LAS1L

protein-coding

LAS1 like ribosome biogenesis factor, the group of Large ribosomal subunit biogenesis complex

Gene summary

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]

MANE transcript

NM_031206.7

Inheritance

ClinVar variants

P:7U:214B:71

Top phenotype

Intellectual developmental disorder, X-linked syndromic, Wilson-Turner type

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chrX:65,438,549-65,534,810

External References & Databases

Ensembl (ENSG00000001497)

Transcript & Mutation Effects

hg38 • Region Span ~96.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Wilson-Turner syndromeSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010665

Submitter: Orphanet

spinal muscular atrophy with respiratory distress type 2SUPPORTIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0018450

Submitter: Orphanet

Wilson-Turner syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010665

Submitter: PanelApp Australia

X-linked syndromic intellectual disabilityLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0020119

Submitter: ClinGen

LAS1L encodes a protein with a critical role in ribosomal biogenesis. Loss of LAS1L in S cerevisiae disrupts the processing of the 47S pre-rRNA at the second intervening sequence (ITS2), which separates the 5.8S and 28S rRNA sequences and affects the biogenesis of the large 60S ribosomal subunit. This curation is focused on evidence for LAS1L in causing X linked syndromic intellectual disability (MONDO: 0020119), but this has also been referred to in the literature as Wilson-Turner syndrome (MONDO:0010665; MIM:309585). LAS1L is localized to chromosome Xq12. Currently, there are only 7 LAS1L variants reported in the literature, 2 of which were seen in affected males of two large families and the rest were seen in singleton cases (PMIDs: 1746601, 25644381, 27479843, 28135719, 24647030, 32193494). Notably, all of the reported LAS1L variants are missense changes thus far. As for genetic evidence, the case level and segregation data add up to a score of 1.7 total points. The available experimental evidence for LAS1L mainly focuses on this gene’s cellular function in ribosome biogenesis and cell cycle (PMIDs: 20647540, 22190735, 22083961). Hence, none of the experimental evidence was scored. Overall, currently there is limited evidence available for LAS1L and X-linked syndromic intellectual disability. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 09/21/2021 (SOP Version 8).

Wilson-Turner syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010665

Submitter: Labcorp Genetics (formerly Invitae)

Wilson-Turner syndromeLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010665

Submitter: G2P

Wilson-Turner syndromeLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0010665

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked syndromic, Wilson-Turner typeXL

Manifestation: Craniofacial; Endocrine; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 25644381

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LAS1L variants in ClinVar

10 Conditions Cataloged

Wilson-Turner syndromeTotal: 143

not providedTotal: 107

not specifiedTotal: 47

LAS1L-related disorderTotal: 7

Intellectual disabilityTotal: 2

Inborn genetic diseasesTotal: 2

Neurodevelopmental disorderTotal: 1

Autism spectrum disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031206.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			12 clinvar	55 clinvar	3 clinvar	70
missense	1 clinvar	4 clinvar	174 clinvar	10 clinvar	3 clinvar	192
nonsense		1 clinvar	8 clinvar			9
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			20 clinvar			20
Total	1	6	214	65	6	292

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 107 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031206.7	RefSeq	NP_112483.1	14	MANE Select
ENST00000374811.8	Ensembl	ENSP00000363944.3	14	MANE Select
NM_001170649.2	RefSeq	NP_001164120.1	13	Standard
NM_001170650.2	RefSeq	NP_001164121.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
las1l	Danio rerio	Structure: primary motor neuron Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

las1l

Danio rerio

Structure: primary motor neuron

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

maturation of 5.8S rRNA
maturation of LSU-rRNA
rRNA processing

Molecular Function

RNA binding

Cellular Component

nucleoplasm
nucleolus
cytoplasm
membrane
preribosome, large subunit precursor

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374811
Coding exons: 14
Length: 22194
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125731
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.67	149	273	0.546	0.0000205	4809
Missense (PolyPhen)		8	64.036	0.12493		1169
Synonymous	0.316	110	114	0.962	0.00000910	1380
Loss of Function	4.60	1	26.6	0.0376	0.00000189	457

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000089	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000053	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the biogenesis of the 60S ribosomal subunit. Required for maturation of the 28S rRNA. Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. {ECO:0000269|PubMed:20647540, ECO:0000269|PubMed:22872859}.;
Disease: DISEASE: Wilson-Turner X-linked mental retardation syndrome (WTS) [MIM:309585]: A neurologic disorder characterized by severe intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Affected females have a milder phenotype than affected males. {ECO:0000269|PubMed:25644381}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0807

Intolerance Scores

LoFtool: 0.0366
RVIS EVS: -0.09
RVIS percentile EVS: 46.74

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.944

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium