FUS
FUS RNA binding protein, the group of Zinc fingers RANBP2-type |RNA binding motif containing|Heterogeneous nuclear ribonucleoproteins
Basic information
Region (hg38): 16:31180138-31196963
Previous symbols: [ "ALS6" ]
Links
Phenotypes
GenCC
Source:
- amyotrophic lateral sclerosis type 6 (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis (Definitive), mode of inheritance: AD
- amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
- juvenile amyotrophic lateral sclerosis (Supportive), mode of inheritance: AR
- tremor, hereditary essential, 4 (Limited), mode of inheritance: AD
- amyotrophic lateral sclerosis type 6 (Strong), mode of inheritance: AD
- tremor, hereditary essential, 4 (Limited), mode of inheritance: Unknown
- amyotrophic lateral sclerosis type 6 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia; Tremor, hereditary essential, 4 | AD/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 | Neurologic | 12840784; 12858291; 19741216; 19251627; 19741215; 19251628; 19861302; 20385912; 20577002; 20660363; 20668259; 22863194; 22980027; 22999566; 23046859 |
ClinVar
This is a list of variants' phenotypes submitted to
- Amyotrophic_lateral_sclerosis_type_6 (310 variants)
- Tremor,_hereditary_essential,_4 (288 variants)
- not_provided (133 variants)
- Inborn_genetic_diseases (125 variants)
- FUS-related_disorder (71 variants)
- not_specified (21 variants)
- Juvenile_amyotrophic_lateral_sclerosis (2 variants)
- Amyotrophic_Lateral_Sclerosis,_Dominant (2 variants)
- Dystonic_disorder (1 variants)
- Frontotemporal_dementia (1 variants)
- Myoclonus (1 variants)
- Amyotrophic_lateral_sclerosis_6,_autosomal_recessive (1 variants)
- Amyotrophic_lateral_sclerosis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FUS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004960.4. 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 | 82 | 86 | ||||
| missense | 12 | 146 | 20 | 187 | ||
| nonsense | 5 | |||||
| start loss | 0 | |||||
| frameshift | 12 | 19 | ||||
| splice donor/acceptor (+/-2bp) | 9 | |||||
| Total | 30 | 17 | 152 | 105 | 2 |
Highest pathogenic variant AF is 0.000040296534
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FUS | protein_coding | protein_coding | ENST00000254108 | 15 | 11697 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000695 | 125728 | 0 | 5 | 125733 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.21 | 217 | 330 | 0.658 | 0.0000207 | 3400 |
| Missense in Polyphen | 28 | 63.684 | 0.43967 | 648 | ||
| Synonymous | -2.13 | 147 | 118 | 1.25 | 0.00000745 | 1027 |
| Loss of Function | 5.16 | 4 | 38.6 | 0.104 | 0.00000228 | 381 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000591 | 0.0000591 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000165 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Binds both single-stranded and double-stranded DNA and promotes ATP-independent annealing of complementary single- stranded DNAs and D-loop formation in superhelical double-stranded DNA. May play a role in maintenance of genomic integrity.;
- Disease
- DISEASE: Note=A chromosomal aberration involving FUS is found in a patient with malignant myxoid liposarcoma. Translocation t(12;16)(q13;p11) with DDIT3. {ECO:0000269|PubMed:7503811}.; DISEASE: Note=A chromosomal aberration involving FUS is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with ERG. {ECO:0000269|PubMed:8187069}.; DISEASE: Angiomatoid fibrous histiocytoma (AFH) [MIM:612160]: A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis. {ECO:0000269|PubMed:11063792}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving FUS is found in a patient with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with ATF1 generates a chimeric FUS/ATF1 protein. {ECO:0000269|PubMed:11063792}.; DISEASE: Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia (ALS6) [MIM:608030]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. {ECO:0000269|PubMed:19251627, ECO:0000269|PubMed:19251628, ECO:0000269|PubMed:19861302, ECO:0000269|PubMed:20124201, ECO:0000269|PubMed:27604643}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Tremor, hereditary essential 4 (ETM4) [MIM:614782]: A common movement disorder mainly characterized by postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles also may be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant. {ECO:0000269|PubMed:22863194}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Transcriptional misregulation in cancer - Homo sapiens (human);mRNA Processing;Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA
(Consensus)
Recessive Scores
- pRec
- 0.491
Intolerance Scores
- loftool
- 0.00503
- rvis_EVS
- -1
- rvis_percentile_EVS
- 8.32
Haploinsufficiency Scores
- pHI
- 0.426
- hipred
- Y
- hipred_score
- 0.775
- ghis
- 0.679
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.856
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fus
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; reproductive system 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); normal phenotype; hematopoietic system phenotype; 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- fus
- Affected structure
- CaP motoneuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased length
Gene ontology
- Biological process
- mRNA splicing, via spliceosome;regulation of transcription, DNA-templated;cellular response to calcium ion;positive regulation of nucleic acid-templated transcription
- Cellular component
- nucleus;nucleoplasm;polysome;perikaryon;dendritic spine head;perinuclear region of cytoplasm
- Molecular function
- DNA binding;transcription coactivator activity;RNA binding;protein binding;estrogen receptor binding;myosin V binding;ionotropic glutamate receptor binding;identical protein binding;metal ion binding;retinoid X receptor binding;thyroid hormone receptor binding