MCID: ALP074
MIFTS: 47

Alport Syndrome, Autosomal Dominant

Categories: Genetic diseases, Rare diseases, Ear diseases, Nephrological diseases, Eye diseases, Fetal diseases

Aliases & Classifications for Alport Syndrome, Autosomal Dominant

MalaCards integrated aliases for Alport Syndrome, Autosomal Dominant:

Name: Alport Syndrome, Autosomal Dominant 53 71 28 13 51 69
Autosomal Dominant Alport Syndrome 12 49 55 14
Renal Failure and Sensorineural Hearing Loss 49
Alport Syndrome Dominant Type 49
Nephritis-Deafness Syndrome 71
Nephropathy and Deafness 71
Apsad 71

Characteristics:

Orphanet epidemiological data:

55
autosomal dominant alport syndrome
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
hearing loss is variable


HPO:

31
alport syndrome, autosomal dominant:
Onset and clinical course progressive
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 53 104200
Disease Ontology 12 DOID:0110032
Orphanet 55 ORPHA88918
MESH via Orphanet 42 C536586
UMLS via Orphanet 70 C1567743 C2931253
ICD10 via Orphanet 33 Q87.8
MedGen 39 C1567743
MeSH 41 D009394
UMLS 69 C1567743

Summaries for Alport Syndrome, Autosomal Dominant

OMIM : 53 Alport syndrome classically comprises nephritis, often progressing to renal failure, and sensorineural hearing loss (Alport, 1927). For a general phenotypic description of Alport syndrome, see the X-linked dominant form (301050). Approximately 85% of cases of Alport syndrome are X-linked and about 15% are autosomal recessive (203780); autosomal dominant inheritance is rare (van der Loop et al., 2000). Also see benign familial hematuria (BFH; 141200), a similar but milder disorder also caused by mutation in the COL4A3 gene. An autosomal dominant disorder sharing the clinical features of Alport syndrome but with the addition of macrothrombocytopenia, known as Fechtner syndrome (153640), is caused by mutation in the MYH9 gene (160775) on chromosome 22q11. (104200)

MalaCards based summary : Alport Syndrome, Autosomal Dominant, also known as autosomal dominant alport syndrome, is related to alport syndrome, x-linked and malignant cylindroma, and has symptoms including hypertension, sensorineural hearing impairment and proteinuria. An important gene associated with Alport Syndrome, Autosomal Dominant is COL4A3 (Collagen Type IV Alpha 3 Chain), and among its related pathways/superpathways are ERK Signaling and Developmental Biology. Affiliated tissues include eye and kidney, and related phenotypes are homeostasis/metabolism and immune system

UniProtKB/Swiss-Prot : 71 Alport syndrome, autosomal dominant: A syndrome characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.

NIH Rare Diseases : 49 Autosomal dominant Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. Most affected individuals experience progressive loss of kidney function, usually resulting in end-stage kidney disease. People with Alport syndrome frequently develop sensorineural hearing loss in late childhood or early adolescence. The eye abnormalities seen in this condition seldom lead to vision loss. Alport syndrome can have different patterns of inheritance. Alport syndrome has autosomal dominant inheritance in about 5 percent of cases. People with this form of Alport syndrome have one mutation in either the COL4A3 or COL4A4 gene in each cell. Last updated: 10/24/2011

Disease Ontology : 12 An Alport syndrome that has_material -basis_in heterozygous mutation in the COL4A3 gene.

Related Diseases for Alport Syndrome, Autosomal Dominant

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



Diseases related to Alport Syndrome, Autosomal Dominant

Symptoms & Phenotypes for Alport Syndrome, Autosomal Dominant

Symptoms via clinical synopsis from OMIM:

53
Cardiovascular Vascular:
hypertension

Laboratory Abnormalities:
proteinuria
hematuria, gross and microscopic

Genitourinary Kidneys:
proteinuria
glomerulonephropathy
hematuria, gross and microscopic
end-stage renal failure
thinning of the glomerular basement membrane (early in the disease)
more
Head And Neck Ears:
deafness, sensorineural, especially affecting high frequencies


Clinical features from OMIM:

104200

Human phenotypes related to Alport Syndrome, Autosomal Dominant:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 hypertension 31 HP:0000822
2 sensorineural hearing impairment 31 HP:0000407
3 proteinuria 31 HP:0000093
4 hypophosphatemia 31 HP:0002148
5 myopia 31 HP:0000545
6 nephrotic syndrome 31 HP:0000100
7 hematuria 31 HP:0000790
8 nephrocalcinosis 31 HP:0000121
9 stage 5 chronic kidney disease 31 HP:0003774
10 azotemia 31 HP:0002157
11 anterior polar cataract 31 HP:0001134
12 glomerulonephritis 31 HP:0000099
13 thickening of the glomerular basement membrane 31 HP:0004722
14 lenticonus 31 HP:0001142
15 diffuse glomerular basement membrane lamellation 31 HP:0030034

MGI Mouse Phenotypes related to Alport Syndrome, Autosomal Dominant:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.8 MYH9 AGPS COL4A1 COL4A3 COL4A4 COL4A5
2 immune system MP:0005387 9.73 MYH9 COL4A1 COL4A3 COL4A4 COL4A5 IGBP1
3 mortality/aging MP:0010768 9.63 MYH9 AGPS COL4A1 COL4A3 COL4A4 COL4A5
4 renal/urinary system MP:0005367 9.35 MYH9 COL4A1 COL4A3 COL4A4 COL4A5
5 vision/eye MP:0005391 9.1 AGPS COL4A1 COL4A3 COL4A4 COL4A5 MYH9

Drugs & Therapeutics for Alport Syndrome, Autosomal Dominant

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Biomarker for Patient With Alport Disease or Highly Suspected for Alport Disease Recruiting NCT02718027

Search NIH Clinical Center for Alport Syndrome, Autosomal Dominant

Genetic Tests for Alport Syndrome, Autosomal Dominant

Genetic tests related to Alport Syndrome, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Alport Syndrome, Autosomal Dominant 28 COL4A3

Anatomical Context for Alport Syndrome, Autosomal Dominant

MalaCards organs/tissues related to Alport Syndrome, Autosomal Dominant:

38
Eye, Kidney

Publications for Alport Syndrome, Autosomal Dominant

Articles related to Alport Syndrome, Autosomal Dominant:

(show all 17)
# Title Authors Year
1
Mutation analysis of COL4A3 and COL4A4 genes in a Chinese autosomal-dominant Alport syndrome family. ( 28674241 )
2017
2
Identification of a novel collagen type IV alpha-4 (COL4A4) mutation in a Chinese family with autosomal dominant Alport syndrome using exome sequencing. ( 27934798 )
2016
3
Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome. ( 27281700 )
2016
4
Study of the True Clinical Progression of Autosomal Dominant Alport Syndrome in a European Population. ( 26277931 )
2015
5
A new mutation in the COL4A3 gene responsible for autosomal dominant Alport syndrome, which only generates hearing loss in some carriers. ( 25450602 )
2015
6
COL4A4 gene study of a European population: description of new mutations causing autosomal dominant Alport syndrome. ( 25755845 )
2014
7
Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases. ( 24033287 )
2013
8
Autosomal dominant Alport syndrome: molecular analysis of the COL4A4 gene and clinical outcome. ( 19129241 )
2009
9
Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene. ( 15086897 )
2004
10
A novel model of autosomal dominant Alport syndrome in Dalmatian dogs. ( 12454218 )
2002
11
Correlation of histopathological features and renal impairment in autosomal dominant Alport syndrome in Bull terriers. ( 12401844 )
2002
12
Identification of a new mutation in the alpha4(IV) collagen gene in a family with autosomal dominant Alport syndrome and hypercholesterolaemia. ( 11572889 )
2001
13
Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation. ( 11044206 )
2000
14
Absence of ocular manifestations in autosomal dominant Alport syndrome associated with haematological abnormalties. ( 11135492 )
2000
15
Genetic linkage of autosomal-dominant Alport syndrome with leukocyte inclusions and macrothrombocytopenia (Fechtner syndrome) to chromosome 22q11-13. ( 10577925 )
1999
16
Autosomal dominant Alport syndrome linked to the type IV collage alpha 3 and alpha 4 genes (COL4A3 and COL4A4). ( 9269635 )
1997
17
Bull terrier hereditary nephritis: a model for autosomal dominant Alport syndrome. ( 7752574 )
1995

Variations for Alport Syndrome, Autosomal Dominant

UniProtKB/Swiss-Prot genetic disease variations for Alport Syndrome, Autosomal Dominant:

71
# Symbol AA change Variation ID SNP ID
1 COL4A3 p.Gly1167Arg VAR_011211 rs267606745

ClinVar genetic disease variations for Alport Syndrome, Autosomal Dominant:

6 (show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 COL4A3 COL4A3, IVS21DS, G-A, -1 single nucleotide variant Pathogenic
2 COL4A3 NM_000091.4(COL4A3): c.3499G> A (p.Gly1167Arg) single nucleotide variant Pathogenic rs267606745 GRCh37 Chromosome 2, 228159760: 228159760
3 COL4A3 NM_000091.4(COL4A3): c.998G> C (p.Gly333Ala) single nucleotide variant Pathogenic rs1057519376 GRCh37 Chromosome 2, 228122329: 228122329
4 COL4A3 NM_000091.4(COL4A3): c.4382C> T (p.Pro1461Leu) single nucleotide variant Pathogenic rs760462252 GRCh37 Chromosome 2, 228172555: 228172555
5 COL4A3 NM_000091.4(COL4A3): c.4474A> T (p.Ser1492Cys) single nucleotide variant Pathogenic rs1057519377 GRCh37 Chromosome 2, 228173626: 228173626
6 COL4A3 NM_000091.4(COL4A3): c.833dupT (p.Pro279Alafs) duplication Likely pathogenic GRCh37 Chromosome 2, 228119376: 228119376
7 COL4A3 NM_000091.4(COL4A3): c.2083G> A (p.Gly695Arg) single nucleotide variant Likely pathogenic rs200287952 GRCh37 Chromosome 2, 228142227: 228142227
8 COL4A3 NM_000091.4(COL4A3): c.3244_3247delAAAG (p.Lys1082Glufs) deletion Pathogenic rs1057516204 GRCh37 Chromosome 2, 228157940: 228157943
9 COL4A3 NM_000091.4(COL4A3): c.5010_*14del18 deletion Likely pathogenic rs1064792902 GRCh37 Chromosome 2, 228176583: 228176600
10 COL4A3 NM_000091.4(COL4A3): c.3546_3548dup (p.Gly1183_Asn1184insGly) duplication Likely pathogenic GRCh37 Chromosome 2, 228160013: 228160015
11 COL4A3 NM_000091.4(COL4A3): c.4019G> A (p.Gly1340Glu) single nucleotide variant Likely pathogenic rs748901402 GRCh37 Chromosome 2, 228168638: 228168638

Expression for Alport Syndrome, Autosomal Dominant

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

Pathways for Alport Syndrome, Autosomal Dominant

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

(show all 22)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.47 COL4A1 COL4A3 COL4A4 COL4A5 MYH9
2
Show member pathways
13.19 COL4A1 COL4A3 COL4A4 COL4A5 MYH9
3
Show member pathways
13.04 COL4A1 COL4A3 COL4A4 COL4A5
4
Show member pathways
12.78 COL4A1 COL4A3 COL4A4 COL4A5
5
Show member pathways
12.7 COL4A1 COL4A3 COL4A4 COL4A5
6
Show member pathways
12.64 COL4A1 COL4A3 COL4A4 COL4A5
7 12.57 COL4A1 COL4A3 COL4A4 COL4A5
8
Show member pathways
12.56 COL4A1 COL4A3 COL4A4 COL4A5
9
Show member pathways
12.48 COL4A1 COL4A3 COL4A4 COL4A5
10
Show member pathways
12.41 COL4A1 COL4A3 COL4A4 COL4A5 MYH9
11
Show member pathways
12.33 COL4A1 COL4A3 COL4A4 COL4A5
12
Show member pathways
12 COL4A1 COL4A3 COL4A4 COL4A5 MYH9
13
Show member pathways
11.95 COL4A1 COL4A3 COL4A4 COL4A5
14 11.73 COL4A1 COL4A3 COL4A4 COL4A5
15 11.69 COL4A1 COL4A3 COL4A4 COL4A5
16 11.64 COL4A1 COL4A3 COL4A4 COL4A5
17 11.49 COL4A3 COL4A4 COL4A5 MYH9
18 11.34 COL4A1 COL4A3 COL4A4 COL4A5
19 11.15 COL4A1 COL4A3 COL4A4 COL4A5
20 10.86 COL4A1 COL4A3 COL4A4 COL4A5
21 10.76 COL4A1 COL4A3 COL4A4 COL4A5
22 10.49 COL4A1 COL4A3 COL4A4 COL4A5

GO Terms for Alport Syndrome, Autosomal Dominant

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

# Name GO ID Score Top Affiliating Genes
1 proteinaceous extracellular matrix GO:0005578 9.62 COL4A1 COL4A3 COL4A4 COL4A5
2 endoplasmic reticulum lumen GO:0005788 9.56 COL4A1 COL4A3 COL4A4 COL4A5
3 collagen trimer GO:0005581 9.46 COL4A1 COL4A3 COL4A4 COL4A5
4 neuromuscular junction GO:0031594 9.4 COL4A5 MYH9
5 basal lamina GO:0005605 9.37 COL4A4 COL4A5
6 basement membrane GO:0005604 9.26 COL4A1 COL4A3 COL4A4 COL4A5
7 collagen type IV trimer GO:0005587 8.92 COL4A1 COL4A3 COL4A4 COL4A5

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix organization GO:0030198 9.46 COL4A1 COL4A3 COL4A4 COL4A5
2 neuromuscular junction development GO:0007528 9.32 COL4A1 COL4A5
3 glomerular basement membrane development GO:0032836 9.26 COL4A3 COL4A4
4 collagen-activated tyrosine kinase receptor signaling pathway GO:0038063 9.13 COL4A1 COL4A3 COL4A5
5 collagen catabolic process GO:0030574 8.92 COL4A1 COL4A3 COL4A4 COL4A5

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix structural constituent GO:0005201 8.92 COL4A1 COL4A3 COL4A4 COL4A5

Sources for Alport Syndrome, Autosomal Dominant

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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