LAGE3

L antigen family member 3, the group of KEOPS complex

Basic information

Region (hg38): X:154477775-154479281

Links

ENSG00000196976 ∙ NCBI:8270 ∙ OMIM:300060 ∙ HGNC:26058 ∙ Uniprot:Q14657 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Galloway-Mowat syndrome 2, X-linked (Strong), mode of inheritance: XL
• Galloway-Mowat syndrome (Supportive), mode of inheritance: AR
• Galloway-Mowat syndrome 2, X-linked (Limited), mode of inheritance: XL
• Galloway-Mowat syndrome 2, X-linked (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Galloway-Mowat syndrome 2, X-linked	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; Musculoskeletal; Neurologic; Renal	28805828

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAGE3 gene.

• not_provided (51 variants)
• not_specified (24 variants)
• LAGE3-related_disorder (16 variants)
• Galloway-Mowat_syndrome_2,_X-linked (13 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAGE3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006014.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				13	1	14
missense	2		45	6	5	58
nonsense			1			1
start loss			1			1
frameshift			2			2
splice donor/acceptor (+/-2bp)	1		1			2
Total	3	0	50	19	6

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAGE3	protein_coding	protein_coding	ENST00000357360	3	1569

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.127	0.630	100249	1	1	100251	0.00000998

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.409	46	54.5	0.844	0.00000471	887
Missense in Polyphen		10	18.502	0.5405		286
Synonymous	0.565	19	22.4	0.848	0.00000184	327
Loss of Function	0.487	1	1.68	0.595	1.10e-7	35

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000439	0.0000439
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000145	0.0000107
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. LAGE3 functions as a dimerization module for the complex. {ECO:0000305|PubMed:22912744, ECO:0000305|PubMed:27903914}.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.0834

Haploinsufficiency Scores

• pHI: 0.100
• hipred: N
• hipred_score: 0.112
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lage3

Gene ontology

• Biological process: tRNA processing;biological_process
• Cellular component: EKC/KEOPS complex;nucleus;nucleoplasm;cytoplasm;nuclear body
• Molecular function: protein binding