MCID: ALP073
MIFTS: 50

Alport Syndrome, Autosomal Recessive

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

Aliases & Classifications for Alport Syndrome, Autosomal Recessive

MalaCards integrated aliases for Alport Syndrome, Autosomal Recessive:

Name: Alport Syndrome, Autosomal Recessive 53 71 28 13 51 69
Autosomal Recessive Alport Syndrome 12 49 55 14
Nephropathy and Deafness 49 71
Alport Syndrome Autosomal Recessive 49
Alport Syndrome Recessive Type 49
Nephritis-Deafness Syndrome 71
Apsar 71

Characteristics:

Orphanet epidemiological data:

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

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
genetic heterogeneity
onset in childhood
hearing loss occurs in late childhood
hearing loss and ocular findings are variable
about 1 to 5% of patients who undergo renal transplantation develop anti-glomerular basement membrane nephritis


HPO:

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


Classifications:



External Ids:

OMIM 53 203780
Disease Ontology 12 DOID:0110033
Orphanet 55 ORPHA88919
MESH via Orphanet 42 C536587
UMLS via Orphanet 70 C1567744 C2931254
ICD10 via Orphanet 33 Q87.8
MedGen 39 C1567744
MeSH 41 D009394
UMLS 69 C1567744

Summaries for Alport Syndrome, Autosomal Recessive

NIH Rare Diseases : 49 Autosomal recessive 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. About 15 percent of Alport syndrome cases are inherited in an autosomal recessive pattern and are caused by mutations in both copies of the COL4A3 or COL4A4 genes. Treatment is based on the symptoms present and may include medications to delay the progression of kidney disease. In most cases, a kidney transplant is eventually needed.  Last updated: 6/14/2016

MalaCards based summary : Alport Syndrome, Autosomal Recessive, also known as autosomal recessive alport syndrome, is related to alport syndrome, x-linked and corneal dystrophy, posterior polymorphous, 3, and has symptoms including hypertension, hearing impairment and cataract. An important gene associated with Alport Syndrome, Autosomal Recessive is COL4A4 (Collagen Type IV Alpha 4 Chain), and among its related pathways/superpathways are Developmental Biology and Integrin Pathway. Affiliated tissues include eye, kidney and endothelial, and related phenotypes are homeostasis/metabolism and mortality/aging

OMIM : 53 Alport syndrome is a hereditary disorder of the basement membrane, resulting in a glomerulonephropathy causing renal failure. Progressive deafness and ocular anomalies may also occur (Mochizuki et al., 1994; Colville et al. (1997)). 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; autosomal dominant inheritance (104200) is rare (van der Loop et al., 2000). See also benign familial hematuria (BFH; 141200), a similar but milder disorder. (203780)

UniProtKB/Swiss-Prot : 71 Alport syndrome, autosomal recessive: 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.

Disease Ontology : 12 An Alport syndrome that has_material -basis_in homozygous or compound heterozygous mutation in the COL4A3 or the COL4A4 gene, both of which map to chromosome 2q

Related Diseases for Alport Syndrome, Autosomal Recessive

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



Diseases related to Alport Syndrome, Autosomal Recessive

Symptoms & Phenotypes for Alport Syndrome, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

53
Cardiovascular Vascular:
hypertension

Head And Neck Eyes:
myopia
cataracts
corneal erosions
anterior lenticonus
lens opacities
more
Genitourinary Kidneys:
glomerulonephropathy
end-stage renal failure
thinning of the glomerular basement membrane (early in the disease)
thickening of the glomerular basement membrane (later in the disease)
splitting of the glomerular basement membrane
more
Laboratory Abnormalities:
proteinuria
nephrotic syndrome
hematuria, gross and microscopic

Head And Neck Ears:
deafness, sensorineural, especially affecting high frequencies


Clinical features from OMIM:

203780

Human phenotypes related to Alport Syndrome, Autosomal Recessive:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 hypertension 31 HP:0000822
2 hearing impairment 31 HP:0000365
3 cataract 31 HP:0000518
4 proteinuria 31 HP:0000093
5 corneal erosion 31 HP:0200020
6 myopia 31 HP:0000545
7 nephrotic syndrome 31 HP:0000100
8 hematuria 31 HP:0000790
9 stage 5 chronic kidney disease 31 HP:0003774
10 nephritis 31 HP:0000123
11 anterior lenticonus 31 HP:0011501
12 thickening of the glomerular basement membrane 31 HP:0004722
13 diffuse glomerular basement membrane lamellation 31 HP:0030034

MGI Mouse Phenotypes related to Alport Syndrome, Autosomal Recessive:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.87 COL4A3 COL4A4 COL4A5 KLF4 LIN28A LMX1B
2 mortality/aging MP:0010768 9.86 COL4A3 COL4A4 COL4A5 KLF4 LIN28A LMX1B
3 normal MP:0002873 9.63 COL4A6 KLF4 LIN28A LMX1B MYCL MYH9
4 renal/urinary system MP:0005367 9.35 MYH9 COL4A3 COL4A4 COL4A5 LMX1B
5 vision/eye MP:0005391 9.1 COL4A3 COL4A4 COL4A5 KLF4 LMX1B MYH9

Drugs & Therapeutics for Alport Syndrome, Autosomal Recessive

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 Recessive

Genetic Tests for Alport Syndrome, Autosomal Recessive

Genetic tests related to Alport Syndrome, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Alport Syndrome, Autosomal Recessive 28 COL4A3 COL4A4

Anatomical Context for Alport Syndrome, Autosomal Recessive

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

38
Eye, Kidney, Endothelial

Publications for Alport Syndrome, Autosomal Recessive

Articles related to Alport Syndrome, Autosomal Recessive:

(show all 25)
# Title Authors Year
1
COL4A6 is dispensable for autosomal recessive Alport syndrome. ( 27377778 )
2016
2
Early RAAS Blockade Exerts Renoprotective Effects in Autosomal Recessive Alport Syndrome. ( 27904025 )
2016
3
Alport syndrome and pregnancy: Good obstetric and nephrological outcomes in a pregnant woman with homozygous autosomal recessive Alport syndrome. ( 26628290 )
2016
4
X-Linked and Autosomal Recessive Alport Syndrome: Pathogenic Variant Features and Further Genotype-Phenotype Correlations. ( 27627812 )
2016
5
Carriers of Autosomal Recessive Alport Syndrome with Thin Basement Membrane Nephropathy Presenting as Focal Segmental Glomerulosclerosis in Later Life. ( 26201269 )
2015
6
Novel COL4A3 gene mutations in a consanguineous family with autosomal recessive Alport syndrome. ( 26194984 )
2015
7
Natural history of genetically proven autosomal recessive Alport syndrome. ( 24633401 )
2014
8
COL4A3/COL4A4 mutations and features in individuals with autosomal recessive Alport syndrome. ( 24052634 )
2013
9
A novel COL4A3 mutation causes autosomal-recessive Alport syndrome in a large Turkish family. ( 23297803 )
2013
10
A founder mutation in COL4A3 causes autosomal recessive Alport syndrome in the Ashkenazi Jewish population. ( 23927549 )
2013
11
Genotype-phenotype correlations in 17 Chinese patients with autosomal recessive Alport syndrome. ( 22887978 )
2012
12
Novel COL4A3 mutations in African American siblings with autosomal recessive Alport syndrome. ( 18436078 )
2008
13
Characterization of the peripheral retinopathy in X-linked and autosomal recessive Alport syndrome. ( 17071739 )
2007
14
Autosomal recessive Alport syndrome: an in-depth clinical and molecular analysis of five families. ( 16338941 )
2006
15
Living related kidney transplantation in a patient with autosomal-recessive Alport syndrome. ( 12823249 )
2003
16
Three novel COL4A4 mutations resulting in stop codons and their clinical effects in autosomal recessive Alport syndrome. ( 12325029 )
2002
17
Autosomal recessive Alport syndrome: linkage analysis and clinical features in two families. ( 10193810 )
1999
18
A model of autosomal recessive Alport syndrome in English cocker spaniel dogs. ( 9734596 )
1998
19
Determination of the genomic structure of the COL4A4 gene and of novel mutations causing autosomal recessive Alport syndrome. ( 9792860 )
1998
20
Ocular manifestations of autosomal recessive Alport syndrome. ( 9361309 )
1997
21
Autosomal recessive Alport syndrome: mutation in the COL4A3 gene in a woman with Alport syndrome and posttransplant antiglomerular basement membrane nephritis. ( 7780062 )
1995
22
Splice-mediated insertion of an Alu sequence in the COL4A3 mRNA causing autosomal recessive Alport syndrome. ( 7633417 )
1995
23
Autosomal recessive Alport syndrome: immunohistochemical study of type IV collagen chain distribution. ( 7783412 )
1995
24
Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. ( 7987396 )
1994
25
Mutations in the type IV collagen alpha 3 (COL4A3) gene in autosomal recessive Alport syndrome. ( 7987301 )
1994

Variations for Alport Syndrome, Autosomal Recessive

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

71 (show all 14)
# Symbol AA change Variation ID SNP ID
1 COL4A3 p.Gly297Glu VAR_011204
2 COL4A3 p.Gly407Arg VAR_011206
3 COL4A3 p.Gly640Arg VAR_011210 rs200672668
4 COL4A3 p.Gly1207Glu VAR_011212
5 COL4A3 p.Gly1277Ser VAR_011215 rs190598500
6 COL4A3 p.Gly1334Glu VAR_011217 rs375290088
7 COL4A3 p.Arg1661Cys VAR_011219 rs201697532
8 COL4A3 p.Gly532Asp VAR_030945 rs371405814
9 COL4A3 p.Gly739Arg VAR_030946 rs375040636
10 COL4A3 p.Gly853Arg VAR_030947 rs763726708
11 COL4A3 p.Gly1216Arg VAR_030950
12 COL4A4 p.Gly1201Ser VAR_001913 rs121912858
13 COL4A4 p.Gly1030Val VAR_008153
14 COL4A4 p.Pro1572Leu VAR_008155 rs121912863

ClinVar genetic disease variations for Alport Syndrome, Autosomal Recessive:

6 (show all 23)
# Gene Variation Type Significance SNP ID Assembly Location
1 COL4A4 NM_000092.4(COL4A4): c.3601G> A (p.Gly1201Ser) single nucleotide variant Pathogenic rs121912858 GRCh37 Chromosome 2, 227896969: 227896969
2 COL4A4 NM_000092.4(COL4A4): c.3713C> A (p.Ser1238Ter) single nucleotide variant Pathogenic rs121912859 GRCh37 Chromosome 2, 227896765: 227896765
3 COL4A4 NM_000092.4(COL4A4): c.4129C> T (p.Arg1377Ter) single nucleotide variant Pathogenic rs121912861 GRCh37 Chromosome 2, 227886851: 227886851
4 COL4A4 NM_000092.4(COL4A4): c.4923C> A (p.Cys1641Ter) single nucleotide variant Pathogenic rs121912862 GRCh37 Chromosome 2, 227872191: 227872191
5 COL4A4 NM_000092.4(COL4A4): c.4715C> T (p.Pro1572Leu) single nucleotide variant Pathogenic rs121912863 GRCh37 Chromosome 2, 227872828: 227872828
6 COL4A3 COL4A3, 5-BP DEL, NT4414 deletion Pathogenic
7 COL4A3 NM_000091.4(COL4A3): c.4441C> T (p.Arg1481Ter) single nucleotide variant Pathogenic rs121912824 GRCh37 Chromosome 2, 228172614: 228172614
8 COL4A3 NM_000091.4(COL4A3): c.4571C> G (p.Ser1524Ter) single nucleotide variant Pathogenic rs121912825 GRCh37 Chromosome 2, 228173723: 228173723
9 COL4A3 COL4A3, ALU INS, EX6 insertion Pathogenic
10 COL4A3 NM_000091.4(COL4A3): c.40_63del24 (p.Leu14_Leu21del) deletion Pathogenic rs876657397 GRCh38 Chromosome 2, 227164766: 227164789
11 COL4A3 NM_000091.4(COL4A3): c.833dupT (p.Pro279Alafs) duplication Likely pathogenic GRCh37 Chromosome 2, 228119376: 228119376
12 COL4A3 NM_000091.4(COL4A3): c.4981C> T (p.Arg1661Cys) single nucleotide variant Pathogenic/Likely pathogenic rs201697532 GRCh37 Chromosome 2, 228176554: 228176554
13 COL4A4 NM_000092.4(COL4A4): c.446G> T (p.Gly149Val) single nucleotide variant Likely pathogenic rs374815903 GRCh37 Chromosome 2, 227983404: 227983404
14 COL4A3 NM_000091.4(COL4A3): c.1918G> A (p.Gly640Arg) single nucleotide variant Likely pathogenic rs200672668 GRCh38 Chromosome 2, 227273108: 227273108
15 COL4A3 NM_000091.4(COL4A3): c.2215G> A (p.Gly739Arg) single nucleotide variant Likely pathogenic rs375040636 GRCh38 Chromosome 2, 227279882: 227279882
16 COL4A3 NM_000091.4(COL4A3): c.3955G> A (p.Gly1319Arg) single nucleotide variant Pathogenic rs765661521 GRCh37 Chromosome 2, 228167826: 228167826
17 COL4A3 NM_000091.4(COL4A3): c.2371C> T (p.Arg791Ter) single nucleotide variant Likely pathogenic rs1060499654 GRCh38 Chromosome 2, 227280587: 227280587
18 COL4A3 NM_000091.4(COL4A3): c.1175G> A (p.Gly392Glu) single nucleotide variant Pathogenic rs1114167371 GRCh37 Chromosome 2, 228128520: 228128520
19 COL4A4 NM_000092.4(COL4A4): c.3574_3577+8delTCAGGTAAGCAC deletion Likely pathogenic GRCh38 Chromosome 2, 227033402: 227033413
20 COL4A4 NM_000092.4(COL4A4): c.3089G> A (p.Gly1030Asp) single nucleotide variant Likely pathogenic rs772699709 GRCh37 Chromosome 2, 227915754: 227915754
21 COL4A4 NM_000092.4(COL4A4): c.2662G> A (p.Gly888Arg) single nucleotide variant Likely pathogenic GRCh37 Chromosome 2, 227920715: 227920715
22 COL4A4 NM_000092.4(COL4A4): c.594+1G> A single nucleotide variant Pathogenic GRCh37 Chromosome 2, 227976393: 227976393
23 COL4A4 NM_000092.4(COL4A4): c.2638_2639delGC (p.Ala880Thrfs) deletion Pathogenic GRCh37 Chromosome 2, 227920738: 227920739

Expression for Alport Syndrome, Autosomal Recessive

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

Pathways for Alport Syndrome, Autosomal Recessive

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

(show all 22)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.21 COL4A3 COL4A4 COL4A5 KLF4 LIN28A MYH9
2
Show member pathways
13.04 COL4A3 COL4A4 COL4A5 COL4A6
3
Show member pathways
12.78 COL4A3 COL4A4 COL4A5 COL4A6
4
Show member pathways
12.71 COL4A3 COL4A4 COL4A5 COL4A6
5
Show member pathways
12.64 COL4A3 COL4A4 COL4A5 COL4A6
6 12.58 COL4A3 COL4A4 COL4A5 COL4A6
7
Show member pathways
12.57 COL4A3 COL4A4 COL4A5 COL4A6
8
Show member pathways
12.49 COL4A3 COL4A4 COL4A5 COL4A6
9
Show member pathways
12.39 COL4A3 COL4A4 COL4A5 COL4A6 MYH9
10
Show member pathways
12.33 COL4A3 COL4A4 COL4A5 COL4A6
11
Show member pathways
12 COL4A3 COL4A4 COL4A5 COL4A6 MYH9
12
Show member pathways
11.93 COL4A3 COL4A4 COL4A5 COL4A6
13 11.7 COL4A3 COL4A4 COL4A5 COL4A6
14 11.65 COL4A3 COL4A4 COL4A5 COL4A6
15 11.59 COL4A3 COL4A4 COL4A5 COL4A6
16 11.34 COL4A3 COL4A4 COL4A5 COL4A6
17
Show member pathways
11.29 KLF4 LIN28A
18 11.22 COL4A3 COL4A4 COL4A5
19 11.15 COL4A3 COL4A4 COL4A5 COL4A6
20 10.89 COL4A3 COL4A4 COL4A5 LMX1B MYH9
21 10.86 COL4A3 COL4A4 COL4A5 COL4A6
22 10.77 COL4A3 COL4A4 COL4A5 COL4A6

GO Terms for Alport Syndrome, Autosomal Recessive

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

# Name GO ID Score Top Affiliating Genes
1 proteinaceous extracellular matrix GO:0005578 9.62 COL4A3 COL4A4 COL4A5 COL4A6
2 endoplasmic reticulum lumen GO:0005788 9.56 COL4A3 COL4A4 COL4A5 COL4A6
3 collagen trimer GO:0005581 9.46 COL4A3 COL4A4 COL4A5 COL4A6
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 COL4A3 COL4A4 COL4A5 COL4A6
7 collagen type IV trimer GO:0005587 8.92 COL4A3 COL4A4 COL4A5 COL4A6

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix organization GO:0030198 9.46 COL4A3 COL4A4 COL4A5 COL4A6
2 somatic stem cell population maintenance GO:0035019 9.37 KLF4 LIN28A
3 stem cell population maintenance GO:0019827 9.32 KLF4 LIN28A
4 glomerular basement membrane development GO:0032836 9.26 COL4A3 COL4A4
5 collagen catabolic process GO:0030574 9.26 COL4A3 COL4A4 COL4A5 COL4A6
6 collagen-activated tyrosine kinase receptor signaling pathway GO:0038063 8.8 COL4A3 COL4A5 COL4A6

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix structural constituent GO:0005201 8.92 COL4A3 COL4A4 COL4A5 COL4A6

Sources for Alport Syndrome, Autosomal Recessive

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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