ADAMTS18

ADAM metallopeptidase with thrombospondin type 1 motif 18, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Basic information

Region (hg38): 16:77247813-77435034

Previous symbols: [ "ADAMTS21" ]

Links

ENSG00000140873 ∙ NCBI:170692 ∙ OMIM:607512 ∙ HGNC:17110 ∙ Uniprot:Q8TE60 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• inherited retinal dystrophy (Limited), mode of inheritance: AR
• microcornea-myopic chorioretinal atrophy (Strong), mode of inheritance: AR
• microcornea-myopic chorioretinal atrophy (Definitive), mode of inheritance: AR
• microcornea-myopic chorioretinal atrophy (Supportive), mode of inheritance: AR
• microcornea-myopic chorioretinal atrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcornea, myopic chorioretinal atrophy, and telecanthus	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Ophthalmologic	21862674; 22686506; 23356391; 23818446

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAMTS18 gene.

• not_provided (1080 variants)
• Inborn_genetic_diseases (220 variants)
• ADAMTS18-related_disorder (37 variants)
• Microcornea-myopic_chorioretinal_atrophy (13 variants)
• Retinal_dystrophy (8 variants)
• not_specified (5 variants)
• Leber_congenital_amaurosis (2 variants)
• Retinitis_pigmentosa (2 variants)
• Knobloch_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTS18 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000199355.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	289	24	316
missense	1	1	584	36	8	630
nonsense	26	2	2			30
start loss						0
frameshift	11		2			13
splice donor/acceptor (+/-2bp)		11	1			12
Total	38	14	592	325	32

Highest pathogenic variant AF is 0.000238539

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTS18	protein_coding	protein_coding	ENST00000282849	23	187302

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.07e-29	0.140	125601	0	147	125748	0.000585

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-3.51	919	665	1.38	0.0000390	7914
Missense in Polyphen		270	256.49	1.0527		2927
Synonymous	-6.37	390	260	1.50	0.0000168	2336
Loss of Function	2.07	56	75.4	0.743	0.00000489	805

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00112	0.00112
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000802	0.000783
Middle Eastern	0.000163	0.000163
South Asian	0.000589	0.000588
Other	0.000817	0.000652

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) [MIM:615458]: A ocular syndrome characterized by microcornea and myopic chorioretinal atrophy. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye. In addition to ocular findings, some patients have telecanthus and posteriorly rotated ears. {ECO:0000269|PubMed:23818446}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Degradation of the extracellular matrix;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.0954

Intolerance Scores

• loftool: 0.825
• rvis_EVS: -0.09
• rvis_percentile_EVS: 47

Haploinsufficiency Scores

• pHI: 0.235
• hipred: Y
• hipred_score: 0.604
• ghis: 0.496

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.160

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Adamts18
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; neoplasm; reproductive system phenotype; respiratory system phenotype

Gene ontology

• Biological process: eye development;proteolysis;negative regulation of platelet aggregation
• Cellular component: extracellular region
• Molecular function: metalloendopeptidase activity;metal ion binding