ADAMTSL3

Chr 15

ADAMTS like 3

Also known as: ADAMTSL-3

NCBI Gene: 57188 ENSG00000156218 UniProt: P82987

The protein is predicted to be involved in extracellular matrix organization and is located in intracellular membrane-bounded organelles. This gene is highly constrained against loss-of-function variants (pLI ~0, LOEUF 0.65), but specific disease associations and inheritance patterns have not been definitively established in the provided data.

ResearchSummary from RefSeq

Predicted to be involved in extracellular matrix organization. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.65

Clinical Summary— ADAMTSL3

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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

242 VUS of 373 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.65LOEUF

pLI 0.000

Z-score 4.39

OE 0.51 (0.40–0.65)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.48Z-score

OE missense 0.96 (0.91–1.01)

917 obs / 958.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.51 (0.40–0.65)

0≤0.351.4

Missense OE?0.96 (0.91–1.01)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 47 / 92.6Missense obs/exp: 917 / 958.4Syn Z: 0.29

This gene — mechanism propensity

0.7132th %ile

GOF

0.6150th %ile

LOF

0.3261th %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

373 submitted variants in ClinVar

ClinVar

Classification Summary

VUS242

Likely Benign19

Benign89

Conflicting1

242

VUS

Likely Benign

Benign

Conflicting

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	0	0	0	0	0
VUS	0	238	4	0	242
Likely Benign	0	15	0	4	19
Benign	0	11	70	8	89
Conflicting	—				1
Total	0	264	74	12	351

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

View in ClinVar →

34 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap ADAMTSL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →