This gene encodes a brain-specific membrane associated collagen. A product of proteolytic processing of the encoded protein, CLAC (collagenous Alzheimer amyloid plaque component), binds to amyloid beta-peptides found in Alzheimer amyloid plaques but CLAC inhibits rather than facilitates amyloid fibril elongation (PMID: 16300410). A study of over-expression of this collagen in m... See more...

Aliases for COL25A1 Gene

Aliases for COL25A1 Gene

  • Collagen Type XXV Alpha 1 Chain 2 3 5
  • Alzheimer Disease Amyloid-Associated Protein 3 4
  • Collagen Alpha-1(XXV) Chain 3 4
  • CLAC-P 3 4
  • AMY 3 4
  • Collagen-Like Alzheimer Amyloid Plaque Component 3
  • Collagenous Alzheimer Amyloid Plaque Component 3
  • Collagen, Type XXV, Alpha 1 2
  • CFEOM5 3
  • CLACP 3
  • CLAC 3

External Ids for COL25A1 Gene

Previous GeneCards Identifiers for COL25A1 Gene

  • GC04M110125
  • GC04M110203
  • GC04M110193
  • GC04M110092
  • GC04M109954
  • GC04M109731
  • GC04M105467

Summaries for COL25A1 Gene

Entrez Gene Summary for COL25A1 Gene

  • This gene encodes a brain-specific membrane associated collagen. A product of proteolytic processing of the encoded protein, CLAC (collagenous Alzheimer amyloid plaque component), binds to amyloid beta-peptides found in Alzheimer amyloid plaques but CLAC inhibits rather than facilitates amyloid fibril elongation (PMID: 16300410). A study of over-expression of this collagen in mice, however, found changes in pathology and behavior suggesting that the encoded protein may promote amyloid plaque formation (PMID: 19548013). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

GeneCards Summary for COL25A1 Gene

COL25A1 (Collagen Type XXV Alpha 1 Chain) is a Protein Coding gene. Diseases associated with COL25A1 include Fibrosis Of Extraocular Muscles, Congenital, 5 and Congenital Ptosis. Among its related pathways are ERK Signaling and T Cell Co-Signaling Pathway: Ligand-Receptor Interactions. Gene Ontology (GO) annotations related to this gene include heparin binding and amyloid-beta binding. An important paralog of this gene is COL5A3.

UniProtKB/Swiss-Prot Summary for COL25A1 Gene

  • Inhibits fibrillization of amyloid-beta peptide during the elongation phase. Has also been shown to assemble amyloid fibrils into protease-resistant aggregates. Binds heparin.

Gene Wiki entry for COL25A1 Gene

Additional gene information for COL25A1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for COL25A1 Gene

Genomics for COL25A1 Gene

GeneHancer (GH) Regulatory Elements for COL25A1 Gene

Promoters and enhancers for COL25A1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04J109300 Promoter/Enhancer 1.5 Ensembl ENCODE CraniofacialAtlas 500.7 +0.3 322 2.4 ZIC2 ZNF423 ZBTB26 TRIM28 EZH2 ZNF341 POLR2A HDAC2 SMC3 SP2 COL25A1 COL25A1-DT lnc-ETNPPL-2 RBMXP4
GH04J108830 Enhancer 0.9 Ensembl ENCODE 11.6 +471.9 471852 1.4 ZSCAN5C TRIM28 OSR2 BCL11A WT1 NFIC ZBTB17 NR2F2 ZNF610 ZNF335 SEC24B-AS1 CYP2U1 RBMXP4 COL25A1 COL25A1-DT RRH ETNPPL lnc-COL25A1-4 RCC2P8 lnc-ETNPPL-2
GH04J108955 Enhancer 0.7 Ensembl 14 +347.3 347251 0.6 RFX1 NCOR1 FOSL1 CUX1 STAT5A PKNOX1 NFE2 SMARCA4 DPF2 JUN COL25A1 RF00017-4383 piR-47162-108 lnc-ETNPPL-2
GH04J109278 Enhancer 0.8 Ensembl 11.3 +24.1 24051 0.6 ZBTB40 EP300 TRIM22 BCL11A ZNF316 SRF ARNT MEF2B NBN MAFK COL25A1 COL25A1-DT lnc-ETNPPL-2 FJ601684-352
GH04J109408 Enhancer 0.7 Ensembl ENCODE 10.3 -108.4 -108449 4.8 ZIC2 NFIC USF1 NFE2 ETS1 ZNF2 PRDM4 NFIA NFIB FOXA1 piR-41306-208 RBMXP4 COL25A1 COL25A1-DT LRIT3 SEC24B RF00017-4385 SEC24B-AS1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around COL25A1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for COL25A1

Top Transcription factor binding sites by QIAGEN in the COL25A1 gene promoter:
  • C/EBPbeta
  • E2F
  • E2F-1
  • FOXF2
  • HFH-1
  • MIF-1
  • MyoD
  • NF-1
  • NF-1/L
  • POU2F1

Genomic Locations for COL25A1 Gene

Genomic Locations for COL25A1 Gene
chr4:108,808,725-109,302,752
(GRCh38/hg38)
Size:
494,028 bases
Orientation:
Minus strand
chr4:109,731,877-110,223,813
(GRCh37/hg19)
Size:
491,937 bases
Orientation:
Minus strand

Genomic View for COL25A1 Gene

Genes around COL25A1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
COL25A1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for COL25A1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for COL25A1 Gene

Proteins for COL25A1 Gene

  • Protein details for COL25A1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BXS0-COPA1_HUMAN
    Recommended name:
    Collagen alpha-1(XXV) chain
    Protein Accession:
    Q9BXS0
    Secondary Accessions:
    • A8MPZ6
    • Q9BXR9

    Protein attributes for COL25A1 Gene

    Size:
    654 amino acids
    Molecular mass:
    64771 Da
    Quaternary structure:
    • Forms homodimers and homotrimers. Binds to the fibrillized forms of amyloid-beta protein 40 (beta-APP40) and amyloid-beta protein 42 (beta-APP42). Found associated with beta-APP42 more frequently than with beta-APP40.

    Alternative splice isoforms for COL25A1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for COL25A1 Gene

Post-translational modifications for COL25A1 Gene

  • Undergoes proteolytic cleavage by furin protease to yield the soluble collagen-like Alzheimer amyloid plaque component.
  • Glycosylated.
  • Hydroxylated on 11% of proline residues and 49% of lysine residues.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for COL25A1 Gene

Domains & Families for COL25A1 Gene

Gene Families for COL25A1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for COL25A1 Gene

Blocks:
  • Collagen triple helix repeat
  • Collagen helix repeat
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for COL25A1 Gene

GenScript: Design optimal peptide antigens:
  • CLAC-P (COPA1_HUMAN)
  • COL25A1 protein (Q8NE08_HUMAN)
genes like me logo Genes that share domains with COL25A1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for COL25A1 Gene

Function for COL25A1 Gene

Molecular function for COL25A1 Gene

UniProtKB/Swiss-Prot Function:
Inhibits fibrillization of amyloid-beta peptide during the elongation phase. Has also been shown to assemble amyloid fibrils into protease-resistant aggregates. Binds heparin.

Phenotypes From GWAS Catalog for COL25A1 Gene

Gene Ontology (GO) - Molecular Function for COL25A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001540 amyloid-beta binding IDA 11927537
GO:0008201 heparin binding IEA,IDA 15522881
GO:0030020 extracellular matrix structural constituent conferring tensile strength RCA 25037231
genes like me logo Genes that share ontologies with COL25A1: view
genes like me logo Genes that share phenotypes with COL25A1: view

Human Phenotype Ontology for COL25A1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for COL25A1 Gene

MGI Knock Outs for COL25A1:

Clone Products

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targets and HOMER Transcription for COL25A1 Gene

Localization for COL25A1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for COL25A1 Gene

Membrane; Single-pass type II membrane protein. Note=After proteolytic cleavage, CLAC is secreted.

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 COL25A1 gene
Compartment Confidence
plasma membrane 5
extracellular 5
endoplasmic reticulum 4
cytosol 3
cytoskeleton 1
mitochondrion 1
nucleus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Endoplasmic reticulum (2)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for COL25A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IDA,TAS --
GO:0005581 collagen trimer IEA --
GO:0005615 extracellular space IDA 11927537
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with COL25A1: view

Pathways & Interactions for COL25A1 Gene

PathCards logo

SuperPathways for COL25A1 Gene

SuperPathway Contained pathways
1 Integrin Pathway
.67
.67
.56
.56
.50
.38
2 Collagen chain trimerization
.48
.46
3 ERK Signaling
.61
.61
.58
.51
.49
4 Degradation of the extracellular matrix
5 Phospholipase-C Pathway
.56
.56
genes like me logo Genes that share pathways with COL25A1: view

Pathways by source for COL25A1 Gene

15 Qiagen pathways for COL25A1 Gene
  • Blood Coagulation Cascade
  • ERK Signaling
  • FAK1 Signaling
  • GnRH Signaling
  • ILK Signaling

Gene Ontology (GO) - Biological Process for COL25A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0060385 axonogenesis involved in innervation IEA --
genes like me logo Genes that share ontologies with COL25A1: view

No data available for SIGNOR curated interactions for COL25A1 Gene

Drugs & Compounds for COL25A1 Gene

No Compound Related Data Available

Transcripts for COL25A1 Gene

mRNA/cDNA for COL25A1 Gene

3 REFSEQ mRNAs :
5 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for COL25A1 Gene

No ASD Table

Relevant External Links for COL25A1 Gene

GeneLoc Exon Structure for
COL25A1

Expression for COL25A1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for COL25A1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for COL25A1 Gene

This gene is overexpressed in Testis (x11.2), Adipose - Subcutaneous (x4.5), and Adipose - Visceral (Omentum) (x4.4).

Protein differential expression in normal tissues from HIPED for COL25A1 Gene

This gene is overexpressed in Plasma (45.9) and Platelet (23.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for COL25A1 Gene



Protein tissue co-expression partners for COL25A1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for COL25A1

SOURCE GeneReport for Unigene cluster for COL25A1 Gene:

Hs.658842

mRNA Expression by UniProt/SwissProt for COL25A1 Gene:

Q9BXS0-COPA1_HUMAN
Tissue specificity: Expressed predominantly in brain. Deposited preferentially in primitive or neuritic amyloid plaques which are typical of Alzheimer disease.

Phenotype-based relationships between genes and organs from Gene ORGANizer for COL25A1 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • digestive
  • integumentary
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cranial nerve
  • eye
  • eyelid
  • face
  • forehead
  • head
  • lip
  • skull
Thorax:
  • chest wall
  • rib
  • rib cage
  • sternum
Pelvis:
  • pelvis
  • rectum
Limb:
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • toe
  • upper limb
General:
  • hair
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with COL25A1: view

No data available for Evidence on tissue expression from TISSUES for COL25A1 Gene

Orthologs for COL25A1 Gene

This gene was present in the common ancestor of animals.

Orthologs for COL25A1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia COL25A1 31 30
  • 99.39 (n)
OneToOne
dog
(Canis familiaris)
Mammalia COL25A1 31 30
  • 92.66 (n)
OneToOne
cow
(Bos Taurus)
Mammalia COL25A1 31 30
  • 92.2 (n)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia COL25A1 31
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Col25a1 17 31 30
  • 89.19 (n)
oppossum
(Monodelphis domestica)
Mammalia COL25A1 31
  • 89 (a)
OneToOne
chicken
(Gallus gallus)
Aves COL25A1 31 30
  • 79.61 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia COL25A1 31
  • 86 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia col25a1.2 30
  • 75.75 (n)
zebrafish
(Danio rerio)
Actinopterygii COL25A1 31
  • 75 (a)
OneToOne
LOC101882764 30
  • 68.37 (n)
worm
(Caenorhabditis elegans)
Secernentea col-135 31
  • 33 (a)
OneToMany
Species where no ortholog for COL25A1 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)
  • wheat (Triticum aestivum)

Evolution for COL25A1 Gene

ENSEMBL:
Gene Tree for COL25A1 (if available)
TreeFam:
Gene Tree for COL25A1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for COL25A1: view image

Paralogs for COL25A1 Gene

(4) SIMAP similar genes for COL25A1 Gene using alignment to 7 proteins:

  • COPA1_HUMAN
  • A8MWQ5_HUMAN
  • D6R8Y2_HUMAN
  • E9PNV9_HUMAN
  • H0YAE1_HUMAN
  • Q4W5I4_HUMAN
  • Q8NE08_HUMAN
genes like me logo Genes that share paralogs with COL25A1: view

Variants for COL25A1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for COL25A1 Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
714989 Benign: not provided 108,974,557(-) G/T NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
717345 Benign: not provided 109,050,126(-) G/A INTRON_VARIANT
721553 Likely Benign: not provided 109,301,732(-) A/G NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
722320 Likely Benign: not provided 108,819,309(-) C/T SYNONYMOUS_VARIANT
723285 Likely Benign: not provided 109,300,620(-) G/A NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for COL25A1 Gene

Structural Variations from Database of Genomic Variants (DGV) for COL25A1 Gene

Variant ID Type Subtype PubMed ID
dgv113e19 CNV gain 19470904
dgv2875n106 CNV deletion 24896259
esv2436931 CNV insertion 19546169
esv26012 CNV loss 19812545
esv2657117 CNV deletion 23128226
esv2664386 CNV deletion 23128226
esv2728123 CNV deletion 23290073
esv2728124 CNV deletion 23290073
esv2728125 CNV deletion 23290073
esv275332 CNV loss 21479260
esv3302701 CNV tandem duplication 20981092
esv3304254 CNV mobile element insertion 20981092
esv3305609 CNV mobile element insertion 20981092
esv3309451 CNV mobile element insertion 20981092
esv3329381 CNV insertion 20981092
esv3365857 CNV insertion 20981092
esv3380051 CNV insertion 20981092
esv3564424 CNV deletion 23714750
esv3569650 CNV loss 25503493
esv3569651 CNV loss 25503493
esv3601731 CNV loss 21293372
esv3601732 CNV loss 21293372
esv3601734 OTHER inversion 21293372
esv7089 CNV gain 19470904
esv8308 CNV gain 19470904
nsv1073790 CNV deletion 25765185
nsv1128086 CNV deletion 24896259
nsv1136899 CNV deletion 24896259
nsv1143102 CNV tandem duplication 24896259
nsv1153416 CNV insertion 26484159
nsv293715 CNV insertion 16902084
nsv4459 CNV insertion 18451855
nsv461613 CNV gain 19166990
nsv461614 CNV loss 19166990
nsv476458 CNV novel sequence insertion 20440878
nsv515893 CNV loss 19592680
nsv519227 CNV loss 19592680
nsv595128 CNV loss 21841781
nsv595129 CNV gain 21841781
nsv595130 CNV loss 21841781
nsv595131 CNV loss 21841781
nsv830034 CNV loss 17160897
nsv830035 CNV gain 17160897

Variation tolerance for COL25A1 Gene

Residual Variation Intolerance Score: 11.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.60; 45.07% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for COL25A1 Gene

Human Gene Mutation Database (HGMD)
COL25A1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
COL25A1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for COL25A1 Gene

Disorders for COL25A1 Gene

MalaCards: The human disease database

(10) MalaCards diseases for COL25A1 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

COPA1_HUMAN
  • Fibrosis of extraocular muscles, congenital, 5 (CFEOM5) [MIM:616219]: An ocular motility disorder characterized by congenital dysinnervation of various cranial nerves to ocular muscles. Clinical features are ophthalmoplegia, anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. {ECO:0000269 PubMed:25500261}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for COL25A1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with COL25A1: view

No data available for Genatlas for COL25A1 Gene

Publications for COL25A1 Gene

  1. CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV. (PMID: 11927537) Hashimoto T … Iwatsubo T (The EMBO journal 2002) 2 3 4 23 54
  2. Genetic association to the amyloid plaque associated protein gene COL25A1 in Alzheimer's disease. (PMID: 18501477) Forsell C … Graff C (Neurobiology of aging 2010) 3 23 41 54
  3. Molecular identification of AMY, an Alzheimer disease amyloid-associated protein. (PMID: 14656069) Söderberg L … Näslund J (Journal of neuropathology and experimental neurology 2003) 3 4 23 54
  4. Recessive mutations in COL25A1 are a cause of congenital cranial dysinnervation disorder. (PMID: 25500261) Shinwari JM … Al Tassan N (American journal of human genetics 2015) 3 4 54
  5. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41 54

Products for COL25A1 Gene

Sources for COL25A1 Gene