LAS1L

Chr XXLR

LAS1 like ribosome biogenesis factor

Also known as: Las1, Las1-like, MRXSWTS, WTS, dJ475B7.2

NCBI Gene: 81887ENSG00000001497UniProt: Q9Y4W2

Enables RNA binding activity. Involved in rRNA processing. Located in nucleolus. Part of MLL1 complex. Implicated in Wilson-Turner syndrome. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Wilson-Turner syndromeMIM #309585
XLR
UniProtIntellectual developmental disorder, X-linked, syndromic, Wilson-Turner type
308
ClinVar variants
55
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— LAS1L
🧬
Gene-Disease Validity (ClinGen)
X-linked syndromic intellectual disability · XLLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 146 VUS of 308 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.18LOEUF
pLI 1.000
Z-score 4.60
OE 0.04 (0.01–0.18)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.67Z-score
OE missense 0.55 (0.48–0.63)
149 obs / 273.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.04 (0.01–0.18)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.48–0.63)
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.0.96
0≤1.21.6
LoF obs/exp: 1 / 26.6Missense obs/exp: 149 / 273.0Syn Z: 0.32

ClinVar Variant Classifications

308 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic5
VUS146
Likely Benign81
Benign20
Conflicting6
50
Pathogenic
5
Likely Pathogenic
146
VUS
81
Likely Benign
20
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
50
0
50
Likely Pathogenic
1
2
2
0
5
VUS
1
123
22
0
146
Likely Benign
0
6
23
52
81
Benign
0
3
14
3
20
Conflicting
—6
Total213411155308

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

View in ClinVar →

Protein Context — Lollipop Plot

LAS1L · protein map & ClinVar variants

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

Gene2Phenotype Curations

LAS1L-related intellectual disability

limited
Monoallelic X HemizygousUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Wilson-Turner syndrome

MIM #309585

Molecular basis of disorder known

X-linked recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes.
Hu H et al.·Mol Psychiatry
2016
Inhibiting β-catenin disables nucleolar functions in triple-negative breast cancer.
Weeks SE et al.·Cell Death Dis
2021
New genes involved in Angelman syndrome-like: Expanding the genetic spectrum.
Aguilera C et al.·PLoS One
2021
Congenital lethal motor neuron disease with a novel defect in ribosome biogenesis.
Butterfield RJ et al.·Neurology
2014
Severe Infantile Axonal Neuropathy with Respiratory Failure Caused by Novel Mutation in X-Linked LAS1L Gene.
Stembalska A et al.·Genes (Basel)
2022Case report
Genetic landscape of autism spectrum disorder in Vietnamese children.
Tran KT et al.·Sci Rep
2020
Pericentromeric regions of homozygosity on the X chromosome: Another likely benign population variant.
Barrie ES et al.·Eur J Med Genet
2018
Tentative clinical diagnosis of Lujan-Fryns syndrome--A conglomeration of different genetic entities?
Hackmann K et al.·Am J Med Genet A
2016
Integrative genomic, transcriptomic, and RNAi analysis indicates a potential oncogenic role for FAM110B in castration-resistant prostate cancer.
Vainio P et al.·Prostate
2012
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