LAS1L

Chr XXLR

LAS1 like ribosome biogenesis factor

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

This protein is required for synthesis of the 60S ribosomal subunit and maturation of 28S rRNA through processing of internal transcribed spacer 2. Mutations cause Wilson-Turner syndrome, an X-linked recessive disorder characterized by intellectual disability and distinctive facial features. The gene is highly constrained against loss-of-function variants in the population, indicating that such variants are likely to be pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.181 OMIM phenotype
Clinical SummaryLAS1L
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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.
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ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 148 VUS of 400 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 4.60
OE 0.04 (0.010.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.67Z-score
OE missense 0.55 (0.480.63)
149 obs / 273.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.010.18)
00.351.4
Missense OE0.55 (0.480.63)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 1 / 26.6Missense obs/exp: 149 / 273.0Syn Z: 0.32
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedLAS1L-related intellectual disabilityOTHERXLR
DN
0.2499th %ile
GOF
0.2796th %ile
LOF
0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.18

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

400 submitted variants in ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic5
VUS148
Likely Benign81
Benign20
Conflicting7
47
Pathogenic
5
Likely Pathogenic
148
VUS
81
Likely Benign
20
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
47
0
47
Likely Pathogenic
2
2
1
0
5
VUS
1
129
18
0
148
Likely Benign
0
7
22
52
81
Benign
0
4
13
3
20
Conflicting
7
Total314210155308

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC