LAGE3

protein-coding

L antigen family member 3, the group of KEOPS complex

Gene summary

This gene belongs to the ESO/LAGE gene family, members of which are clustered together on chromosome Xq28, and have similar exon-intron structures. Unlike the other family members which are normally expressed only in testis and activated in a wide range of human tumors, this gene is ubiquitously expressed in somatic tissues. The latter, combined with the finding that it is highly conserved in mouse and rat, suggests that the encoded protein is functionally important. An intronless pseudogene with high sequence similarity to this gene is located on chromosome 9. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006014.5

Inheritance

XL, AR

ClinVar variants

P:3U:70B:31

Top phenotype

Galloway-Mowat syndrome 2, X-linked

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chrX:154,477,775-154,479,281

External References & Databases

Ensembl (ENSG00000196976)

Transcript & Mutation Effects

hg38 • Region Span ~1.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Galloway-Mowat syndrome 2, X-linkedSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0033006

Submitter: Labcorp Genetics (formerly Invitae)

Galloway-Mowat syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009627

Submitter: Orphanet

Galloway-Mowat syndrome 2, X-linkedSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0033006

Submitter: PanelApp Australia

Galloway-Mowat syndrome 2, X-linkedLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0033006

Submitter: Ambry Genetics

Galloway-Mowat syndrome 2, X-linkedLIMITED

Inheritance Pattern: XL

Disease ID:MONDO:0033006

Submitter: G2P

Clinical Genomic Database (CGD)

Galloway-Mowat syndrome 2, X-linkedXL

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Renal

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: 28805828

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LAGE3 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 63

not specifiedTotal: 31

LAGE3-related disorderTotal: 19

Galloway-Mowat syndrome 2, X-linkedTotal: 16

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006014.5. 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			4 clinvar	17 clinvar	1 clinvar	22
missense	2 clinvar		58 clinvar	9 clinvar	4 clinvar	73
nonsense			1 clinvar			1
start loss			1 clinvar			1
frameshift			5 clinvar			5
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	3	0	70	26	5	104

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006014.5	RefSeq	NP_006005.2	3	MANE Select
ENST00000357360.5	Ensembl	ENSP00000349923.4	3	MANE Select
ENST00000973350.1	Ensembl	ENSP00000643167.1	3	Standard
ENST00001132821.1	Ensembl	ENSP00000808554.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

tRNA modification in the nucleus and cytosol
tRNA processing
Metabolism of RNA

Biological Process

tRNA processing
biological_process

Molecular Function

protein binding

Cellular Component

EKC/KEOPS complex
nucleus
nucleoplasm
cytoplasm
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357360
Coding exons: 3
Length: 1569
Individuals with no LoFs: 100249
Homozygous LoFs: 1
Heterozygous LoFs: 1
Defined: 100251
p: 0.00000998

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.409	46	54.5	0.844	0.00000471	887
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000044	0.000036	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000014	0.000011	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.0834

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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