ADAMTSL1

Chr 9

ADAMTS like 1

Also known as: ADAMTSL-1, ADAMTSR1, C9orf94, PUNCTIN

NCBI Gene: 92949ENSG00000178031UniProt: Q8N6G6

This gene encodes a secreted protein and member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) family. This protein lacks the metalloproteinase and disintegrin-like domains, which are typical of the ADAMTS family, but contains other ADAMTS domains, including the thrombospondin type 1 motif. This protein may have important functions in the extracellular matrix. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

495
ClinVar variants
86
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ADAMTSL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
86 Pathogenic / Likely Pathogenic· 242 VUS of 495 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.53LOEUF
pLI 0.000
Z-score 5.24
OE 0.40 (0.31–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.97Z-score
OE missense 1.08 (1.03–1.14)
1138 obs / 1049.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.40 (0.31–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.08 (1.03–1.14)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.22
0≤1.21.6
LoF obs/exp: 36 / 89.5Missense obs/exp: 1138 / 1049.6Syn Z: -3.68

ClinVar Variant Classifications

495 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic81
Likely Pathogenic5
VUS242
Likely Benign26
Benign8
Conflicting1
81
Pathogenic
5
Likely Pathogenic
242
VUS
26
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
81
0
81
Likely Pathogenic
0
0
5
0
5
VUS
2
227
13
0
242
Likely Benign
0
10
9
7
26
Benign
0
0
0
8
8
Conflicting
—1
Total223710815363

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

View in ClinVar →

Protein Context — Lollipop Plot

ADAMTSL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ADAMTSL1-related syndromic congenital glaucoma

limited
ADDominant NegativeAltered Gene Product Structure
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ADAMTSL1 and mandibular prognathism.
Kantaputra PN et al.·Clin Genet
2019
Identification and functional analysis of an ADAMTSL1 variant associated with a complex phenotype including congenital glaucoma, craniofacial, and other systemic features in a three-generation human pedigree.
Hendee K et al.·Hum Mutat
2017Case report
Protein C-Mannosylation and C-Mannosyl Tryptophan in Chemical Biology and Medicine.
Minakata S et al.·Molecules
2021Review
Unravelling morphoea aetiopathogenesis by next-generation sequencing of paired skin biopsies.
Saracino AM et al.·Arch Dermatol Res
2023
Genetic and Molecular Determinants of Familial Transmission of Skeletal Malocclusions.
Dehesa-Santos A et al.·Orthod Craniofac Res
2025Review
Identification of potential causal variants for premature ovarian failure by whole exome sequencing.
Jin H et al.·BMC Med Genomics
2020
Preliminary study of genome-wide association identifies novel susceptibility genes for serum mineral elements in the Chinese Han population.
Guo D et al.·Biol Trace Elem Res
2022
The Role of Gene Expression Dysregulation in the Pathogenesis of Mucopolysaccharidosis: A Comparative Analysis of Shared and Specific Molecular Markers in Neuronopathic and Non-Neuronopathic Types of the Disease.
Wiśniewska K et al.·Int J Mol Sci
2024
Hedgehog pathway inhibition in chondrosarcoma using the smoothened inhibitor IPI-926 directly inhibits sarcoma cell growth.
Campbell VT et al.·Mol Cancer Ther
2014
Peters'-plus syndrome is a congenital disorder of glycosylation caused by a defect in the beta1,3-glucosyltransferase that modifies thrombospondin type 1 repeats.
Heinonen TY et al.·Ann Med
2009Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools