GLE1

GLE1 RNA export mediator, the group of Nucleoporins

Basic information

Region (hg38): 9:128504655-128543874

Previous symbols: [ "GLE1L", "LCCS1" ]

Links

ENSG00000119392 ∙ NCBI:2733 ∙ OMIM:603371 ∙ HGNC:4315 ∙ Uniprot:Q53GS7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lethal arthrogryposis-anterior horn cell disease syndrome (Definitive), mode of inheritance: AR
• amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
• lethal congenital contracture syndrome 1 (Supportive), mode of inheritance: AR
• lethal arthrogryposis-anterior horn cell disease syndrome (Supportive), mode of inheritance: AR
• lethal congenital contracture syndrome 1 (Strong), mode of inheritance: AR
• amyotrophic lateral sclerosis (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital arthrogryposis with anterior horn cell disease; Lethal congenital contracture syndrome 1	AR	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; Ophthalmologic	7966188; 7897624; 18204449; 30239721

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GLE1 gene.

• not provided (81 variants)
• Lethal arthrogryposis-anterior horn cell disease syndrome (2 variants)
• Lethal congenital contracture syndrome 1 (1 variants)
• Lethal congenital contractural syndrome Finnish type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLE1 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	216	2	219
missense		5	54	7	1	67
nonsense	31	1				32
start loss						0
frameshift	46	3	1			50
inframe indel						0
splice donor/acceptor (+/-2bp)	3	21				24
splice region			1	48	1	50
non coding	1		24	132	29	186
Total	81	30	80	355	32

Highest pathogenic variant AF is 0.000766

Variants in GLE1

This is a list of pathogenic ClinVar variants found in the GLE1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-128504698-C-A		Lethal arthrogryposis-anterior horn cell disease syndrome • Lethal congenital contracture syndrome 1	Uncertain significance (Jan 13, 2018)
9-128504722-A-C		Lethal arthrogryposis-anterior horn cell disease syndrome • Lethal congenital contracture syndrome 1	Uncertain significance (Jan 13, 2018)
9-128504725-C-T		Lethal congenital contracture syndrome 1 • Lethal arthrogryposis-anterior horn cell disease syndrome	Uncertain significance (Jan 13, 2018)
9-128504755-G-A		Lethal arthrogryposis-anterior horn cell disease syndrome • Lethal congenital contracture syndrome 1	Uncertain significance (Jan 13, 2018)
9-128504761-T-C		Lethal arthrogryposis-anterior horn cell disease syndrome • Lethal congenital contracture syndrome 1 • Lethal arthrogryposis-anterior horn cell disease syndrome;Lethal congenital contracture syndrome 1	Conflicting classifications of pathogenicity (Sep 20, 2024)
9-128504772-G-A		Lethal arthrogryposis-anterior horn cell disease syndrome • Lethal congenital contracture syndrome 1	Uncertain significance (Jan 13, 2018)
9-128504810-C-G		Lethal congenital contracture syndrome 1 • Lethal arthrogryposis-anterior horn cell disease syndrome • Lethal arthrogryposis-anterior horn cell disease syndrome;Lethal congenital contracture syndrome 1 • GLE1-related disorder	Conflicting classifications of pathogenicity (Jan 31, 2024)
9-128504811-G-A			Likely benign (Jul 22, 2021)
9-128504811-G-T			Likely benign (Sep 27, 2023)
9-128504823-C-G			Likely benign (Sep 26, 2017)
9-128504836-T-C			Likely benign (Mar 10, 2022)
9-128504859-C-G		Lethal arthrogryposis-anterior horn cell disease syndrome • Lethal congenital contracture syndrome 1 • Lethal arthrogryposis-anterior horn cell disease syndrome;Lethal congenital contracture syndrome 1	Conflicting classifications of pathogenicity (Sep 20, 2024)
9-128504868-C-G			Likely benign (Mar 09, 2023)
9-128504881-C-G		Lethal congenital contracture syndrome 1 • Lethal arthrogryposis-anterior horn cell disease syndrome • Inborn genetic diseases	Uncertain significance (May 03, 2023)
9-128504892-G-A			Likely benign (Feb 05, 2023)
9-128504900-GC-G			Pathogenic (Feb 17, 2023)
9-128504902-G-T			Pathogenic (Jun 14, 2023)
9-128504911-G-T			Likely benign (Sep 16, 2021)
9-128504914-G-A			Likely benign (Jul 16, 2023)
9-128504915-GC-G			Benign (Sep 10, 2023)
9-128504917-C-T			Likely benign (Jun 15, 2023)
9-128504918-C-G			Likely benign (Nov 20, 2023)
9-128504919-C-G			Likely benign (Oct 20, 2023)
9-128504919-C-T			Likely benign (Sep 22, 2023)
9-128504933-C-G		Lethal arthrogryposis-anterior horn cell disease syndrome • Lethal congenital contracture syndrome 1	Benign (Jul 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLE1	protein_coding	protein_coding	ENST00000309971	16	37589

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.05e-10	0.998	125674	0	74	125748	0.000294

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.806	335	379	0.884	0.0000215	4568
Missense in Polyphen		88	120.45	0.7306		1437
Synonymous	0.835	128	141	0.910	0.00000738	1329
Loss of Function	2.86	23	43.3	0.531	0.00000220	479

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000358	0.000358
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000308	0.000308
Middle Eastern	0.0000546	0.0000544
South Asian	0.000719	0.000719
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm. May be involved in the terminal step of the mRNA transport through the nuclear pore complex (NPC). {ECO:0000269|PubMed:12668658, ECO:0000269|PubMed:16000379, ECO:0000269|PubMed:9618489}.
• Disease: DISEASE: Lethal congenital contracture syndrome 1 (LCCS1) [MIM:253310]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS1 patients manifest early fetal hydrops and akinesia, micrognathia, pulmonary hypoplasia, pterygia, and multiple joint contractures. It leads to prenatal death. {ECO:0000269|PubMed:18204449}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Lethal arthrogryposis with anterior horn cell disease (LAAHD) [MIM:611890]: A disorder characterized by fetal akinesia, arthrogryposis and motor neuron loss. The fetus often survives delivery, but dies early as a result of respiratory failure. Neuropathological findings resemble those of lethal congenital contracture syndrome type 1, but are less severe. {ECO:0000269|PubMed:18204449}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.923
• rvis_EVS: -0.09
• rvis_percentile_EVS: 47.06

Haploinsufficiency Scores

• pHI: 0.337
• hipred: Y
• hipred_score: 0.548
• ghis: 0.623

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.647

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gle1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: gle1
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: branchiness

Gene ontology

• Biological process: mRNA export from nucleus;regulation of translational initiation;regulation of translational termination;poly(A)+ mRNA export from nucleus
• Cellular component: extracellular space;nuclear pore;nucleolus;cytoplasm;cytosol;membrane;nuclear membrane;nuclear pore cytoplasmic filaments
• Molecular function: inositol hexakisphosphate binding;protein binding;phospholipid binding;translation initiation factor binding;identical protein binding