ADAMTS18

Chr 16AR

ADAM metallopeptidase with thrombospondin type 1 motif 18

Also known as: ADAMTS21, KNO2, MMCAT

NCBI Gene: 170692 ENSG00000140873 UniProt: Q8TE60 OMIM: 607512

The protein is a metalloproteinase that cleaves extracellular matrix components and may regulate hemostatic balance. Biallelic mutations cause microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT), an autosomal recessive disorder affecting ocular development and retinal function. The gene shows tolerance to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, OMIM

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature protein, which may regulate hemostatic balance and function as a tumor suppressor. Mutations in this gene may be associated with microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) and cone-rod dystrophy in human patients. [provided by RefSeq, May 2016]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.931 OMIM phenotype

Clinical Summary— ADAMTS18

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Gene-Disease Validity (ClinGen)

microcornea-myopic chorioretinal atrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

65 unique Pathogenic / Likely Pathogenic· 647 VUS of 1310 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.000

Z-score 2.07

OE 0.74 (0.60–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-3.51Z-score

OE missense 1.38 (1.31–1.46)

919 obs / 664.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.74 (0.60–0.93)

0≤0.351.4

Missense OE?1.38 (1.31–1.46)

0≤0.61.4

Synonymous OE?1.50

0≤1.21.6

LoF obs/exp: 56 / 75.4Missense obs/exp: 919 / 664.5Syn Z: -6.37

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveADAMTS18-related microcornea, myopic chorioretinal atrophy, and telecanthusLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6260th %ile

GOF

0.5268th %ile

LOF

0.4234th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

1310 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47

Likely Pathogenic18

VUS647

Likely Benign509

Benign56

Conflicting18

Pathogenic

Likely Pathogenic

647

VUS

509

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	43	1	3	0	47
Likely Pathogenic	15	0	3	0	18
VUS	5	606	33	3	647
Likely Benign	0	42	184	283	509
Benign	0	16	16	24	56
Conflicting	—				18
Total	63	665	239	310	1,295

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

33 pathogenic / likely-pathogenic (of 76) ClinVar copy-number / structural variants overlap ADAMTS18 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →