GNE

glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase

Basic information

Region (hg38): 9:36214441-36277042

Previous symbols: [ "IBM2" ]

Links

ENSG00000159921 ∙ NCBI:10020 ∙ OMIM:603824 ∙ HGNC:23657 ∙ Uniprot:Q9Y223 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• GNE myopathy (Definitive), mode of inheritance: AR
• sialuria (Strong), mode of inheritance: AD
• GNE myopathy (Strong), mode of inheritance: AR
• sialuria (Supportive), mode of inheritance: AD
• GNE myopathy (Supportive), mode of inheritance: AD
• platelet-type bleeding disorder 19 (Supportive), mode of inheritance: AR
• sialuria (Limited), mode of inheritance: AD
• GNE myopathy (Strong), mode of inheritance: AR
• sialuria (Strong), mode of inheritance: AD
• macrothrombocytopenia, isolated (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombocytopenia 12 with or without myopathy	AR	Hematologic	The condition can involve thrombocytopenia and risk of bleeding episodes, and awareness may enable preventive measures (eg, related to surgery) and early management of bleeding episodes	Biochemical; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic	7252518; 2443758; 2808337; 1779656; 8439453; 10330343; 11528398; 11486897; 11326336; 12473780; 11916006; 12473753; 12177386; 12473769; 16372135; 17718674; 20059379; 20175955; 20300792; 20301343; 20301439; 20346669; 21131200; 21708040; 22196754; 22507750; 22883483; 23127962; 24685570; 24737350; 24796702; 25257349; 29941673; 30171045; 34788986

ClinVar

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

• Sialuria;GNE myopathy (32 variants)
• not provided (24 variants)
• GNE myopathy;Sialuria (19 variants)
• GNE myopathy (19 variants)
• Sialuria (3 variants)
• Thrombocytopenia 12 with or without myopathy (1 variants)
• GNE myopathy;Inclusion body myositis (1 variants)
• Hereditary nonpolyposis colon cancer (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GNE 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		2	201	1	205
missense	12	29	279	1		321
nonsense	14	25				39
start loss			2			2
frameshift	25	32				57
inframe indel		1	7			8
splice donor/acceptor (+/-2bp)	6	11				17
splice region	1		21	39		61
non coding	2		62	124	36	224
Total	60	98	352	326	37

Highest pathogenic variant AF is 0.0000921

Variants in GNE

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

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

Position	Type	Phenotype	Significance	ClinVar
9-36214458-ATT-A		Sialuria • GNE myopathy • Inclusion Body Myopathy, Recessive	Uncertain significance (Jun 14, 2016)
9-36214488-A-G		GNE myopathy • Inclusion Body Myopathy, Recessive • Sialuria	Uncertain significance (Jan 12, 2018)
9-36214518-A-G		GNE myopathy • Inclusion Body Myopathy, Recessive • Sialuria	Uncertain significance (Jan 13, 2018)
9-36214576-C-T		Sialuria • GNE myopathy • Inclusion Body Myopathy, Recessive	Benign/Likely benign (Jan 13, 2018)
9-36214599-A-G		Inclusion Body Myopathy, Recessive • Sialuria • GNE myopathy	Uncertain significance (Jan 13, 2018)
9-36214656-A-G		Sialuria • GNE myopathy	Uncertain significance (Jan 12, 2018)
9-36214686-C-T		Inclusion Body Myopathy, Recessive • Sialuria • GNE myopathy	Uncertain significance (Jan 13, 2018)
9-36214789-T-C		Sialuria • Inclusion Body Myopathy, Recessive • GNE myopathy	Likely benign (Apr 27, 2017)
9-36214815-C-T		GNE myopathy • Sialuria	Uncertain significance (Jan 13, 2018)
9-36214828-C-T		GNE myopathy • Sialuria	Uncertain significance (Jan 13, 2018)
9-36214912-G-T		Sialuria • GNE myopathy	Uncertain significance (Jan 13, 2018)
9-36214917-T-C		Inclusion Body Myopathy, Recessive • GNE myopathy • Sialuria	Uncertain significance (Jan 12, 2018)
9-36214934-T-C		GNE myopathy • Sialuria	Uncertain significance (Jan 13, 2018)
9-36214950-A-T		Sialuria • Inclusion Body Myopathy, Recessive • GNE myopathy	Conflicting classifications of pathogenicity (Jan 13, 2018)
9-36214955-C-G		Inclusion Body Myopathy, Recessive • GNE myopathy • Sialuria	Uncertain significance (Jun 14, 2016)
9-36214974-G-A		Sialuria • Inclusion Body Myopathy, Recessive • GNE myopathy	Benign (May 13, 2021)
9-36215096-G-A		Sialuria • GNE myopathy • Inclusion Body Myopathy, Recessive	Likely benign (Apr 27, 2017)
9-36215120-T-A		Sialuria • GNE myopathy	Uncertain significance (Jan 13, 2018)
9-36215154-G-C		GNE myopathy • Inclusion Body Myopathy, Recessive • Sialuria	Benign/Likely benign (Jan 13, 2018)
9-36215168-C-CA		Sialuria • GNE myopathy • Inclusion Body Myopathy, Recessive	Benign (Jun 14, 2016)
9-36215180-A-T		GNE myopathy • Sialuria	Uncertain significance (Jan 15, 2018)
9-36215209-C-G		Inclusion Body Myopathy, Recessive • Sialuria • GNE myopathy	Benign (Jan 12, 2018)
9-36215309-G-A		Sialuria • Inclusion Body Myopathy, Recessive • GNE myopathy	Benign/Likely benign (Jan 13, 2018)
9-36215511-G-A		GNE myopathy • Sialuria	Uncertain significance (Jan 13, 2018)
9-36215539-C-G		GNE myopathy • Inclusion Body Myopathy, Recessive • Sialuria	Benign (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GNE	protein_coding	protein_coding	ENST00000396594	12	62616

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.48e-16	0.0599	125691	0	57	125748	0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.59	271	420	0.645	0.0000233	4958
Missense in Polyphen		90	168.57	0.53389		1949
Synonymous	1.59	128	153	0.837	0.00000846	1505
Loss of Function	0.828	27	32.1	0.842	0.00000194	367

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000391	0.000391
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000363	0.000352
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates and initiates biosynthesis of N- acetylneuraminic acid (NeuAc), a precursor of sialic acids. Plays an essential role in early development (By similarity). Required for normal sialylation in hematopoietic cells. Sialylation is implicated in cell adhesion, signal transduction, tumorigenicity and metastatic behavior of malignant cells. {ECO:0000250, ECO:0000269|PubMed:10334995}.
• Disease: DISEASE: Sialuria (SIALURIA) [MIM:269921]: In sialuria, free sialic acid accumulates in the cytoplasm and gram quantities of neuraminic acid are secreted in the urine. The metabolic defect involves lack of feedback inhibition of UDP-GlcNAc 2-epimerase by CMP-Neu5Ac, resulting in constitutive overproduction of free Neu5Ac. Clinical features include variable degrees of developmental delay, coarse facial features and hepatomegaly. Sialuria inheritance is autosomal dominant. {ECO:0000269|PubMed:10330343, ECO:0000269|PubMed:10356312, ECO:0000269|PubMed:11326336, ECO:0000269|PubMed:2808337}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Nonaka myopathy (NM) [MIM:605820]: Autosomal recessive muscular disorder, allelic to inclusion body myopathy 2. It is characterized by weakness of the anterior compartment of the lower limbs with onset in early adulthood, and sparing of the quadriceps muscles. As the inclusion body myopathy, NM is histologically characterized by the presence of numerous rimmed vacuoles without inflammatory changes in muscle specimens. {ECO:0000269|PubMed:11528398, ECO:0000269|PubMed:11916006, ECO:0000269|PubMed:12177386, ECO:0000269|PubMed:12325084, ECO:0000269|PubMed:12409274, ECO:0000269|PubMed:12473753, ECO:0000269|PubMed:12473769, ECO:0000269|PubMed:12473780, ECO:0000269|PubMed:12497639, ECO:0000269|PubMed:12811782, ECO:0000269|PubMed:12913203, ECO:0000269|PubMed:15146476}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Sialuria or French Type Sialuria;Sialuria or French Type Sialuria;Amino Sugar Metabolism;G(M2)-Gangliosidosis: Variant B, Tay-sachs disease;Tay-Sachs Disease;Salla Disease/Infantile Sialic Acid Storage Disease;Aminosugars metabolism;Post-translational protein modification;Metabolism of proteins;CMP-<i>N</i>-acetylneuraminate biosynthesis I (eukaryotes);Sialic acid metabolism;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.257

Intolerance Scores

• loftool: 0.0436
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.436
• hipred: N
• hipred_score: 0.362
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.971

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gne
• Phenotype: growth/size/body region phenotype; muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); renal/urinary system phenotype

Zebrafish Information Network

• Gene name: gne
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: N-acetylglucosamine biosynthetic process;UDP-N-acetylglucosamine metabolic process;N-acetylneuraminate metabolic process;cell adhesion;carbohydrate phosphorylation
• Cellular component: cytoplasm;cytosol
• Molecular function: hydrolase activity, hydrolyzing O-glycosyl compounds;protein binding;ATP binding;UDP-N-acetylglucosamine 2-epimerase activity;N-acylmannosamine kinase activity;metal ion binding