ARCS2
MCID: ART063
MIFTS: 37

Arthrogryposis, Renal Dysfunction, and Cholestasis 2 (ARCS2)

Categories: Blood diseases, Fetal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases
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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 11 28 12 5 14 38 71
Arcs2 57 11 73
Arthrogryposis, Renal Dysfunction and Cholestasis Syndrome 2 73
Arthrogryposis Renal Dysfunction and Cholestasis 2 73

Characteristics:


Inheritance:

Autosomal recessive 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
death in infancy, usually from sepsis, dehydration, or acidosis


Classifications:



Summaries for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

OMIM®: 57 Arthrogryposis, renal dysfunction, and cholestasis-2 (ARCS2) is a multisystem disorder associated with abnormalities in polarized liver and kidney cells (Qiu et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of ARCS, see ARCS1 (208085). (613404) (Updated 08-Dec-2022)

MalaCards based summary: Arthrogryposis, Renal Dysfunction, and Cholestasis 2, also known as arcs2, is related to arthrogryposis, renal dysfunction, and cholestasis 1 and cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, 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 NAD metabolism. Affiliated tissues include liver and kidney, and related phenotypes are nephrogenic diabetes insipidus and lissencephaly

UniProtKB/Swiss-Prot: 73 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.

Disease Ontology: 11 An arthrogryposis, renal dysfunction, and cholestasis that has material basis in homozygous or compound heterozygous mutation in VIPAS39 on 14q24.3.

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 arthrogryposis, renal dysfunction, and cholestasis 1 29.5 VPS33B VIPAS39 USP25 TNKS2 TNKS BABAM1
2 cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome 10.0 VPS33B VIPAS39
3 obstructive jaundice 9.9 VPS33B VIPAS39
4 gray platelet syndrome 9.9 VPS33B VIPAS39
5 cholestasis, progressive familial intrahepatic, 1 9.9 VPS33B VIPAS39
6 progressive familial intrahepatic cholestasis 9.8 VPS33B VIPAS39
7 fanconi syndrome 9.7 VPS33B VIPAS39
8 cherubism 9.4 TNKS2 TNKS BABAM1

Graphical network of the top 20 diseases related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2:



Diseases related to Arthrogryposis, Renal Dysfunction, and Cholestasis 2

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

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

30 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nephrogenic diabetes insipidus 30 Occasional (7.5%) HP:0009806
2 lissencephaly 30 Occasional (7.5%) HP:0001339
3 hepatomegaly 30 Very rare (1%) HP:0002240
4 proteinuria 30 Very rare (1%) HP:0000093
5 aminoaciduria 30 Very rare (1%) HP:0003355
6 cholestatic liver disease 30 Very rare (1%) HP:0002611
7 arthrogryposis multiplex congenita 30 Very rare (1%) HP:0002804
8 pruritus 30 Very rare (1%) HP:0000989
9 metabolic acidosis 30 Very rare (1%) HP:0001942
10 glycosuria 30 Very rare (1%) HP:0003076
11 failure to thrive 30 HP:0001508
12 global developmental delay 30 HP:0001263
13 hip dysplasia 30 HP:0001385
14 microcephaly 30 HP:0000252
15 ichthyosis 30 HP:0008064
16 nephropathy 30 HP:0000112
17 low-set ears 30 HP:0000369
18 elevated hepatic transaminase 30 HP:0002910
19 jaundice 30 HP:0000952
20 nephrocalcinosis 30 HP:0000121
21 ventricular septal defect 30 HP:0001629
22 sloping forehead 30 HP:0000340
23 generalized hypotonia 30 HP:0001290
24 conjugated hyperbilirubinemia 30 HP:0002908
25 renal tubular acidosis 30 HP:0001947
26 talipes calcaneovalgus 30 HP:0001884
27 right ventricular hypertrophy 30 HP:0001667
28 giant cell hepatitis 30 HP:0200084

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
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:
hypotonia
global developmental delay
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 08-Dec-2022)

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 28 VIPAS39

Anatomical Context for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

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

MalaCards : Liver, Kidney
ODiseA: Liver

Publications for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

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

# Title Authors PMID Year
1
Novel missense mutation in VPS33B is associated with isolated low gamma-glutamyltransferase cholestasis: Attenuated, incomplete phenotype of arthrogryposis, renal dysfunction, and cholestasis syndrome. 57 5
31479177 2019
2
Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization. 57 5
20190753 2010
3
Novel gene mutations in three Japanese patients with ARC syndrome associated mild phenotypes: a case series. 62
35151346 2022

Variations for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

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

5 (show all 15)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 VIPAS39 NM_001193315.2(VIPAS39):c.535C>T (p.Gln179Ter) SNV Pathogenic
111 rs267607173 GRCh37: 14:77910654-77910654
GRCh38: 14:77444311-77444311
2 VIPAS39 NM_001193315.2(VIPAS39):c.749_753del (p.Thr250fs) DEL Pathogenic
112 rs794726653 GRCh37: 14:77907418-77907422
GRCh38: 14:77441075-77441079
3 VIPAS39 NM_001193315.2(VIPAS39):c.658C>T (p.Arg220Ter) SNV Pathogenic
113 rs200370925 GRCh37: 14:77908979-77908979
GRCh38: 14:77442636-77442636
4 VIPAS39 NM_001193315.2(VIPAS39):c.871C>T (p.Gln291Ter) SNV Pathogenic
114 rs267607171 GRCh37: 14:77902228-77902228
GRCh38: 14:77435885-77435885
5 VIPAS39 NM_001193315.2(VIPAS39):c.2T>G (p.Met1Arg) SNV Pathogenic
115 rs267607172 GRCh37: 14:77920444-77920444
GRCh38: 14:77454101-77454101
6 VIPAS39 NM_001193315.2(VIPAS39):c.177_179delinsAAA (p.Trp59_Ser60delinsTer) INDEL Pathogenic
1701817 GRCh37: 14:77919659-77919661
GRCh38: 14:77453316-77453318
7 VIPAS39 NM_001193315.2(VIPAS39):c.1141C>T (p.Arg381Ter) SNV Pathogenic
1701818 GRCh37: 14:77900223-77900223
GRCh38: 14:77433880-77433880
8 VIPAS39 NM_001193315.2(VIPAS39):c.1184G>A (p.Trp395Ter) SNV Pathogenic
522399 rs1555364979 GRCh37: 14:77896106-77896106
GRCh38: 14:77429763-77429763
9 VIPAS39 NM_001193315.2(VIPAS39):c.677A>G (p.His226Arg) SNV Likely Pathogenic
522398 rs1555366438 GRCh37: 14:77908960-77908960
GRCh38: 14:77442617-77442617
10 VIPAS39 NM_001193315.2(VIPAS39):c.618_626dup (p.Arg206_Leu208dup) DUP Likely Pathogenic
627536 rs1594910243 GRCh37: 14:77909466-77909467
GRCh38: 14:77443123-77443124
11 VIPAS39 NM_001193315.2(VIPAS39):c.1003A>G (p.Thr335Ala) SNV Uncertain Significance
1028746 rs867268041 GRCh37: 14:77901646-77901646
GRCh38: 14:77435303-77435303
12 VIPAS39 NM_001193315.2(VIPAS39):c.1366G>A (p.Asp456Asn) SNV Uncertain Significance
1028747 rs2078466084 GRCh37: 14:77894808-77894808
GRCh38: 14:77428465-77428465
13 VIPAS39 NM_001193315.2(VIPAS39):c.494G>A (p.Arg165Gln) SNV Uncertain Significance
285001 rs376797384 GRCh37: 14:77914847-77914847
GRCh38: 14:77448504-77448504
14 VIPAS39 NM_001193315.2(VIPAS39):c.1455C>A (p.Ser485Arg) SNV Uncertain Significance
498683 rs145453157 GRCh37: 14:77894719-77894719
GRCh38: 14:77428376-77428376
15 VIPAS39 NM_001193315.2(VIPAS39):c.632-14T>C SNV Likely Benign
1301768 GRCh37: 14:77909019-77909019
GRCh38: 14:77442676-77442676

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
11.16 TNKS2 TNKS
3
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 9.46 TNKS2 TNKS
2 HOPS complex GO:0030897 9.13 VPS33B VIPAS39
3 vesicle tethering complex GO:0099023 8.92 VPS33B VIPAS39

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

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 collagen fibril organization GO:0030199 9.85 VPS33B VIPAS39
2 intracellular transport GO:0046907 9.83 VPS33B VIPAS39
3 positive regulation of telomere maintenance via telomerase GO:0032212 9.8 TNKS2 TNKS
4 protein K63-linked deubiquitination GO:0070536 9.78 USP25 BABAM1
5 positive regulation of telomere capping GO:1904355 9.76 TNKS2 TNKS
6 phagosome-lysosome fusion GO:0090385 9.73 VIPAS39 VPS33B
7 endosome to lysosome transport GO:0008333 9.71 VPS33B VIPAS39
8 collagen metabolic process GO:0032963 9.71 VPS33B VIPAS39
9 protein auto-ADP-ribosylation GO:0070213 9.67 TNKS2 TNKS
10 protein localization to chromosome, telomeric region GO:0070198 9.62 TNKS2 TNKS
11 negative regulation of telomere maintenance via telomere lengthening GO:1904357 9.56 TNKS2 TNKS
12 autophagosome maturation GO:0097352 9.51 VPS33B VIPAS39
13 protein poly-ADP-ribosylation GO:0070212 9.46 TNKS2 TNKS
14 peptidyl-lysine hydroxylation GO:0017185 9.26 VPS33B VIPAS39
15 obsolete protein ADP-ribosylation GO:0006471 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 nucleotidyltransferase activity GO:0016779 9.46 TNKS2 TNKS
2 NAD+ ADP-ribosyltransferase activity GO:0003950 9.26 TNKS2 TNKS
3 NAD+-protein ADP-ribosyltransferase activity GO:1990404 8.92 TNKS2 TNKS

Sources for Arthrogryposis, Renal Dysfunction, and Cholestasis 2

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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