ARCS2
MCID: ART063
MIFTS: 32

Arthrogryposis, Renal Dysfunction, and Cholestasis 2 (ARCS2)

Categories: Fetal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Rare diseases, Skin diseases

Aliases & Classifications for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

MalaCards integrated aliases for Arthrogryposis, Renal Dysfunction, and Cholestasis 2:

Name: Arthrogryposis, Renal Dysfunction, and Cholestasis 2 57 12 29 13 6 15 39 70
Arcs2 57 12 72
Arthrogryposis, Renal Dysfunction and Cholestasis Syndrome 2 72
Arthrogryposis Renal Dysfunction and Cholestasis 2 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
death in infancy, usually from sepsis, dehydration, or acidosis


HPO:

31
arthrogryposis, renal dysfunction, and cholestasis 2:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

UniProtKB/Swiss-Prot : 72 Arthrogryposis, renal dysfunction and cholestasis syndrome 2: A multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase activity. Platelet dysfunction is common.

MalaCards based summary : Arthrogryposis, Renal Dysfunction, and Cholestasis 2, also known as arcs2, is related to cherubism and arthrogryposis, renal dysfunction, and cholestasis 1, and has symptoms including icterus An important gene associated with Arthrogryposis, Renal Dysfunction, and Cholestasis 2 is VIPAS39 (VPS33B Interacting Protein, Apical-Basolateral Polarity Regulator, Spe-39 Homolog), and among its related pathways/superpathways are Deubiquitination and Telomere Extension by Telomerase. Affiliated tissues include liver, and related phenotypes are nephrogenic diabetes insipidus and lissencephaly

Disease Ontology : 12 An arthrogryposis, renal dysfunction, and cholestasis that has material basis in homozygous or compound heterozygous mutation in VIPAS39 on 14q24.3.

More information from OMIM: 613404 PS208085

Related Diseases for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Diseases in the Arthrogryposis, Renal Dysfunction, and Cholestasis 1 family:

Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Diseases related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cherubism 9.1 TNKS2 TNKS SH3BP2 BABAM1
2 arthrogryposis, renal dysfunction, and cholestasis 1 8.3 VIPAS39 USP25 TNKS2 TNKS SH3BP2 LNPEP

Symptoms & Phenotypes for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Human phenotypes related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 nephrogenic diabetes insipidus 31 occasional (7.5%) HP:0009806
2 lissencephaly 31 occasional (7.5%) HP:0001339
3 failure to thrive 31 HP:0001508
4 global developmental delay 31 HP:0001263
5 hip dysplasia 31 HP:0001385
6 microcephaly 31 HP:0000252
7 ichthyosis 31 HP:0008064
8 nephropathy 31 HP:0000112
9 low-set ears 31 HP:0000369
10 elevated hepatic transaminase 31 HP:0002910
11 cholestatic liver disease 31 HP:0002611
12 jaundice 31 HP:0000952
13 nephrocalcinosis 31 HP:0000121
14 ventricular septal defect 31 HP:0001629
15 arthrogryposis multiplex congenita 31 HP:0002804
16 sloping forehead 31 HP:0000340
17 generalized hypotonia 31 HP:0001290
18 conjugated hyperbilirubinemia 31 HP:0002908
19 renal tubular acidosis 31 HP:0001947
20 talipes calcaneovalgus 31 HP:0001884
21 right ventricular hypertrophy 31 HP:0001667
22 giant cell hepatitis 31 HP:0200084

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive

Skeletal Pelvis:
hip dysplasia

Skin Nails Hair Skin:
ichthyosis
jaundice

Head And Neck Ears:
low-set ears

Skeletal:
arthrogryposis multiplex congenita
fractures at birth

Metabolic Features:
metabolic acidosis

Skeletal Feet:
talipes calcaneovalgus

Hematology:
severe bleeding after biopsies (uncommon)

Neurologic Central Nervous System:
global developmental delay
hypotonia
lissencephaly (reported in 1 patient)

Head And Neck Head:
microcephaly

Genitourinary Kidneys:
nephropathy
nephrocalcinosis
renal tubular acidosis
fanconi syndrome
nephrogenic diabetes insipidus (less common)
more
Abdomen Liver:
cholestatic liver disease
giant cell hepatitis
bile duct abnormalities (paucity, proliferation)
pigmentary deposits
portal tract fibrosis

Head And Neck Face:
sloping forehead

Laboratory Abnormalities:
conjugated hyperbilirubinemia
abnormal liver function tests

Cardiovascular Heart:
ventricular septal defects
atrial septal defects
structural cardiac defects (uncommon)
persistent foramen ovale
right ventricular hypertrophy (report in 2 sibs)

Immunology:
recurrent febrile illnesses
b and t cell defects (reported in 2 sibs)

Clinical features from OMIM®:

613404 (Updated 20-May-2021)

UMLS symptoms related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2:


icterus

Drugs & Therapeutics for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Search Clinical Trials , NIH Clinical Center for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Genetic Tests for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Genetic tests related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2:

# Genetic test Affiliating Genes
1 Arthrogryposis, Renal Dysfunction, and Cholestasis 2 29 VIPAS39

Anatomical Context for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

MalaCards organs/tissues related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2:

40
Liver

Publications for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Articles related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2:

# Title Authors PMID Year
1
Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization. 6 57
20190753 2010

Variations for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

ClinVar genetic disease variations for Arthrogryposis, Renal Dysfunction, and Cholestasis 2:

6 (show all 13)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 VIPAS39 NM_022067.4(VIPAS39):c.535C>T (p.Gln179Ter) SNV Pathogenic 111 rs267607173 GRCh37: 14:77910654-77910654
GRCh38: 14:77444311-77444311
2 VIPAS39 NM_022067.4(VIPAS39):c.749_753del (p.Thr250fs) Deletion Pathogenic 112 rs794726653 GRCh37: 14:77907418-77907422
GRCh38: 14:77441075-77441079
3 VIPAS39 NM_022067.4(VIPAS39):c.658C>T (p.Arg220Ter) SNV Pathogenic 113 rs200370925 GRCh37: 14:77908979-77908979
GRCh38: 14:77442636-77442636
4 VIPAS39 NM_022067.4(VIPAS39):c.871C>T (p.Gln291Ter) SNV Pathogenic 114 rs267607171 GRCh37: 14:77902228-77902228
GRCh38: 14:77435885-77435885
5 VIPAS39 NM_022067.4(VIPAS39):c.2T>G (p.Met1Arg) SNV Pathogenic 115 rs267607172 GRCh37: 14:77920444-77920444
GRCh38: 14:77454101-77454101
6 VIPAS39 NM_022067.4(VIPAS39):c.1184G>A (p.Trp395Ter) SNV Pathogenic 522399 rs1555364979 GRCh37: 14:77896106-77896106
GRCh38: 14:77429763-77429763
7 VIPAS39 NM_001193315.2(VIPAS39):c.643C>T (p.Arg215Ter) SNV Pathogenic 1033995 GRCh37: 14:77908994-77908994
GRCh38: 14:77442651-77442651
8 VIPAS39 NM_022067.4(VIPAS39):c.677A>G (p.His226Arg) SNV Likely pathogenic 522398 rs1555366438 GRCh37: 14:77908960-77908960
GRCh38: 14:77442617-77442617
9 VIPAS39 NM_022067.4(VIPAS39):c.618_626dup (p.Arg206_Leu208dup) Duplication Likely pathogenic 627536 rs1594910243 GRCh37: 14:77909466-77909467
GRCh38: 14:77443123-77443124
10 VIPAS39 NM_001193315.2(VIPAS39):c.1003A>G (p.Thr335Ala) SNV Uncertain significance 1028746 GRCh37: 14:77901646-77901646
GRCh38: 14:77435303-77435303
11 VIPAS39 NM_001193315.2(VIPAS39):c.1366G>A (p.Asp456Asn) SNV Uncertain significance 1028747 GRCh37: 14:77894808-77894808
GRCh38: 14:77428465-77428465
12 VIPAS39 NM_022067.4(VIPAS39):c.494G>A (p.Arg165Gln) SNV Uncertain significance 285001 rs376797384 GRCh37: 14:77914847-77914847
GRCh38: 14:77448504-77448504
13 VIPAS39 NM_022067.4(VIPAS39):c.1455C>A (p.Ser485Arg) SNV Uncertain significance 498683 rs145453157 GRCh37: 14:77894719-77894719
GRCh38: 14:77428376-77428376

Expression for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Search GEO for disease gene expression data for Arthrogryposis, Renal Dysfunction, and Cholestasis 2.

Pathways for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Pathways related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.64 USP25 TNKS2 TNKS BABAM1
2
Show member pathways
10.28 TNKS2 TNKS

GO Terms for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Cellular components related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 pericentriolar material GO:0000242 8.62 TNKS2 TNKS

Biological processes related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein polyubiquitination GO:0000209 9.63 TNKS2 TNKS LNPEP
2 positive regulation of canonical Wnt signaling pathway GO:0090263 9.48 TNKS2 TNKS
3 positive regulation of telomere maintenance via telomerase GO:0032212 9.43 TNKS2 TNKS
4 protein K63-linked deubiquitination GO:0070536 9.4 USP25 BABAM1
5 protein ADP-ribosylation GO:0006471 9.37 TNKS2 TNKS
6 positive regulation of telomere capping GO:1904355 9.32 TNKS2 TNKS
7 negative regulation of telomere maintenance via telomere lengthening GO:1904357 9.26 TNKS2 TNKS
8 protein auto-ADP-ribosylation GO:0070213 9.16 TNKS2 TNKS
9 protein localization to chromosome, telomeric region GO:0070198 8.96 TNKS2 TNKS
10 protein poly-ADP-ribosylation GO:0070212 8.62 TNKS2 TNKS

Molecular functions related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 NAD+ ADP-ribosyltransferase activity GO:0003950 8.96 TNKS2 TNKS
2 protein ADP-ribosylase activity GO:1990404 8.62 TNKS2 TNKS

Sources for Arthrogryposis, Renal Dysfunction, and Cholestasis 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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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