LAS1L

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

Basic information

Region (hg38): X:65438548-65534810

Links

ENSG00000001497 ∙ NCBI:81887 ∙ OMIM:300964 ∙ HGNC:25726 ∙ Uniprot:Q9Y4W2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Limited), mode of inheritance: XLR
• Wilson-Turner syndrome (Limited), mode of inheritance: XL
• Wilson-Turner syndrome (Supportive), mode of inheritance: XL
• spinal muscular atrophy with respiratory distress type 2 (Supportive), mode of inheritance: Unknown
• intellectual disability, autosomal dominant 40 (Limited), mode of inheritance: XL
• Wilson-Turner syndrome (Strong), mode of inheritance: XL
• X-linked syndromic intellectual disability (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked syndromic, Wilson-Turner type	XL	General	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	Craniofacial; Endocrine; Musculoskeletal; Neurologic	25644381

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAS1L gene.

• Wilson-Turner syndrome (94 variants)
• not provided (65 variants)
• Inborn genetic diseases (29 variants)
• not specified (2 variants)
• Global developmental delay (1 variants)
• Intellectual disability (1 variants)
• Neurodevelopmental disorder (1 variants)
• Autism spectrum disorder (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAS1L gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	37	4	42
missense		3	72	2	3	80
nonsense		1				1
start loss						0
frameshift						0
inframe indel			2		2	4
splice donor/acceptor (+/-2bp)						0
splice region			4	4		8
non coding			15	9	14	38
Total	0	4	90	48	23

Variants in LAS1L

This is a list of pathogenic ClinVar variants found in the LAS1L region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-65488859-G-A		not specified	Uncertain significance (Jul 20, 2021)
X-65488920-T-C		not specified	Uncertain significance (Dec 01, 2022)
X-65488953-T-C		not specified	Uncertain significance (Jan 30, 2024)
X-65488991-G-A		not specified	Uncertain significance (Jan 25, 2023)
X-65488991-G-T		not specified	Uncertain significance (Dec 06, 2022)
X-65489028-C-T		not specified	Uncertain significance (Dec 14, 2021)
X-65489064-G-A		not specified	Likely benign (May 16, 2022)
X-65489127-A-G			Benign (May 18, 2018)
X-65502074-C-T		not specified	Uncertain significance (Jan 03, 2024)
X-65502090-G-A			Benign (Jul 16, 2018)
X-65502120-C-G		not specified	Uncertain significance (Jan 04, 2024)
X-65502128-C-T		not specified	Uncertain significance (Oct 06, 2021)
X-65502304-A-C		not specified	Uncertain significance (Nov 09, 2023)
X-65502428-G-A		not specified	Uncertain significance (Jun 03, 2022)
X-65502454-C-T		not specified	Uncertain significance (May 25, 2022)
X-65502532-G-A		not specified	Uncertain significance (Oct 27, 2023)
X-65502568-C-G		not specified	Uncertain significance (Jun 29, 2023)
X-65502583-C-T		not specified	Likely benign (Dec 20, 2021)
X-65502623-A-G		not specified	Uncertain significance (Oct 05, 2023)
X-65502631-G-A		not specified	Uncertain significance (Dec 28, 2022)
X-65502817-T-C		not specified	Uncertain significance (Feb 08, 2023)
X-65502845-G-A		not specified	Uncertain significance (Oct 26, 2022)
X-65502852-A-G			Likely benign (Feb 01, 2023)
X-65502914-C-T		not specified	Uncertain significance (Dec 14, 2021)
X-65503035-G-A		not specified	Uncertain significance (Apr 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAS1L	protein_coding	protein_coding	ENST00000374811	14	22194

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000450	125729	0	2	125731	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.67	149	273	0.546	0.0000205	4809
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000886	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.0000528	0.0000327
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.107
• hipred: Y
• hipred_score: 0.556
• ghis: 0.542

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.944

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Las1l

Zebrafish Information Network

• Gene name: las1l
• Affected structure: primary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: maturation of 5.8S rRNA;maturation of LSU-rRNA;rRNA processing
• Cellular component: nucleoplasm;nucleolus;cytoplasm;membrane;preribosome, large subunit precursor;MLL1 complex
• Molecular function: RNA binding