COL18A1

collagen type XVIII alpha 1 chain, the group of MicroRNA protein coding host genes|Collagens

Basic information

Region (hg38): 21:45405165-45513720

Previous symbols: [ "KNO" ]

Links

ENSG00000182871 ∙ NCBI:80781 ∙ OMIM:120328 ∙ HGNC:2195 ∙ Uniprot:P39060 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Knobloch syndrome 1 (Definitive), mode of inheritance: AR
• Knobloch syndrome 1 (Strong), mode of inheritance: AR
• Knobloch syndrome (Supportive), mode of inheritance: AR
• Knobloch syndrome (Strong), mode of inheritance: AR
• Knobloch syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glaucoma, primary, closed-angle; Knobloch syndrome 1	AD/AR	Ophthalmologic	Primary open-angle glaucoma can involve loss of vision, and awareness of disease risk may allow surveillance and early treatment; Knobloch syndrome can involve increased risk of retinal detachment, and awareness may allow early diagnosis and management	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	1554013; 7802003; 10942434; 14695535; 17546652; 19160445; 20799329; 21085708; 21862674; 21937992; 30007336

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL18A1 gene.

• not provided (107 variants)
• Knobloch syndrome (12 variants)
• Knobloch syndrome 1 (5 variants)
• Retinal dystrophy (3 variants)
• COL18A1-related disorder (2 variants)
• Cataract;Nystagmus;High myopia;Retinal dystrophy (2 variants)
• Glaucoma, primary closed-angle (1 variants)
• Retinitis pigmentosa (1 variants)
• Macular dystrophy (1 variants)
• Knobloch syndrome 1;Glaucoma, primary closed-angle (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL18A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			58	495	48	601
missense		1	951	56	14	1022
nonsense	20	6				26
start loss						0
frameshift	87	7	13			107
inframe indel			38	16	7	61
splice donor/acceptor (+/-2bp)	4	31				35
splice region			76	112	5	193
non coding		1	111	387	198	697
Total	111	46	1171	954	267

Highest pathogenic variant AF is 0.000952

Variants in COL18A1

This is a list of pathogenic ClinVar variants found in the COL18A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
21-45405193-A-C		Knobloch syndrome	Uncertain significance (Jan 13, 2018)
21-45405204-C-G		Knobloch syndrome	Uncertain significance (Jan 13, 2018)
21-45405221-TG-T			Likely benign (Apr 01, 2022)
21-45405229-G-A		Knobloch syndrome • not specified	Uncertain significance (Oct 13, 2023)
21-45405235-C-T			Uncertain significance (Feb 09, 2022)
21-45405236-GC-G			Pathogenic (Nov 28, 2021)
21-45405239-G-A			Likely benign (Aug 24, 2023)
21-45405240-A-G			Uncertain significance (Jun 13, 2022)
21-45405241-G-A			Uncertain significance (Dec 08, 2021)
21-45405249-C-T			Likely benign (Oct 18, 2022)
21-45405249-CG-C			Benign (Jun 18, 2023)
21-45405250-G-T			Likely benign (Nov 20, 2023)
21-45405251-G-C			Likely benign (Dec 18, 2023)
21-45405255-T-C			Likely benign (Jan 14, 2024)
21-45405260-G-GGGTCC			Likely benign (Jul 14, 2023)
21-45405285-C-CGGCTGCGG			Benign (May 11, 2021)
21-45405285-C-CGGCTGCGGGGGCTGCGG			Benign (May 11, 2021)
21-45405299-G-C			Benign (May 10, 2021)
21-45405298-C-CCT			Benign (May 11, 2021)
21-45405308-G-C			Benign (May 10, 2021)
21-45405314-C-G			Benign (May 10, 2021)
21-45405320-C-T			Benign (May 10, 2021)
21-45405319-C-CTGGGT			Benign (May 11, 2021)
21-45405320-C-CCTGCGG			Benign (May 11, 2021)
21-45405327-TGCGGGGGTC-T			Benign (May 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL18A1	protein_coding	protein_coding	ENST00000355480	41	108583

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.74e-10	1.00	124692	0	119	124811	0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.797	1057	987	1.07	0.0000700	9439
Missense in Polyphen		311	300.39	1.0353		2734
Synonymous	-5.14	567	431	1.32	0.0000348	3344
Loss of Function	4.94	31	78.2	0.397	0.00000416	847

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000975	0.000922
Ashkenazi Jewish	0.000100	0.0000993
East Asian	0.000393	0.000389
Finnish	0.000146	0.000139
European (Non-Finnish)	0.000543	0.000512
Middle Eastern	0.000393	0.000389
South Asian	0.000565	0.000556
Other	0.00176	0.00165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube. {ECO:0000269|PubMed:10942434}.; FUNCTION: Endostatin: Potently inhibits endothelial cell proliferation and angiogenesis (PubMed:9459295). May inhibit angiogenesis by binding to the heparan sulfate proteoglycans involved in growth factor signaling (By similarity). Inhibits VEGFA-induced endothelial cell proliferation and migration. Seems to inhibit VEGFA-mediated signaling by blocking the interaction of VEGFA to its receptor KDR/VEGFR2. Modulates endothelial cell migration in an integrin-dependent manner implicating integrin ITGA5:ITGB1 and to a lesser extent ITGAV:ITGB3 and ITGAV:ITGB5 (By similarity). May negatively regulate the activity of homotrimeric non-collagenous domain 1 (PubMed:11257123). {ECO:0000250|UniProtKB:P39061, ECO:0000269|PubMed:11257123, ECO:0000269|PubMed:9459295}.
• Disease: DISEASE: Knobloch syndrome 1 (KNO1) [MIM:267750]: A developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia. {ECO:0000269|PubMed:10942434, ECO:0000269|PubMed:23667181}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Assembly of collagen fibrils and other multimeric structures;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Integrin cell surface interactions;Laminin interactions;Collagen degradation;Collagen formation;Extracellular matrix organization;Activation of Matrix Metalloproteinases;Integrin;Degradation of the extracellular matrix;FOXA1 transcription factor network;Direct p53 effectors;Validated nuclear estrogen receptor alpha network;Beta1 integrin cell surface interactions (Consensus)

Intolerance Scores

• loftool: 0.155
• rvis_EVS: 0.74
• rvis_percentile_EVS: 86.36

Haploinsufficiency Scores

• pHI: 0.351
• hipred: N
• hipred_score: 0.478
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.828

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Col18a1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; vision/eye phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: col18a1a
• Affected structure: neural crest cell migration
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: angiogenesis;endothelial cell morphogenesis;cell adhesion;visual perception;positive regulation of cell population proliferation;negative regulation of cell population proliferation;animal organ morphogenesis;extracellular matrix organization;positive regulation of cell migration;response to drug;response to hydrostatic pressure;positive regulation of endothelial cell apoptotic process
• Cellular component: extracellular region;collagen trimer;basement membrane;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: extracellular matrix structural constituent;extracellular matrix structural constituent conferring tensile strength;metal ion binding