DRS2
MCID: RBN017
MIFTS: 46

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 sensorineural hearing impairment 31 occasional (7.5%) HP:0000407
4 short stature 31 occasional (7.5%) HP:0004322
5 micrognathia 31 occasional (7.5%) HP:0000347
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 gingival overgrowth 31 HP:0000212
10 hypertelorism 31 HP:0000316
11 macrocephaly 31 HP:0000256
12 dental malocclusion 31 HP:0000689
13 short nose 31 HP:0003196
14 anteverted nares 31 HP:0000463
15 broad thumb 31 HP:0011304
16 frontal bossing 31 HP:0002007
17 cryptorchidism 31 HP:0000028
18 dental crowding 31 HP:0000678
19 brachydactyly 31 HP:0001156
20 micropenis 31 HP:0000054
21 thin upper lip vermilion 31 HP:0000219
22 long philtrum 31 HP:0000343
23 proptosis 31 HP:0000520
24 high forehead 31 HP:0000348
25 short distal phalanx of finger 31 HP:0009882
26 midface retrusion 31 HP:0011800
27 clinodactyly 31 HP:0030084
28 triangular mouth 31 HP:0000207

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
prominent eyes

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

Genitourinary Internal Genitalia Male:
cryptorchidism

Skeletal Hands:
brachydactyly
clinodactyly
broad thumbs
hypoplastic distal phalanges

Genitourinary External Genitalia Male:
micropenis

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 Head:
macrocephaly

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

Head And Neck Teeth:
dental crowding
malocclusion
dental anomalies

Skeletal Feet:
brachydactyly
hypoplastic distal phalanges
broad first toes

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

MGI Mouse Phenotypes related to Robinow Syndrome, Autosomal Dominant 2:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.32 ATP8A2 ATP8B1 CYTH1 DVL1 DVL3 FZD2

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 61)
# 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. 56 6
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. 56 6
22431878 2012
5
Robinow syndrome in monozygotic twins with normal stature. 6 56
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
Yeast synaptobrevin, Snc1, engages distinct routes of postendocytic recycling mediated by a sorting nexin, Rcy1-COPI, and retromer. 61
32074001 2020
9
Conserved mechanism of phospholipid substrate recognition by the P4-ATPase Neo1 from Saccharomyces cerevisiae. 61
31786280 2020
10
The PQ-loop protein Any1 segregates Drs2 and Neo1 functions required for viability and plasma membrane phospholipid asymmetry. 61
30824614 2019
11
Action of Arl1 GTPase and golgin Imh1 in Ypt6-independent retrograde transport from endosomes to the trans-Golgi network. 61
30726160 2019
12
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
13
Quantitative high-content imaging identifies novel regulators of Neo1 trafficking at endosomes. 61
28404745 2017
14
C-terminus of the P4-ATPase ATP8A2 functions in protein folding and regulation of phospholipid flippase activity. 61
27932490 2017
15
The Essential Neo1 Protein from Budding Yeast Plays a Role in Establishing Aminophospholipid Asymmetry of the Plasma Membrane. 61
27235400 2016
16
Phosphatidylserine translocation at the yeast trans-Golgi network regulates protein sorting into exocytic vesicles. 61
26466678 2015
17
Plasma membrane aminoglycerolipid flippase function is required for signaling competence in the yeast mating pheromone response pathway. 61
25378585 2015
18
New examples of membrane protein expression and purification using the yeast based Pdr1-3 expression strategy. 61
25036752 2014
19
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
20
Auto-inhibition of Drs2p, a yeast phospholipid flippase, by its carboxyl-terminal tail. 61
24045945 2013
21
Phosphatidylserine flipping enhances membrane curvature and negative charge required for vesicular transport. 61
24019533 2013
22
Type IV P-type ATPases distinguish mono- versus diacyl phosphatidylserine using a cytofacial exit gate in the membrane domain. 61
23709217 2013
23
Two-gate mechanism for phospholipid selection and transport by type IV P-type ATPases. 61
23302692 2013
24
Identification of residues defining phospholipid flippase substrate specificity of type IV P-type ATPases. 61
22308393 2012
25
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
26
Protein kinase C inhibitors in the treatment of diabetic retinopathy. Review. 61
20939796 2011
27
Coordination of Golgi functions by phosphatidylinositol 4-kinases. 61
21282087 2011
28
A protein kinase network regulates the function of aminophospholipid flippases. 61
19966303 2010
29
A putative P-type ATPase, Apt1, is involved in stress tolerance and virulence in Cryptococcus neoformans. 61
19949048 2010
30
Diabetic macular oedema and visual loss: relationship to location, severity and duration. 61
19817721 2009
31
Control of protein and sterol trafficking by antagonistic activities of a type IV P-type ATPase and oxysterol binding protein homologue. 61
19403696 2009
32
Effect of ruboxistaurin on the visual acuity decline associated with long-standing diabetic macular edema. 61
18708615 2009
33
Sustained moderate visual loss as a predictive end point for visual loss in non-proliferative diabetic retinopathy. 61
18989348 2009
34
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
35
Protein kinases Fpk1p and Fpk2p are novel regulators of phospholipid asymmetry. 61
18199685 2008
36
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
37
A noncoding RNA in Saccharomyces cerevisiae is an RNase P substrate. 61
17379814 2007
38
Endocytic recycling in yeast is regulated by putative phospholipid translocases and the Ypt31p/32p-Rcy1p pathway. 61
17093059 2007
39
Ruboxistaurin: LY 333531. 61
17472415 2007
40
Characterization of novel genes expressed specifically in the sexual organs of the planarian Dugesia ryukyuensis. 61
17554688 2007
41
Roles for the Drs2p-Cdc50p complex in protein transport and phosphatidylserine asymmetry of the yeast plasma membrane. 61
16956384 2006
42
Lipid specific activation of the murine P4-ATPase Atp8a1 (ATPase II). 61
16618126 2006
43
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
44
Drs2p-coupled aminophospholipid translocase activity in yeast Golgi membranes and relationship to in vivo function. 61
15249668 2004
45
Cdc50p, a protein required for polarized growth, associates with the Drs2p P-type ATPase implicated in phospholipid translocation in Saccharomyces cerevisiae. 61
15090616 2004
46
Drs2p-dependent formation of exocytic clathrin-coated vesicles in vivo. 61
12372257 2002
47
An essential subfamily of Drs2p-related P-type ATPases is required for protein trafficking between Golgi complex and endosomal/vacuolar system. 61
12221123 2002
48
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
49
Chilling tolerance in Arabidopsis involves ALA1, a member of a new family of putative aminophospholipid translocases. 61
11148289 2000
50
Role for Drs2p, a P-type ATPase and potential aminophospholipid translocase, in yeast late Golgi function. 61
10601336 1999

Variations for Robinow Syndrome, Autosomal Dominant 2

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

6 (show all 21) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 DVL1 NM_001330311.2(DVL1):c.1547del (p.Thr516fs)deletion Pathogenic 807594 1:1273524-1273524 1:1338144-1338144
2 DVL1 NM_001330311.2(DVL1):c.1690del (p.Ser564fs)deletion Pathogenic 208047 rs797044837 1:1273381-1273381 1:1338001-1338001
3 DVL1 NM_001330311.2(DVL1):c.1651_1658delinsG (p.Pro551fs)indel Pathogenic 208050 rs797044840 1:1273413-1273420 1:1338033-1338040
4 DVL1 NM_001330311.2(DVL1):c.1645_1646delinsC (p.Phe549fs)indel Pathogenic 208043 rs797044833 1:1273425-1273426 1:1338045-1338046
5 DVL1 NM_001330311.2(DVL1):c.1637del (p.Pro546fs)deletion Pathogenic 208049 rs797044839 1:1273434-1273434 1:1338054-1338054
6 DVL1 NM_001330311.2(DVL1):c.1604del (p.Gly535fs)deletion Pathogenic 208048 rs797044838 1:1273467-1273467 1:1338087-1338087
7 DVL1 NM_001330311.2(DVL1):c.1594del (p.Trp532fs)deletion Pathogenic 208045 rs797044835 1:1273477-1273477 1:1338097-1338097
8 DVL1 NM_001330311.2(DVL1):c.1580_1592del (p.His527fs)deletion Pathogenic 208044 rs797044834 1:1273479-1273491 1:1338099-1338111
9 DVL1 NM_001330311.2(DVL1):c.1583del (p.Pro528fs)deletion Pathogenic 208046 rs797044836 1:1273488-1273488 1:1338108-1338108
10 DVL1 NM_001330311.2(DVL1):c.1598del (p.Pro533fs)deletion Pathogenic 219223 rs869025220 1:1273473-1273473 1:1338093-1338093
11 FZD2 NM_001466.4(FZD2):c.1644G>A (p.Trp548Ter)SNV Pathogenic 617609 rs1568105666 17:42636700-42636700 17:44559332-44559332
12 DVL1 NM_001330311.2(DVL1):c.1683_1698del (p.Ser562fs)deletion Likely pathogenic 488048 rs1553173368 1:1273373-1273388 1:1337993-1338008
13 DVL1 NM_001330311.2(DVL1):c.1698del (p.Ser567fs)deletion Likely pathogenic 488046 rs1553173367 1:1273373-1273373 1:1337993-1337993
14 DVL1 NM_001330311.2(DVL1):c.1687_1691dup (p.Ser564fs)duplication Likely pathogenic 488045 rs1553173372 1:1273379-1273380 1:1337999-1338000
15 DVL1 NM_001330311.2(DVL1):c.1571_1583del (p.Pro524fs)deletion Likely pathogenic 488047 rs1553173420 1:1273488-1273500 1:1338108-1338120
16 DVL3 NM_004423.4(DVL3):c.1617del (p.Gln539fs)deletion Likely pathogenic 488049 rs1553811652 3:183887912-183887912 3:184170124-184170124
17 FZD2 NM_001466.4(FZD2):c.1130G>A (p.Trp377Ter)SNV Likely pathogenic 488051 rs1555657045 17:42636186-42636186 17:44558818-44558818
18 FZD2 NM_001466.4(FZD2):c.1300G>A (p.Gly434Ser)SNV Likely pathogenic 488061 rs1223920489 17:42636356-42636356 17:44558988-44558988
19 FZD2 NM_001466.4(FZD2):c.1301_1302delinsTT (p.Gly434Val)indel Likely pathogenic 488052 rs1555657074 17:42636357-42636358 17:44558989-44558990
20 DVL1 NM_001330311.2(DVL1):c.737C>T (p.Ser246Phe)SNV Uncertain significance 692090 1:1275659-1275659 1:1340279-1340279
21 DVL1 NM_001330311.2(DVL1):c.1502G>C (p.Cys501Ser)SNV Likely benign 749017 1:1273654-1273654 1:1338274-1338274

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 11.74 FZD2 DVL3 DVL1
5
Show member pathways
11.66 ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2 ATP8A1
6 11.45 FZD2 DVL3 DVL1
7 10.81 FZD2 DVL3 DVL1
8
Show member pathways
10.57 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 10.21 VTI1B TMEM30A SNX4 SACM1L OSBP NMUR2
2 integral component of membrane GO:0016021 10.13 VTI1B TMEM30A SACM1L NMUR2 NEO1 FZD2
3 plasma membrane GO:0005886 10.06 TMEM30A SNX4 OSBP NMUR2 NEO1 FZD2
4 endoplasmic reticulum GO:0005783 9.91 TMEM30A SACM1L OSBP ATP8B3 ATP8B1 ATP8A1
5 perinuclear region of cytoplasm GO:0048471 9.85 VTI1B OSBP ATP9B ATP9A ARF1
6 endosome GO:0005768 9.83 VTI1B SNX4 ATP9B ATP9A ATP8A2
7 Golgi apparatus GO:0005794 9.73 VTI1B TMEM30A SACM1L OSBP NEO1 ATP9B
8 recycling endosome GO:0055037 9.58 VTI1B ATP9A ATP11C
9 trans-Golgi network GO:0005802 9.28 OSBP ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2

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

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of neuron projection development GO:0010976 9.72 TMEM30A DVL1 ATP8A2
2 Wnt signaling pathway, planar cell polarity pathway GO:0060071 9.7 FZD2 DVL3 DVL1
3 lipid transport GO:0006869 9.7 TMEM30A OSBP ATP8B3 ATP8B1 ATP8A2 ATP8A1
4 canonical Wnt signaling pathway GO:0060070 9.67 FZD2 DVL3 DVL1
5 cochlea morphogenesis GO:0090103 9.56 FZD2 DVL1
6 phospholipid translocation GO:0045332 9.56 TMEM30A ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2
7 regulation of cellular protein localization GO:1903827 9.54 DVL3 DVL1
8 non-canonical Wnt signaling pathway GO:0035567 9.54 FZD2 DVL3 DVL1
9 inner ear receptor cell development GO:0060119 9.51 FZD2 ATP8B1
10 beta-catenin destruction complex disassembly GO:1904886 9.5 FZD2 DVL3 DVL1
11 positive regulation of neuron projection arborization GO:0150012 9.48 DVL3 DVL1
12 aminophospholipid transport GO:0015917 9.46 TMEM30A ATP8B1
13 drug transmembrane transport GO:0006855 9.43 TMEM30A ATP8B1
14 planar cell polarity pathway involved in neural tube closure GO:0090179 9.43 FZD2 DVL3 DVL1
15 positive regulation of phospholipid translocation GO:0061092 9.4 ATP8A2 ATP8A1
16 phospholipid transport GO:0015914 9.23 TMEM30A ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2

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 9.8 ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2 ATP8A1
2 nucleotide binding GO:0000166 9.76 ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2 ATP8A1
3 magnesium ion binding GO:0000287 9.23 ATP9B ATP9A ATP8B3 ATP8B1 ATP8A2 ATP8A1
4 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
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
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
Content
Loading form....