SOST2
MCID: SCL042
MIFTS: 40

Sclerosteosis 2 (SOST2)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Sclerosteosis 2

MalaCards integrated aliases for Sclerosteosis 2:

Name: Sclerosteosis 2 57 12 72 29 13 6 15 70
Sost2 57 12 72
Sclerosteosis, Type 2 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive
autosomal dominant



Classifications:



External Ids:

Disease Ontology 12 DOID:0060757
OMIM® 57 614305
OMIM Phenotypic Series 57 PS269500
MeSH 44 D015576
ICD10 32 M85.2
MedGen 41 C3280402
UMLS 70 C3280402

Summaries for Sclerosteosis 2

UniProtKB/Swiss-Prot : 72 Sclerosteosis 2: A sclerosing bone dysplasia characterized by a generalized hyperostosis and sclerosis leading to a markedly thickened skull, with mandible, ribs, clavicles and all long bones also being affected. Due to narrowing of the foramina of the cranial nerves, facial nerve palsy, hearing loss and atrophy of the optic nerves can occur. Sclerosteosis is clinically and radiologically very similar to van Buchem disease, mainly differentiated by hand malformations and a large stature in sclerosteosis patients.

MalaCards based summary : Sclerosteosis 2, also known as sost2, is related to congenital myasthenic syndrome and sclerosteosis. An important gene associated with Sclerosteosis 2 is LRP4 (LDL Receptor Related Protein 4), and among its related pathways/superpathways are Signaling by Wnt and Wnt signaling pathway. Affiliated tissues include bone, and related phenotypes are macrocephaly and frontal bossing

Disease Ontology : 12 A sclerosteosis that has material basis in heterozygous or homozygous mutation in the LRP4 gene on chromosome 11p11.

OMIM® : 57 Sclerosteosis is a severe sclerosing bone dysplasia characterized by progressive skeletal overgrowth. Syndactyly is a variable manifestation. The disorder is rare and the majority of affected individuals have been reported in the Afrikaner population of South Africa (summary by Brunkow et al., 2001). For a discussion of genetic heterogeneity of sclerosteosis, see SOST1 (269500). (614305) (Updated 05-Apr-2021)

Related Diseases for Sclerosteosis 2

Diseases in the Sclerosteosis family:

Sclerosteosis 1 Sclerosteosis 2

Diseases related to Sclerosteosis 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 27)
# Related Disease Score Top Affiliating Genes
1 congenital myasthenic syndrome 29.8 RAPSN LRP4 DOK7
2 sclerosteosis 29.0 SOST LRP5 LRP4-AS1 LRP4 KREMEN1
3 cenani-lenz syndactyly syndrome 28.3 STIMATE SOST RAPSN LRP5 LRP4-AS1 LRP4
4 myasthenic syndrome, congenital, 17 10.2 LRP4-AS1 LRP4
5 myasthenic syndrome, congenital, 21, presynaptic 10.1 RAPSN DOK7
6 myasthenic syndrome, congenital, 13 10.1 RAPSN DOK7
7 myasthenic syndrome, congenital, 19 10.0 RAPSN DOK7
8 myasthenic syndrome, congenital, 5 10.0 RAPSN DOK7
9 facial nerve disease 10.0 SOST LRP5
10 facial paralysis 10.0 SOST LRP5
11 osteoporosis, juvenile 9.9 SOST LRP5
12 chromosome 2q35 duplication syndrome 9.9
13 postsynaptic congenital myasthenic syndromes 9.9 RAPSN LRP4 DOK7
14 mccune-albright syndrome 9.9 SOST LRP5
15 neuromuscular junction disease 9.9 RAPSN LRP4 DOK7
16 endosteal hyperostosis, autosomal dominant 9.9 SOST LRP5
17 bone resorption disease 9.9 SOST LRP5
18 ptosis 9.8 RAPSN LRP4 DOK7
19 sclerosteosis 1 9.8 SOST LRP5 LRP4
20 polyhydramnios 9.8 RAPSN DOK7
21 neuromuscular disease 9.8 RAPSN LRP4 DOK7
22 bone remodeling disease 9.8 SOST LRP5
23 multiple pterygium syndrome, escobar variant 9.7 RAPSN DOK7
24 osteoporosis-pseudoglioma syndrome 9.7 SOST LRP5 KREMEN1
25 van buchem disease 9.6 SOST LRP5 LRP4 KREMEN1
26 hyperostosis 9.6 SOST LRP5 LRP4 KREMEN1
27 craniodiaphyseal dysplasia 9.6 SOST RSPO2 LRP5

Graphical network of the top 20 diseases related to Sclerosteosis 2:



Diseases related to Sclerosteosis 2

Symptoms & Phenotypes for Sclerosteosis 2

Human phenotypes related to Sclerosteosis 2:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 31 HP:0000256
2 frontal bossing 31 HP:0002007
3 facial palsy 31 HP:0010628
4 hearing impairment 31 HP:0000365
5 hypertelorism 31 HP:0000316
6 mandibular prognathia 31 HP:0000303
7 facial asymmetry 31 HP:0000324
8 short finger 31 HP:0009381
9 cutaneous finger syndactyly 31 HP:0010554
10 nail dysplasia 31 HP:0002164
11 tetraparesis 31 HP:0002273

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Face:
frontal bossing
prognathism
facial asymmetry due to facial nerve palsy

Skeletal Feet:
cutaneous syndactyly

Head And Neck Ears:
hearing loss

Skeletal Skull:
sclerotic calvarium
enlarged, sclerotic mandible

Skeletal Hands:
hypoplastic digits
bony syndactyly of digits
radial deviation of distal phalanx

Chest Ribs Sternum Clavicles And Scapulae:
wide and dense clavicles
wide and dense ribs

Skeletal Pelvis:
sclerotic pelvic bones

Head And Neck Eyes:
hypertelorism

Head And Neck Head:
increased head circumference

Skin Nails Hair Nails:
dysplastic nails

Neurologic Central Nervous System:
facial nerve palsy
spastic-ataxic tetraparesis

Growth Height:
increased stature

Skeletal Spine:
sclerotic vertebral end plates and pedicles

Skeletal Limbs:
cortical hyperostosis of long bones

Clinical features from OMIM®:

614305 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Sclerosteosis 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 9.02 KREMEN1 LRP4 LRP5 RSPO2 SOST

Drugs & Therapeutics for Sclerosteosis 2

Search Clinical Trials , NIH Clinical Center for Sclerosteosis 2

Genetic Tests for Sclerosteosis 2

Genetic tests related to Sclerosteosis 2:

# Genetic test Affiliating Genes
1 Sclerosteosis 2 29 LRP4

Anatomical Context for Sclerosteosis 2

MalaCards organs/tissues related to Sclerosteosis 2:

40
Bone

Publications for Sclerosteosis 2

Articles related to Sclerosteosis 2:

# Title Authors PMID Year
1
Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. 6 57
21471202 2011
2
Syndactyly/brachyphalangy and nail dysplasias as marker lesions for sclerosteosis. 6 57
11385236 2001
3
Sclerosteosis in a Spanish male: first report in a person of Mediterranean origin. 57 6
7891385 1994
4
LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner. 6 61
24234652 2014
5
Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. 57
11179006 2001
6
A novel biallelic splice-site variant in the LRP4 gene causes sclerosteosis 2. 61
32286743 2020
7
Sclerosteosis: Report of type 1 or 2 in three Indian Tamil families and literature review. 61
30077757 2018
8
Mutations in the fourth β-propeller domain of LRP4 are associated with isolated syndactyly with fusion of the third and fourth fingers. 61
29524275 2018

Variations for Sclerosteosis 2

ClinVar genetic disease variations for Sclerosteosis 2:

6 (show top 50) (show all 210)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LRP4 NM_002334.4(LRP4):c.3508C>T (p.Arg1170Trp) SNV Pathogenic 30411 rs387906884 GRCh37: 11:46898045-46898045
GRCh38: 11:46876494-46876494
2 LRP4 NM_002334.4(LRP4):c.2866G>T (p.Glu956Ter) SNV Pathogenic 576661 rs1565785959 GRCh37: 11:46900815-46900815
GRCh38: 11:46879264-46879264
3 LRP4 NM_002334.4(LRP4):c.3557G>C (p.Trp1186Ser) SNV Pathogenic 30410 rs387906883 GRCh37: 11:46897497-46897497
GRCh38: 11:46875946-46875946
4 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5660C>G (p.Ser1887Cys) SNV Conflicting interpretations of pathogenicity 282957 rs149082597 GRCh37: 11:46880592-46880592
GRCh38: 11:46859041-46859041
5 LRP4 NM_002334.4(LRP4):c.3839A>G (p.Lys1280Arg) SNV Uncertain significance 653192 rs371205300 GRCh37: 11:46897093-46897093
GRCh38: 11:46875542-46875542
6 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5126G>C (p.Arg1709Pro) SNV Uncertain significance 657674 rs560103351 GRCh37: 11:46886699-46886699
GRCh38: 11:46865148-46865148
7 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5669A>G (p.Asp1890Gly) SNV Uncertain significance 659389 rs749482785 GRCh37: 11:46880583-46880583
GRCh38: 11:46859032-46859032
8 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.4544G>C (p.Gly1515Ala) SNV Uncertain significance 659855 rs758635404 GRCh37: 11:46894690-46894690
GRCh38: 11:46873139-46873139
9 LRP4 NM_002334.4(LRP4):c.2009C>T (p.Thr670Met) SNV Uncertain significance 660225 rs752512047 GRCh37: 11:46911578-46911578
GRCh38: 11:46890027-46890027
10 LRP4 NM_002334.4(LRP4):c.826C>T (p.Arg276Cys) SNV Uncertain significance 663838 rs557300271 GRCh37: 11:46918516-46918516
GRCh38: 11:46896965-46896965
11 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.4850G>A (p.Cys1617Tyr) SNV Uncertain significance 664077 rs1592515719 GRCh37: 11:46890252-46890252
GRCh38: 11:46868701-46868701
12 LRP4 NM_002334.4(LRP4):c.65G>T (p.Ser22Ile) SNV Uncertain significance 665829 rs777229906 GRCh37: 11:46924468-46924468
GRCh38: 11:46902917-46902917
13 LRP4 NM_002334.4(LRP4):c.3407G>A (p.Arg1136Gln) SNV Uncertain significance 281554 rs61736853 GRCh37: 11:46898146-46898146
GRCh38: 11:46876595-46876595
14 LRP4 NM_002334.4(LRP4):c.539A>G (p.Glu180Gly) SNV Uncertain significance 535802 rs201957426 GRCh37: 11:46920946-46920946
GRCh38: 11:46899395-46899395
15 LRP4 NM_002334.4(LRP4):c.1435C>T (p.Arg479Cys) SNV Uncertain significance 304888 rs143207358 GRCh37: 11:46916245-46916245
GRCh38: 11:46894694-46894694
16 LRP4 NM_002334.4(LRP4):c.2746C>T (p.Arg916Cys) SNV Uncertain significance 535801 rs147259655 GRCh37: 11:46903321-46903321
GRCh38: 11:46881770-46881770
17 LRP4 NM_002334.4(LRP4):c.1255T>G (p.Trp419Gly) SNV Uncertain significance 535800 rs1032020389 GRCh37: 11:46916771-46916771
GRCh38: 11:46895220-46895220
18 LRP4 NM_002334.4(LRP4):c.1001T>G (p.Val334Gly) SNV Uncertain significance 535799 rs767110056 GRCh37: 11:46917808-46917808
GRCh38: 11:46896257-46896257
19 LRP4 NM_002334.4(LRP4):c.1130A>G (p.Gln377Arg) SNV Uncertain significance 535798 rs139006210 GRCh37: 11:46917488-46917488
GRCh38: 11:46895937-46895937
20 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5650A>G (p.Arg1884Gly) SNV Uncertain significance 304845 rs377204138 GRCh37: 11:46880602-46880602
GRCh38: 11:46859051-46859051
21 LRP4 NM_002334.4(LRP4):c.4154A>G (p.Asn1385Ser) SNV Uncertain significance 581226 rs768733310 GRCh37: 11:46896426-46896426
GRCh38: 11:46874875-46874875
22 LRP4 NM_002334.4(LRP4):c.1175C>T (p.Thr392Met) SNV Uncertain significance 582098 rs776484311 GRCh37: 11:46917443-46917443
GRCh38: 11:46895892-46895892
23 LRP4 NM_002334.4(LRP4):c.2738G>A (p.Gly913Glu) SNV Uncertain significance 582578 rs376848284 GRCh37: 11:46903329-46903329
GRCh38: 11:46881778-46881778
24 LRP4 NM_002334.4(LRP4):c.605G>A (p.Arg202His) SNV Uncertain significance 582703 rs149056824 GRCh37: 11:46920526-46920526
GRCh38: 11:46898975-46898975
25 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5414_5416AGA[1] (p.Lys1806del) Microsatellite Uncertain significance 582866 rs769465803 GRCh37: 11:46880833-46880835
GRCh38: 11:46859282-46859284
26 LRP4 NM_002334.4(LRP4):c.2626A>C (p.Thr876Pro) SNV Uncertain significance 639435 rs1592529316 GRCh37: 11:46903441-46903441
GRCh38: 11:46881890-46881890
27 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5259_5267del (p.Lys1753_Asp1756delinsAsn) Deletion Uncertain significance 639677 rs1592509652 GRCh37: 11:46884275-46884283
GRCh38: 11:46862724-46862732
28 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5101G>A (p.Asp1701Asn) SNV Uncertain significance 645722 rs1241649761 GRCh37: 11:46886724-46886724
GRCh38: 11:46865173-46865173
29 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.4928C>G (p.Pro1643Arg) SNV Uncertain significance 646002 rs767372563 GRCh37: 11:46890174-46890174
GRCh38: 11:46868623-46868623
30 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.4579C>T (p.Arg1527Cys) SNV Uncertain significance 646163 rs756059712 GRCh37: 11:46894655-46894655
GRCh38: 11:46873104-46873104
31 LRP4 NM_002334.4(LRP4):c.2980G>A (p.Val994Ile) SNV Uncertain significance 646493 rs370091369 GRCh37: 11:46900701-46900701
GRCh38: 11:46879150-46879150
32 LRP4 NM_002334.4(LRP4):c.1832G>A (p.Arg611His) SNV Uncertain significance 650564 rs140282454 GRCh37: 11:46911911-46911911
GRCh38: 11:46890360-46890360
33 LRP4 NM_002334.4(LRP4):c.968G>A (p.Arg323His) SNV Uncertain significance 304891 rs745607286 GRCh37: 11:46917841-46917841
GRCh38: 11:46896290-46896290
34 LRP4 NM_002334.4(LRP4):c.1048C>T (p.Arg350Trp) SNV Uncertain significance 651503 rs368744612 GRCh37: 11:46917761-46917761
GRCh38: 11:46896210-46896210
35 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5426T>A (p.Ile1809Asn) SNV Uncertain significance 651553 rs373162825 GRCh37: 11:46880826-46880826
GRCh38: 11:46859275-46859275
36 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5378A>C (p.Lys1793Thr) SNV Uncertain significance 651771 rs778676466 GRCh37: 11:46884164-46884164
GRCh38: 11:46862613-46862613
37 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5182A>G (p.Ile1728Val) SNV Uncertain significance 288220 rs148865136 GRCh37: 11:46886060-46886060
GRCh38: 11:46864509-46864509
38 LRP4 NM_002334.4(LRP4):c.3919C>T (p.Pro1307Ser) SNV Uncertain significance 467788 rs771126504 GRCh37: 11:46897013-46897013
GRCh38: 11:46875462-46875462
39 LRP4 NM_002334.4(LRP4):c.3255_3256delinsAC (p.Ile1086Leu) Indel Uncertain significance 467786 rs1555172311 GRCh37: 11:46898771-46898772
GRCh38: 11:46877220-46877221
40 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.4505A>C (p.Asp1502Ala) SNV Uncertain significance 467790 rs200506943 GRCh37: 11:46894729-46894729
GRCh38: 11:46873178-46873178
41 LRP4 NM_002334.4(LRP4):c.1126G>A (p.Val376Met) SNV Uncertain significance 467778 rs1243051904 GRCh37: 11:46917492-46917492
GRCh38: 11:46895941-46895941
42 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5054G>A (p.Arg1685Gln) SNV Uncertain significance 467792 rs138238230 GRCh37: 11:46889563-46889563
GRCh38: 11:46868012-46868012
43 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.4516C>T (p.Arg1506Trp) SNV Uncertain significance 567349 rs766025454 GRCh37: 11:46894718-46894718
GRCh38: 11:46873167-46873167
44 LRP4 NM_002334.4(LRP4):c.2387C>A (p.Thr796Asn) SNV Uncertain significance 567984 rs753109967 GRCh37: 11:46907913-46907913
GRCh38: 11:46886362-46886362
45 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.4990A>G (p.Met1664Val) SNV Uncertain significance 569474 rs1455143794 GRCh37: 11:46889627-46889627
GRCh38: 11:46868076-46868076
46 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.5194C>T (p.Leu1732Phe) SNV Uncertain significance 569902 rs1447336134 GRCh37: 11:46886048-46886048
GRCh38: 11:46864497-46864497
47 LRP4 NM_002334.4(LRP4):c.3830G>A (p.Arg1277His) SNV Uncertain significance 189821 rs746136135 GRCh37: 11:46897102-46897102
GRCh38: 11:46875551-46875551
48 LRP4 NM_002334.4(LRP4):c.851G>A (p.Arg284His) SNV Uncertain significance 572607 rs369307795 GRCh37: 11:46918491-46918491
GRCh38: 11:46896940-46896940
49 LRP4 NM_002334.4(LRP4):c.4144C>T (p.Pro1382Ser) SNV Uncertain significance 573237 rs765240067 GRCh37: 11:46896436-46896436
GRCh38: 11:46874885-46874885
50 LRP4 , LRP4-AS1 NM_002334.4(LRP4):c.4699A>T (p.Arg1567Trp) SNV Uncertain significance 573912 rs199747378 GRCh37: 11:46890677-46890677
GRCh38: 11:46869126-46869126

UniProtKB/Swiss-Prot genetic disease variations for Sclerosteosis 2:

72
# Symbol AA change Variation ID SNP ID
1 LRP4 p.Arg1170Trp VAR_066630 rs387906884
2 LRP4 p.Trp1186Ser VAR_066631 rs387906883

Expression for Sclerosteosis 2

Search GEO for disease gene expression data for Sclerosteosis 2.

Pathways for Sclerosteosis 2

GO Terms for Sclerosteosis 2

Cellular components related to Sclerosteosis 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neuromuscular junction GO:0031594 8.62 RAPSN LRP4

Biological processes related to Sclerosteosis 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of canonical Wnt signaling pathway GO:0090090 9.43 SOST LRP4 KREMEN1
2 limb development GO:0060173 9.33 RSPO2 LRP4 KREMEN1
3 embryonic digit morphogenesis GO:0042733 9.32 LRP5 LRP4
4 negative regulation of ossification GO:0030279 9.13 SOST LRP4 KREMEN1
5 Wnt signaling pathway GO:0016055 9.02 SOST RSPO2 LRP5 LRP4 KREMEN1

Sources for Sclerosteosis 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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