COL6A3

Protein identityUniProt · HPA

UniProt accession

P12111

Gene

COL6A3

Ensembl

ENSG00000163359

Chromosome

2

Canonical length

3177 aa

Protein class

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

Subcellular location

Endoplasmic reticulum,Vesicles

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

This gene encodes the alpha-3 chain, one of the three alpha chains of type VI collagen, a beaded filament collagen found in most connective tissues. The alpha-3 chain of type VI collagen is much larger than the alpha-1 and -2 chains. This difference in size is largely due to an increase in the number of subdomains, similar to von Willebrand Factor type A domains, that are found in the amino terminal globular domain of all the alpha chains. These domains have been shown to bind extracellular matrix proteins, an interaction that explains the importance of this collagen in organizing matrix components. Mutations in the type VI collagen genes are associated with Bethlem myopathy, a rare autosomal dominant proximal myopathy with early childhood onset. Mutations in this gene are also a cause of Ullrich congenital muscular dystrophy, also referred to as Ullrich scleroatonic muscular dystrophy, an autosomal recessive congenital myopathy that is more severe than Bethlem myopathy. Multiple transcript variants have been identified, but the full-length nature of only some of these variants has been described. [provided by RefSeq, Jun 2009]

Canonical amino-acid sequenceUniProt

3177 residues, UniProt reviewed canonical sequence.

>P12111|COL6A3
     1  MRKHRHLPLV AVFCLFLSGF PTTHAQQQQA DVKNGAAADI IFLVDSSWTI GEEHFQLVRE
    61  FLYDVVKSLA VGENDFHFAL VQFNGNPHTE FLLNTYRTKQ EVLSHISNMS YIGGTNQTGK
   121  GLEYIMQSHL TKAAGSRAGD GVPQVIVVLT DGHSKDGLAL PSAELKSADV NVFAIGVEDA
   181  DEGALKEIAS EPLNMHMFNL ENFTSLHDIV GNLVSCVHSS VSPERAGDTE TLKDITAQDS
   241  ADIIFLIDGS NNTGSVNFAV ILDFLVNLLE KLPIGTQQIR VGVVQFSDEP RTMFSLDTYS
   301  TKAQVLGAVK ALGFAGGELA NIGLALDFVV ENHFTRAGGS RVEEGVPQVL VLISAGPSSD
   361  EIRYGVVALK QASVFSFGLG AQAASRAELQ HIATDDNLVF TVPEFRSFGD LQEKLLPYIV
   421  GVAQRHIVLK PPTIVTQVIE VNKRDIVFLV DGSSALGLAN FNAIRDFIAK VIQRLEIGQD
   481  LIQVAVAQYA DTVRPEFYFN THPTKREVIT AVRKMKPLDG SALYTGSALD FVRNNLFTSS
   541  AGYRAAEGIP KLLVLITGGK SLDEISQPAQ ELKRSSIMAF AIGNKGADQA ELEEIAFDSS
   601  LVFIPAEFRA APLQGMLPGL LAPLRTLSGT PEVHSNKRDI IFLLDGSANV GKTNFPYVRD
   661  FVMNLVNSLD IGNDNIRVGL VQFSDTPVTE FSLNTYQTKS DILGHLRQLQ LQGGSGLNTG
   721  SALSYVYANH FTEAGGSRIR EHVPQLLLLL TAGQSEDSYL QAANALTRAG ILTFCVGASQ
   781  ANKAELEQIA FNPSLVYLMD DFSSLPALPQ QLIQPLTTYV SGGVEEVPLA QPESKRDILF
   841  LFDGSANLVG QFPVVRDFLY KIIDELNVKP EGTRIAVAQY SDDVKVESRF DEHQSKPEIL
   901  NLVKRMKIKT GKALNLGYAL DYAQRYIFVK SAGSRIEDGV LQFLVLLVAG RSSDRVDGPA
   961  SNLKQSGVVP FIFQAKNADP AELEQIVLSP AFILAAESLP KIGDLHPQIV NLLKSVHNGA
  1021  PAPVSGEKDV VFLLDGSEGV RSGFPLLKEF VQRVVESLDV GQDRVRVAVV QYSDRTRPEF
  1081  YLNSYMNKQD VVNAVRQLTL LGGPTPNTGA ALEFVLRNIL VSSAGSRITE GVPQLLIVLT
  1141  ADRSGDDVRN PSVVVKRGGA VPIGIGIGNA DITEMQTISF IPDFAVAIPT FRQLGTVQQV
  1201  ISERVTQLTR EELSRLQPVL QPLPSPGVGG KRDVVFLIDG SQSAGPEFQY VRTLIERLVD
  1261  YLDVGFDTTR VAVIQFSDDP KVEFLLNAHS SKDEVQNAVQ RLRPKGGRQI NVGNALEYVS
  1321  RNIFKRPLGS RIEEGVPQFL VLISSGKSDD EVDDPAVELK QFGVAPFTIA RNADQEELVK
  1381  ISLSPEYVFS VSTFRELPSL EQKLLTPITT LTSEQIQKLL ASTRYPPPAV ESDAADIVFL
  1441  IDSSEGVRPD GFAHIRDFVS RIVRRLNIGP SKVRVGVVQF SNDVFPEFYL KTYRSQAPVL
  1501  DAIRRLRLRG GSPLNTGKAL EFVARNLFVK SAGSRIEDGV PQHLVLVLGG KSQDDVSRFA
  1561  QVIRSSGIVS LGVGDRNIDR TELQTITNDP RLVFTVREFR ELPNIEERIM NSFGPSAATP
  1621  APPGVDTPPP SRPEKKKADI VFLLDGSINF RRDSFQEVLR FVSEIVDTVY EDGDSIQVGL
  1681  VQYNSDPTDE FFLKDFSTKR QIIDAINKVV YKGGRHANTK VGLEHLRVNH FVPEAGSRLD
  1741  QRVPQIAFVI TGGKSVEDAQ DVSLALTQRG VKVFAVGVRN IDSEEVGKIA SNSATAFRVG
  1801  NVQELSELSE QVLETLHDAM HETLCPGVTD AAKACNLDVI LGFDGSRDQN VFVAQKGFES
  1861  KVDAILNRIS QMHRVSCSGG RSPTVRVSVV ANTPSGPVEA FDFDEYQPEM LEKFRNMRSQ
  1921  HPYVLTEDTL KVYLNKFRQS SPDSVKVVIH FTDGADGDLA DLHRASENLR QEGVRALILV
  1981  GLERVVNLER LMHLEFGRGF MYDRPLRLNL LDLDYELAEQ LDNIAEKACC GVPCKCSGQR
  2041  GDRGPIGSIG PKGIPGEDGY RGYPGDEGGP GERGPPGVNG TQGFQGCPGQ RGVKGSRGFP
  2101  GEKGEVGEIG LDGLDGEDGD KGLPGSSGEK GNPGRRGDKG PRGEKGERGD VGIRGDPGNP
  2161  GQDSQERGPK GETGDLGPMG VPGRDGVPGG PGETGKNGGF GRRGPPGAKG NKGGPGQPGF
  2221  EGEQGTRGAQ GPAGPAGPPG LIGEQGISGP RGSGGAAGAP GERGRTGPLG RKGEPGEPGP
  2281  KGGIGNRGPR GETGDDGRDG VGSEGRRGKK GERGFPGYPG PKGNPGEPGL NGTTGPKGIR
  2341  GRRGNSGPPG IVGQKGDPGY PGPAGPKGNR GDSIDQCALI QSIKDKCPCC YGPLECPVFP
  2401  TELAFALDTS EGVNQDTFGR MRDVVLSIVN DLTIAESNCP RGARVAVVTY NNEVTTEIRF
  2461  ADSKRKSVLL DKIKNLQVAL TSKQQSLETA MSFVARNTFK RVRNGFLMRK VAVFFSNTPT
  2521  RASPQLREAV LKLSDAGITP LFLTRQEDRQ LINALQINNT AVGHALVLPA GRDLTDFLEN
  2581  VLTCHVCLDI CNIDPSCGFG SWRPSFRDRR AAGSDVDIDM AFILDSAETT TLFQFNEMKK
  2641  YIAYLVRQLD MSPDPKASQH FARVAVVQHA PSESVDNASM PPVKVEFSLT DYGSKEKLVD
  2701  FLSRGMTQLQ GTRALGSAIE YTIENVFESA PNPRDLKIVV LMLTGEVPEQ QLEEAQRVIL
  2761  QAKCKGYFFV VLGIGRKVNI KEVYTFASEP NDVFFKLVDK STELNEEPLM RFGRLLPSFV
  2821  SSENAFYLSP DIRKQCDWFQ GDQPTKNLVK FGHKQVNVPN NVTSSPTSNP VTTTKPVTTT
  2881  KPVTTTTKPV TTTTKPVTII NQPSVKPAAA KPAPAKPVAA KPVATKMATV RPPVAVKPAT
  2941  AAKPVAAKPA AVRPPAAAAA KPVATKPEVP RPQAAKPAAT KPATTKPMVK MSREVQVFEI
  3001  TENSAKLHWE RAEPPGPYFY DLTVTSAHDQ SLVLKQNLTV TDRVIGGLLA GQTYHVAVVC
  3061  YLRSQVRATY HGSFSTKKSQ PPPPQPARSA SSSTINLMVS TEPLALTETD ICKLPKDEGT
  3121  CRDFILKWYY DPNTKSCARF WYGGCGGNEN KFGSQKECEK VCAPVLAKPG VISVMGT

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against COL6A3 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

Highest tissue expression

392 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about COL6A3.

Disease | AllUniProt

Conditions COL6A3 is implicated in, by any mechanism.

• Bethlem myopathy 1C (BTHLM1C) MIM:620726
• Ullrich congenital muscular dystrophy 1C (UCMD1C) MIM:620728
• Dystonia 27 (DYT27) MIM:616411

Disease | GeneticClinVar

207 pathogenic / likely-pathogenic of 3,971 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Bethlem myopathy 1A
• Ullrich congenital muscular dystrophy 1A
• Bethlem myopathy 1C
• Ullrich congenital muscular dystrophy 1C
• COL6A3-related disorder

Disease | ImmuneIEDB

Conditions an epitope on COL6A3 was assayed in.

• pancreatic ductal adenocarcinoma T cell
• breast cancer B cell
• colon cancer B cell
• stomach cancer B cell
• skin melanoma B cell
• lung non-small cell carcinoma B cell
• lung small cell carcinoma B cell
• ovarian cancer B cell
• pancreatic cancer B cell
• prostate cancer B cell

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)

0.56

gnomAD pLI

0

gnomAD missense Z

-0.61

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell adhesion
• muscle organ development
• neuron apoptotic process
• phosphatidylinositol 3-kinase/protein kinase B signal transduction
• response to glucose
• response to UV

Molecular functions

• extracellular matrix structural constituent conferring tensile strength
• serine-type endopeptidase inhibitor activity

Cellular components

• collagen type VI trimer
• endoplasmic reticulum lumen
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• extracellular vesicle
• sarcolemma

Protein domainsUniProt · Pfam · InterPro

• von Willebrand factor, type A
• Pancreatic trypsin inhibitor Kunitz domain
• Fibronectin type III
• Collagen triple helix repeat
• Immunoglobulin-like fold
• Proteinase inhibitor I2, Kunitz, conserved site
• Fibronectin type III superfamily
• von Willebrand factor A-like domain superfamily
• Pancreatic trypsin inhibitor Kunitz domain superfamily
• Extracellular Matrix Assembly and Organization
• Kunitz/Bovine pancreatic trypsin inhibitor domain
• von Willebrand factor type A domain
• Collagen triple helix repeat (20 copies)
• Collagen alpha-3(VI) chain, vWA domain

KeywordsUniProt

• Cell adhesion
• Collagen
• Congenital muscular dystrophy
• Disulfide bond
• Dystonia
• Extracellular matrix
• Glycoprotein
• Hydroxylation
• Phosphoprotein
• Protease inhibitor
• Repeat
• Secreted
• Serine protease inhibitor
• Signal