COL25A1 (collagen type XXV alpha 1 chain)

Gene

• Entrez ID: 84570
• Gene name: Collagen type XXV alpha 1 chain
• Gene symbol: COL25A1
• Synonyms (NCBI Gene): AMY, CFEOM5, CLAC, CLAC-P, CLACP
• Chromosome: 4
• Chromosome location: 4q25
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs780209390	C>T	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs886037741	C>A	Pathogenic	Coding sequence variant, intron variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2447434	hsa-miR-4694-3p	CLIP-seq
MIRT2447435	hsa-miR-548c-3p	CLIP-seq
MIRT2447436	hsa-miR-711	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001540	Function	Amyloid-beta binding	IBA
GO:0001540	Function	Amyloid-beta binding	IDA	11927537, 15215182, 15522881, 15615705
GO:0005576	Component	Extracellular region	IDA	11927537
GO:0005576	Component	Extracellular region	TAS
GO:0005581	Component	Collagen trimer	IEA
GO:0005615	Component	Extracellular space	IDA	11927537
GO:0005788	Component	Endoplasmic reticulum lumen	IEA
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0005886	Component	Plasma membrane	IDA	11927537
GO:0005886	Component	Plasma membrane	TAS
GO:0008201	Function	Heparin binding	IDA	15522881
GO:0008201	Function	Heparin binding	IEA
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	NAS	11927537
GO:0030020	Function	Extracellular matrix structural constituent conferring tensile strength	RCA	25037231
GO:0031012	Component	Extracellular matrix	HDA	25037231
GO:0042802	Function	Identical protein binding	IPI	15522881
GO:0060385	Process	Axonogenesis involved in innervation	IEA

Other IDs

• MIM: 610004
• HGNC: 18603
• e!Ensembl: ENSG00000188517

Protein

• UniProt ID: Q9BXS0
• Protein name: Collagen alpha-1(XXV) chain (Alzheimer disease amyloid-associated protein) (AMY) (CLAC-P) [Cleaved into: Collagen-like Alzheimer amyloid plaque component (CLAC)]
• Protein 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. {ECO:0000269|PubMed:15522881, ECO:0000269|PubMed:15615705, ECO:000026
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01391	Collagen	118 → 165	Collagen triple helix repeat (20 copies)	Repeat
  PF01391	Collagen	310 → 372	Collagen triple helix repeat (20 copies)	Repeat
  PF01391	Collagen	371 → 427	Collagen triple helix repeat (20 copies)	Repeat
  PF01391	Collagen	447 → 505	Collagen triple helix repeat (20 copies)	Repeat
  PF01391	Collagen	574 → 647	Collagen triple helix repeat (20 copies)	Repeat

• Tissue specificity: TISSUE SPECIFICITY: Expressed predominantly in brain. Deposited preferentially in primitive or neuritic amyloid plaques which are typical of Alzheimer disease. {ECO:0000269|PubMed:11927537}.
• Sequence:

  MLLKKHAGKGGGREPRSEDPTPAEQHCARTMPPCAVLAALLSVVAVVSCLYLGVKTNDLQ
  ARIAALESAKGAPSIHLLPDTLDHLKTMVQEKVERLLAQKSYEHMAKIRIAREAPSECNC
  PAGPPGKRGKRGRRGESGPPGQPGPQGPPGPKGDKGEQGDQGPRMVFPKINHGFLSADQQ
  LIKRRLIKGDQGQAGPPGPPGPPGPRGPPGDTGKDGPRGMPGVPGEPGKPGEQGLMGPLG
  PPGQKGSIGAPGIPGMNGQKGEPGLPGAVGQNGIPGPKGEPGEQGEKGDAGENGPKGDTG
  EKGDPGSSAAGIKGEPGESGRPGQKGEPGLPGLPGLPGIKGEPGFIGPQGEPGLPGLPGT
  KGERGEAGPPGRGERGEPGAPGPKGKQGESGTRGPKGSKGDRGEKGDSGAQGPRGPPGQK
  GDQGATEIIDYNGNLHEALQRITTLTVTGPPGPPGPQGLQGPKGEQGSPGIPGMDGEQGL
  KGSKGDMGDPGMTGEKGGIGLPGLPGANGMKGEKGDSGMPGPQGPSIIGPPGPPGPHGPP
  GPMGPHGLPGPKGTDGPMGPHGPAGPKGERGEKGAMGEPGPRGPYGLPGKDGEPGLDGFP
  GPRGEKGDLGEKGEKGFRGVKGEKGEPGQPGLDGLDAPCQLGPDGLPMPGCWQK

• Sequence length: 654

Pathways

KEGG:

Protein digestion and absorption

Reactome:

Collagen degradation
Collagen biosynthesis and modifying enzymes
Collagen chain trimerization

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Arthrogryposis	Likely pathogenic	rs1274380766	RCV004764971	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Fibrosis of extraocular muscles, congenital, 5	Likely pathogenic; Pathogenic	rs1274380766, rs759316372, rs2125927453, rs780209390, rs886037741, rs2476579225	RCV001780813 RCV002272850 RCV002272920 RCV000157645 RCV000157646 RCV003228197	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ARTHROGRYPOSIS MULTIPLEX CONGENITA NEUROGENIC TYPE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CLEAR CELL RENAL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COL25A1-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL FIBROSIS OF EXTRAOCULAR MUSCLES	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL PTOSIS	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LATE-ONSET ALZHEIMER'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERICARDITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RESPIRATORY SYSTEM DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SYSTEMIC LUPUS ERYTHEMATOSUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute pancreatitis	Pancreatitis	BEFREE	29441717		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	15522881, 15615705, 22297151	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Amyloidosis	Amyloidosis	BEFREE	29615111		★☆☆☆☆ Found in Text Mining only
Aniridia	Aniridia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Antisocial Personality Disorder	Antisocial Personality Disorder	BEFREE	22297151		★☆☆☆☆ Found in Text Mining only
Antisocial Personality Disorder	Antisocial personality disorder	Pubtator	22297151	Associate	★☆☆☆☆ Found in Text Mining only
Arthrogryposis	Arthrogryposis	Pubtator	35077597	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Blepharophimosis	Blepharophimosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharospasm	Blepharospasm	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	23018867	Associate	★☆☆☆☆ Found in Text Mining only
CARDIAC CONDUCTION DISEASE WITH OR WITHOUT DILATED CARDIOMYOPATHY	Cardiac Conduction Disease With Or Without Dilated Cardiomyopathy	BEFREE	25500261		★☆☆☆☆ Found in Text Mining only
Coloboma of the Retina	Retinal coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Camptodactyly	Congenital Camptodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital clubfoot	Congenital Clubfoot	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital coloboma of iris	Congenital Coloboma Of Iris	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of radius	Congenital Hypoplasia Of Radius	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital ptosis	Congenital ptosis	ORPHANET_DG	25500261, 26486031		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital ptosis	Congenital ptosis	BEFREE	26486031		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital ptosis	Congenital ptosis	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dementia	Dementia	BEFREE	29615111		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Down Syndrome	Down Syndrome	BEFREE	10393833		★☆☆☆☆ Found in Text Mining only
Duane Retraction Syndrome	Duane Retraction Syndrome	ORPHANET_DG	25500261, 26486031		★☆☆☆☆ Found in Text Mining only
Duane Retraction Syndrome	Duane Retraction Syndrome	BEFREE	27663630		★☆☆☆☆ Found in Text Mining only
Ectopic kidney	Ectopic kidney	HPO_DG			★☆☆☆☆ Found in Text Mining only
FIBROSIS OF EXTRAOCULAR MUSCLES, CONGENITAL, 5	Fibrosis Of Extraocular Muscles	UNIPROT_DG	25500261		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
FIBROSIS OF EXTRAOCULAR MUSCLES, CONGENITAL, 5	Fibrosis Of Extraocular Muscles	GENOMICS_ENGLAND_DG	25500261		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
FIBROSIS OF EXTRAOCULAR MUSCLES, CONGENITAL, 5	Fibrosis Of Extraocular Muscles	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
FIBROSIS OF EXTRAOCULAR MUSCLES, CONGENITAL, 5	Fibrosis Of Extraocular Muscles	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Fundus coloboma	Fundus Coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of optic disc	Hypoplasia Of Optic Disc	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	12104089		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	12104089		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microcornea	Microcornea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Micrognathism	Micrognathism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mouth Diseases	Mouth disease	Pubtator	23018867	Associate	★☆☆☆☆ Found in Text Mining only
Neck webbing	Neck Webbing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	29191090		★☆☆☆☆ Found in Text Mining only
Oculomotor Nerve Paralysis	Oculomotor nerve palsy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Periodontitis	Periodontitis	BEFREE	28879212, 30111112, 30915073		★☆☆☆☆ Found in Text Mining only
Phenylketonurias	Phenylketonuria	BEFREE	293128		★☆☆☆☆ Found in Text Mining only
Plagiocephaly	Plagiocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Polydactyly preaxial type 1	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Presenile dementia	Senile Dementia	BEFREE	29615111		★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Senile Plaques	Senile Plaques	BEFREE	18501477, 19548013, 22297151		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spina Bifida Occulta	Spina bifida occulta	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stenosis of external auditory canal	Stenosis Of External Auditory Canal	HPO_DG			★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only