GNE
glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase
Basic information
Region (hg38): 9:36214441-36277042
Previous symbols: [ "IBM2" ]
Links
Phenotypes
GenCC
Source:
- 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
- congenital myopathy (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| 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
- GNE_myopathy (873 variants)
- Sialuria (755 variants)
- not_provided (281 variants)
- not_specified (45 variants)
- Thrombocytopenia_12_with_or_without_myopathy (37 variants)
- Inborn_genetic_diseases (31 variants)
- GNE-related_disorder (20 variants)
- Inclusion_Body_Myopathy,_Recessive (8 variants)
- Thrombocytopenia (2 variants)
- Myopathy,_autophagic_vacuolar,_infantile-onset (2 variants)
- Hereditary_nonpolyposis_colon_cancer (1 variants)
- See_cases (1 variants)
- Isolated_hereditary_giant_platelet_disorder (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. These statistics are base on transcript: NM_000005476.7. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 230 | 242 | ||||
| missense | 14 | 74 | 335 | 428 | ||
| nonsense | 23 | 21 | 44 | |||
| start loss | 1 | 1 | ||||
| frameshift | 32 | 37 | 69 | |||
| splice donor/acceptor (+/-2bp) | 16 | 23 | ||||
| Total | 78 | 148 | 345 | 235 | 1 |
Highest pathogenic variant AF is 0.00074525713
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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