SOST1
MCID: SCL045
MIFTS: 47

Sclerosteosis 1 (SOST1)

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

Aliases & Classifications for Sclerosteosis 1

MalaCards integrated aliases for Sclerosteosis 1:

Name: Sclerosteosis 1 57 12 72 29 6 15
Sost1 57 12 72
Cortical Hyperostosis with Syndactyly 57 72
Sclerosteosis 72 70
Sost 57 72
Sclerosteosis, Type 1 39

Characteristics:

OMIM®:

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

Miscellaneous:
majority of cases in the afrikaner population of south africa
sudden death secondary to impaction of medulla oblongata
facial palsy often transient in infancy


HPO:

31
sclerosteosis 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Sclerosteosis 1

UniProtKB/Swiss-Prot : 72 Sclerosteosis 1: An autosomal recessive 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 1, also known as sost1, is related to hyperostosis and craniodiaphyseal dysplasia, and has symptoms including unspecified visual loss An important gene associated with Sclerosteosis 1 is SOST (Sclerostin), and among its related pathways/superpathways are Wnt signaling pathway and Parathyroid hormone synthesis, secretion and action. The drug Diphosphonates has been mentioned in the context of this disorder. Affiliated tissues include bone and medulla oblongata, and related phenotypes are frontal bossing and nystagmus

Disease Ontology : 12 A sclerosteosis that has material basis in homozygous mutation in the SOST gene on chromosome 17q21.

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). (269500) (Updated 05-Apr-2021)

Related Diseases for Sclerosteosis 1

Diseases in the Sclerosteosis family:

Sclerosteosis 1 Sclerosteosis 2

Diseases related to Sclerosteosis 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 107)
# Related Disease Score Top Affiliating Genes
1 hyperostosis 31.6 SOST LRP5 LRP4
2 craniodiaphyseal dysplasia 31.6 SOST LRP5 DKK1
3 facial paralysis 31.4 SOST LRP5
4 autosomal recessive hypophosphatemic rickets 31.4 SOST DMP1
5 facial nerve disease 31.4 SOST LRP5
6 spondylitis 31.4 SOST DKK1
7 sclerosteosis 2 31.4 SOST LRP5 LRP4
8 endosteal hyperostosis, autosomal dominant 31.4 SP7 SOST LRP5
9 renal osteodystrophy 31.3 SOST BGLAP
10 kummell's disease 31.3 SOST DKK1
11 van buchem disease 31.3 SP7 SOST LRP5 LRP4 DKK1 BGLAP
12 exostosis 31.2 SOST BGLAP
13 mccune-albright syndrome 31.2 SOST LRP5 BGLAP
14 sclerosteosis 31.1 SP7 SOST LRP5 LRP4 DKK1 BGLAP
15 osteoporosis-pseudoglioma syndrome 31.1 SOST LRP5 DKK1
16 cenani-lenz syndactyly syndrome 31.1 SOST LRP5 LRP4
17 paget's disease of bone 31.1 SOST DKK1 BGLAP
18 ankylosis 31.1 SP7 SOST BGLAP
19 parathyroid gland disease 31.0 SOST BGLAP
20 craniometaphyseal dysplasia, autosomal dominant 31.0 SP7 SOST BGLAP
21 hypophosphatemic rickets, x-linked dominant 31.0 SOST DMP1 BGLAP
22 bone development disease 31.0 SP7 SOST BGLAP
23 bone disease 30.8 SP7 SOST LRP5 DKK1 BGLAP
24 ischemic bone disease 30.6 SP7 SOST DKK1 BGLAP
25 osteoporosis 30.5 SP7 SOST LRP5 DMP1 DKK1 BGLAP
26 bone resorption disease 30.5 SP7 SOST LRP5 DKK1 BGLAP
27 brittle bone disorder 30.4 SP7 SOST LRP5 DKK1 BGLAP
28 osteoporosis, juvenile 30.3 SP7 SOST LRP5 DKK1 BGLAP
29 bone remodeling disease 30.3 SP7 SOST LRP5 DKK1 BGLAP
30 odontochondrodysplasia 30.3 SP7 SOST LRP5 DKK1 BGLAP
31 glucocorticoid-induced osteoporosis 29.4 DKK1 BGLAP
32 craniodiaphyseal dysplasia, autosomal dominant 11.3
33 sost-related sclerosing bone dysplasias 11.2
34 type 2 diabetes mellitus 11.0
35 primary hyperparathyroidism 11.0
36 chronic kidney disease 11.0
37 diabetes mellitus 11.0
38 chromosome 2q35 duplication syndrome 10.9
39 osteogenesis imperfecta, type vi 10.9
40 pycnodysostosis 10.8
41 connective tissue disease 10.8
42 overgrowth syndrome 10.4
43 bone mineral density quantitative trait locus 8 10.3
44 bone mineral density quantitative trait locus 15 10.3
45 primary bone dysplasia with increased bone density 10.2
46 osteoarthritis 10.1
47 branchiootic syndrome 1 10.1
48 osteogenic sarcoma 10.0
49 chiari malformation type i 10.0 LRP4 DKK1
50 chiari malformation 10.0 LRP4 DKK1

Graphical network of the top 20 diseases related to Sclerosteosis 1:



Diseases related to Sclerosteosis 1

Symptoms & Phenotypes for Sclerosteosis 1

Human phenotypes related to Sclerosteosis 1:

31 (show all 31)
# Description HPO Frequency HPO Source Accession
1 frontal bossing 31 HP:0002007
2 nystagmus 31 HP:0000639
3 facial palsy 31 HP:0010628
4 hearing impairment 31 HP:0000365
5 depressed nasal bridge 31 HP:0005280
6 hypertelorism 31 HP:0000316
7 mandibular prognathia 31 HP:0000303
8 dental malocclusion 31 HP:0000689
9 increased intracranial pressure 31 HP:0002516
10 wide nasal bridge 31 HP:0000431
11 optic atrophy 31 HP:0000648
12 cognitive impairment 31 HP:0100543
13 broad ribs 31 HP:0000885
14 proptosis 31 HP:0000520
15 malar flattening 31 HP:0000272
16 abnormality of pelvic girdle bone morphology 31 HP:0002644
17 headache 31 HP:0002315
18 midface retrusion 31 HP:0011800
19 nail dysplasia 31 HP:0002164
20 deviation of finger 31 HP:0004097
21 constriction of peripheral visual field 31 HP:0001133
22 visual loss 31 HP:0000572
23 sclerotic vertebral endplates 31 HP:0004576
24 2-3 finger syndactyly 31 HP:0001233
25 esotropia 31 HP:0000565
26 broad clavicles 31 HP:0000916
27 overgrowth 31 HP:0001548
28 sudden death 31 HP:0001699
29 sclerotic scapulae 31 HP:0001474
30 cortically dense long tubular bones 31 HP:0006415
31 facial palsy secondary to cranial hyperostosis 31 HP:0007285

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
nystagmus
hypertelorism
optic atrophy
proptosis
vision loss
more
Neurologic Central Nervous System:
increased intracranial pressure
facial palsy, secondary to cranial hyperostosis
chronic headaches
intellectual impairment

Skeletal Spine:
sclerotic vertebral endplates
sclerotic pedicles

Growth Other:
overgrowth

Skeletal Limbs:
cortically dense long tubular bones
lack of diaphyseal modeling

Growth Height:
gigantism, mild-moderate

Head And Neck Nose:
broad, flat nasal root

Skeletal Pelvis:
sclerotic pelvis

Head And Neck Teeth:
dental malocclusion

Skin Nails Hair Nails:
nail dysplasia

Skeletal Hands:
2-3 finger syndactyly
deviation of terminal phalanges

Chest Ribs Sternum Clavicles And Scapulae:
sclerotic scapulae
broad, dense clavicles
broad, dense ribs

Head And Neck Face:
midface hypoplasia
prognathism
frontal prominence

Head And Neck Ears:
deafness, secondary to cranial hyperostosis

Skeletal Skull:
prominent, asymmetric mandible
cranial hyperostosis (onset in infancy)
occlusion of cranial foramina

Clinical features from OMIM®:

269500 (Updated 05-Apr-2021)

UMLS symptoms related to Sclerosteosis 1:


unspecified visual loss

MGI Mouse Phenotypes related to Sclerosteosis 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.97 BGLAP CHRD DKK1 DMP1 LRP4 LRP5
2 homeostasis/metabolism MP:0005376 9.86 BGLAP CHRD DKK1 DMP1 LRP4 LRP5
3 craniofacial MP:0005382 9.72 CHRD DKK1 DMP1 LRP4 LRP5
4 limbs/digits/tail MP:0005371 9.63 DKK1 DMP1 LRP4 LRP5 SOST SP7
5 respiratory system MP:0005388 9.35 CHRD DAND5 DKK1 LRP4 SP7
6 skeleton MP:0005390 9.23 BGLAP CHRD DKK1 DMP1 LRP4 LRP5

Drugs & Therapeutics for Sclerosteosis 1

Drugs for Sclerosteosis 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Diphosphonates

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Assessment of 4 Bone Turnover Markers (C-terminal Telopeptides of Type I Collagene (CTX), Amino-terminal Telopeptide of Type 1 Collagen (NTX), Dickkopf-1 (DKK-1) and Sclerostin (SOST)) in Multiple Myeloma Patients Treated With Intravenous Bisphosphonate Recruiting NCT04111809

Search NIH Clinical Center for Sclerosteosis 1

Genetic Tests for Sclerosteosis 1

Genetic tests related to Sclerosteosis 1:

# Genetic test Affiliating Genes
1 Sclerosteosis 1 29 SOST

Anatomical Context for Sclerosteosis 1

MalaCards organs/tissues related to Sclerosteosis 1:

40
Bone, Medulla Oblongata

Publications for Sclerosteosis 1

Articles related to Sclerosteosis 1:

(show all 22)
# Title Authors PMID Year
1
Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. 57 6
11179006 2001
2
Sclerosteosis: report of a case in a black African man. 6 57
9712543 1998
3
The natural history of sclerosteosis. 57
12694228 2003
4
Dental and oral manifestations of sclerosteosis. 57
11570544 2001
5
Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). 6
11181578 2001
6
Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21. 57
10330353 1999
7
Van Buchem disease (hyperostosis corticalis generalisata) maps to chromosome 17q12-q21. 57
9463328 1998
8
Sclerosteosis. 57
3351908 1988
9
The syndromic status of sclerosteosis and van Buchem disease. 57
6323069 1984
10
Sclerosteosis: neurogenetic and pathophysiologic analysis of an American kinship. 57
6681869 1983
11
Sclerosteosis involving the temporal bone: clinical and radiologic aspects. 57
6673595 1983
12
Sclerosteosis in old age. 57
7404164 1980
13
Endocrine function in sclerosteosis. 57
225834 1979
14
Sclerosteosis - an autosomal recessive disorder. 57
187366 1977
15
The radiology of sclerosteosis. 57
188507 1976
16
The clinical features of sclerosteosis. A review of the manifestations in twenty-five affected individuals. 57
1259284 1976
17
Sclerosteosis. A case report. 57
163261 1975
18
The neurologic manifestations of osteopetrosis (Albers-Schonberg's disease). 57
14033572 1963
19
Osteopetrosis with syndactyly; a morphological variant of Albers-Schönberg's disease. 57
13539104 1958
20
Albers-Schönberg disease; a family survey. 57
20274620 1946
21
Effects of dihydrotestosterone on osteoblast activity in curdlan-administered SKG mice and osteoprogenitor cells in patients with ankylosing spondylitis. 61
32448352 2020
22
Sclerosteosis: Report of type 1 or 2 in three Indian Tamil families and literature review. 61
30077757 2018

Variations for Sclerosteosis 1

ClinVar genetic disease variations for Sclerosteosis 1:

6 (show all 41)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SOST SOST, IVS1DS, A-T, +3 AND/OR IVS1AS, A-C, -67 SNV Pathogenic 4784 GRCh37:
GRCh38:
2 SOST NM_025237.3(SOST):c.70C>T (p.Gln24Ter) SNV Pathogenic 4783 rs387906320 GRCh37: 17:41836040-41836040
GRCh38: 17:43758672-43758672
3 SOST NM_025237.3(SOST):c.372G>A (p.Trp124Ter) SNV Pathogenic 4785 rs104894644 GRCh37: 17:41832980-41832980
GRCh38: 17:43755612-43755612
4 SOST NM_025237.3(SOST):c.376C>T (p.Arg126Ter) SNV Pathogenic 4786 rs104894645 GRCh37: 17:41832976-41832976
GRCh38: 17:43755608-43755608
5 SOST NM_025237.3(SOST):c.461C>T (p.Pro154Leu) SNV Uncertain significance 323438 rs760883576 GRCh37: 17:41832891-41832891
GRCh38: 17:43755523-43755523
6 SOST NM_025237.3(SOST):c.*314C>G SNV Uncertain significance 323435 rs765892196 GRCh37: 17:41832396-41832396
GRCh38: 17:43755028-43755028
7 SOST NM_025237.3(SOST):c.*140A>G SNV Uncertain significance 323436 rs886052979 GRCh37: 17:41832570-41832570
GRCh38: 17:43755202-43755202
8 SOST NM_025237.3(SOST):c.328G>A (p.Gly110Ser) SNV Uncertain significance 323439 rs886052981 GRCh37: 17:41833024-41833024
GRCh38: 17:43755656-43755656
9 SOST NM_025237.3(SOST):c.*1498G>A SNV Uncertain significance 888823 GRCh37: 17:41831212-41831212
GRCh38: 17:43753844-43753844
10 SOST NM_025237.3(SOST):c.448G>A (p.Gly150Ser) SNV Uncertain significance 888898 GRCh37: 17:41832904-41832904
GRCh38: 17:43755536-43755536
11 SOST NM_025237.3(SOST):c.303C>T (p.Thr101=) SNV Uncertain significance 888899 GRCh37: 17:41833049-41833049
GRCh38: 17:43755681-43755681
12 SOST NM_025237.3(SOST):c.177G>A (p.Ala59=) SNV Uncertain significance 764169 rs201706408 GRCh37: 17:41835933-41835933
GRCh38: 17:43758565-43758565
13 SOST NM_025237.3(SOST):c.143C>T (p.Pro48Leu) SNV Uncertain significance 888900 GRCh37: 17:41835967-41835967
GRCh38: 17:43758599-43758599
14 SOST NM_025237.3(SOST):c.114C>T (p.Pro38=) SNV Uncertain significance 888901 GRCh37: 17:41835996-41835996
GRCh38: 17:43758628-43758628
15 SOST NM_025237.3(SOST):c.*1402T>G SNV Uncertain significance 890522 GRCh37: 17:41831308-41831308
GRCh38: 17:43753940-43753940
16 SOST NM_025237.3(SOST):c.*1529T>C SNV Uncertain significance 323425 rs182899606 GRCh37: 17:41831181-41831181
GRCh38: 17:43753813-43753813
17 SOST NM_025237.3(SOST):c.*1176A>G SNV Uncertain significance 323431 rs886052978 GRCh37: 17:41831534-41831534
GRCh38: 17:43754166-43754166
18 SOST NM_025237.3(SOST):c.*1363C>T SNV Uncertain significance 890524 GRCh37: 17:41831347-41831347
GRCh38: 17:43753979-43753979
19 SOST NM_025237.3(SOST):c.*1267C>G SNV Uncertain significance 890525 GRCh37: 17:41831443-41831443
GRCh38: 17:43754075-43754075
20 SOST NM_025237.3(SOST):c.*1063C>T SNV Uncertain significance 890526 GRCh37: 17:41831647-41831647
GRCh38: 17:43754279-43754279
21 SOST NM_025237.3(SOST):c.*902T>C SNV Uncertain significance 891082 GRCh37: 17:41831808-41831808
GRCh38: 17:43754440-43754440
22 SOST NM_025237.3(SOST):c.*883A>T SNV Uncertain significance 891083 GRCh37: 17:41831827-41831827
GRCh38: 17:43754459-43754459
23 SOST NM_025237.3(SOST):c.*689T>C SNV Uncertain significance 891084 GRCh37: 17:41832021-41832021
GRCh38: 17:43754653-43754653
24 SOST NM_025237.3(SOST):c.*666T>C SNV Uncertain significance 891085 GRCh37: 17:41832044-41832044
GRCh38: 17:43754676-43754676
25 SOST NM_025237.3(SOST):c.*569G>T SNV Uncertain significance 891086 GRCh37: 17:41832141-41832141
GRCh38: 17:43754773-43754773
26 SOST NM_025237.3(SOST):c.153G>A (p.Glu51=) SNV Uncertain significance 323440 rs150640883 GRCh37: 17:41835957-41835957
GRCh38: 17:43758589-43758589
27 SOST NM_025237.3(SOST):c.533A>G (p.Glu178Gly) SNV Uncertain significance 323437 rs886052980 GRCh37: 17:41832819-41832819
GRCh38: 17:43755451-43755451
28 SOST NM_025237.3(SOST):c.*219T>C SNV Uncertain significance 892298 GRCh37: 17:41832491-41832491
GRCh38: 17:43755123-43755123
29 SOST NM_025237.3(SOST):c.*203G>A SNV Uncertain significance 892299 GRCh37: 17:41832507-41832507
GRCh38: 17:43755139-43755139
30 SOST NM_025237.3(SOST):c.-10G>A SNV Likely benign 193461 rs190743758 GRCh37: 17:41836119-41836119
GRCh38: 17:43758751-43758751
31 SOST NM_025237.3(SOST):c.56G>A (p.Arg19His) SNV Likely benign 890596 GRCh37: 17:41836054-41836054
GRCh38: 17:43758686-43758686
32 SOST NM_025237.3(SOST):c.-21T>G SNV Likely benign 890597 GRCh37: 17:41836130-41836130
GRCh38: 17:43758762-43758762
33 SOST NM_025237.3(SOST):c.*1391G>C SNV Likely benign 890523 GRCh37: 17:41831319-41831319
GRCh38: 17:43753951-43753951
34 SOST NM_025237.3(SOST):c.*222A>G SNV Likely benign 892297 GRCh37: 17:41832488-41832488
GRCh38: 17:43755120-43755120
35 SOST NM_025237.3(SOST):c.*866C>T SNV Benign 323433 rs75901553 GRCh37: 17:41831844-41831844
GRCh38: 17:43754476-43754476
36 SOST NM_025237.3(SOST):c.*1004G>A SNV Benign 323432 rs17886183 GRCh37: 17:41831706-41831706
GRCh38: 17:43754338-43754338
37 SOST NM_025237.3(SOST):c.*562G>A SNV Benign 323434 rs17881518 GRCh37: 17:41832148-41832148
GRCh38: 17:43754780-43754780
38 SOST NM_025237.3(SOST):c.28G>A (p.Val10Ile) SNV Benign 323442 rs17882143 GRCh37: 17:41836082-41836082
GRCh38: 17:43758714-43758714
39 SOST NM_025237.3(SOST):c.*1394C>G SNV Benign 323428 rs75335214 GRCh37: 17:41831316-41831316
GRCh38: 17:43753948-43753948
40 SOST NM_025237.3(SOST):c.*178C>T SNV Benign 892300 GRCh37: 17:41832532-41832532
GRCh38: 17:43755164-43755164
41 SOST NM_025237.3(SOST):c.*320C>T SNV Benign 892296 GRCh37: 17:41832390-41832390
GRCh38: 17:43755022-43755022

UniProtKB/Swiss-Prot genetic disease variations for Sclerosteosis 1:

72
# Symbol AA change Variation ID SNP ID
1 SOST p.Cys167Arg VAR_063982

Expression for Sclerosteosis 1

Search GEO for disease gene expression data for Sclerosteosis 1.

Pathways for Sclerosteosis 1

GO Terms for Sclerosteosis 1

Cellular components related to Sclerosteosis 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.1 SOST DMP1 DKK1 DAND5 CHRD BGLAP

Biological processes related to Sclerosteosis 1 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of canonical Wnt signaling pathway GO:0090090 9.58 SOST LRP4 DKK1
2 response to mechanical stimulus GO:0009612 9.54 SOST BGLAP
3 bone development GO:0060348 9.52 LRP5 BGLAP
4 negative regulation of Wnt signaling pathway GO:0030178 9.51 SOST DKK1
5 negative regulation of osteoblast differentiation GO:0045668 9.49 LRP5 CHRD
6 embryonic digit morphogenesis GO:0042733 9.48 LRP5 LRP4
7 limb development GO:0060173 9.46 LRP4 DKK1
8 Wnt signaling pathway GO:0016055 9.46 SOST LRP5 LRP4 DKK1
9 biomineral tissue development GO:0031214 9.43 DMP1 BGLAP
10 ossification GO:0001503 9.43 SOST DMP1 BGLAP
11 positive regulation of mesenchymal cell proliferation GO:0002053 9.37 LRP5 CHRD
12 osteoblast development GO:0002076 9.32 LRP5 BGLAP
13 negative regulation of BMP signaling pathway GO:0030514 9.13 SOST DAND5 CHRD
14 negative regulation of ossification GO:0030279 8.8 SOST LRP4 DKK1

Sources for Sclerosteosis 1

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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