 HBB ATP6V1B1 ATP6V0A4
2 cell GO:0005623 9.91 TCIRG1 SLC4A4 SLC4A1 ATP6V1B1 ATP6V0A4 ATP6V0A2
3 endosome GO:0005768 9.85 STX8 PLEKHM1 ATP6V0A4 ATP6V0A2 ABCB6
4 lysosomal membrane GO:0005765 9.73 TCIRG1 STX8 PLEKHM1 CLCN7 ATP6V0A4 ATP6V0A2
5 endosome membrane GO:0010008 9.72 TCIRG1 PLEKHM1 ATP6V0A4 ATP6V0A2 ABCB6
6 phagocytic vesicle membrane GO:0030670 9.58 TCIRG1 ATP6V0A4 ATP6V0A2
7 proton-transporting V-type ATPase, V0 domain GO:0033179 9.33 TCIRG1 ATP6V0A4 ATP6V0A2
8 vacuolar proton-transporting V-type ATPase, V0 domain GO:0000220 9.13 TCIRG1 ATP6V0A4 ATP6V0A2
9 vacuolar proton-transporting V-type ATPase complex GO:0016471 8.92 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

Biological processes related to Osteopetrosis, Autosomal Recessive 6 according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.83 TCIRG1 CLCN7 ATP6V1B1 ATP6V0A4 ATP6V0A2
2 ion transport GO:0006811 9.76 TCIRG1 SLC4A4 SLC4A1 CLCN7 ATP6V1B1 ATP6V0A4
3 ossification GO:0001503 9.71 TNFSF11 TCIRG1 ATP6V1B1 ATP6V0A4
4 regulation of macroautophagy GO:0016241 9.7 PRKAG2 ATP6V1B1 ATP6V0A2
5 insulin receptor signaling pathway GO:0008286 9.67 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
6 bicarbonate transport GO:0015701 9.65 SLC4A4 SLC4A1 HBB
7 proton transmembrane transport GO:1902600 9.65 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2 ATP5F1A
8 bone resorption GO:0045453 9.56 TNFSF11 TCIRG1
9 positive regulation of bone resorption GO:0045780 9.55 TNFSF11 PLEKHM1
10 regulation of pH GO:0006885 9.54 ATP6V1B1 ATP6V0A4
11 tooth eruption GO:0044691 9.51 TNFSF11 TCIRG1
12 vacuolar acidification GO:0007035 9.5 TCIRG1 ATP6V0A4 ATP6V0A2
13 pH reduction GO:0045851 9.49 TCIRG1 ATP6V1B1
14 osteoclast proliferation GO:0002158 9.46 TNFSF11 TCIRG1
15 transferrin transport GO:0033572 9.26 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2
16 phagosome acidification GO:0090383 8.92 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

Molecular functions related to Osteopetrosis, Autosomal Recessive 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATPase binding GO:0051117 9.5 TCIRG1 ATP6V0A4 ATP6V0A2
2 chloride transmembrane transporter activity GO:0015108 9.43 SLC4A1 CLCN7
3 anion transmembrane transporter activity GO:0008509 9.4 SLC4A4 SLC4A1
4 inorganic anion exchanger activity GO:0005452 9.37 SLC4A4 SLC4A1
5 hemoglobin binding GO:0030492 9.26 SLC4A1 HBB
6 adenyl ribonucleotide binding GO:0032559 9.16 PRKAG2 ATP5F1A
7 proton-transporting ATPase activity, rotational mechanism GO:0046961 9.13 TCIRG1 ATP6V0A4 ATP6V0A2
8 proton transmembrane transporter activity GO:0015078 8.92 TCIRG1 ATP6V1B1 ATP6V0A4 ATP6V0A2

Sources for Osteopetrosis, Autosomal Recessive 6

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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