COL18A1 collagen type XVIII alpha 1 chain [Homo sapiens (human)] - Gene

Summary

Official Symbol: COL18A1provided by HGNC
Official Full Name: collagen type XVIII alpha 1 chainprovided by HGNC
Primary source: HGNC:HGNC:2195
See related: Ensembl:ENSG00000182871 MIM:120328; AllianceGenome:HGNC:2195
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: KS; KNO; GLCC; KNO1
Summary: This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. A long isoform of the protein has an N-terminal domain that is homologous to the extracellular part of frizzled receptors. Proteolytic processing at several endogenous cleavage sites in the C-terminal domain results in production of endostatin, a potent antiangiogenic protein that is able to inhibit angiogenesis and tumor growth. Mutations in this gene are associated with Knobloch syndrome. The main features of this syndrome involve retinal abnormalities, so type XVIII collagen may play an important role in retinal structure and in neural tube closure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
Annotation information: Annotation category: suggests misassembly
Expression: Ubiquitous expression in liver (RPKM 68.9), kidney (RPKM 46.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 21q22.3

Exon count:: 43

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	21	NC_000021.9 (45405165..45513720)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	21	NC_060945.1 (43770922..43881831)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	21	NC_000021.8 (46825080..46933634)

Chromosome 21 - NC_000021.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Temporally and spatially regulated collagen XVIII isoforms are involved in ureteric tree development via the TSP1-like domain.
Title: Temporally and spatially regulated collagen XVIII isoforms are involved in ureteric tree development via the TSP1-like domain.
Knobloch Syndrome Associated with Novel COL18A1 Variants in Chinese Population.
Title: Knobloch Syndrome Associated with Novel COL18A1 Variants in Chinese Population.
Variable phenotype of Knobloch syndrome due to biallelic COL18A1 mutations in children.
Title: Variable phenotype of Knobloch syndrome due to biallelic COL18A1 mutations in children.
Collagen type XVIII alpha 1 chain (COL18A1) variants affect the risk of anti-tuberculosis drug-induced hepatotoxicity: A prospective study.
Title: Collagen type XVIII alpha 1 chain (COL18A1) variants affect the risk of anti-tuberculosis drug-induced hepatotoxicity: A prospective study.
Elevated Endostatin Expression Is Regulated by the pIgA Immune Complex and Associated with Disease Severity of IgA Nephropathy.
Title: Elevated Endostatin Expression Is Regulated by the pIgA Immune Complex and Associated with Disease Severity of IgA Nephropathy.
Knobloch syndrome in a patient from Chile.
Title: Knobloch syndrome in a patient from Chile.
Three cases of molecularly confirmed Knobloch syndrome.
Title: Three cases of molecularly confirmed Knobloch syndrome.
Serum Endostatin Is a Novel Marker for COPD Associated with Lower Lung Function, Exacerbation and Systemic Inflammation.
Title: Serum Endostatin Is a Novel Marker for COPD Associated with Lower Lung Function, Exacerbation and Systemic Inflammation.
COL18A1/ES expression is markedly increased in remodeled pulmonary vessels in PAH.
Title: Functional Impact of Human Genetic Variants of COL18A1/Endostatin on Pulmonary Endothelium.
our study demonstrated that down-regulation of COL18A1 in vitro resulted in inhibition of keratinization of epithelial cells. Moreover, deletion of Col18a1 in vivo led to an inadequate keratinization phenotype of oral mucosa in the Col18-KO mice, as demonstrated by a suppressed KRT10 expression and remarkably smaller size of KHG in the granular layer of epithelial tissue in those mice.
Title: Type XVIII Collagen Modulates Keratohyalin Granule Formation and Keratinization in Oral Mucosa.

Submit: New GeneRIF Correction See all GeneRIFs (146)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Glaucoma, primary closed-angle MedGen: C5394374 OMIM: 618880 GeneReviews: Not available	not available
Knobloch syndrome 1 MedGen: C4551775 OMIM: 267750 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Multiple loci influencing hippocampal degeneration identified by genome scan. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS_CEB248 (e-PCR)
- UniSTS:255252

COL18A1_540.2 (e-PCR)
- UniSTS:280615

STS_CEB286 (e-PCR)
- UniSTS:255274

STS_CEB287 (e-PCR)
- UniSTS:255275

SHGC-12530 (e-PCR)
- UniSTS:98863

SHGC-8080 (e-PCR)
- UniSTS:7730

NoName (e-PCR)
- UniSTS:483681

SHGC-87711 (e-PCR)
- UniSTS:81506

RH98711 (e-PCR)
- UniSTS:83564

D1S3693 (e-PCR)
- UniSTS:474271

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables extracellular matrix structural constituent conferring tensile strength	IBA Inferred from Biological aspect of Ancestor more info
enables extracellular matrix structural constituent conferring tensile strength	RCA inferred from Reviewed Computational Analysis more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in angiogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in animal organ morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in endothelial cell morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in extracellular matrix organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of cell population proliferation	TAS Traceable Author Statement more info	PubMed
involved_in response to hydrostatic pressure	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in skeletal system development	IBA Inferred from Biological aspect of Ancestor more info
involved_in visual perception	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in basement membrane	IEA Inferred from Electronic Annotation more info
part_of collagen trimer	IBA Inferred from Biological aspect of Ancestor more info
colocalizes_with collagen-containing extracellular matrix	HDA more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in collagen-containing extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
colocalizes_with collagen-containing extracellular matrix	TAS Traceable Author Statement more info	PubMed
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: collagen alpha-1(XVIII) chain

Names: antiangiogenic agent; collagen, type XVIII, alpha 1; endostatin; multi-functional protein MFP

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011903.1 RefSeqGene

Range

5001..113529

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001379500.1 → NP_001366429.1 collagen alpha-1(XVIII) chain isoform 4 preproprotein

Status: REVIEWED

Source sequence(s)

BX322561, BX322562

Consensus CDS

CCDS42971.1

UniProtKB/TrEMBL

A0AAG2UW65

Related

ENSP00000498485.1, ENST00000651438.1
NM_030582.4 → NP_085059.2 collagen alpha-1(XVIII) chain isoform 1 preproprotein

See identical proteins and their annotated locations for NP_085059.2

Status: REVIEWED

Description

Transcript Variant: This variant (1, also known as NCI-493) uses an alternate splice donor in the 5' terminal exon compared to variant 3. The encoded isoform (1) is shorter than isoform 3.

Source sequence(s)

AF018082, BC063833, BX322561

Consensus CDS

CCDS42972.1

UniProtKB/Swiss-Prot

A8MVI4, P39060, Q58EX6, Q6RZ39, Q6RZ40, Q6RZ41, Q8N4S4, Q8WXI5, Q96T70, Q9UK38, Q9Y6Q7, Q9Y6Q8

UniProtKB/TrEMBL

A0AAG2UXZ5

Related

ENSP00000347665.5, ENST00000355480.10

Conserved Domains (4) summary

pfam01391
Location:822 → 872

Collagen; Collagen triple helix repeat (20 copies)

smart00210
Location:221 → 409

TSPN; Thrombospondin N-terminal -like domains

cd00247
Location:1340 → 1510

Endostatin-like; Endostatin-like domain; the angiogenesis inhibitor endostatin is a C-terminal fragment of collagen XV/XVIII, a proteoglycan/collagen found in vessel walls and basement membranes; this domain has a compact globular fold similar to that of C-type lectins; ...

pfam06121
Location:25 → 194

DUF959; Domain of Unknown Function (DUF959)
NM_130444.3 → NP_569711.2 collagen alpha-1(XVIII) chain isoform 3 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (3, also known as NCI-728) represents the longest transcript and encodes the longest isoform (3).

Source sequence(s)

AF018082, BC063833, BX322561

Consensus CDS

CCDS77643.1

UniProtKB/Swiss-Prot

A8MVI4, P39060, Q58EX6, Q6RZ39, Q6RZ40, Q6RZ41, Q8N4S4, Q8WXI5, Q96T70, Q9UK38, Q9Y6Q7, Q9Y6Q8

Related

ENSP00000352798.4, ENST00000359759.8

Conserved Domains (5) summary

cd07455
Location:330 → 452

CRD_Collagen_XVIII; Cysteine-rich domain of the variant 3 of collagen XVIII (V3C18 )

pfam01391
Location:1057 → 1107

Collagen; Collagen triple helix repeat (20 copies)

smart00210
Location:456 → 644

TSPN; Thrombospondin N-terminal -like domains

cd00247
Location:1575 → 1745

Endostatin-like; Endostatin-like domain; the angiogenesis inhibitor endostatin is a C-terminal fragment of collagen XV/XVIII, a proteoglycan/collagen found in vessel walls and basement membranes; this domain has a compact globular fold similar to that of C-type lectins; ...

pfam06121
Location:25 → 194

DUF959; Domain of Unknown Function (DUF959)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000021.9 Reference GRCh38.p14 Primary Assembly

Range

45405165..45513720

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GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 PATCHES

Genomic

NW_025791815.1 Reference GRCh38.p14 PATCHES

Range

22400..130946

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060945.1 Alternate T2T-CHM13v2.0

Range

43770922..43881831

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_130445.4: Suppressed sequence

Description

NM_130445.4: This RefSeq was removed by NCBI staff. Please email info@ncbi.nlm.nih.gov for more information.