ALGS2
MCID: ALG016
MIFTS: 34

Alagille Syndrome 2 (ALGS2)

Categories: Cardiovascular diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Nephrological diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Alagille Syndrome 2

MalaCards integrated aliases for Alagille Syndrome 2:

Name: Alagille Syndrome 2 57 72 29 13 6 70
Algs2 57 72
Syndromic Bile Duct Paucity Due to a Notch2 Point Mutation 58
Alagille-Watson Syndrome Due to a Notch2 Point Mutation 58
Arteriohepatic Dysplasia Due to a Notch2 Point Mutation 58
Alagille Syndrome Due to a Notch2 Point Mutation 58
Cholestasis with Peripheral Pulmonary Stenosis 72
Syndrome, Alagille, Type 2 39
Alagille-Watson Syndrome 72
Algs 72
Aws 72

Characteristics:

OMIM®:

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

Miscellaneous:
variable phenotype


HPO:

31
alagille syndrome 2:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Rare cardiac malformations
Rare hepatic diseases
Rare renal diseases
Developmental anomalies during embryogenesis


External Ids:

OMIM® 57 610205
OMIM Phenotypic Series 57 PS118450
MeSH 44 D016738
ICD10 via Orphanet 33 Q44.7
Orphanet 58 ORPHA261629
MedGen 41 C1857761
UMLS 70 C1857761

Summaries for Alagille Syndrome 2

UniProtKB/Swiss-Prot : 72 Alagille syndrome 2: A form of Alagille syndrome, an autosomal dominant multisystem disorder. It is clinically defined by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems.

MalaCards based summary : Alagille Syndrome 2, also known as algs2, is related to alagille syndrome 1 and watson syndrome. An important gene associated with Alagille Syndrome 2 is NOTCH2 (Notch Receptor 2). The drugs Bevacizumab and Pharmaceutical Solutions have been mentioned in the context of this disorder. Affiliated tissues include liver, eye and kidney, and related phenotypes are hypertension and proteinuria

More information from OMIM: 610205 PS118450

Related Diseases for Alagille Syndrome 2

Diseases in the Alagille Syndrome 1 family:

Alagille Syndrome 2

Diseases related to Alagille Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 alagille syndrome 1 11.2
2 watson syndrome 10.2
3 withdrawal disorder 10.1
4 liver cirrhosis 10.1
5 myasthenia gravis 10.0
6 hemifacial microsomia 9.9
7 rheumatoid arthritis 9.9
8 craniosynostosis with fibular aplasia 9.9
9 coffin-lowry syndrome 9.9
10 cardiac arrest 9.9
11 tongue carcinoma 9.9
12 klippel-feil syndrome 9.9
13 supine hypotensive syndrome 9.9
14 hydrocephalus 9.9
15 respiratory failure 9.9
16 ovarian cyst 9.9
17 arthritis 9.9
18 hypopharynx cancer 9.9
19 craniofacial microsomia 9.9
20 aids wasting syndrome 9.9

Graphical network of the top 20 diseases related to Alagille Syndrome 2:



Diseases related to Alagille Syndrome 2

Symptoms & Phenotypes for Alagille Syndrome 2

Human phenotypes related to Alagille Syndrome 2:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 hypertension 31 HP:0000822
2 proteinuria 31 HP:0000093
3 renal insufficiency 31 HP:0000083
4 atrial septal defect 31 HP:0001631
5 cholestatic liver disease 31 HP:0002611
6 hematuria 31 HP:0000790
7 tetralogy of fallot 31 HP:0001636
8 posterior embryotoxon 31 HP:0000627
9 renal hypoplasia 31 HP:0000089
10 pointed chin 31 HP:0000307
11 broad forehead 31 HP:0000337
12 pulmonic stenosis 31 HP:0001642
13 peripheral pulmonary artery stenosis 31 HP:0004969
14 triangular face 31 HP:0000325
15 long nose 31 HP:0003189
16 renal cyst 31 HP:0000107
17 renal tubular acidosis 31 HP:0001947

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Cardiovascular Vascular:
hypertension

Cardiovascular Heart:
atrial septal defect
tetralogy of fallot
pulmonic stenosis

Head And Neck Eyes:
posterior embryotoxon

Head And Neck Nose:
long nose
bulbous tip

Genitourinary Kidneys:
proteinuria
renal insufficiency
hematuria
renal tubular acidosis
small kidneys
more
Abdomen Liver:
cholestatic liver disease

Head And Neck Face:
pointed chin
broad forehead

Clinical features from OMIM®:

610205 (Updated 05-Apr-2021)

Drugs & Therapeutics for Alagille Syndrome 2

Drugs for Alagille Syndrome 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Bevacizumab Approved, Investigational Phase 2 216974-75-3
2 Pharmaceutical Solutions Phase 1, Phase 2
3 Angiogenesis Inhibitors Phase 2
4 Antineoplastic Agents, Immunological Phase 2
5 Immunosuppressive Agents Phase 2
6 Immunologic Factors Phase 2
7 Thymoglobulin Phase 2
8 Cyclosporins Phase 2
9 Antilymphocyte Serum Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Safety And Efficacy Study Of ALG-1001 In Human Subjects With Wet Age-Related Macular Degeneration Completed NCT01749891 Phase 1, Phase 2 ALG 1001
2 A Randomized Controlled, Double-Masked, Crossover Clinical Trial Designed To Evaluate The Safety And Exploratory Efficacy Of 1.0 Mg Luminate® (Alg-1001) As A Treatment For Non-Exudative Macular Degeneration Completed NCT03626636 Phase 2 Risuteganib
3 A Phase 2 Randomized, Controlled, Double-Masked, Multicenter Clinical Trial Designed to Evaluate the Safety and Exploratory Efficacy of Luminate® (ALG-1001) as Compared to Avastin® in the Treatment of Diabetic Macular Edema (DME) Completed NCT02348918 Phase 2 Luminate 1.0mg;Luminate 2.0mg;Luminate 3.0mg;Avastin;Luminate 0.5mg
4 A Non-randomized, Phase II Study of Eltrombopag in Combination With Rabbit Anti-thymocyte Globulin/Cyclosporine A (ATG/CsA) in Subjects With Moderate or More Severe Aplastic Anemia Who Have Not Received Prior ATG/Anti-lymphocyte Globulin (ALG)-Based Immunosuppressive Therapy Completed NCT02404025 Phase 2 Eltrombopag;Rabbit ATG;CsA
5 A Safety And Efficacy Study Of Alg-1001 In Human Subjects With Symptomatic Focal Vitreomacular Adhesion Completed NCT02153476 Phase 2 2.0mg of ALG-1001;Balanced Salt Solution
6 Safety Study of ALG 1001 to Treat Diabetic Macular Edema Withdrawn NCT01482871 Phase 1, Phase 2 ALG-1001;ALG-1001;ALG-1001;ALG-1001
7 A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-human Study of Subcutaneously Administered ALG-010133 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Ascending Doses (Part 1) and Multiple Ascending Doses in Healthy Volunteers (Part 2), and Multiple Doses in Subjects With Chronic Hepatitis B (Part 3) Recruiting NCT04485663 Phase 1 ALG-010133;Placebo
8 A Phase 1, Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study of Orally Administered ALG-000184 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single-Ascending Doses (Part 1) and Multiple-Ascending Doses in Healthy Volunteers (Part 2), and Multiple Doses in Subjects With Chronic Hepatitis B (Part 3) Recruiting NCT04536337 Phase 1 ALG-000184;Placebo

Search NIH Clinical Center for Alagille Syndrome 2

Genetic Tests for Alagille Syndrome 2

Genetic tests related to Alagille Syndrome 2:

# Genetic test Affiliating Genes
1 Alagille Syndrome 2 29 NOTCH2

Anatomical Context for Alagille Syndrome 2

MalaCards organs/tissues related to Alagille Syndrome 2:

40
Liver, Eye, Kidney

Publications for Alagille Syndrome 2

Articles related to Alagille Syndrome 2:

# Title Authors PMID Year
1
NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. 6 57
16773578 2006
2
Individual exome analysis in diagnosis and management of paediatric liver failure of indeterminate aetiology. 6
25016221 2014
3
Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. 57
11171333 2001
4
Variants Associated with Infantile Cholestatic Syndromes Detected in Extrahepatic Biliary Atresia by Whole Exome Studies: A 20-Case Series from Thailand. 61
29707407 2018
5
Oral absorbable fat-soluble vitamin formulation in pediatric patients with cholestasis. 61
22595974 2012
6
The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage. 61
19914235 2010

Variations for Alagille Syndrome 2

ClinVar genetic disease variations for Alagille Syndrome 2:

6 (show all 19)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NOTCH2 NM_024408.4(NOTCH2):c.5930-1G>A SNV Pathogenic 9229 rs312262798 GRCh37: 1:120460386-120460386
GRCh38: 1:119917763-119917763
2 NOTCH2 NM_024408.4(NOTCH2):c.1331G>A (p.Cys444Tyr) SNV Pathogenic 9230 rs111033632 GRCh37: 1:120510178-120510178
GRCh38: 1:119967555-119967555
3 NOTCH2 NM_024408.4(NOTCH2):c.5222C>T (p.Ser1741Leu) SNV Pathogenic 684618 rs1570660422 GRCh37: 1:120464424-120464424
GRCh38: 1:119921801-119921801
4 NOTCH2 NM_024408.4(NOTCH2):c.5644C>T (p.His1882Tyr) SNV Pathogenic 684619 rs1570658378 GRCh37: 1:120462072-120462072
GRCh38: 1:119919449-119919449
5 NOTCH2 NM_024408.4(NOTCH2):c.6125T>C (p.Met2042Thr) SNV Pathogenic 1012187 GRCh37: 1:120459220-120459220
GRCh38: 1:119916597-119916597
6 NOTCH2 NM_024408.4(NOTCH2):c.2587C>T (p.Pro863Ser) SNV Likely pathogenic 1034042 GRCh37: 1:120491642-120491642
GRCh38: 1:119949019-119949019
7 NOTCH2 NM_024408.4(NOTCH2):c.5431C>T (p.Gln1811Ter) SNV Likely pathogenic 599225 rs1557804111 GRCh37: 1:120462900-120462900
GRCh38: 1:119920277-119920277
8 NOTCH2 NM_024408.4(NOTCH2):c.6460del (p.Ser2153_Leu2154insTer) Deletion Likely pathogenic 635423 rs1570655570 GRCh37: 1:120458885-120458885
GRCh38: 1:119916262-119916262
9 NOTCH2 NM_024408.4(NOTCH2):c.4647T>G (p.Ile1549Met) SNV Uncertain significance 812146 rs1396873392 GRCh37: 1:120466472-120466472
GRCh38: 1:119923849-119923849
10 NOTCH2 NM_024408.4(NOTCH2):c.5132T>C (p.Leu1711Pro) SNV Uncertain significance 829914 rs1570660922 GRCh37: 1:120464940-120464940
GRCh38: 1:119922317-119922317
11 NOTCH2 NM_024408.4(NOTCH2):c.6178C>T (p.Arg2060Cys) SNV Uncertain significance 829922 rs746551843 GRCh37: 1:120459167-120459167
GRCh38: 1:119916544-119916544
12 NOTCH2 NM_024408.4(NOTCH2):c.5327T>C (p.Leu1776Ser) SNV Uncertain significance 931169 GRCh37: 1:120463004-120463004
GRCh38: 1:119920381-119920381
13 NOTCH2 NM_024408.4(NOTCH2):c.836T>G (p.Val279Gly) SNV Uncertain significance 989251 GRCh37: 1:120529621-120529621
GRCh38: 1:119986998-119986998
14 NOTCH2 NM_024408.4(NOTCH2):c.6893G>A (p.Arg2298Gln) SNV Uncertain significance 291198 rs140832430 GRCh37: 1:120458452-120458452
GRCh38: 1:119915829-119915829
15 NOTCH2 NM_024408.4(NOTCH2):c.3206G>A (p.Arg1069Gln) SNV Uncertain significance 134965 rs146014987 GRCh37: 1:120480611-120480611
GRCh38: 1:119937988-119937988
16 NOTCH2 NM_024408.4(NOTCH2):c.5031G>T (p.Gln1677His) SNV Uncertain significance 1028811 GRCh37: 1:120465041-120465041
GRCh38: 1:119922418-119922418
17 NOTCH2 NM_024408.4(NOTCH2):c.5732G>A (p.Arg1911His) SNV Uncertain significance 502328 rs1216790064 GRCh37: 1:120461984-120461984
GRCh38: 1:119919361-119919361
18 NOTCH2 NM_024408.4(NOTCH2):c.6325A>G (p.Lys2109Glu) SNV Uncertain significance 1028813 GRCh37: 1:120459020-120459020
GRCh38: 1:119916397-119916397
19 NOTCH2 NM_024408.4(NOTCH2):c.686C>A (p.Pro229His) SNV Uncertain significance 1028814 GRCh37: 1:120539685-120539685
GRCh38: 1:119997062-119997062

UniProtKB/Swiss-Prot genetic disease variations for Alagille Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 NOTCH2 p.Cys444Tyr VAR_029361 rs111033632

Expression for Alagille Syndrome 2

Search GEO for disease gene expression data for Alagille Syndrome 2.

Pathways for Alagille Syndrome 2

GO Terms for Alagille Syndrome 2

Sources for Alagille Syndrome 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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....