LAGE3

Summary

LAGE3 (L antigen family member 3, HGNC:26058) is a protein-coding gene on chromosome Xq28, encoding EKC/KEOPS complex subunit LAGE3 (Q14657). 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. It is a selective cancer dependency (DepMap: 11.3% of cell lines).

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.

Source: NCBI Gene 8270 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Galloway-Mowat syndrome 2, X-linked (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 116 total — 3 pathogenic
• GTEx eGene: eQTL in 30 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 49
• Cancer dependency (DepMap): dependent in 11.3% of screened cell lines
• MANE Select transcript: NM_006014

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26058
Approved symbol	LAGE3
Name	L antigen family member 3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	ITBA2, CVG5, DXS9951E, DXS9879E, ESO3, Pcc1
Ensembl gene	ENSG00000196976
Ensembl biotype	protein_coding
OMIM	300060
Entrez	8270

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

MANE Select: ENST00000357360

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000357360, ENST00000973350, ENST00001132821

RefSeq mRNA: 1 — MANE Select: NM_006014 NM_006014

CCDS: CCDS14753

Canonical transcript exons

ENST00000357360 — 3 exons

Exon	Start	End
ENSE00001408883	154478283	154478411
ENSE00001431841	154478728	154479281
ENSE00001929073	154477775	154478058

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 98.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.4745 / max 179.3704, expressed in 1808 samples.

Highest expression (Bgee): oocyte, secondary oocyte, Brodmann (1909) area 10, middle frontal gyrus, endometrium epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LAGE3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 30 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	7.0e-22	+0.21	X:154370045:T:C
Artery Tibial	eqtl	6.8e-16	+0.19	X:154370045:T:C
Skin Sun Exposed Lower leg	eqtl	2.0e-10	-0.14	X:154484549:T:C
Brain Cerebellum	eqtl	1.2e-07	-0.27	X:154469004:T:C
Skin Not Sun Exposed Suprapubic	eqtl	1.7e-07	+0.13	X:154351080:A:G
Artery Aorta	eqtl	1.6e-06	+0.17	X:154370045:T:C
Esophagus Gastroesophageal Junction	eqtl	1.8e-05	+0.54	X:154859556:C:T
Brain Cerebellar Hemisphere	eqtl	2.3e-05	-0.17	X:154463703:A:G
Pancreas	eqtl	5.8e-05	+0.77	X:153649921:C:A
Minor Salivary Gland	eqtl	1.3e-04	+1.00	X:153649921:C:A
Cells Cultured fibroblasts	eqtl	5.2e-04	+0.15	X:154451760:G:A
Lung	eqtl	7.9e-04	+0.42	X:154551170:G:A
Prostate	eqtl	1.3e-03	+1.26	X:154551170:G:A
Testis	eqtl	1.5e-03	-0.12	X:154485691:T:G
Cells EBV-transformed lymphocytes	eqtl	1.6e-03	+0.24	X:154521834:C:T
Brain Substantia nigra	eqtl	4.3e-03	+0.19	X:154477925:C:G
Small Intestine Terminal Ileum	eqtl	7.3e-03	+0.38	X:154744884:C:T
Adipose Subcutaneous	eqtl	1.0e-02	+0.08	X:154384715:T:G
Whole Blood	eqtl	1.4e-02	-0.08	X:154485112:T:C
Adrenal Gland	eqtl	1.5e-02	+0.66	X:153649921:C:A

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
201029	11.0139	1736
201028	9.6523	1755
201025	4.6404	1453
201026	2.2392	1069
201032	1.8785	965
201031	0.4757	275
201027	0.3793	221
201030	0.1952	81

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	98.23	gold quality
secondary oocyte	CL:0000655	95.55	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.69	gold quality
middle frontal gyrus	UBERON:0002702	93.97	gold quality
endometrium epithelium	UBERON:0004811	93.53	gold quality
frontal pole	UBERON:0002795	93.37	gold quality
anterior cingulate cortex	UBERON:0009835	92.96	gold quality
cingulate cortex	UBERON:0003027	92.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.41	gold quality
nucleus accumbens	UBERON:0001882	91.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.92	gold quality
right frontal lobe	UBERON:0002810	91.66	gold quality
putamen	UBERON:0001874	91.60	gold quality
endothelial cell	CL:0000115	91.55	gold quality
amygdala	UBERON:0001876	91.51	gold quality
caudate nucleus	UBERON:0001873	91.35	gold quality
prefrontal cortex	UBERON:0000451	90.88	gold quality
neocortex	UBERON:0001950	90.75	gold quality
frontal cortex	UBERON:0001870	90.61	gold quality
cerebral cortex	UBERON:0000956	90.47	gold quality
telencephalon	UBERON:0001893	90.19	gold quality
pituitary gland	UBERON:0000007	90.14	gold quality
Ammon’s horn	UBERON:0001954	90.08	gold quality
forebrain	UBERON:0001890	89.95	gold quality
temporal lobe	UBERON:0001871	89.64	gold quality
paraflocculus	UBERON:0005351	89.63	gold quality
adenohypophysis	UBERON:0002196	89.61	gold quality
brain	UBERON:0000955	88.95	gold quality
central nervous system	UBERON:0001017	88.91	gold quality
left adrenal gland cortex	UBERON:0035825	88.74	gold quality
right adrenal gland	UBERON:0001233	88.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.57	gold quality
right adrenal gland cortex	UBERON:0035827	88.52	gold quality
cranial nerve II	UBERON:0000941	88.47	gold quality
left adrenal gland	UBERON:0001234	88.39	gold quality
hypothalamus	UBERON:0001898	88.34	gold quality
adrenal cortex	UBERON:0001235	88.10	gold quality
superior frontal gyrus	UBERON:0002661	87.96	gold quality
CA1 field of hippocampus	UBERON:0003881	87.94	gold quality
primary visual cortex	UBERON:0002436	87.68	gold quality
spinal cord	UBERON:0002240	87.64	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.56	gold quality
mucosa of transverse colon	UBERON:0004991	87.50	gold quality
orbitofrontal cortex	UBERON:0004167	87.49	gold quality
substantia nigra	UBERON:0002038	87.37	gold quality
entorhinal cortex	UBERON:0002728	87.25	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.18	gold quality
midbrain	UBERON:0001891	86.80	gold quality
granulocyte	CL:0000094	86.63	gold quality
gastrocnemius	UBERON:0001388	86.56	gold quality
adrenal gland	UBERON:0002369	86.53	gold quality
apex of heart	UBERON:0002098	86.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.33	gold quality
right atrium auricular region	UBERON:0006631	86.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.94	gold quality
occipital lobe	UBERON:0002021	85.93	gold quality
pons	UBERON:0000988	85.92	gold quality
parietal lobe	UBERON:0001872	85.92	gold quality
middle temporal gyrus	UBERON:0002771	85.87	gold quality
postcentral gyrus	UBERON:0002581	85.81	gold quality
cerebellar hemisphere	UBERON:0002245	85.66	gold quality
cerebellar cortex	UBERON:0002129	85.63	gold quality
muscle of leg	UBERON:0001383	85.60	gold quality
heart left ventricle	UBERON:0002084	85.55	gold quality
cerebellum	UBERON:0002037	85.32	gold quality
cardiac ventricle	UBERON:0002082	85.27	gold quality
body of pancreas	UBERON:0001150	85.15	gold quality
pigmented layer of retina	UBERON:0001782	85.03	gold quality
cardiac atrium	UBERON:0002081	84.84	gold quality
periodontal ligament	UBERON:0008266	84.73	gold quality
adult organism	UBERON:0007023	84.36	gold quality
cortical plate	UBERON:0005343	84.34	gold quality
right lobe of liver	UBERON:0001114	84.08	gold quality
gingival epithelium	UBERON:0001949	84.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.00	gold quality
trabecular bone tissue	UBERON:0002483	83.95	gold quality
heart	UBERON:0000948	83.93	gold quality
endocervix	UBERON:0000458	83.92	gold quality
lateral nuclear group of thalamus	UBERON:0002736	83.78	gold quality
ectocervix	UBERON:0012249	83.67	gold quality
skin of abdomen	UBERON:0001416	83.56	gold quality
gingiva	UBERON:0001828	83.56	gold quality
skin of leg	UBERON:0001511	83.44	gold quality
right ovary	UBERON:0002118	83.36	gold quality
muscle organ	UBERON:0001630	83.32	gold quality
monocyte	CL:0000576	83.23	gold quality
left ovary	UBERON:0002119	83.15	gold quality
leukocyte	CL:0000738	83.10	gold quality
mononuclear cell	CL:0000842	82.88	gold quality
zone of skin	UBERON:0000014	82.79	gold quality
body of stomach	UBERON:0001161	82.62	gold quality
cerebellar vermis	UBERON:0004720	82.62	gold quality
bone marrow	UBERON:0002371	82.47	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	82.12	silver quality
muscle layer of sigmoid colon	UBERON:0035805	82.09	gold quality
minor salivary gland	UBERON:0001830	81.98	gold quality
inferior vagus X ganglion	UBERON:0005363	81.89	gold quality
saliva-secreting gland	UBERON:0001044	81.85	gold quality
mouth mucosa	UBERON:0003729	81.84	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.82	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	9.98
E-ANND-3	yes	8.78
E-CURD-10	no	52.21

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pituitary gland	tissue	32.2
Caudate putamen	tissue	31.9
Frontal cortex	tissue	31.8
Hippocampus	tissue	26.3	low
Nucleus accumbens	tissue	25.5
Postcentral gyrus	tissue	20.8
Skeletal muscle	tissue	18.5	medium
Spinal cord	tissue	18.4
Locus coeruleus	tissue	18.2
Bone marrow	tissue	17.9	high
Choroid plexus	tissue	16.2
Corpus callosum	tissue	15.1
Hippocampal formation	tissue	14.9
Cerebral cortex	tissue	14.7	medium
Motor cortex	tissue	14.7
Substantia nigra	tissue	14.6
Midbrain	tissue	14.4
Thalamus	tissue	14.4
Superior colliculi	tissue	14.4
Medulla oblongata	tissue	14.3
Putamen	tissue	14.0
Pons	tissue	13.7
Salivary gland	tissue	13.6	high
Temporal cortex	tissue	13.5
Hypothalamus	tissue	13.3
Entorhinal cortex	tissue	13.3
Pancreas	tissue	13.0	high
Adrenal gland	tissue	13.0	high
Insular cortex	tissue	12.9
Vagina	tissue	12.8	medium
Retrosplenial cortex	tissue	12.6
Prefrontal cortex	tissue	12.5
Somatosensory cortex	tissue	12.4
Thymus	tissue	12.2
Septum	tissue	12.2
Occipital cortex	tissue	12.2
Retrosplenial and cingulate cortex	tissue	12.1
Amygdala	tissue	11.5
Basal ganglia	tissue	11.4	medium
Ventral forebrain	tissue	11.2
Periaqueductal gray	tissue	11.1
Ovary	tissue	10.9	medium
Olfactory bulb	tissue	9.5
Lymph node	tissue	9.3	medium
Tongue	tissue	9.3
Skin 1	tissue	9.1	high
Spleen	tissue	8.7	medium
Stomach 1	tissue	8.5	high
Heart muscle	tissue	8.4	medium
Adipose tissue	tissue	8.4	low
Liver	tissue	8.3	medium
Parathyroid gland	tissue	8.2	medium
Cerebellum	tissue	8.2	medium
Tonsil	tissue	8.1	medium
Epididymis	tissue	7.7	high
Colon	tissue	7.2	medium
Appendix	tissue	7.1	medium
Cervix	tissue	6.9	high
Prostate	tissue	6.9	medium
Urinary bladder	tissue	6.7	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Hippocampus, CA1 (31.4), Hippocampus, CA2 (29.0), Occipital cortex (white matter) (28.9), Temporo-occipital transitional zone (28.9), Perirhinal gyrus (28.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LAGE3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

15 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-562	97.66	65.63	698

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000357360 — one region, missense o/e 1.10. DepMap (CRISPR cell-line fitness): dependent in 11.3% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): TM-87 (-1.157), CL-40 (-1.008), JL-1 (-1.004), OCI-M2 (-0.994), C75 (-0.958), HNT-34 (-0.933), LB1047-RCC (-0.925), NOS-1 (-0.88), DBTRG-05MG (-0.875), 697 (-0.87), ES8 (-0.846), Mero-95 (-0.843), A-673 (-0.84), NCI-H28 (-0.84), SUM-185PE (-0.836).

Literature-anchored findings (GeneRIF, showing 6)

• Upregulation of LAGE3 correlates with prognosis and immune infiltrates in colorectal cancer: A bioinformatic analysis. (PMID:32438075)
• LAGE3 correlates with tumorigenic immune infiltrates in the clear cell renal cell carcinoma microenvironment. (PMID:32683301)
• lncRNA NEAT1 regulates the proliferation and migration of hepatocellular carcinoma cells by acting as a miR320a molecular sponge and targeting L antigen family member 3. (PMID:32945386)
• Identification and validation of L Antigen Family Member 3 as an immune-related biomarker associated with the progression of papillary thyroid cancer. (PMID:33310661)
• LAGE3 promoted cell proliferation, migration, and invasion and inhibited cell apoptosis of hepatocellular carcinoma by facilitating the JNK and ERK signaling pathway. (PMID:34837962)
• LAGE3 promotes cell metastasis and stemness in non-small cell lung cancer companied with AKT/PI3K signaling pathway activation. (PMID:37473499)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000116344
mus_musculus	Lage3	ENSMUSG00000015289
drosophila_melanogaster	Tcs6	FBGN0260224

Paralogs (3): CTAG2 (ENSG00000126890), CTAG1B (ENSG00000184033), CTAG1A (ENSG00000268651)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1913442) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal sternum morphology	1
increased neutrophil cell number	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Schizosaccharomyces pombe 972h-	Q10220	33.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GDI1	protein-coding	2664
ATP6AP1	protein-coding	537
PLXNA3	protein-coding	55558
UBL4A	protein-coding	8266
FAM50A	protein-coding	9130
MIR6858	ncRNA	102465517
ATP6AP1-DT	ncRNA	158960
SLC10A3	protein-coding	8273
FAM3A	protein-coding	60343

Protein

Protein identifiers

EKC/KEOPS complex subunit LAGE3 — Q14657 (reviewed: Q14657)

Alternative names: L antigen family member 3, Protein ESO-3, Protein ITBA2

All UniProt accessions (1): Q14657

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Component of the EKC/KEOPS complex composed of at least GON7, TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Disease relevance. Galloway-Mowat syndrome 2, X-linked (GAMOS2) [MIM:301006] A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CTAG/PCC1 family.

RefSeq proteins (1): NP_006005* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR015419	CTAG/Pcc1	Family

Pfam: PF09341

UniProt features (12 total): helix 3, strand 3, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
6GWJ	Human OSGEP / LAGE3 / GON7 complex	X-RAY DIFFRACTION	1.95
9FL9	Cryo-EM structure of the human KEOPS complex	ELECTRON MICROSCOPY	3.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14657-F1	76.32	0.45

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; nuclear bodies

Antibody reliability (HPA): IH approved · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-8953854	Metabolism of RNA	—
R-HSA-6782315	tRNA modification in the nucleus and cytosol	electronic
R-HSA-72306	tRNA processing	—

MSigDB gene sets: 231 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KAAB_FAILED_HEART_ATRIUM_DN, PAL_PRMT5_TARGETS_UP, GOBP_TRNA_METABOLIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, PATIL_LIVER_CANCER, GOBP_TRANSLATION, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOBP_TRNA_THREONYLCARBAMOYLADENOSINE_METABOLIC_PROCESS, HAN_SATB1_TARGETS_DN, MARKEY_RB1_ACUTE_LOF_UP, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, DANG_BOUND_BY_MYC, CONCANNON_APOPTOSIS_BY_EPOXOMICIN_DN

GO Biological Process (2): tRNA processing (GO:0008033), maintenance of translational fidelity (GO:1990145)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): EKC/KEOPS complex (GO:0000408), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604)

Reactome top-level categories

2 top-level categories:

Category	Pathways
tRNA processing	1
Metabolism of RNA	1

GO top-level categories

12 GO namespaces:

Category	Terms
cellular anatomical structure	2
RNA processing	1
tRNA metabolic process	1
translation	1
macromolecule biosynthetic process	1
binding	1
transferase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
EKC/KEOPS complex	CC	direct assay
cytoplasm	CC	direct assay
nuclear body	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 542 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAGE3	TMEM187	Q14656	927
LAGE3	TPRKB	Q9Y3C4	905
LAGE3	OSGEP	Q9NPF4	868
LAGE3	TP53RK	Q96S44	863
LAGE3	YRDC	Q86U90	811
LAGE3	OSGEPL1	Q9H4B0	808
LAGE3	GON7	Q9BXV9	797
LAGE3	WDR73	Q6P4I2	714
LAGE3	L1CAM	P32004	667
LAGE3	HCFC1	P51610	663
LAGE3	FAM216A	Q8WUB2	463
LAGE3	WDR4	P57081	407
LAGE3	CTAG2	O75638	400
LAGE3	NUP107	P57740	375
LAGE3	TMEM101	Q96IK0	349

IntAct

Human interaction partners of LAGE3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

27 partners by confidence:

Partner	Interaction type	MIscore	Records
GON7	physical association	0.880	15
OSGEP	physical association	0.850	4
POP7	physical association	0.740	3
KRT40	physical association	0.720	6
PSMB9	physical association	0.600	4
PDE9A	physical association	0.560	6
HYKK	physical association	0.560	4
AKAP8L	physical association	0.560	3
CYSRT1	physical association	0.560	3
GOLGA6L9	physical association	0.560	3
HSF2BP	physical association	0.560	3
KRTAP10-8	physical association	0.560	3
KRTAP6-3	physical association	0.560	3
MID2	physical association	0.560	3
MIPOL1	physical association	0.560	3
MKRN3	physical association	0.560	3
PLEKHJ1	physical association	0.560	3
PNMA1	physical association	0.560	3
TRIM23	physical association	0.560	3
TRIM27	physical association	0.560	3
VPS37C	physical association	0.560	3
CTSA	association	0.530	1
ANO4	association	0.350	1
PPIAL4C	association	0.350	1
CCDC28B	physical association	0.000	1
HLA-B	physical association	0.000	1
IKBKE	physical association	0.000	1

BioGRID (148 interactions; top human partners by supporting records): OSGEP (Affinity Capture-MS; 11 records), PRAME (Affinity Capture-MS; 5 records), TP53RK (Affinity Capture-MS; 5 records), TPRKB (Affinity Capture-MS; 4 records), C14orf142 (Two-hybrid; 3 records), NUP43 (Affinity Capture-MS; 3 records), TCEB2 (Co-fractionation; 3 records), CCDC28B (Affinity Capture-MS; 2 records), CUL2 (Affinity Capture-MS; 2 records), HYKK (Two-hybrid; 2 records), KRT40 (Two-hybrid; 2 records), PDE9A (Two-hybrid; 2 records), POP7 (Two-hybrid; 2 records), TCEB1 (Affinity Capture-MS; 2 records), AGO2 (Affinity Capture-RNA)

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
PRAME complex	7	LAGE3, OSGEP, PRAME, RBX1, CUL2, ELOB, ELOC
KEOPS complex	4	LAGE3, OSGEP, TP53RK, TPRKB

Disease & clinical

Genetic variants

Variant evidence for LAGE3: 116 ClinVar records (3 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

116 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	61
Likely benign	20
Benign	9

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
444871	NM_006014.5(LAGE3):c.316G>T (p.Val106Phe)	Pathogenic	no assertion criteria provided	1
444872	NM_006014.5(LAGE3):c.410T>C (p.Phe137Ser)	Pathogenic	no assertion criteria provided	1
444873	NM_006014.5(LAGE3):c.188+1G>A	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore LAGE3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 15 predictions of 212):

Position(s)	Effect	Δscore	Sites
X:154478059–154478060	acceptor_loss	0.9900	6
X:154478065	acceptor_gain	0.9900
X:154478667	donor_gain	0.9800
X:154479040	donor_gain	0.9700
X:154479134	donor_gain	0.9400
X:154478057	acceptor_gain	0.9300
X:154478382	acceptor_gain	0.9300
X:154478726	donor_loss	0.9300
X:154479164	donor_gain	0.9100
X:154478726	donor_loss	0.8900

AlphaMissense

140 missense substitutions predicted likely pathogenic (of 910 scored), across 47 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F69	8	0.911	0.966
W108	7	0.885	0.960
F137	7	0.879	0.974
D112	7	0.697	0.765
F123	6	0.834	0.925
F63	6	0.807	0.898
K95	6	0.787	0.939
I77	5	0.796	0.909
G138	5	0.772	0.858
V67	5	0.764	0.932
T133	5	0.723	0.877
V130	5	0.700	0.878
A75	4	0.814	0.955
L127	3	0.843	0.884
L116	3	0.815	0.871
S119	3	0.812	0.822
L65	3	0.810	0.873
L82	3	0.797	0.831
L104	3	0.795	0.845
A110	3	0.770	0.920

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	5.82e-06
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	1.9e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000167
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000356
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	0.000695

Disease associations

OMIM: gene MIM:300060 | disease phenotypes: MIM:301006

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
Galloway-Mowat syndrome 2, X-linked	Strong	X-linked	4
Galloway-Mowat syndrome	Supportive	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Fetal anomalies	green
Proteinuric renal disease	green
Severe microcephaly	green
Unexplained young onset end-stage renal disease	green

Mondo (2): Galloway-Mowat syndrome 2, X-linked (MONDO:0033006), Galloway-Mowat syndrome (MONDO:0009627)

HPO phenotypes

49 phenotypes (HPO-id order):

HPO	Term
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000112	Nephropathy
HP:0000164	Abnormality of the dentition
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000400	Macrotia
HP:0000565	Esotropia
HP:0000601	Hypotelorism
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0001166	Arachnodactyly
HP:0001181	Adducted thumb
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001302	Pachygyria
HP:0001310	Dysmetria
HP:0001419	X-linked recessive inheritance
HP:0001511	Intrauterine growth retardation
HP:0001622	Premature birth
HP:0002036	Hiatus hernia
HP:0002059	Cerebral atrophy
HP:0002126	Polymicrogyria
HP:0002269	Abnormality of neuronal migration
HP:0002353	EEG abnormality
HP:0002410	Aqueductal stenosis
HP:0002650	Scoliosis
HP:0003593	Infantile onset
HP:0003774	Stage 5 chronic kidney disease
HP:0004322	Short stature
HP:0004374	Hemiplegia/hemiparesis
HP:0005108	Abnormal intervertebral disk morphology
HP:0010978	Abnormality of immune system physiology
HP:0011451	Primary microcephaly
HP:0011463	Childhood onset
HP:0011968	Feeding difficulties
HP:0012579	Minimal change glomerulonephritis
HP:0100490	Camptodactyly of finger
HP:0100543	Cognitive impairment
HP:0100720	Hypoplasia of the ear cartilage

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C537548	Galloway Mowat syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066468 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	increases expression, affects response to substance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
methylselenic acid	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
pyrachlostrobin	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Methotrexate	decreases expression	1
Smoke	decreases expression	1
Testosterone	increases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651676	Binding	Binding affinity to human LAGE3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

9 trials:

NCT	Phase	Status	Title
NCT07531251	Phase 4	RECRUITING	Clinical Trial in Patients With Barth Syndrome- 4TAZPower
NCT03098797	Phase 2/3	COMPLETED	A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects With Barth Syndrome
NCT01194141	Not specified	COMPLETED	Exercise Training in Barth Syndrome
NCT01461304	Not specified	NO_LONGER_AVAILABLE	Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism
NCT01625663	Not specified	COMPLETED	Heart and Muscle Metabolism in Barth Syndrome
NCT01629459	Not specified	COMPLETED	Resistance Exercise in Barth Syndrome
NCT03655223	Not specified	ACTIVE_NOT_RECRUITING	Early Check: Expanded Screening in Newborns
NCT04689360	Not specified	AVAILABLE	An Intermediate Size Expanded Access Protocol of Elamipretide
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LAGE3 across ~30M SureChEMBL compounds — explore on Sugi Predict.