ADAMTS16

Chr 5

ADAM metallopeptidase with thrombospondin type 1 motif 16

Also known as: ADAMTS16s

NCBI Gene: 170690 ENSG00000145536 UniProt: Q8TE57 OMIM: 607510

This gene encodes a metalloproteinase with thrombospondin motifs that may regulate blood pressure and inhibit chondrosarcoma cell proliferation and migration. The gene is highly constrained against loss-of-function variants (pLI=0.0004, LOEUF=0.431), but no established Mendelian diseases have been definitively associated with ADAMTS16 mutations. Further research is needed to determine the clinical significance of variants in this gene.

OMIM ResearchSummary from RefSeq

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 inhibit chondrosarcoma cell proliferation and migration. This gene may regulate blood pressure. [provided by RefSeq, May 2016]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.43

Clinical Summary— ADAMTS16

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 183 VUS of 221 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.000

Z-score 5.26

OE 0.29 (0.20–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.41Z-score

OE missense 0.96 (0.90–1.02)

682 obs / 712.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.29 (0.20–0.43)

0≤0.351.4

Missense OE?0.96 (0.90–1.02)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 19 / 64.7Missense obs/exp: 682 / 712.6Syn Z: -1.32

This gene — mechanism propensity

0.7229th %ile

GOF

0.5857th %ile

LOF

0.3065th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

221 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS183

Likely Benign16

Benign1

Likely Pathogenic

183

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	0	0	1
VUS	0	183	0	0	183
Likely Benign	0	7	2	7	16
Benign	0	1	0	0	1
Total	1	191	2	7	201

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

View in ClinVar →

117 pathogenic / likely-pathogenic (of 123) ClinVar copy-number / structural variants overlap ADAMTS16 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →