Details of Disease

General Information of Disease (ID: DIS7GHNM)

• Disease Name: Osteopetrosis
• Synonyms: Albers-Schoenberg disease; osteosclerosis fragilis; osteopetrosis and related disorders; osteopetroses; marble bones; marble bone; osteopetrosis (disease); Albers-Schonberg disease; osteopetrosis; marble bone disease
• Disease Class: LD24: Skeletal anomaly
• Definition: Osteopetrosis, also known as marble bone disease, is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterized by increased bone density on radiographs.
• Disease Hierarchy:
  DISHH6XB: Familial osteosclerosis
  DIS5Z8U6: Skeletal dysplasia
  DIS7GHNM: Osteopetrosis
• ICD Code:
  ICD-11: ICD-11: LD24.10
  ICD-10: ICD-10: Q78.2
  Expand ICD-11: 'LD24.10
  Expand ICD-10: 'Q78.2
• Disease Identifiers:
  MONDO ID: MONDO_0017198
  MESH ID: D010022
  UMLS CUI: C0029454
  MedGen ID: 18223
  HPO ID: HP:0011002
  Orphanet ID: 2781
  SNOMED CT ID: 1926006

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Bazedoxifene	DMY85QW	Approved	Small molecular drug	[1]

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Apomine	DM6B9HP	Phase 2	Small molecular drug	[2]

This Disease is Treated as An Indication in 1 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ODS-656	DMLKPAZ	Investigative	NA	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ARF1	TT70KXY	Limited	Biomarker	[4]
CA2	TTANPDJ	Limited	Genetic Variation	[5]
CLCN1	TTUYAF3	Limited	Genetic Variation	[6]
CSF1	TT0IQER	Limited	Genetic Variation	[7]
GHR	TTHJWYD	Limited	Biomarker	[8]
MCOLN1	TT9XBVO	Limited	Biomarker	[9]
TCIRG1	TTVRN05	Limited	Genetic Variation	[10]
PDE11A	TTTWC79	Disputed	Genetic Variation	[11]
TNFRSF11A	TT3K9S2	moderate	Biomarker	[12]
CSF1R	TT7MRDV	Strong	Biomarker	[11]
CTSK	TTDZN01	Strong	Biomarker	[13]
TNFRSF11B	TT2CJ75	Strong	Altered Expression	[14]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC4A2	DTF7GAL	Limited	Genetic Variation	[15]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ACP5	DESITDW	Strong	Genetic Variation	[16]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATP6V0D2	OTMOZJO0	Limited	Biomarker	[17]
CCDC154	OTFGNMNP	Limited	Biomarker	[18]
CKB	OTUCKOTT	Limited	Biomarker	[19]
DEGS1	OT4WXPKW	Limited	Biomarker	[20]
EXTL2	OT8U672K	Limited	Biomarker	[21]
EXTL3	OT2BRUBN	Limited	Biomarker	[21]
OSTM1	OTKNJDH7	Limited	Biomarker	[22]
PLEKHM1	OT1SLPGD	Limited	Biomarker	[23]
IGSF23	OTORIW79	Disputed	Genetic Variation	[24]
ADO	OTRLGQ7V	Strong	Genetic Variation	[25]
ATP6V1B1	OT8FQ7MN	Strong	Genetic Variation	[26]
CLC	OTYMYR85	Strong	Genetic Variation	[27]
FERMT3	OTFQOT3C	Strong	Genetic Variation	[28]
IKBKG	OTNWJWSD	Strong	Genetic Variation	[29]
MRGPRF	OT74OZ2Z	Strong	Biomarker	[30]
RASGRP2	OTABVLVQ	Strong	Autosomal recessive	[31]
RBFOX2	OTXY1WVH	Strong	Biomarker	[30]
SNX10	OT05B7BT	Strong	Genetic Variation	[32]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7355).
• [2] A phase II open-label trial of apomine (SR-45023A) in patients with refractory melanoma. Invest New Drugs. 2006 Jan;24(1):89-94.
• [3] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [4] Identification of potential microRNA-target pairs associated with osteopetrosis by deep sequencing, iTRAQ proteomics and bioinformatics.Eur J Hum Genet. 2014 May;22(5):625-32. doi: 10.1038/ejhg.2013.221. Epub 2013 Oct 2.
• [5] Molecular modelling and dynamics of CA2 missense mutations causative to carbonic anhydrase 2 deficiency syndrome.J Biomol Struct Dyn. 2020 Sep;38(14):4067-4080. doi: 10.1080/07391102.2019.1671899. Epub 2019 Oct 8.
• [6] Type II benign osteopetrosis (Albers-Schnberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations.Calcif Tissue Int. 2004 Jan;74(1):42-6. doi: 10.1007/s00223-002-1087-5. Epub 2003 Nov 26.
• [7] Change in Populations of Macrophages Promotes Development of Delayed Gastric Emptying in Mice.Gastroenterology. 2018 Jun;154(8):2122-2136.e12. doi: 10.1053/j.gastro.2018.02.027. Epub 2018 Mar 6.
• [8] Reduced growth hormone receptor immunoreactivity in osteoclasts adjacent to the erupting molar in the incisor-absent (osteopetrotic) rat.Eur J Oral Sci. 2003 Dec;111(6):503-9. doi: 10.1111/j.0909-8836.2003.00075.x.
• [9] Lysosomal Ca(2+) Signaling is Essential for Osteoclastogenesis and Bone Remodeling.J Bone Miner Res. 2017 Feb;32(2):385-396. doi: 10.1002/jbmr.2986. Epub 2016 Sep 26.
• [10] CLCN7 and TCIRG1 mutations in a single family: Evidence for digenic inheritance of osteopetrosis.Mol Med Rep. 2019 Jan;19(1):595-600. doi: 10.3892/mmr.2018.9648. Epub 2018 Nov 13.
• [11] Autozygosity reveals recessive mutations and novel mechanisms in dominant genes: implications in variant interpretation.Genet Med. 2017 Oct;19(10):1144-1150. doi: 10.1038/gim.2017.22. Epub 2017 Apr 6.
• [12] CLCN7 and TCIRG1 mutations differentially affect bone matrix mineralization in osteopetrotic individuals.J Bone Miner Res. 2014 Apr;29(4):982-91. doi: 10.1002/jbmr.2100.
• [13] ClC-7 Regulates the Pattern and Early Development of Craniofacial Bone and Tooth.Theranostics. 2019 Feb 20;9(5):1387-1400. doi: 10.7150/thno.29761. eCollection 2019.
• [14] Linkage and association analyses of the osteoprotegerin gene locus with human osteoporosis.J Hum Genet. 2002;47(8):400-6. doi: 10.1007/s100380200058.
• [15] A deletion mutation in bovine SLC4A2 is associated with osteopetrosis in Red Angus cattle.BMC Genomics. 2010 May 27;11:337. doi: 10.1186/1471-2164-11-337.
• [16] A new heterozygous mutation (R714C) of the osteopetrosis gene, pleckstrin homolog domain containing family M (with run domain) member 1 (PLEKHM1), impairs vesicular acidification and increases TRACP secretion in osteoclasts.J Bone Miner Res. 2008 Mar;23(3):380-91. doi: 10.1359/jbmr.071107.
• [17] ClC-7/Ostm1 contribute to the ability of tea polyphenols to maintain bone homeostasis in C57BL/6 mice, protecting against fluorosis.Int J Mol Med. 2017 May;39(5):1155-1163. doi: 10.3892/ijmm.2017.2933. Epub 2017 Mar 22.
• [18] Overexpression of a novel osteopetrosis-related gene CCDC154 suppresses cell proliferation by inducing G2/M arrest.Cell Cycle. 2012 Sep 1;11(17):3270-9. doi: 10.4161/cc.21642. Epub 2012 Aug 16.
• [19] Creatine kinase brain isoenzyme in infantile osteopetrosis.Pediatr Neurol. 1987 Jan-Feb;3(1):54-7. doi: 10.1016/0887-8994(87)90057-9.
• [20] Haploidentical bone marrow transplantation in leukemia and genetic diseases.Haematologica. 2000 Nov;85(11 Suppl):37-40.
• [21] Structure, chromosomal location, and expression profile of EXTR1 and EXTR2, new members of the multiple exostoses gene family.Biochem Biophys Res Commun. 1998 Feb 4;243(1):61-6. doi: 10.1006/bbrc.1997.8062.
• [22] Ostm1 Bifunctional Roles in Osteoclast Maturation: Insights From a Mouse Model Mimicking a Human OSTM1 Mutation.J Bone Miner Res. 2018 May;33(5):888-898. doi: 10.1002/jbmr.3378. Epub 2018 Feb 14.
• [23] Characterization of a Relatively Malignant Form of Osteopetrosis Caused by a Novel Mutation in the PLEKHM1 Gene.J Bone Miner Res. 2016 Nov;31(11):1979-1987. doi: 10.1002/jbmr.2885. Epub 2016 Jul 13.
• [24] Osteoclastogenesis inhibition by mutated IGSF23 results in human osteopetrosis.Cell Prolif. 2019 Nov;52(6):e12693. doi: 10.1111/cpr.12693. Epub 2019 Sep 27.
• [25] Report of two Chinese patients suffering from CLCN7-related osteopetrosis and root dysplasia.J Craniomaxillofac Surg. 2012 Jul;40(5):416-20. doi: 10.1016/j.jcms.2011.07.014. Epub 2011 Oct 1.
• [26] A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis. J Med Genet. 2003 Feb;40(2):115-21. doi: 10.1136/jmg.40.2.115.
• [27] Physiological functions of CLC Cl- channels gleaned from human genetic disease and mouse models.Annu Rev Physiol. 2005;67:779-807. doi: 10.1146/annurev.physiol.67.032003.153245.
• [28] Hematopoietic stem cell transplantation corrects osteopetrosis in a child carrying a novel homozygous mutation in the FERMT3 gene.Bone. 2017 Apr;97:126-129. doi: 10.1016/j.bone.2017.01.012. Epub 2017 Jan 14.
• [29] Absence of an osteopetrosis phenotype in IKBKG (NEMO) mutation-positive women: A case-control study.Bone. 2019 Apr;121:243-254. doi: 10.1016/j.bone.2019.01.014. Epub 2019 Jan 16.
• [30] Familial pure proximal renal tubular acidosis--a clinical and genetic study.Nephrol Dial Transplant. 2008 Apr;23(4):1211-5. doi: 10.1093/ndt/gfm583. Epub 2007 Sep 19.
• [31] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [32] SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts.Sci Rep. 2017 Jun 7;7(1):3012. doi: 10.1038/s41598-017-02533-2.