APSAD
MCID: ALP074
MIFTS: 45

Alport Syndrome, Autosomal Dominant (APSAD)

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

Aliases & Classifications for Alport Syndrome, Autosomal Dominant

MalaCards integrated aliases for Alport Syndrome, Autosomal Dominant:

Name: Alport Syndrome, Autosomal Dominant 57 75 29 13 55 6 73
Autosomal Dominant Alport Syndrome 12 53 59 15
Renal Failure and Sensorineural Hearing Loss 53
Syndrome, Alport, Autosomal Dominant 40
Alport Syndrome Dominant Type 53
Nephritis-Deafness Syndrome 75
Nephropathy and Deafness 75
Apsad 75

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant alport syndrome
Inheritance: Autosomal dominant; Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
hearing loss is variable


HPO:

32
alport syndrome, autosomal dominant:
Onset and clinical course progressive
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 104200
Disease Ontology 12 DOID:0110032
Orphanet 59 ORPHA88918
UMLS via Orphanet 74 C1567743 C2931253
MESH via Orphanet 45 C536586
ICD10 via Orphanet 34 Q87.8
MedGen 42 C1567743
MeSH 44 D009394
UMLS 73 C1567743

Summaries for Alport Syndrome, Autosomal Dominant

OMIM : 57 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. An important gene associated with Alport Syndrome, Autosomal Dominant is COL4A3 (Collagen Type IV Alpha 3 Chain), and among its related pathways/superpathways are Developmental Biology and Integrin Pathway. Affiliated tissues include eye and kidney, and related phenotypes are hypertension and sensorineural hearing impairment

UniProtKB/Swiss-Prot : 75 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 : 53 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.

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:

57
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:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 hypertension 32 HP:0000822
2 sensorineural hearing impairment 32 HP:0000407
3 renal insufficiency 32 HP:0000083
4 proteinuria 32 HP:0000093
5 hypophosphatemia 32 HP:0002148
6 myopia 32 HP:0000545
7 nephrotic syndrome 32 HP:0000100
8 hematuria 32 HP:0000790
9 nephrocalcinosis 32 HP:0000121
10 stage 5 chronic kidney disease 32 HP:0003774
11 azotemia 32 HP:0002157
12 anterior polar cataract 32 HP:0001134
13 glomerulonephritis 32 HP:0000099
14 thickening of the glomerular basement membrane 32 HP:0004722
15 lenticonus 32 HP:0001142
16 diffuse glomerular basement membrane lamellation 32 HP:0030034

MGI Mouse Phenotypes related to Alport Syndrome, Autosomal Dominant:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 immune system MP:0005387 9.63 COL4A1 COL4A3 COL4A4 COL4A5 IGBP1 MYH9
2 renal/urinary system MP:0005367 9.35 COL4A1 COL4A3 COL4A4 COL4A5 MYH9
3 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 29 COL4A3

Anatomical Context for Alport Syndrome, Autosomal Dominant

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

41
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
Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome. ( 27281700 )
2016
3
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
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
Correlation of histopathological features and renal impairment in autosomal dominant Alport syndrome in Bull terriers. ( 12401844 )
2002
11
A novel model of autosomal dominant Alport syndrome in Dalmatian dogs. ( 12454218 )
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:

75
# 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 top 50) (show all 93)
# 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.3499G> A (p.Gly1167Arg) single nucleotide variant Pathogenic rs267606745 GRCh38 Chromosome 2, 227295044: 227295044
4 COL4A4 NM_000092.4(COL4A4): c.1321_1369+3del deletion Pathogenic GRCh37 Chromosome 2, 227958838: 227958889
5 COL4A4 NM_000092.4(COL4A4): c.1321_1369+3del deletion Pathogenic GRCh38 Chromosome 2, 227094122: 227094173
6 COL4A3 NM_000091.4(COL4A3): c.998G> C (p.Gly333Ala) single nucleotide variant Pathogenic rs1057519376 GRCh37 Chromosome 2, 228122329: 228122329
7 COL4A3 NM_000091.4(COL4A3): c.998G> C (p.Gly333Ala) single nucleotide variant Pathogenic rs1057519376 GRCh38 Chromosome 2, 227257613: 227257613
8 COL4A3 NM_000091.4(COL4A3): c.4382C> T (p.Pro1461Leu) single nucleotide variant Pathogenic rs760462252 GRCh37 Chromosome 2, 228172555: 228172555
9 COL4A3 NM_000091.4(COL4A3): c.4382C> T (p.Pro1461Leu) single nucleotide variant Pathogenic rs760462252 GRCh38 Chromosome 2, 227307839: 227307839
10 COL4A3 NM_000091.4(COL4A3): c.4474A> T (p.Ser1492Cys) single nucleotide variant Pathogenic rs1057519377 GRCh37 Chromosome 2, 228173626: 228173626
11 COL4A3 NM_000091.4(COL4A3): c.4474A> T (p.Ser1492Cys) single nucleotide variant Pathogenic rs1057519377 GRCh38 Chromosome 2, 227308910: 227308910
12 COL4A3 NM_000091.4(COL4A3): c.833dupT (p.Pro279Alafs) duplication Likely pathogenic GRCh37 Chromosome 2, 228119376: 228119376
13 COL4A3 NM_000091.4(COL4A3): c.833dupT (p.Pro279Alafs) duplication Likely pathogenic GRCh38 Chromosome 2, 227254660: 227254660
14 COL4A3 NM_000091.4(COL4A3): c.127G> C (p.Gly43Arg) single nucleotide variant Benign rs13424243 GRCh38 Chromosome 2, 227238007: 227238007
15 COL4A3 NM_000091.4(COL4A3): c.127G> C (p.Gly43Arg) single nucleotide variant Benign rs13424243 GRCh37 Chromosome 2, 228102723: 228102723
16 COL4A3 NM_000091.4(COL4A3): c.422T> C (p.Leu141Pro) single nucleotide variant Benign rs10178458 GRCh37 Chromosome 2, 228111435: 228111435
17 COL4A3 NM_000091.4(COL4A3): c.422T> C (p.Leu141Pro) single nucleotide variant Benign rs10178458 GRCh38 Chromosome 2, 227246719: 227246719
18 COL4A3 NM_000091.4(COL4A3): c.485A> G (p.Glu162Gly) single nucleotide variant Benign rs6436669 GRCh38 Chromosome 2, 227248459: 227248459
19 COL4A3 NM_000091.4(COL4A3): c.485A> G (p.Glu162Gly) single nucleotide variant Benign rs6436669 GRCh37 Chromosome 2, 228113175: 228113175
20 COL4A3 NM_000091.4(COL4A3): c.805G> A (p.Glu269Lys) single nucleotide variant Benign/Likely benign rs80109666 GRCh37 Chromosome 2, 228118867: 228118867
21 COL4A3 NM_000091.4(COL4A3): c.805G> A (p.Glu269Lys) single nucleotide variant Benign/Likely benign rs80109666 GRCh38 Chromosome 2, 227254151: 227254151
22 COL4A3 NM_000091.4(COL4A3): c.976G> T (p.Asp326Tyr) single nucleotide variant Benign/Likely benign rs55703767 GRCh37 Chromosome 2, 228121101: 228121101
23 COL4A3 NM_000091.4(COL4A3): c.976G> T (p.Asp326Tyr) single nucleotide variant Benign/Likely benign rs55703767 GRCh38 Chromosome 2, 227256385: 227256385
24 COL4A3 NM_000091.4(COL4A3): c.1195C> T (p.Leu399=) single nucleotide variant Benign rs10205042 GRCh37 Chromosome 2, 228128540: 228128540
25 COL4A3 NM_000091.4(COL4A3): c.1195C> T (p.Leu399=) single nucleotide variant Benign rs10205042 GRCh38 Chromosome 2, 227263824: 227263824
26 COL4A3 NM_000091.4(COL4A3): c.1223G> A (p.Arg408His) single nucleotide variant Benign/Likely benign rs34505188 GRCh37 Chromosome 2, 228128568: 228128568
27 COL4A3 NM_000091.4(COL4A3): c.1223G> A (p.Arg408His) single nucleotide variant Benign/Likely benign rs34505188 GRCh38 Chromosome 2, 227263852: 227263852
28 COL4A3 NM_000091.4(COL4A3): c.1452G> A (p.Gly484=) single nucleotide variant Benign/Likely benign rs34019152 GRCh37 Chromosome 2, 228131752: 228131752
29 COL4A3 NM_000091.4(COL4A3): c.1452G> A (p.Gly484=) single nucleotide variant Benign/Likely benign rs34019152 GRCh38 Chromosome 2, 227267036: 227267036
30 COL4A3 NM_000091.4(COL4A3): c.1721C> T (p.Pro574Leu) single nucleotide variant Benign rs28381984 GRCh37 Chromosome 2, 228135631: 228135631
31 COL4A3 NM_000091.4(COL4A3): c.1721C> T (p.Pro574Leu) single nucleotide variant Benign rs28381984 GRCh38 Chromosome 2, 227270915: 227270915
32 COL4A3 NM_000091.4(COL4A3): c.2610G> A (p.Leu870=) single nucleotide variant Uncertain significance rs886039889 GRCh37 Chromosome 2, 228147202: 228147202
33 COL4A3 NM_000091.4(COL4A3): c.2610G> A (p.Leu870=) single nucleotide variant Uncertain significance rs886039889 GRCh38 Chromosome 2, 227282486: 227282486
34 COL4A3 NM_000091.4(COL4A3): c.399G> A (p.Gly133=) single nucleotide variant Benign/Likely benign rs75683214 GRCh38 Chromosome 2, 227246696: 227246696
35 COL4A3 NM_000091.4(COL4A3): c.399G> A (p.Gly133=) single nucleotide variant Benign/Likely benign rs75683214 GRCh37 Chromosome 2, 228111412: 228111412
36 COL4A3 NM_000091.4(COL4A3): c.4041C> A (p.Asp1347Glu) single nucleotide variant Benign/Likely benign rs73996414 GRCh38 Chromosome 2, 227304032: 227304032
37 COL4A3 NM_000091.4(COL4A3): c.4041C> A (p.Asp1347Glu) single nucleotide variant Benign/Likely benign rs73996414 GRCh37 Chromosome 2, 228168748: 228168748
38 COL4A4 NM_000092.4(COL4A4): c.81_86delACTCAT (p.Ile29_Leu30del) deletion Uncertain significance rs771943519 GRCh37 Chromosome 2, 228009260: 228009265
39 COL4A4 NM_000092.4(COL4A4): c.81_86delACTCAT (p.Ile29_Leu30del) deletion Uncertain significance rs771943519 GRCh38 Chromosome 2, 227144544: 227144549
40 COL4A3 NM_000091.4(COL4A3): c.2083G> A (p.Gly695Arg) single nucleotide variant Likely pathogenic rs200287952 GRCh37 Chromosome 2, 228142227: 228142227
41 COL4A3 NM_000091.4(COL4A3): c.2083G> A (p.Gly695Arg) single nucleotide variant Likely pathogenic rs200287952 GRCh38 Chromosome 2, 227277511: 227277511
42 COL4A3 NM_000091.4(COL4A3): c.2115T> A (p.Pro705=) single nucleotide variant Uncertain significance rs201419174 GRCh37 Chromosome 2, 228142259: 228142259
43 COL4A3 NM_000091.4(COL4A3): c.2115T> A (p.Pro705=) single nucleotide variant Uncertain significance rs201419174 GRCh38 Chromosome 2, 227277543: 227277543
44 COL4A3 NM_000091.4(COL4A3): c.3244_3247delAAAG (p.Lys1082Glufs) deletion Pathogenic rs1057516204 GRCh37 Chromosome 2, 228157940: 228157943
45 COL4A3 NM_000091.4(COL4A3): c.3244_3247delAAAG (p.Lys1082Glufs) deletion Pathogenic rs1057516204 GRCh38 Chromosome 2, 227293224: 227293227
46 COL4A3 NM_000091.4(COL4A3): c.3416C> T (p.Pro1139Leu) single nucleotide variant Uncertain significance rs1057516186 GRCh38 Chromosome 2, 227294568: 227294568
47 COL4A3 NM_000091.4(COL4A3): c.3416C> T (p.Pro1139Leu) single nucleotide variant Uncertain significance rs1057516186 GRCh37 Chromosome 2, 228159284: 228159284
48 COL4A4 NM_000092.4(COL4A4): c.2549C> T (p.Ala850Val) single nucleotide variant Uncertain significance rs758199486 GRCh37 Chromosome 2, 227920828: 227920828
49 COL4A4 NM_000092.4(COL4A4): c.2549C> T (p.Ala850Val) single nucleotide variant Uncertain significance rs758199486 GRCh38 Chromosome 2, 227056112: 227056112
50 COL4A3 NM_000091.4(COL4A3): c.4882T> G (p.Ser1628Ala) single nucleotide variant Uncertain significance rs773905198 GRCh38 Chromosome 2, 227310902: 227310902

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 19)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.19 COL4A1 COL4A3 COL4A4 COL4A5 MYH9
2
Show member pathways
13.08 COL4A1 COL4A3 COL4A4 COL4A5 MYH9
3
Show member pathways
12.78 COL4A1 COL4A3 COL4A4 COL4A5
4
Show member pathways
12.74 COL4A1 COL4A3 COL4A4 COL4A5
5
Show member pathways
12.69 COL4A1 COL4A3 COL4A4 COL4A5
6
Show member pathways
12.6 COL4A1 COL4A3 COL4A4 COL4A5
7
Show member pathways
12.55 COL4A1 COL4A3 COL4A4 COL4A5
8 12.53 COL4A1 COL4A3 COL4A4 COL4A5
9
Show member pathways
12.45 COL4A1 COL4A3 COL4A4 COL4A5
10
Show member pathways
12.41 COL4A1 COL4A3 COL4A4 COL4A5 MYH9
11
Show member pathways
11.95 COL4A1 COL4A3 COL4A4 COL4A5
12 11.73 COL4A1 COL4A3 COL4A4 COL4A5
13 11.69 COL4A1 COL4A3 COL4A4 COL4A5
14 11.64 COL4A1 COL4A3 COL4A4 COL4A5
15 11.49 COL4A3 COL4A4 COL4A5 MYH9
16 11.34 COL4A1 COL4A3 COL4A4 COL4A5
17 11.15 COL4A1 COL4A3 COL4A4 COL4A5
18 10.86 COL4A1 COL4A3 COL4A4 COL4A5
19 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 endoplasmic reticulum lumen GO:0005788 9.56 COL4A1 COL4A3 COL4A4 COL4A5
2 collagen trimer GO:0005581 9.46 COL4A1 COL4A3 COL4A4 COL4A5
3 neuromuscular junction GO:0031594 9.37 COL4A5 MYH9
4 basal lamina GO:0005605 9.32 COL4A4 COL4A5
5 basement membrane GO:0005604 9.26 COL4A1 COL4A3 COL4A4 COL4A5
6 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
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9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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45 MESH via Orphanet
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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