DRS2
MCID: RBN017
MIFTS: 45

Robinow Syndrome, Autosomal Dominant 2 (DRS2)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Rare diseases, Reproductive diseases, Smell/Taste diseases

Aliases & Classifications for Robinow Syndrome, Autosomal Dominant 2

MalaCards integrated aliases for Robinow Syndrome, Autosomal Dominant 2:

Name: Robinow Syndrome, Autosomal Dominant 2 56 73 29 6
Drs2 56 12 73
Autosomal Dominant Robinow Syndrome 2 12 15
Robinow Syndrome, Autosomal Dominant, Type 2 39

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth


HPO:

31
robinow syndrome, autosomal dominant 2:
Inheritance autosomal dominant inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Robinow Syndrome, Autosomal Dominant 2

OMIM : 56 Robinow syndrome is a skeletal dysplasia characterized by distinctive facial features, including midface hypoplasia, hypertelorism, a short nose, and a broad mouth, known collectively as 'fetal facies.' Additional features include mesomelic dwarfism, macrocephaly, gingival hypertrophy, dental malocclusion, genital hypoplasia, and brachydactyly (summary by Bunn et al., 2015). Additionally, increased skull bone density and appendicular osteosclerosis are present in patients with DRS2 (White et al., 2015; Bunn et al., 2015). For a discussion of genetic heterogeneity of Robinow syndrome, see RRS (268310). (616331)

MalaCards based summary : Robinow Syndrome, Autosomal Dominant 2, also known as drs2, is related to robinow syndrome, autosomal dominant 3 and autosomal dominant robinow syndrome. An important gene associated with Robinow Syndrome, Autosomal Dominant 2 is DVL1 (Dishevelled Segment Polarity Protein 1), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Cardiac conduction. Affiliated tissues include bone, eye and brain, and related phenotypes are umbilical hernia and thickened calvaria

Disease Ontology : 12 A Robinow syndrome characterized by autosomal dominant inheritance of mesomelic limb shortening, genital hypoplasia, and distinctive facial features that has material basis in heterozygous mutation in the DVL1 gene on chromosome 1p36.

UniProtKB/Swiss-Prot : 73 Robinow syndrome, autosomal dominant 2: A rare skeletal dysplasia syndrome characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, costovertebral segmentation defects, and renal anomalies.

Related Diseases for Robinow Syndrome, Autosomal Dominant 2

Graphical network of the top 20 diseases related to Robinow Syndrome, Autosomal Dominant 2:



Diseases related to Robinow Syndrome, Autosomal Dominant 2

Symptoms & Phenotypes for Robinow Syndrome, Autosomal Dominant 2

Human phenotypes related to Robinow Syndrome, Autosomal Dominant 2:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 umbilical hernia 31 occasional (7.5%) HP:0001537
2 thickened calvaria 31 occasional (7.5%) HP:0002684
3 short stature 31 occasional (7.5%) HP:0004322
4 micrognathia 31 occasional (7.5%) HP:0000347
5 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
6 conductive hearing impairment 31 occasional (7.5%) HP:0000405
7 increased bone mineral density 31 occasional (7.5%) HP:0011001
8 mesomelia 31 occasional (7.5%) HP:0003027
9 macrocephaly 31 HP:0000256
10 hypertelorism 31 HP:0000316
11 frontal bossing 31 HP:0002007
12 clinodactyly 31 HP:0030084
13 gingival overgrowth 31 HP:0000212
14 dental malocclusion 31 HP:0000689
15 short nose 31 HP:0003196
16 brachydactyly 31 HP:0001156
17 cryptorchidism 31 HP:0000028
18 anteverted nares 31 HP:0000463
19 broad thumb 31 HP:0011304
20 midface retrusion 31 HP:0011800
21 long philtrum 31 HP:0000343
22 thin upper lip vermilion 31 HP:0000219
23 micropenis 31 HP:0000054
24 proptosis 31 HP:0000520
25 high forehead 31 HP:0000348
26 dental crowding 31 HP:0000678
27 short distal phalanx of finger 31 HP:0009882
28 triangular mouth 31 HP:0000207

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly

Head And Neck Face:
frontal bossing
long philtrum
high forehead
midface hypoplasia
micrognathia (in some patients)

Head And Neck Nose:
short nose
anteverted nares
wide, low nasal bridge

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Teeth:
dental crowding
malocclusion
dental anomalies

Growth Height:
short stature (in some patients)

Abdomen External Features:
umbilical hernia (in some patients)

Skeletal:
osteosclerosis (in some patients)

Skeletal Limbs:
mesomelia (in some patients)
undertubulated long bones (in some patients)

Head And Neck Eyes:
hypertelorism
prominent eyes

Skeletal Hands:
clinodactyly
brachydactyly
broad thumbs
hypoplastic distal phalanges

Skeletal Feet:
brachydactyly
hypoplastic distal phalanges
broad first toes

Genitourinary External Genitalia Male:
micropenis

Head And Neck Mouth:
triangular mouth
thin upper lip
gingival hyperplasia

Head And Neck Ears:
sensorineural hearing loss (in some patients)
conductive hearing loss (in some patients)
abnormal ear shape (in some patients)
abnormal ear position (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
pectus anomalies

Skeletal Skull:
thickened calvaria (in some patients)

Clinical features from OMIM:

616331

GenomeRNAi Phenotypes related to Robinow Syndrome, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased epidermal growth factor receptor (EGFR) surface abundance GR00355-A 8.8 CYTH1 DVL1 OSBP

Drugs & Therapeutics for Robinow Syndrome, Autosomal Dominant 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Comparison of Islet Cell Transplantation With Medical Therapy on the Risk of Progression of Diabetic Retinopathy and Diabetic Macular Edema Withdrawn NCT00853424 Phase 3

Search NIH Clinical Center for Robinow Syndrome, Autosomal Dominant 2

Genetic Tests for Robinow Syndrome, Autosomal Dominant 2

Genetic tests related to Robinow Syndrome, Autosomal Dominant 2:

# Genetic test Affiliating Genes
1 Robinow Syndrome, Autosomal Dominant 2 29 DVL1

Anatomical Context for Robinow Syndrome, Autosomal Dominant 2

MalaCards organs/tissues related to Robinow Syndrome, Autosomal Dominant 2:

40
Bone, Eye, Brain

Publications for Robinow Syndrome, Autosomal Dominant 2

Articles related to Robinow Syndrome, Autosomal Dominant 2:

(show top 50) (show all 60)
# Title Authors PMID Year
1
Mutations in DVL1 cause an osteosclerotic form of Robinow syndrome. 56 6
25817014 2015
2
DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome. 6 56
25817016 2015
3
An osteosclerotic form of Robinow syndrome. 6 56
25045061 2014
4
Bilateral conductive hearing impairment with hyperostosis of the temporal bone: a new finding in Robinow syndrome. 6 56
22431878 2012
5
Robinow syndrome in monozygotic twins with normal stature. 56 6
10319206 1999
6
DVL3 Alleles Resulting in a -1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome. 56
26924530 2016
7
Autosomal Dominant Robinow Syndrome 6
25577943 2015
8
Conserved mechanism of phospholipid substrate recognition by the P4-ATPase Neo1 from Saccharomyces cerevisiae. 61
31786280 2019
9
The PQ-loop protein Any1 segregates Drs2 and Neo1 functions required for viability and plasma membrane phospholipid asymmetry. 61
30824614 2019
10
Action of Arl1 GTPase and golgin Imh1 in Ypt6-independent retrograde transport from endosomes to the trans-Golgi network. 61
30726160 2019
11
Hygromycin B hypersensitive (hhy) mutants implicate an intact trans-Golgi and late endosome interface in efficient Tor1 vacuolar localization and TORC1 function. 61
27812735 2017
12
Quantitative high-content imaging identifies novel regulators of Neo1 trafficking at endosomes. 61
28404745 2017
13
C-terminus of the P4-ATPase ATP8A2 functions in protein folding and regulation of phospholipid flippase activity. 61
27932490 2017
14
The Essential Neo1 Protein from Budding Yeast Plays a Role in Establishing Aminophospholipid Asymmetry of the Plasma Membrane. 61
27235400 2016
15
Phosphatidylserine translocation at the yeast trans-Golgi network regulates protein sorting into exocytic vesicles. 61
26466678 2015
16
Plasma membrane aminoglycerolipid flippase function is required for signaling competence in the yeast mating pheromone response pathway. 61
25378585 2015
17
New examples of membrane protein expression and purification using the yeast based Pdr1-3 expression strategy. 61
25036752 2014
18
Interaction of the phospholipid flippase Drs2p with the F-box protein Rcy1p plays an important role in early endosome to trans-Golgi network vesicle transport in yeast. 61
24272750 2014
19
Auto-inhibition of Drs2p, a yeast phospholipid flippase, by its carboxyl-terminal tail. 61
24045945 2013
20
Phosphatidylserine flipping enhances membrane curvature and negative charge required for vesicular transport. 61
24019533 2013
21
Type IV P-type ATPases distinguish mono- versus diacyl phosphatidylserine using a cytofacial exit gate in the membrane domain. 61
23709217 2013
22
Two-gate mechanism for phospholipid selection and transport by type IV P-type ATPases. 61
23302692 2013
23
Identification of residues defining phospholipid flippase substrate specificity of type IV P-type ATPases. 61
22308393 2012
24
Effect of ruboxistaurin (RBX) On visual acuity decline over a 6-year period with cessation and reinstitution of therapy: results of an open-label extension of the Protein Kinase C Diabetic Retinopathy Study 2 (PKC-DRS2). 61
21386766 2011
25
Protein kinase C inhibitors in the treatment of diabetic retinopathy. Review. 61
20939796 2011
26
Coordination of Golgi functions by phosphatidylinositol 4-kinases. 61
21282087 2011
27
A putative P-type ATPase, Apt1, is involved in stress tolerance and virulence in Cryptococcus neoformans. 61
19949048 2010
28
A protein kinase network regulates the function of aminophospholipid flippases. 61
19966303 2010
29
Diabetic macular oedema and visual loss: relationship to location, severity and duration. 61
19817721 2009
30
Control of protein and sterol trafficking by antagonistic activities of a type IV P-type ATPase and oxysterol binding protein homologue. 61
19403696 2009
31
Effect of ruboxistaurin on the visual acuity decline associated with long-standing diabetic macular edema. 61
18708615 2009
32
Sustained moderate visual loss as a predictive end point for visual loss in non-proliferative diabetic retinopathy. 61
18989348 2009
33
The putative aminophospholipid translocases, DNF1 and DNF2, are not required for 7-nitrobenz-2-oxa-1,3-diazol-4-yl-phosphatidylserine flip across the plasma membrane of Saccharomyces cerevisiae. 61
18931395 2008
34
Protein kinases Fpk1p and Fpk2p are novel regulators of phospholipid asymmetry. 61
18199685 2008
35
Global screening of genes essential for growth in high-pressure and cold environments: searching for basic adaptive strategies using a yeast deletion library. 61
18245339 2008
36
A noncoding RNA in Saccharomyces cerevisiae is an RNase P substrate. 61
17379814 2007
37
Endocytic recycling in yeast is regulated by putative phospholipid translocases and the Ypt31p/32p-Rcy1p pathway. 61
17093059 2007
38
Characterization of novel genes expressed specifically in the sexual organs of the planarian Dugesia ryukyuensis. 61
17554688 2007
39
Ruboxistaurin: LY 333531. 61
17472415 2007
40
Roles for the Drs2p-Cdc50p complex in protein transport and phosphatidylserine asymmetry of the yeast plasma membrane. 61
16956384 2006
41
Lipid specific activation of the murine P4-ATPase Atp8a1 (ATPase II). 61
16618126 2006
42
Molecular interactions of yeast Neo1p, an essential member of the Drs2 family of aminophospholipid translocases, and its role in membrane trafficking within the endomembrane system. 61
15314152 2004
43
Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and relationship to in vivo function. 61
15249668 2004
44
Cdc50p, a protein required for polarized growth, associates with the Drs2p P-type ATPase implicated in phospholipid translocation in Saccharomyces cerevisiae. 61
15090616 2004
45
An essential subfamily of Drs2p-related P-type ATPases is required for protein trafficking between Golgi complex and endosomal/vacuolar system. 61
12221123 2002
46
Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo. 61
12372257 2002
47
Depth of lesion model in children and adolescents with moderate to severe traumatic brain injury: use of SPGR MRI to predict severity and outcome. 61
11181858 2001
48
Chilling tolerance in Arabidopsis involves ALA1, a member of a new family of putative aminophospholipid translocases. 61
11148289 2000
49
Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. 61
10601336 1999
50
Rapid transbilayer movement of fluorescent phospholipid analogues in the plasma membrane of endocytosis-deficient yeast cells does not require the Drs2 protein. 61
10429211 1999

Variations for Robinow Syndrome, Autosomal Dominant 2

ClinVar genetic disease variations for Robinow Syndrome, Autosomal Dominant 2:

6 (show all 17) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DVL1 NM_001330311.2(DVL1):c.1690del (p.Ser564fs)deletion Pathogenic 208047 rs797044837 1:1273381-1273381 1:1338001-1338001
2 DVL1 NM_001330311.2(DVL1):c.1651_1658delinsG (p.Pro551fs)indel Pathogenic 208050 rs797044840 1:1273413-1273420 1:1338033-1338040
3 DVL1 NM_001330311.2(DVL1):c.1645_1646delinsC (p.Phe549fs)indel Pathogenic 208043 rs797044833 1:1273425-1273426 1:1338045-1338046
4 DVL1 NM_001330311.2(DVL1):c.1637del (p.Pro546fs)deletion Pathogenic 208049 rs797044839 1:1273434-1273434 1:1338054-1338054
5 DVL1 NM_001330311.2(DVL1):c.1604del (p.Gly535fs)deletion Pathogenic 208048 rs797044838 1:1273467-1273467 1:1338087-1338087
6 DVL1 NM_001330311.2(DVL1):c.1594del (p.Trp532fs)deletion Pathogenic 208045 rs797044835 1:1273477-1273477 1:1338097-1338097
7 DVL1 NM_001330311.2(DVL1):c.1580_1592del (p.His527fs)deletion Pathogenic 208044 rs797044834 1:1273479-1273491 1:1338099-1338111
8 DVL1 NM_001330311.2(DVL1):c.1583del (p.Pro528fs)deletion Pathogenic 208046 rs797044836 1:1273488-1273488 1:1338108-1338108
9 DVL1 NM_001330311.2(DVL1):c.1598del (p.Pro533fs)deletion Pathogenic 219223 rs869025220 1:1273474-1273474 1:1338094-1338094
10 DVL1 NM_001330311.2(DVL1):c.1683_1698del (p.Ser562fs)deletion Likely pathogenic 488048 rs1553173368 1:1273373-1273388 1:1337993-1338008
11 DVL1 NM_001330311.2(DVL1):c.1698del (p.Ser567fs)deletion Likely pathogenic 488046 rs1553173367 1:1273373-1273373 1:1337993-1337993
12 DVL1 NM_001330311.2(DVL1):c.1687_1691dup (p.Ser564fs)duplication Likely pathogenic 488045 rs1553173372 1:1273380-1273384 1:1338000-1338004
13 DVL1 NM_001330311.2(DVL1):c.1571_1583del (p.Pro524fs)deletion Likely pathogenic 488047 rs1553173420 1:1273488-1273500 1:1338108-1338120
14 DVL3 NM_004423.4(DVL3):c.1617del (p.Gln539fs)deletion Likely pathogenic 488049 rs1553811652 3:183887912-183887912 3:184170124-184170124
15 FZD2 NM_001466.4(FZD2):c.1130G>A (p.Trp377Ter)SNV Likely pathogenic 488051 rs1555657045 17:42636186-42636186 17:44558818-44558818
16 FZD2 NM_001466.4(FZD2):c.1300G>A (p.Gly434Ser)SNV Likely pathogenic 488061 rs1223920489 17:42636356-42636356 17:44558988-44558988
17 FZD2 NM_001466.4(FZD2):c.1301_1302delinsTT (p.Gly434Val)indel Likely pathogenic 488052 rs1555657074 17:42636357-42636358 17:44558989-44558990

Expression for Robinow Syndrome, Autosomal Dominant 2

Search GEO for disease gene expression data for Robinow Syndrome, Autosomal Dominant 2.

Pathways for Robinow Syndrome, Autosomal Dominant 2

Pathways related to Robinow Syndrome, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.93 ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2 ATP8A1
2
Show member pathways
12.23 ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2 ATP8A1
3 11.8 FZD2 DVL3 DVL1
4
Show member pathways
11.74 FZD2 DVL3 DVL1
5 11.69 FZD2 DVL3 DVL1
6
Show member pathways
11.66 ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2 ATP8A1
7 10.81 FZD2 DVL3 DVL1
8
Show member pathways
10.53 DVL3 DVL1

GO Terms for Robinow Syndrome, Autosomal Dominant 2

Cellular components related to Robinow Syndrome, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.19 TMEM30A SNX4 SACM1L OSBP NMUR2 NEO1
2 integral component of membrane GO:0016021 10.18 TMEM30CP TMEM30A SACM1L NMUR2 NEO1 FZD2
3 plasma membrane GO:0005886 10.06 TMEM30CP TMEM30A SNX4 NMUR2 NEO1 FZD2
4 endoplasmic reticulum GO:0005783 9.92 TMEM30CP TMEM30A SACM1L OSBP ATP8B3 ATP8B1
5 Golgi apparatus GO:0005794 9.73 TMEM30CP TMEM30A SACM1L OSBP NEO1 ATP9B
6 trans-Golgi network GO:0005802 9.17 OSBP ATP9B ATP9A ATP8A2 ATP8A1 ATP11C

Biological processes related to Robinow Syndrome, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.85 NMUR2 ATP8B1 ATP8A1 ATP11C
2 positive regulation of neuron projection development GO:0010976 9.73 TMEM30A DVL1 ATP8A2
3 Wnt signaling pathway, planar cell polarity pathway GO:0060071 9.7 FZD2 DVL3 DVL1
4 lipid transport GO:0006869 9.7 TMEM30A OSBP ATP8B3 ATP8B1 ATP8A2 ATP8A1
5 canonical Wnt signaling pathway GO:0060070 9.65 FZD2 DVL3 DVL1
6 cochlea morphogenesis GO:0090103 9.57 FZD2 DVL1
7 phospholipid transport GO:0015914 9.56 TMEM30A ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2
8 regulation of cellular protein localization GO:1903827 9.54 DVL3 DVL1
9 non-canonical Wnt signaling pathway GO:0035567 9.54 FZD2 DVL3 DVL1
10 drug transmembrane transport GO:0006855 9.51 TMEM30A ATP8B1
11 beta-catenin destruction complex disassembly GO:1904886 9.5 FZD2 DVL3 DVL1
12 inner ear receptor cell development GO:0060119 9.49 FZD2 ATP8B1
13 positive regulation of neuron projection arborization GO:0150012 9.46 DVL3 DVL1
14 aminophospholipid transport GO:0015917 9.43 TMEM30A ATP8B1
15 planar cell polarity pathway involved in neural tube closure GO:0090179 9.43 FZD2 DVL3 DVL1
16 positive regulation of phospholipid translocation GO:0061092 9.4 ATP8A2 ATP8A1
17 phospholipid translocation GO:0045332 9.28 TMEM30CP TMEM30A ATP9B ATP9A ATP8B3 ATP8B1

Molecular functions related to Robinow Syndrome, Autosomal Dominant 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.7 ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2 ATP8A1
2 magnesium ion binding GO:0000287 9.23 ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2 ATP8A1
3 aminophospholipid transmembrane transporter activity GO:0015247 9.13 TMEM30A ATP8B1 ATP8A2

Sources for Robinow Syndrome, Autosomal Dominant 2

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
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43 MeSH
44 MESH via Orphanet
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48 NCI
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50 NDF-RT
53 NINDS
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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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