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COL4A4 Gene(Protein Coding)

Collagen Type IV Alpha 4 Chain

GCID:
GC02M226967
GIFtS:
58
Genes Participants
UDN Logo

Aliases for COL4A4 Gene

Aliases for COL4A4 Gene

  • Collagen Type IV Alpha 4 Chain 2 3 5
  • Collagen Of Basement Membrane, Alpha-4 Chain 2 3
  • Collagen, Type IV, Alpha 4 2 3
  • Collagen IV, Alpha-4 Polypeptide 3
  • Collagen Alpha-4(IV) Chain 3
  • CA44 3

External Ids for COL4A4 Gene

Previous GeneCards Identifiers for COL4A4 Gene

  • GC02M225892
  • GC02M226590
  • GC02M227833
  • GC02M228072
  • GC02M227695
  • GC02M227578
  • GC02M227867
  • GC02M219710
  • GC02M226969

Summaries for COL4A4 Gene

Entrez Gene Summary for COL4A4 Gene

  • This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. This particular collagen IV subunit, however, is only found in a subset of basement membranes. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Mutations in this gene are associated with type II autosomal recessive Alport syndrome (hereditary glomerulonephropathy) and with familial benign hematuria (thin basement membrane disease). Two transcripts, differing only in their transcription start sites, have been identified for this gene and, as is common for collagen genes, multiple polyadenylation sites are found in the 3' UTR. [provided by RefSeq, Jul 2008]

GeneCards Summary for COL4A4 Gene

COL4A4 (Collagen Type IV Alpha 4 Chain) is a Protein Coding gene. Diseases associated with COL4A4 include Alport Syndrome, Autosomal Recessive and Hematuria, Benign Familial. Among its related pathways are Collagen chain trimerization and Phospholipase-C Pathway. GO annotations related to this gene include extracellular matrix structural constituent. An important paralog of this gene is COL4A6.

UniProtKB/Swiss-Prot for COL4A4 Gene

  • Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a chicken-wire meshwork together with laminins, proteoglycans and entactin/nidogen.

Gene Wiki entry for COL4A4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for COL4A4 Gene

Genomics for COL4A4 Gene

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  1. Regulatory Element

Regulatory Elements for COL4A4 Gene

Enhancers for COL4A4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02G227189 0.5 ENCODE 11.5 -23.9 -23901 0.2 JUND ASH2L GABPA NR2F2 COL4A3 COL4A4 GC02P227300
GH02G227188 0.4 ENCODE 11.5 -24.4 -24426 0.6 POLR2A NR2F2 COL4A3 COL4A4 GC02P227300
GH02G227153 0.6 FANTOM5 3.2 +11.1 11116 0.2 RFX1 MXI1 SMC3 MAX RAD21 EP300 RFX5 COL4A4 GC02M227121
GH02G227155 0.4 ENCODE 0.4 +9.4 9430 0.2 NR3C1 COL4A4 GC02M227121
GH02G227156 0.4 ENCODE 0.4 +9.3 9269 0.1 NR3C1 COL4A4 GC02M227121
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around COL4A4 on UCSC Golden Path with GeneCards custom track

Promoters for COL4A4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000131406 159 1201 ZFP64 SIN3A GLIS2 SCRT2 KLF7 EGR2 ZNF263 SP3 ZNF398 ZNF610

Transcription factor binding sites by QIAGEN in the COL4A4 gene promoter:

Genomic Location for COL4A4 Gene

Chromosome:
2
Start:
226,967,532 bp from pter
End:
227,164,559 bp from pter
Size:
197,028 bases
Orientation:
Minus strand

Genomic View for COL4A4 Gene

Genes around COL4A4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
COL4A4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for COL4A4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for COL4A4 Gene

Proteins for COL4A4 Gene

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  • Protein details for COL4A4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P53420-CO4A4_HUMAN
    Recommended name:
    Collagen alpha-4(IV) chain
    Protein Accession:
    P53420
    Secondary Accessions:
    • A8MTZ1
    • Q53RW9
    • Q53S42
    • Q53WR1

    Protein attributes for COL4A4 Gene

    Size:
    1690 amino acids
    Molecular mass:
    164038 Da
    Quaternary structure:
    • There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. The alpha 3(IV) chain forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this triple helical structure dimerizes through NC1-NC1 domain interactions such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV) chains of the opposite protomer, respectively. Associates with LAMB2 at the neuromuscular junction and in GBM (By similarity).

neXtProt entry for COL4A4 Gene

Protein Expression for COL4A4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for COL4A4 Gene

  • Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
  • The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.
  • Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.
  • Ubiquitination at Lys1229
  • Glycosylation at posLast=142142 and Asn669
  • Modification sites at PhosphoSitePlus

Other Protein References for COL4A4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for COL4A4 Gene

Domains & Families for COL4A4 Gene

Gene Families for COL4A4 Gene

HGNC:

Protein Domains for COL4A4 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for COL4A4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P53420

UniProtKB/Swiss-Prot:

CO4A4_HUMAN :
  • Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.
  • Belongs to the type IV collagen family.
Domain:
  • Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.
Family:
  • Belongs to the type IV collagen family.
genes like me logo Genes that share domains with COL4A4: view

Function for COL4A4 Gene

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Molecular function for COL4A4 Gene

GENATLAS Biochemistry:
collagen type IV,alpha 4,glomerular basement membrane,Bowman capsule,distal TBM,neuromuscular junction,preferentially expressed early in development,suggesting a potential role in dermoepidermal junction (DEJ) formation
UniProtKB/Swiss-Prot Function:
Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a chicken-wire meshwork together with laminins, proteoglycans and entactin/nidogen.

Gene Ontology (GO) - Molecular Function for COL4A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005201 extracellular matrix structural constituent IMP 17942953
genes like me logo Genes that share ontologies with COL4A4: view
genes like me logo Genes that share phenotypes with COL4A4: view

Human Phenotype Ontology for COL4A4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

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No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for COL4A4 Gene

Localization for COL4A4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for COL4A4 Gene

Secreted, extracellular space, extracellular matrix, basement membrane. Note=Colocalizes with COL4A4 and COL4A5 in GBM, tubular basement membrane (TBM) and synaptic basal lamina (BL). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for COL4A4 gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 5
mitochondrion 2
plasma membrane 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for COL4A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005578 proteinaceous extracellular matrix IEA --
GO:0005581 collagen trimer IEA --
GO:0005587 collagen type IV trimer IDA 7523402
GO:0005604 basement membrane IEA --
genes like me logo Genes that share ontologies with COL4A4: view

Pathways & Interactions for COL4A4 Gene

genes like me logo Genes that share pathways with COL4A4: view

Gene Ontology (GO) - Biological Process for COL4A4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0030198 extracellular matrix organization TAS --
GO:0030574 collagen catabolic process TAS --
GO:0032836 glomerular basement membrane development IMP 17942953
genes like me logo Genes that share ontologies with COL4A4: view

No data available for SIGNOR curated interactions for COL4A4 Gene

Drugs & Compounds for COL4A4 Gene

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  1. Drug
No Compound Related Data Available

Transcripts for COL4A4 Gene

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  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
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mRNA/cDNA for COL4A4 Gene

(22) REFSEQ mRNAs :
(3) Additional mRNA sequences :
(8) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for COL4A4 Gene

Collagen, type IV, alpha 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

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Alternative Splicing Database (ASD) splice patterns (SP) for COL4A4 Gene

No ASD Table

Relevant External Links for COL4A4 Gene

GeneLoc Exon Structure for
COL4A4
ECgene alternative splicing isoforms for
COL4A4

Expression for COL4A4 Gene

Products:

  1. Primer

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for COL4A4 Gene

mRNA expression in normal human tissues for COL4A4 Gene
mRNA expression by BioGPS for COL4A4 GenemRNA expression by GTEx for COL4A4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for COL4A4 Gene

This gene is overexpressed in Kidney - Cortex (x6.1) and Pituitary (x4.5).

Protein differential expression in normal tissues from HIPED for COL4A4 Gene

This gene is overexpressed in Retina (27.5), Lung (17.6), Gallbladder (9.7), and Heart (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for COL4A4 Gene



Protein tissue co-expression partners for COL4A4 Gene

NURSA nuclear receptor signaling pathways regulating expression of COL4A4 Gene:

COL4A4

SOURCE GeneReport for Unigene cluster for COL4A4 Gene:

Hs.591645

mRNA Expression by UniProt/SwissProt for COL4A4 Gene:

P53420-CO4A4_HUMAN
Tissue specificity: Alpha 3 and alpha 4 type IV collagens are colocalized and present in kidney, eye, basement membranes of lens capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal kidney and fetal lung. PubMed:8083201 reports similar levels of expression of alpha 3 and alpha 4 type IV collagens in kidney, but PubMed:7523402 reports that in kidney levels of alpha 3 type IV collagen are significantly lower than those of alpha 4 type IV collagen. Highest levels of expression of alpha 4 type IV collagen are detected in kidney, calvaria, neuroretina and cardiac muscle. Lower levels of expression are observed in brain, lung and thymus, and no expression is detected in choroid plexus, liver, adrenal, pancreas, ileum or skin.

Evidence on tissue expression from TISSUES for COL4A4 Gene

  • Kidney(4.5)
  • Eye(4.3)

Phenotype-based relationships between genes and organs from Gene ORGANizer for COL4A4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • immune
  • integumentary
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Organs:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • eyelid
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • neck
  • skull
Thorax:
  • chest wall
  • clavicle
  • diaphragm
  • heart
  • lung
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • kidney
Pelvis:
  • pelvis
  • ureter
  • urinary bladder
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood
  • blood vessel
  • coagulation system
  • peripheral nervous system
  • red blood cell
  • skin
  • spinal column
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with COL4A4: view

Primer Products

Orthologs for COL4A4 Gene

This gene was present in the common ancestor of animals.

Orthologs for COL4A4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia COL4A4 34 35
  • 99.21 (n)
dog
(Canis familiaris)
 Mammalia COL4A4 34 35
  • 85.01 (n)
mouse
(Mus musculus)
 Mammalia Col4a4 34 16 35
  • 80.81 (n)
cow
(Bos Taurus)
 Mammalia COL4A4 35
  • 79 (a)
 OneToOne
oppossum
(Monodelphis domestica)
 Mammalia COL4A4 35
  • 70 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia COL4A4 35
  • 68 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves COL4A4 35
  • 58 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia COL4A4 35
  • 59 (a)
 OneToOne
zebrafish
(Danio rerio)
 Actinopterygii col4a4 35
  • 47 (a)
 OneToOne
worm
(Caenorhabditis elegans)
 Secernentea let-2 36
  • 56 (a)
emb-9 36
  • 37 (a)
Species where no ortholog for COL4A4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for COL4A4 Gene

ENSEMBL:
Gene Tree for COL4A4 (if available)
TreeFam:
Gene Tree for COL4A4 (if available)

Paralogs for COL4A4 Gene

Paralogs for COL4A4 Gene

(7) SIMAP similar genes for COL4A4 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with COL4A4: view

Variants for COL4A4 Gene

Sequence variations from dbSNP and Humsavar for COL4A4 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs121912858 Pathogenic, Alport syndrome, autosomal recessive (APSAR) [MIM:203780] 227,032,253(-) CACCT(A/G)GTCCA nc-transcript-variant, reference, missense
rs121912860 Pathogenic, Hematuria, benign familial (BFH) [MIM:141200] 227,055,971(-) TGATG(A/G)GCTAC nc-transcript-variant, reference, missense
rs121912863 Pathogenic, Alport syndrome, autosomal recessive (APSAR) [MIM:203780] 227,008,112(-) GGCCC(C/T)GGCCC intron-variant, nc-transcript-variant, reference, missense
rs13027659 Benign, Hematuria, benign familial (BFH) [MIM:141200] 227,051,131(+) TTCTC(C/T)CTTGC nc-transcript-variant, reference, missense
rs769783985 Hematuria, benign familial (BFH) [MIM:141200] 227,052,395(+) ATCTC(C/T)GGGAG nc-transcript-variant, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for COL4A4 Gene

Variant ID Type Subtype PubMed ID
esv25855 CNV gain+loss 19812545
esv2661705 CNV deletion 23128226
esv2721548 CNV deletion 23290073
esv3306813 CNV mobile element insertion 20981092
esv3327714 CNV insertion 20981092
esv3594526 CNV loss 21293372
esv3594529 CNV loss 21293372
nsv1116832 CNV deletion 24896259
nsv526108 CNV loss 19592680
nsv584594 CNV gain 21841781

Variation tolerance for COL4A4 Gene

Residual Variation Intolerance Score: 14% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 14.26; 96.25% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for COL4A4 Gene

Human Gene Mutation Database (HGMD)
COL4A4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
COL4A4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for COL4A4 Gene

Disorders for COL4A4 Gene

MalaCards: The human disease database

(12) MalaCards diseases for COL4A4 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
alport syndrome, autosomal recessive
  • autosomal recessive alport syndrome
hematuria, benign familial
  • thin basement membrane nephropathy
alport syndrome, autosomal dominant
  • autosomal dominant alport syndrome
col4a4-related nephropathy
alport syndrome
  • alport syndrome, x-linked
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

CO4A4_HUMAN
  • Alport syndrome, autosomal recessive (APSAR) [MIM:203780]: 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. {ECO:0000269 PubMed:7987396, ECO:0000269 PubMed:9792860}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Hematuria, benign familial (BFH) [MIM:141200]: An autosomal dominant condition characterized by non-progressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane. {ECO:0000269 PubMed:11961012, ECO:0000269 PubMed:12631110, ECO:0000269 PubMed:8787673}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for COL4A4

Genetic Association Database (GAD)
COL4A4
Human Genome Epidemiology (HuGE) Navigator
COL4A4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
COL4A4
genes like me logo Genes that share disorders with COL4A4: view

No data available for Genatlas for COL4A4 Gene

Publications for COL4A4 Gene

  1. Mutations in the COL4A4 gene in thin basement membrane disease. (PMID: 12631110) Buzza M. … Savige J. (Kidney Int. 2003) 3 4 22 46 64
  2. Identification of novel variants in the COL4A4 gene in Korean patients with thin basement membrane nephropathy. (PMID: 19675380) Baek J.I. … Kim U.K. (Indian J. Med. Res. 2009) 3 22 46 64
  3. Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus. (PMID: 20029656) Stabuc-Silih M. … Strazisar M. (Mol. Vis. 2009) 3 22 46 64
  4. Two genes, COL4A3 and COL4A4 coding for the human alpha3(IV) and alpha4(IV) collagen chains are arranged head-to-head on chromosome 2q36. (PMID: 9537506) Momota R. … Ninomiya Y. (FEBS Lett. 1998) 3 4 22 64
  5. Determination of the genomic structure of the COL4A4 gene and of novel mutations causing autosomal recessive Alport syndrome. (PMID: 9792860) Boye E. … Antignac C. (Am. J. Hum. Genet. 1998) 3 4 22 64

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