Paget Disease of Bone 2, Early-Onset disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: PGT009 MIFTS: 24	Paget Disease of Bone 2, Early-Onset Categories: Genetic diseases, Bone diseases
Genes Variations Tissues Related diseases Pathways Symptoms & Phenotypes Download Expand all tables

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Aliases & Classifications for Paget Disease of Bone 2, Early-Onset

MalaCards integrated aliases for Paget Disease of Bone 2, Early-Onset:

Name: Paget Disease of Bone 2, Early-Onset ⁵⁷ ⁷⁵ ²⁹ ⁶

Pdb2 ⁵⁷ ⁷⁵

Paget Disease of Bone, Type 2, Early-Onset ⁴⁰

Characteristics:

OMIM:

⁵⁷

Inheritance:
autosomal dominant

Miscellaneous:
variable severity
progressive disorder
onset in teens or early twenties

HPO:

³²

paget disease of bone 2, early-onset:
Onset and clinical course variable expressivity progressive
Inheritance heterogeneous autosomal dominant inheritance

Classifications:

MalaCards categories:
Global: Genetic diseases
Anatomical: Bone diseases

See all MalaCards categories (disease lists)

External Ids:

OMIM ⁵⁷ 602080

MedGen ⁴² C4085251 C0029401

MeSH ⁴⁴ D010001

SNOMED-CT via HPO ⁶⁹ 263681008 91327001 1845001 more

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Summaries for Paget Disease of Bone 2, Early-Onset

UniProtKB/Swiss-Prot : ⁷⁵ Paget disease of bone 2, early-onset: A form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone.

MalaCards based summary : Paget Disease of Bone 2, Early-Onset, also known as pdb2, is related to paget's disease of bone and familial expansile osteolysis. An important gene associated with Paget Disease of Bone 2, Early-Onset is TNFRSF11A (TNF Receptor Superfamily Member 11a), and among its related pathways/superpathways are RANK Signaling in Osteoclasts and Osteoclast differentiation. Affiliated tissues include bone and brain, and related phenotypes are tetraparesis and paraparesis

OMIM : ⁵⁷ Paget disease is a metabolic bone disease characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Bone lesions in this disorder show evidence of increased osteoclastic bone resorption and disorganized bone structure. See reviews by Ralston et al. (2008) and Ralston and Albagha (2014). For a discussion of genetic heterogeneity of Paget disease of bone, see 167250. (602080)

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Related Diseases for Paget Disease of Bone 2, Early-Onset

Diseases related to Paget Disease of Bone 2, Early-Onset via text searches within MalaCards or GeneCards Suite gene sharing:

#	Related Disease	Score	Top Affiliating Genes
1	paget's disease of bone	28.4	SQSTM1 TNFRSF11A
2	familial expansile osteolysis	9.3	SQSTM1 TNFRSF11A
3	periostitis	9.2	SQSTM1 TNFRSF11A

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Symptoms & Phenotypes for Paget Disease of Bone 2, Early-Onset

Symptoms via clinical synopsis from OMIM:

⁵⁷

Skeletal:
bone pain
mixed regions of osteosclerosis and osteolysis
abnormal uptake of radio-labelled bisphosphates in affected sites on bone scan
deformity or enlargement of bones

Head And Neck Ears:
hearing loss, progressive

Head And Neck Head:
swelling and deformity of the mandible and maxilla

Skeletal Limbs:
deformities and bowing of the long bones

Laboratory Abnormalities:
elevated alkaline phosphatase

Head And Neck Teeth:
premature tooth loss

Skeletal Skull:
swelling and deformity of the mandible and maxilla

Skeletal Hands:
swelling of the proximal and distal interphalangeal joints

Clinical features from OMIM:

602080

Human phenotypes related to Paget Disease of Bone 2, Early-Onset:

³² (show all 15)

#	Description	HPO Frequency	HPO Source Accession
1	tetraparesis ³²		HP:0002273
2	paraparesis ³²		HP:0002385
3	long-tract signs ³²		HP:0002423
4	brain stem compression ³²		HP:0002512
5	abnormality of pelvic girdle bone morphology ³²		HP:0002644
6	bone pain ³²		HP:0002653
7	increased susceptibility to fractures ³²		HP:0002659
8	osteolysis ³²		HP:0002797
9	vertebral compression fractures ³²		HP:0002953
10	hydroxyprolinuria ³²		HP:0003080
11	fractures of the long bones ³²		HP:0003084
12	elevated alkaline phosphatase ³²		HP:0003155
13	premature loss of teeth ³²		HP:0006480
14	cranial nerve paralysis ³²		HP:0006824
15	bilateral conductive hearing impairment ³²	very rare (1%)	HP:0008513

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Drugs & Therapeutics for Paget Disease of Bone 2, Early-Onset

Search Clinical Trials , NIH Clinical Center for Paget Disease of Bone 2, Early-Onset

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Genetic Tests for Paget Disease of Bone 2, Early-Onset

Genetic tests related to Paget Disease of Bone 2, Early-Onset:

#	Genetic test	Affiliating Genes
1	Paget Disease of Bone 2, Early-Onset ²⁹	SQSTM1 TNFRSF11A

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Anatomical Context for Paget Disease of Bone 2, Early-Onset

MalaCards organs/tissues related to Paget Disease of Bone 2, Early-Onset:

⁴¹

Bone, Brain

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Publications for Paget Disease of Bone 2, Early-Onset

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Genes for Paget Disease of Bone 2, Early-Onset

Genes related to Paget Disease of Bone 2, Early-Onset (2 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	TNFRSF11A	TNF Receptor Superfamily Member 11a	Protein Coding	1078.07	Molecular basis known ⁵⁷ Pathogenic ⁶ Genetic Tests ²⁹ Susceptibility factor ⁵⁷ GeneCards inferred via : Disorders Variants (show sections)	10615125 25063546 11771666
2	SQSTM1	Sequestosome 1	Protein Coding	519.83	Pathogenic ⁶ Genetic Tests ²⁹ GeneCards inferred via : Variants (show sections)

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Variations for Paget Disease of Bone 2, Early-Onset

ClinVar genetic disease variations for Paget Disease of Bone 2, Early-Onset:

⁶

(show top 50) (show all 88)

#	Gene	Variation	Type	Significance	SNP ID	Assembly	Location
1	TNFRSF11A	NM_003839.3(TNFRSF11A)	duplication	Pathogenic	rs796051862	GRCh38	Chromosome 18, 62325391: 62325417
2	TNFRSF11A	NM_003839.3(TNFRSF11A)	duplication	Pathogenic	rs796051862	GRCh37	Chromosome 18, 59992624: 59992650
3	SQSTM1	NM_003900.4(SQSTM1): c.970_1165del	single nucleotide variant	Pathogenic	rs796051870	GRCh38	Chromosome 5, 179833783: 179833783
4	SQSTM1	NM_003900.4(SQSTM1): c.970_1165del	single nucleotide variant	Pathogenic	rs796051870	GRCh37	Chromosome 5, 179260783: 179260783
5	TNFRSF11A	NM_003839.3(TNFRSF11A): c.49_63dupCTCTGCGCGCTGCTC (p.Leu21_Ala22insLeuCysAlaLeuLeu)	duplication	Pathogenic	rs879253796	GRCh38	Chromosome 18, 62325401: 62325415
6	TNFRSF11A	NM_003839.3(TNFRSF11A): c.49_63dupCTCTGCGCGCTGCTC (p.Leu21_Ala22insLeuCysAlaLeuLeu)	duplication	Pathogenic	rs879253796	GRCh37	Chromosome 18, 59992634: 59992648
7	SQSTM1	NM_001142298.1(SQSTM1): c.-47-1924C> T	single nucleotide variant	Likely benign	rs200396166	GRCh38	Chromosome 5, 179821034: 179821034
8	SQSTM1	NM_001142298.1(SQSTM1): c.-47-1924C> T	single nucleotide variant	Likely benign	rs200396166	GRCh37	Chromosome 5, 179248034: 179248034
9	SQSTM1	NM_003900.4(SQSTM1): c.822G> C (p.Glu274Asp)	single nucleotide variant	Benign/Likely benign	rs55793208	GRCh37	Chromosome 5, 179260099: 179260099
10	SQSTM1	NM_003900.4(SQSTM1): c.822G> C (p.Glu274Asp)	single nucleotide variant	Benign/Likely benign	rs55793208	GRCh38	Chromosome 5, 179833099: 179833099
11	SQSTM1	NM_003900.4(SQSTM1): c.876C> T (p.Asp292=)	single nucleotide variant	Benign/Likely benign	rs4935	GRCh37	Chromosome 5, 179260153: 179260153
12	SQSTM1	NM_003900.4(SQSTM1): c.876C> T (p.Asp292=)	single nucleotide variant	Benign/Likely benign	rs4935	GRCh38	Chromosome 5, 179833153: 179833153
13	SQSTM1	NM_003900.4(SQSTM1): c.924G> A (p.Ala308=)	single nucleotide variant	Likely benign	rs139482113	GRCh37	Chromosome 5, 179260201: 179260201
14	SQSTM1	NM_003900.4(SQSTM1): c.924G> A (p.Ala308=)	single nucleotide variant	Likely benign	rs139482113	GRCh38	Chromosome 5, 179833201: 179833201
15	SQSTM1	NM_003900.4(SQSTM1): c.936G> A (p.Arg312=)	single nucleotide variant	Benign/Likely benign	rs4797	GRCh37	Chromosome 5, 179260213: 179260213
16	SQSTM1	NM_003900.4(SQSTM1): c.936G> A (p.Arg312=)	single nucleotide variant	Benign/Likely benign	rs4797	GRCh38	Chromosome 5, 179833213: 179833213
17	SQSTM1	NM_003900.4(SQSTM1): c.954C> T (p.Ser318=)	single nucleotide variant	Benign/Likely benign	rs56092424	GRCh37	Chromosome 5, 179260231: 179260231
18	SQSTM1	NM_003900.4(SQSTM1): c.954C> T (p.Ser318=)	single nucleotide variant	Benign/Likely benign	rs56092424	GRCh38	Chromosome 5, 179833231: 179833231
19	SQSTM1	NM_003900.4(SQSTM1): c.961C> T (p.Arg321Cys)	single nucleotide variant	Benign/Likely benign	rs140226523	GRCh37	Chromosome 5, 179260238: 179260238
20	SQSTM1	NM_003900.4(SQSTM1): c.961C> T (p.Arg321Cys)	single nucleotide variant	Benign/Likely benign	rs140226523	GRCh38	Chromosome 5, 179833238: 179833238
21	SQSTM1	NM_003900.4(SQSTM1): c.1044G> A (p.Pro348=)	single nucleotide variant	Benign/Likely benign	rs10058037	GRCh37	Chromosome 5, 179260661: 179260661
22	SQSTM1	NM_003900.4(SQSTM1): c.1044G> A (p.Pro348=)	single nucleotide variant	Benign/Likely benign	rs10058037	GRCh38	Chromosome 5, 179833661: 179833661
23	SQSTM1	NM_003900.4(SQSTM1): c.819A> G (p.Pro273=)	single nucleotide variant	Conflicting interpretations of pathogenicity	rs200388590	GRCh38	Chromosome 5, 179833096: 179833096
24	SQSTM1	NM_003900.4(SQSTM1): c.819A> G (p.Pro273=)	single nucleotide variant	Conflicting interpretations of pathogenicity	rs200388590	GRCh37	Chromosome 5, 179260096: 179260096
25	SQSTM1	NM_003900.4(SQSTM1): c.955G> A (p.Glu319Lys)	single nucleotide variant	Benign/Likely benign	rs61748794	GRCh37	Chromosome 5, 179260232: 179260232
26	SQSTM1	NM_003900.4(SQSTM1): c.955G> A (p.Glu319Lys)	single nucleotide variant	Benign/Likely benign	rs61748794	GRCh38	Chromosome 5, 179833232: 179833232
27	SQSTM1	NM_003900.4(SQSTM1): c.183C> T (p.Gly61=)	single nucleotide variant	Benign/Likely benign	rs767340839	GRCh38	Chromosome 5, 179821119: 179821119
28	SQSTM1	NM_003900.4(SQSTM1): c.183C> T (p.Gly61=)	single nucleotide variant	Benign/Likely benign	rs767340839	GRCh37	Chromosome 5, 179248119: 179248119
29	SQSTM1	NM_003900.4(SQSTM1): c.612A> G (p.Gly204=)	single nucleotide variant	Conflicting interpretations of pathogenicity	rs878982215	GRCh38	Chromosome 5, 179824262: 179824262
30	SQSTM1	NM_003900.4(SQSTM1): c.612A> G (p.Gly204=)	single nucleotide variant	Conflicting interpretations of pathogenicity	rs878982215	GRCh37	Chromosome 5, 179251262: 179251262
31	SQSTM1	NM_003900.4(SQSTM1): c.1230C> T (p.Gly410=)	single nucleotide variant	Likely benign	rs766437927	GRCh37	Chromosome 5, 179263500: 179263500
32	SQSTM1	NM_003900.4(SQSTM1): c.1230C> T (p.Gly410=)	single nucleotide variant	Likely benign	rs766437927	GRCh38	Chromosome 5, 179836500: 179836500
33	SQSTM1	NM_003900.4(SQSTM1): c.46G> A (p.Ala16Thr)	single nucleotide variant	Uncertain significance	rs773552098	GRCh38	Chromosome 5, 179820982: 179820982
34	SQSTM1	NM_003900.4(SQSTM1): c.46G> A (p.Ala16Thr)	single nucleotide variant	Uncertain significance	rs773552098	GRCh37	Chromosome 5, 179247982: 179247982
35	SQSTM1	NM_003900.4(SQSTM1): c.996A> G (p.Ser332=)	single nucleotide variant	Benign/Likely benign	rs141436407	GRCh38	Chromosome 5, 179833613: 179833613
36	SQSTM1	NM_003900.4(SQSTM1): c.996A> G (p.Ser332=)	single nucleotide variant	Benign/Likely benign	rs141436407	GRCh37	Chromosome 5, 179260613: 179260613
37	SQSTM1	NM_003900.4(SQSTM1): c.268G> A (p.Val90Met)	single nucleotide variant	Uncertain significance	rs181263868	GRCh37	Chromosome 5, 179250020: 179250020
38	SQSTM1	NM_003900.4(SQSTM1): c.268G> A (p.Val90Met)	single nucleotide variant	Uncertain significance	rs181263868	GRCh38	Chromosome 5, 179823020: 179823020
39	SQSTM1	NM_003900.4(SQSTM1): c.317G> A (p.Arg106Gln)	single nucleotide variant	Uncertain significance	rs778554903	GRCh38	Chromosome 5, 179823873: 179823873
40	SQSTM1	NM_003900.4(SQSTM1): c.317G> A (p.Arg106Gln)	single nucleotide variant	Uncertain significance	rs778554903	GRCh37	Chromosome 5, 179250873: 179250873
41	SQSTM1	NM_003900.4(SQSTM1): c.888G> A (p.Pro296=)	single nucleotide variant	Benign	rs148984239	GRCh38	Chromosome 5, 179833165: 179833165
42	SQSTM1	NM_003900.4(SQSTM1): c.888G> A (p.Pro296=)	single nucleotide variant	Benign	rs148984239	GRCh37	Chromosome 5, 179260165: 179260165
43	SQSTM1	NM_003900.4(SQSTM1): c.1178G> A (p.Arg393Gln)	single nucleotide variant	Uncertain significance	rs200551825	GRCh37	Chromosome 5, 179263448: 179263448
44	SQSTM1	NM_003900.4(SQSTM1): c.1178G> A (p.Arg393Gln)	single nucleotide variant	Uncertain significance	rs200551825	GRCh38	Chromosome 5, 179836448: 179836448
45	SQSTM1	NM_003900.4(SQSTM1): c.332C> T (p.Pro111Leu)	single nucleotide variant	Uncertain significance	rs371719657	GRCh37	Chromosome 5, 179250888: 179250888
46	SQSTM1	NM_003900.4(SQSTM1): c.332C> T (p.Pro111Leu)	single nucleotide variant	Uncertain significance	rs371719657	GRCh38	Chromosome 5, 179823888: 179823888
47	SQSTM1	NM_003900.4(SQSTM1): c.763G> C (p.Val255Leu)	single nucleotide variant	Uncertain significance	rs182522590	GRCh38	Chromosome 5, 179833040: 179833040
48	SQSTM1	NM_003900.4(SQSTM1): c.763G> C (p.Val255Leu)	single nucleotide variant	Uncertain significance	rs182522590	GRCh37	Chromosome 5, 179260040: 179260040
49	SQSTM1	NM_003900.4(SQSTM1): c.800G> A (p.Arg267His)	single nucleotide variant	Uncertain significance	rs149424705	GRCh37	Chromosome 5, 179260077: 179260077
50	SQSTM1	NM_003900.4(SQSTM1): c.800G> A (p.Arg267His)	single nucleotide variant	Uncertain significance	rs149424705	GRCh38	Chromosome 5, 179833077: 179833077

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Expression for Paget Disease of Bone 2, Early-Onset

Search GEO for disease gene expression data for Paget Disease of Bone 2, Early-Onset.

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Pathways for Paget Disease of Bone 2, Early-Onset

Pathways related to Paget Disease of Bone 2, Early-Onset according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	RANK Signaling in Osteoclasts ⁶⁴ Show member pathways Apoptosis and survival APRIL and BAFF signaling ²² APRIL Pathway ⁶⁴ BAFF in B-Cell Signaling ⁶⁴ RANK Pathway ⁶⁴ RANKL/RANK (Receptor activator of NFKB (ligand)) Signaling Pathway ¹	11.55	SQSTM1 TNFRSF11A
2	Osteoclast differentiation ³⁷	11.06	SQSTM1 TNFRSF11A
3	Apoptosis and survival Anti-apoptotic TNFs/NF-kB/Bcl-2 pathway ²² Show member pathways Apoptosis and survival Anti-apoptotic TNFs/NF-kB/IAP pathway ²²	10.49	SQSTM1 TNFRSF11A

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GO Terms for Paget Disease of Bone 2, Early-Onset

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