COL4A4

Protein identityUniProt · HPA

UniProt accession

P53420

Gene

COL4A4

Ensembl

ENSG00000081052

Chromosome

2

Canonical length

1690 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to extracellular matrix

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

1690 residues, UniProt reviewed canonical sequence.

>P53420|COL4A4
     1  MWSLHIVLMR CSFRLTKSLA TGPWSLILIL FSVQYVYGSG KKYIGPCGGR DCSVCHCVPE
    61  KGSRGPPGPP GPQGPIGPLG APGPIGLSGE KGMRGDRGPP GAAGDKGDKG PTGVPGFPGL
   121  DGIPGHPGPP GPRGKPGMSG HNGSRGDPGF PGGRGALGPG GPLGHPGEKG EKGNSVFILG
   181  AVKGIQGDRG DPGLPGLPGS WGAGGPAGPT GYPGEPGLVG PPGQPGRPGL KGNPGVGVKG
   241  QMGDPGEVGQ QGSPGPTLLV EPPDFCLYKG EKGIKGIPGM VGLPGPPGRK GESGIGAKGE
   301  KGIPGFPGPR GDPGSYGSPG FPGLKGELGL VGDPGLFGLI GPKGDPGNRG HPGPPGVLVT
   361  PPLPLKGPPG DPGFPGRYGE TGDVGPPGPP GLLGRPGEAC AGMIGPPGPQ GFPGLPGLPG
   421  EAGIPGRPDS APGKPGKPGS PGLPGAPGLQ GLPGSSVIYC SVGNPGPQGI KGKVGPPGGR
   481  GPKGEKGNEG LCACEPGPMG PPGPPGLPGR QGSKGDLGLP GWLGTKGDPG PPGAEGPPGL
   541  PGKHGASGPP GNKGAKGDMV VSRVKGHKGE RGPDGPPGFP GQPGSHGRDG HAGEKGDPGP
   601  PGDHEDATPG GKGFPGPLGP PGKAGPVGPP GLGFPGPPGE RGHPGVPGHP GVRGPDGLKG
   661  QKGDTISCNV TYPGRHGPPG FDGPPGPKGF PGPQGAPGLS GSDGHKGRPG TPGTAEIPGP
   721  PGFRGDMGDP GFGGEKGSSP VGPPGPPGSP GVNGQKGIPG DPAFGHLGPP GKRGLSGVPG
   781  IKGPRGDPGC PGAEGPAGIP GFLGLKGPKG REGHAGFPGV PGPPGHSCER GAPGIPGQPG
   841  LPGYPGSPGA PGGKGQPGDV GPPGPAGMKG LPGLPGRPGA HGPPGLPGIP GPFGDDGLPG
   901  PPGPKGPRGL PGFPGFPGER GKPGAEGCPG AKGEPGEKGM SGLPGDRGLR GAKGAIGPPG
   961  DEGEMAIISQ KGTPGEPGPP GDDGFPGERG DKGTPGMQGR RGEPGRYGPP GFHRGEPGEK
  1021  GQPGPPGPPG PPGSTGLRGF IGFPGLPGDQ GEPGSPGPPG FSGIDGARGP KGNKGDPASH
  1081  FGPPGPKGEP GSPGCPGHFG ASGEQGLPGI QGPRGSPGRP GPPGSSGPPG CPGDHGMPGL
  1141  RGQPGEMGDP GPRGLQGDPG IPGPPGIKGP SGSPGLNGLH GLKGQKGTKG ASGLHDVGPP
  1201  GPVGIPGLKG ERGDPGSPGI SPPGPRGKKG PPGPPGSSGP PGPAGATGRA PKDIPDPGPP
  1261  GDQGPPGPDG PRGAPGPPGL PGSVDLLRGE PGDCGLPGPP GPPGPPGPPG YKGFPGCDGK
  1321  DGQKGPVGFP GPQGPHGFPG PPGEKGLPGP PGRKGPTGLP GPRGEPGPPA DVDDCPRIPG
  1381  LPGAPGMRGP EGAMGLPGMR GPSGPGCKGE PGLDGRRGVD GVPGSPGPPG RKGDTGEDGY
  1441  PGGPGPPGPI GDPGPKGFGP GYLGGFLLVL HSQTDQEPTC PLGMPRLWTG YSLLYLEGQE
  1501  KAHNQDLGLA GSCLPVFSTL PFAYCNIHQV CHYAQRNDRS YWLASAAPLP MMPLSEEAIR
  1561  PYVSRCAVCE APAQAVAVHS QDQSIPPCPQ TWRSLWIGYS FLMHTGAGDQ GGGQALMSPG
  1621  SCLEDFRAAP FLECQGRQGT CHFFANKYSF WLTTVKADLQ FSSAPAPDTL KESQAQRQKI
  1681  SRCQVCVKYS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against COL4A4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.61

Highest tissue expression

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about COL4A4.

Disease | AllUniProt

Conditions COL4A4 is implicated in, by any mechanism.

• Alport syndrome 2, autosomal recessive (ATS2) MIM:203780
• Hematuria, benign familial, 1 (BFH1) MIM:141200

Disease | GeneticClinVar

867 pathogenic / likely-pathogenic of 3,740 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal recessive Alport syndrome
• Alport syndrome
• Hematuria, benign familial, 1
• Benign familial hematuria
• Autosomal dominant Alport syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.62

gnomAD pLI

0

gnomAD missense Z

1.02

DepMap mean gene effect

0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• collagen fibril organization
• glomerular basement membrane development

Molecular functions

• extracellular matrix structural constituent
• extracellular matrix structural constituent conferring tensile strength
• molecular adaptor activity

Cellular components

• basement membrane
• collagen type IV trimer
• endoplasmic reticulum lumen
• extracellular matrix
• extracellular region

Protein domainsUniProt · Pfam · InterPro

• Collagen IV, non-collagenous
• Collagen triple helix repeat
• C-type lectin fold
• Collagen IV, non-collagenous domain superfamily
• Collagen superfamily
• Collagen triple helix repeat (20 copies)
• C-terminal tandem repeated domain in type 4 procollagen

KeywordsUniProt

• Alport syndrome
• Basement membrane
• Collagen
• Deafness
• Disulfide bond
• Extracellular matrix
• Glycoprotein
• Hydroxylation
• Repeat
• Secreted
• Signal