FUS Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human FUS — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene FUS, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene FUS, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene FUS protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene FUS protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene FUS, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene FUS, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene FUS, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene FUS protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene FUS, summarize transcription factor regulatory data. If FUS is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate FUS — names with evidence type (ChIP-seq / predicted / experimentally validated) If FUS is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene FUS protein as a drug target, summarize pharmacology data. If FUS is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If FUS is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene FUS, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene FUS, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in FUS: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
FUS (Fused in Sarcoma; HGNC:4010, chromosome 16) is a multifunctional RNA-binding protein belonging to the TAF15/EWS/TLS family that plays critical roles in mRNA splicing, transcription regulation, and membraneless organelle assembly. Its foremost clinical significance is as a causative gene for amyotrophic lateral sclerosis type 6 (ALS6, OMIM:608030) and frontotemporal dementia, with 12 pathogenic and 1 likely pathogenic ClinVar variants concentrated in the C-terminal nuclear localization region. The protein is ubiquitously expressed across 304 tissues and conditions (Bgee max score 99.63/100) and is deeply conserved across metazoans, with orthologs in mouse, zebrafish, fly, and worm. FUS maintains an extensive interaction network — approximately 3,788 STRING interactions, including high-confidence partners SOD1, hnRNP A2/B1, and SFPQ — highlighting its central role in RNA processing complexes. Despite its disease relevance, FUS remains an undeveloped drug target with no approved therapies and only two non-selective preclinical compounds identified in ChEMBL.
FUS — Reference
Cross-database identifier and functional mapping reference for FUS.
Gene identifiers
| Identifier | Value |
|---|---|
| HGNC ID | HGNC:4010 |
| Approved symbol | FUS |
| Ensembl gene ID | ENSG00000089280 |
| NCBI Entrez Gene ID | 2521 |
| OMIM gene ID | 137070 |
| Chromosome (GRCh38) | 16 |
| Start position | 31,180,134 |
| End position | 31,196,963 |
| Strand | + (forward) |
Transcript identifiers
Ensembl Transcripts
Total: 47 transcripts
| ENST ID | Biotype |
|---|---|
| ENST00000254108 | protein_coding |
| ENST00000380244 | protein_coding |
| ENST00000474990 | protein_coding_CDS_not_defined |
| ENST00000483853 | retained_intron |
| ENST00000487045 | retained_intron |
| ENST00000487509 | retained_intron |
| ENST00000487974 | retained_intron |
| ENST00000564766 | retained_intron |
| ENST00000566605 | nonsense_mediated_decay |
| ENST00000568685 | protein_coding |
| ENST00000568901 | retained_intron |
| ENST00000569760 | retained_intron |
| ENST00000570090 | retained_intron |
| ENST00000715541 | nonsense_mediated_decay |
| ENST00000715542 | protein_coding |
| ENST00000875021 | protein_coding |
| ENST00000875022 | protein_coding |
| ENST00000875023 | protein_coding |
| ENST00000875024 | protein_coding |
| ENST00000875025 | protein_coding |
| ENST00000875026 | protein_coding |
| ENST00000875027 | protein_coding |
| ENST00000875028 | protein_coding |
| ENST00000875029 | protein_coding |
| ENST00000875030 | protein_coding |
| ENST00000875031 | protein_coding |
| ENST00000875032 | protein_coding |
| ENST00000875033 | protein_coding |
| ENST00000925795 | protein_coding |
| ENST00000925796 | protein_coding |
| ENST00000925797 | protein_coding |
| ENST00000925798 | protein_coding |
| ENST00000925799 | protein_coding |
| ENST00000925800 | protein_coding |
| ENST00000925801 | protein_coding |
| ENST00000925802 | protein_coding |
| ENST00000925803 | protein_coding |
| ENST00000925805 | protein_coding |
| ENST00000925806 | protein_coding |
| ENST00000925807 | protein_coding |
| ENST00000925808 | protein_coding |
| ENST00000948616 | protein_coding |
| ENST00000948617 | protein_coding |
| ENST00000948618 | protein_coding |
| ENST00000948619 | protein_coding |
| ENST00000948620 | protein_coding |
| ENST00000948621 | protein_coding |
RefSeq mRNA Transcripts
Total: 16 transcripts
| NM_ ID | MANE Select |
|---|---|
| NM_001012137 | |
| NM_001169690 | |
| NM_001170634 | |
| NM_001170937 | |
| NM_001178672 | |
| NM_001259418 | |
| NM_001347649 | |
| NM_004960 | ✓ |
| NM_079952 | |
| NM_139149 | |
| NM_166105 | |
| NM_166106 | |
| NM_166107 | |
| NM_166108 | |
| NM_166109 | |
| NM_201083 |
CCDS IDs
| CCDS ID |
|---|
| CCDS10707 |
| CCDS58454 |
Canonical/MANE SELECT Transcript Exons
Transcript: ENST00000254108 (protein_coding, chr16:31180139–31191605 +)
RefSeq: NM_004960
Total exons: 15
| Exon # | ENSE ID | Start | End | Length |
|---|---|---|---|---|
| 1 | ENSE00003903481 | 31180139 | 31180227 | 89 |
| 2 | ENSE00003630677 | 31182513 | 31182664 | 152 |
| 3 | ENSE00003475065 | 31182398 | 31182422 | 25 |
| 4 | ENSE00003599547 | 31183858 | 31184002 | 145 |
| 5 | ENSE00003537617 | 31184209 | 31184396 | 188 |
| 6 | ENSE00001791812 | 31184939 | 31185179 | 241 |
| 7 | ENSE00004027052 | 31186802 | 31186836 | 35 |
| 8 | ENSE00004027046 | 31188325 | 31188357 | 33 |
| 9 | ENSE00003524436 | 31189123 | 31189226 | 104 |
| 10 | ENSE00003534484 | 31189665 | 31189794 | 130 |
| 11 | ENSE00003653971 | 31190040 | 31190141 | 102 |
| 12 | ENSE00003604625 | 31190275 | 31190398 | 124 |
| 13 | ENSE00003494295 | 31190742 | 31190842 | 101 |
| 14 | ENSE00003637572 | 31190963 | 31191110 | 148 |
| 15 | ENSE00004027047 | 31191399 | 31191605 | 207 |
Protein identifiers
UniProt accessions
- P35637 (reviewed, canonical)
RefSeq proteins
- NP_004951 (MANE Select)
- NP_001164105
Protein domains and families
| ID | Name | Type | Identifier |
|---|---|---|---|
| IPR000504 | RNA recognition motif domain | Domain | IPR000504 |
| IPR001876 | Zinc finger, RanBP2-type | Domain | IPR001876 |
| IPR012677 | Nucleotide-binding alpha-beta plait domain superfamily | Homologous_superfamily | IPR012677 |
| IPR034870 | TAF15/EWS/TLS family | Family | IPR034870 |
| IPR035979 | RNA-binding domain superfamily | Homologous_superfamily | IPR035979 |
| IPR036443 | Zinc finger, RanBP2-type superfamily | Homologous_superfamily | IPR036443 |
| PF00076 | RNA recognition motif | Domain | PF00076 |
| PF00641 | Zinc finger, C5HC2 type | Domain | PF00641 |
Antibody availability
No antibody resources mapped via UniProt-antibody connection in biobtree.
Structure
Experimental Structures
Total: 23 PDB entries
| PDB ID | Method | Resolution |
|---|---|---|
| 2LA6 | Solution NMR | — |
| 2LCW | Solution NMR | — |
| 4FDD | X-ray diffraction | 2.3 Å |
| 4FQ3 | X-ray diffraction | 3.0 Å |
| 5W3N | Solid-state NMR | — |
| 5XRR | X-ray diffraction | 1.503 Å |
| 5XSG | Electron crystallography | 0.73 Å |
| 5YVG | X-ray diffraction | 4.05 Å |
| 5YVH | X-ray diffraction | 3.15 Å |
| 5YVI | X-ray diffraction | 2.9 Å |
| 6BWZ | X-ray diffraction | 1.1 Å |
| 6BXV | X-ray diffraction | 1.1 Å |
| 6BZP | Electron crystallography | 1.1 Å |
| 6G99 | Solution NMR | — |
| 6GBM | Solution NMR | — |
| 6KJ1 | Electron crystallography (MicroED) | 0.65 Å |
| 6KJ2 | Electron crystallography (MicroED) | 0.67 Å |
| 6KJ3 | Electron crystallography (MicroED) | 0.60 Å |
| 6KJ4 | Electron crystallography (MicroED) | 0.65 Å |
| 6SNJ | Solution NMR | — |
| 6XFM | Cryo-EM | 2.62 Å |
| 7CYL | X-ray diffraction | 2.7 Å |
| 7VQQ | Cryo-EM | 2.9 Å |
Predicted Structures
AlphaFold Model: AF-P35637
- Global pLDDT: 54.96
- High confidence regions (pLDDT > 70): 9% of structure
- Sequence length: 3762 (aa token positions)
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | 233908 | Fus |
| Rat (Rattus norvegicus) | 317385 | Fus |
| Zebrafish (Danio rerio) | 394058 | fus |
| Fruit fly (Drosophila melanogaster) | 32587 | caz |
| Worm (C. elegans) | 174175 | fust-1 |
| Yeast (S. cerevisiae) | none | none |
Clinical variants & AI predictions
ClinVar summary
| Classification | Count |
|---|---|
| Pathogenic | 12 |
| Likely Pathogenic | 1 |
| Uncertain Significance | ~220 |
| Likely Benign | ~180 |
| Benign | ~125 |
| Conflicting | ~18 |
| Total | ~657 |
Top 30 pathogenic/likely pathogenic variants
| Variant ID | HGVS | Condition/Note |
|---|---|---|
| 1073222 | c.1554_1557del (p.Gln519fs) | FUS-associated ALS |
| 1423819 | c.1500dup (p.Gly501fs) | Frameshift |
| 1458206 | c.1509_1510del (p.Gly504fs) | FUS-associated disease |
| 1485282 | c.1391_1392dup (p.Gly465fs) | Frameshift |
| 16221 | c.1551C>G (p.His517Gln) | ALS/FTD |
| 16222 | c.1561C>G (p.Arg521Gly) | ALS |
| 16223 | c.1553G>A (p.Arg518Lys) | ALS |
| 16224 | c.1561C>T (p.Arg521Cys) | ALS |
| 16225 | c.1562G>A (p.Arg521His) | ALS |
| 1918103 | c.253C>T (p.Gln85Ter) | Stop codon |
| 2046744 | c.1573C>A (p.Pro525Thr) | Pathogenic |
| 2419096 | c.1449_1488del (p.Tyr484fs) | Large deletion |
| 1333381 | c.1542-1G>C | Likely pathogenic (splice) |
| — | 13 total P/LP variants | See ClinVar for complete list |
AlphaMissense missense pathogenicity predictions
Total likely_pathogenic variants: 156
| Rank | Position | Variant | am_pathogenicity | Effect |
|---|---|---|---|---|
| 1 | 15 | G15W | 0.955 | Gly→Trp |
| 2 | 37 | S37R | 0.944 | Ser→Arg |
| 3 | 5 | D5H | 0.942 | Asp→His |
| 4 | 2 | A2D | 0.919 | Ala→Asp |
| 5 | 53 | S53R | 0.914 | Ser→Arg |
| 6 | 2 | A2V | 0.916 | Ala→Val |
| 7 | 39 | S39R | 0.922 | Ser→Arg |
| 8 | 54 | S54R | 0.931 | Ser→Arg |
| 9 | 5 | D5V | 0.930 | Asp→Val |
| 10 | 15 | G15R | 0.937 | Gly→Arg |
| 11-30 | — | 141 additional likely_pathogenic variants | 0.567–0.927 | Mixed |
SpliceAI splice effect predictions
Total predictions: 1,976
Top variants by effect (first 30):
| Position | Variant | Effect | Score |
|---|---|---|---|
| 16:31180229 | T:A | donor_loss | 1.000 |
| 16:31180225 | ACGG:A | donor_loss | 1.000 |
| 16:31180226 | CGG:C | donor_loss | 1.000 |
| 16:31180228 | G:GG | donor_gain | 1.000 |
| 16:31180430 | G:T | donor_gain | 0.980 |
| 16:31180225 | ACG:A | donor_gain | 0.970 |
| 16:31180430 | G:GT | donor_gain | 0.970 |
| 16:31180224 | AACG:A | donor_gain | 0.950 |
| 16:31180377 | G:GT | donor_gain | 0.950 |
| 16:31180161 | ACTC:A | donor_gain | 0.920 |
| 16:31180367 | G:GG | donor_gain | 0.910 |
| 16:31180365 | GA:G | donor_gain | 0.890 |
| 16:31180366 | A:AG | donor_gain | 0.890 |
| 16:31180381 | C:T | donor_gain | 0.890 |
| 16:31180230 | AG:A | donor_gain | 0.480 |
| 31–1976 | — | Mixed gains/losses | 0.200–0.950 |
Pathways & Gene Ontology
Reactome Pathways
Total: 4 pathways
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-72163 | mRNA Splicing - Major Pathway |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA |
| R-HSA-9770562 | mRNA Polyadenylation |
| R-HSA-9918481 | Dengue Virus-Host Interactions |
MSigDB Gene-Set Membership
Total: 100 gene sets (diverse categories including GO biological processes, MIR targets, TFT targets, phenotype associations, Reactome pathways)
Gene Ontology Annotations
Biological Process: 9 terms
| GO ID | Term |
|---|---|
| GO:0006355 | Regulation of DNA-templated transcription |
| GO:0006357 | Regulation of transcription by RNA polymerase II |
| GO:0008380 | RNA splicing |
| GO:0043484 | Regulation of RNA splicing |
| GO:0048255 | mRNA stabilization |
| GO:0051260 | Protein homooligomerization |
| GO:0140694 | Membraneless organelle assembly |
| GO:1905168 | Positive regulation of double-strand break repair via homologous recombination |
| GO:1990000 | Amyloid fibril formation |
Molecular Function: 9 terms
| GO ID | Term |
|---|---|
| GO:0003677 | DNA binding |
| GO:0003682 | Chromatin binding |
| GO:0003712 | Transcription coregulator activity |
| GO:0003713 | Transcription coactivator activity |
| GO:0003723 | RNA binding |
| GO:0003730 | mRNA 3’-UTR binding |
| GO:0008270 | Zinc ion binding |
| GO:0042802 | Identical protein binding |
| GO:0140693 | Molecular condensate scaffold activity |
Cellular Component: 6 terms
| GO ID | Term |
|---|---|
| GO:0005634 | Nucleus |
| GO:0005654 | Nucleoplasm |
| GO:0098978 | Glutamatergic synapse |
| GO:0098982 | GABA-ergic synapse |
| GO:0099523 | Presynaptic cytosol |
| GO:0099524 | Postsynaptic cytosol |
Protein interactions & networks
Protein-protein Interactions
Total interaction counts:
- STRING: ~3,788 interactions
- BioGRID: 1,068 interactions
- IntAct: 373 curated interactions
TOP 30 highest-confidence STRING interactions (scores 0-1000):
| Rank | UniProt ID | Score | Protein |
|---|---|---|---|
| 1 | Q13148 | 999 | hnRNP A2/B1 |
| 2 | P00441 | 992 | SOD1 |
| 3 | Q9NRR4 | 988 | hnRNP U |
| 4 | A0A087WTZ4 | 986 | hnRNP K |
| 5 | O75494 | 951 | hnRNP M |
| 6 | P22626 | 943 | hnRNP A1 |
| 7 | Q96CV9 | 939 | DDX3X |
| 8 | Q9UHD9 | 934 | DHX29 |
| 9 | P23246 | 933 | SFPQ |
| 10 | Q12906 | 927 | hnRNP D |
| 11 | Q96LT7 | 919 | DDX39A |
| 12 | Q99700 | 918 | EIF4A3 |
| 13 | Q01130 | 899 | hnRNP C |
| 14 | P30807 | 893 | DHX9 |
| 15 | P10636 | 889 | TAF15 |
| 16 | Q70SY1 | 888 | MATR3 |
| 17 | Q7Z333 | 884 | RALY |
| 18 | P07910 | 882 | RPL30 |
| 19 | P43243 | 874 | MATRIN3 |
| 20 | Q92973 | 867 | hnRNP L |
| 21 | P09651 | 856 | hnRNPA1 |
| 22 | P38919 | 843 | SUMO1 |
| 23 | Q13283 | 839 | DDX5 |
| 24 | P31483 | 836 | hnRNP D |
| 25 | O95292 | 835 | SRSF9 |
| 26 | Q8WXF1 | 835 | EWSR1 |
| 27 | P18846 | 829 | hnRNP F |
| 28 | P16990 | 821 | SRSF1 |
| 29 | Q96Q42 | 820 | SRSF3 |
| 30 | Q16637 | 811 | SRSF6 |
TOP 20 BioGRID interactions (experimental evidence): VCP, SFPQ, YWHAZ, YWHAQ, PFN1, FASN, PGK1, CKB, ENO1, LDHB, PAICS, PHGDH, LDHA, GAPDH, PKM, ATXN2L, MTHFD1, ACACA, CA2, ALDOA (all validated by Affinity Capture-MS)
TOP 20 IntAct curated interactions (confidence 0-1.0):
| Protein | Confidence | Interaction Type |
|---|---|---|
| FUS | 0.830 | Physical association (homodimer) |
| SAFB | 0.730 | Physical association |
| MATR3 | 0.730 | Colocalization |
| HNRNPA1 | 0.670 | Association |
| PRMT1 | 0.660 | Physical association/methylation |
| RALY | 0.640 | Physical association/proximity |
| DHX9 | 0.630 | Colocalization |
| Crebbp | 0.600 | Direct interaction |
| EP300 | 0.590 | Physical association |
| TNPO1 | 0.560 | Direct interaction |
| KAT5 | 0.520 | Physical association |
| DDX3X | 0.430 | Association |
| CAPRIN1 | 0.430 | Colocalization |
| KAP104 | 0.440 | Direct interaction |
| CHEK1 | 0.400 | Physical association |
| HVCN1 | 0.400 | Physical association |
| PB1 | 0.370 | Physical association |
| NUPR1 | 0.370 | Physical association |
| DUX4 | 0.380 | Colocalization |
| DUX4L9 | 0.380 | Colocalization/proximity |
Protein Similarity
TOP 20 ESM2 embedding similarity (scores 0-1.0):
| UniProt ID | Top Similarity | Avg Similarity |
|---|---|---|
| A5A6M3 | 1.0000 | 0.9756 |
| P38159 | 1.0000 | 0.9756 |
| P51991 | 1.0000 | 0.9867 |
| Q4R7F0 | 1.0000 | 0.9754 |
| Q6URK4 | 1.0000 | 0.9865 |
| Q8BG05 | 1.0000 | 0.9865 |
| D4AE41 | 0.9992 | 0.9770 |
| P51968 | 0.9994 | 0.9867 |
| P51992 | 0.9994 | 0.9869 |
| Q96E39 | 0.9996 | 0.9759 |
| P09651 | 0.9977 | 0.9868 |
| A0A0D1C8Z4 | 0.9977 | 0.9615 |
| P07909 | 0.9961 | 0.9813 |
| P48810 | 0.9961 | 0.9836 |
| P51989 | 0.9989 | 0.9871 |
| P51990 | 0.9989 | 0.9880 |
| P84586 | 0.9999 | 0.9756 |
| Q01844 | 0.9999 | 0.9750 |
| Q2HJ60 | 0.9999 | 0.9870 |
| Q4V898 | 0.9999 | 0.9759 |
TOP 20 sequence homologs (DIAMOND, identity % | bitscore):
| UniProt ID | Identity | Bitscore | Sequences |
|---|---|---|---|
| Q27W01 | 100.00% | 344 | 100 |
| Q3ZCE8 | 100.00% | 344 | 100 |
| Q9CWZ3 | 100.00% | 344 | 100 |
| Q9Y5S9 | 100.00% | 344 | 100 |
| Q28BZ1 | 98.90% | 339 | 100 |
| P15771 | 68.50% | 479 | 100 |
| Q5D018 | 93.70% | 328 | 100 |
| Q28009 | 90.30% | 415 | 54 |
| B5DGI7 | 92.60% | 316 | 100 |
| P56959 | 86.40% | 396 | 54 |
| Q61545 | 90.90% | 823 | 24 |
| Q01844 | 90.90% | 820 | 26 |
| P35637 | 92.20% | 414 | 54 |
| Q92804 | 65.20% | 226 | 23 |
| Q27294 | 52.80% | 119 | 21 |
| Q9AST1 | 60.00% | 122 | 25 |
| Q94KD0 | 73.10% | 68.9 | 24 |
| O43120 | 39.30% | 65.5 | 7 |
Transcription factor regulatory data
FUS is a transcription factor with regulatory roles, though it primarily functions as an RNA-binding protein. It exhibits DNA-binding, transcription coregulator, and transcription coactivator activities (GO:0003677, GO:0003712, GO:0003713).
Downstream targets
Total identified: 4 (via CollecTRI database)
| Target | Regulation type | Evidence |
|---|---|---|
| DDIT3 | Activation | Curated |
| MDM2 | Repression | Curated |
| AR | Unknown | Curated |
| KLK3 | Unknown | Curated |
Note: Limited downstream target data available in CollecTRI. FUS’s primary function as an RNA-binding protein and transcriptional coregulator (rather than a sequence-specific DNA-binding TF) suggests regulatory activity may be indirect or context-dependent.
DNA binding motifs
JASPAR motifs: None identified
FUS does not have characterized sequence-specific DNA-binding motifs in JASPAR, consistent with its classification as an RNA-binding protein that functions in transcription regulation primarily through protein-protein interactions and RNA binding rather than direct sequence-specific DNA binding.
Upstream regulators
| Regulator | Regulation type | Confidence | Evidence type |
|---|---|---|---|
| TP53 | Unknown | — | Curated (CollecTRI) |
| TBP | Repression | — | Curated (CollecTRI) |
| SP1 | Unknown | Low | Curated (CollecTRI) |
| NFKB | Unknown | Low | Curated (CollecTRI) |
| GTF3A | Unknown | — | Curated (CollecTRI) |
| DDIT3 | Unknown | Low | Curated (CollecTRI) |
| AR | Unknown | Low | Curated (CollecTRI) |
Total: 7 upstream TF regulators identified, primarily through curated transcriptional regulatory networks. Evidence sources include transcriptional regulation databases with varying confidence levels (Low confidence entries require additional experimental validation).
Drug & pharmacology data
FUS is minimally developed as a drug target with limited clinical relevance. Available data shows:
Targeting molecules: 2 compounds total in ChEMBL (no DrugBank records identified):
- CHEMBL3752910 — NVP-BHG712 | Phase 0 (preclinical) | Highly promiscuous kinase inhibitor (1,318 targets)
- CHEMBL5653589 — NVPiso | Phase 0 (preclinical) | Multi-target compound (1,933 targets)
Both compounds show nanomolar binding affinity (Kd 0.086–2.2 nM in available assays) but are not selective for FUS; they inhibit hundreds of other kinases and proteins.
Clinical trials: None identified. No drugs targeting FUS are in clinical development.
Pharmacogenomics: No drug-gene interactions, variant associations, or dosing guidelines documented in PharmGKB or related resources.
Summary: FUS mutations are associated with amyotrophic lateral sclerosis (ALS) and other neurological diseases, but no approved or clinically-evaluated therapeutic drugs target this protein. The two preclinical compounds represent early-stage research interest only and are not selective for FUS.
Unfortunately, biobtree doesn’t have detailed tissue and cell-type-level expression scores stored for query. However, I can provide what data is available from the sources connected through biobtree:
Expression profiles
Based on available biobtree data for human FUS (ENSG00000089280 | P35637):
Overview:
- Expression breadth (Bgee): Ubiquitous - expressed across tissues
- Max expression score (Bgee): 99.63/100
- Total expression-present calls (Bgee): 304 tissues/conditions
Single-cell datasets available (SCXA - Single Cell Expression Atlas):
- E-CURD-79: Human thymic development (152,320 cells)
- E-GEOD-124263: Neonatal and adult human testis (64,206 cells)
- E-GEOD-134144: Human testis puberty development (150,071 cells)
- E-GEOD-149689: COVID-19/Influenza immune profiling (166,852 cells)
- E-MTAB-10283: Endometrial organoids (574,689 cells)
- E-MTAB-10432: Post-MI heart failure bone vascular niche (8,228 cells)
- E-MTAB-10662: Human fetal lung (39,900 cells)
- E-MTAB-4850: Hepatitis C antigen-specific T cells (63 cells)
- E-MTAB-6819: Human embryonic stem cells (1,344 cells)
- E-MTAB-7037: Dermal fibroblasts (590 cells)
- E-MTAB-9435: IDH-wild-type glioblastoma (62,867 cells)
Data limitation: Biobtree references HPA and Expression Atlas but doesn’t expose detailed tissue-by-tissue or cell-type-by-cell-type expression scores. For comprehensive TOP 30 tissue/cell type lists with numerical scores, you’ll need to access these databases directly (gtexportal.org, humanproteinatlas.org, expression-atlas.ebi.ac.uk).
Disease associations
Mendelian / Monogenic Diseases
FUS mutations cause a spectrum of neurological disorders, primarily inherited in an autosomal dominant or autosomal recessive pattern:
| Disease | Disease ID | Inheritance | Evidence Level | Gene-Disease Database |
|---|---|---|---|---|
| Amyotrophic lateral sclerosis type 6 (ALS6) | OMIM:608030, MONDO:0011951, ORPHANET:803 | Autosomal dominant | Strong/Definitive | GENCC, ClinVar |
| Amyotrophic lateral sclerosis | MONDO:0004976, ORPHANET:803 | Autosomal dominant | Definitive | GENCC, ClinVar |
| Juvenile amyotrophic lateral sclerosis | MONDO:0017593, ORPHANET:300605 | Autosomal recessive | Supportive | GENCC, ClinVar |
| Frontotemporal dementia with motor neuron disease | ORPHANET:275872 | - | - | ClinVar |
| Frontotemporal dementia | MONDO:0017276, ORPHANET:282 | - | - | ClinVar |
| Tremor, hereditary essential, 4 | OMIM:614782, MONDO:0013888 | Autosomal dominant | Limited | GENCC, ClinVar |
| Distal hereditary motor neuropathy | MONDO:0018894, ORPHANET:53739 | - | - | ClinVar |
| Nanophthalmos 4 | MONDO:0014426, ORPHANET:35612 | - | - | ClinVar |
| Dystonic disorder | MONDO:0003441 | - | - | ClinVar |
Phenotype Associations
Top 30 clinical phenotypes (HPO terms) associated with FUS mutations:
| HPO ID | Phenotype | Frequency in FUS-Related Disorders |
|---|---|---|
| HP:0007354 | Amyotrophic lateral sclerosis | Core phenotype |
| HP:0002145 | Frontotemporal dementia | Core phenotype |
| HP:0001324 | Muscle weakness | Very common |
| HP:0001257 | Spasticity | Very common |
| HP:0002380 | Fasciculations | Very common |
| HP:0001308 | Tongue fasciculations | Very common |
| HP:0003700 | Generalized amyotrophy | Very common |
| HP:0003693 | Distal amyotrophy | Common |
| HP:0002483 | Bulbar signs | Common |
| HP:0002145 | Frontotemporal dementia | Common |
| HP:0001332 | Dystonia | Common |
| HP:0002015 | Dysphagia | Common |
| HP:0001260 | Dysarthria | Common |
| HP:0001283 | Bulbar palsy | Common |
| HP:0001264 | Spastic diplegia | Occasional |
| HP:0001288 | Gait disturbance | Common |
| HP:0003484 | Upper limb muscle weakness | Common |
| HP:0007340 | Lower limb muscle weakness | Common |
| HP:0002313 | Spastic paraparesis | Occasional |
| HP:0001347 | Hyperreflexia | Common |
| HP:0001348 | Brisk reflexes | Common |
| HP:0003487 | Babinski sign | Occasional |
| HP:0002094 | Dyspnea | Common |
| HP:0002878 | Respiratory failure | Severe cases |
| HP:0100543 | Cognitive impairment | Common in FTD-ALS |
| HP:0002463 | Language impairment | Common in FTD-ALS |
| HP:0000712 | Emotional lability | Common in FTD-ALS |
| HP:0000741 | Apathy | Common in FTD-ALS |
| HP:0000716 | Depression | Common |
| HP:0012473 | Tongue atrophy | Common |
Complex Disease / GWAS Associations
Limited GWAS associations identified; FUS-linked variants show weak associations with psychiatric and metabolic traits:
| Trait/Disease | Mapped Gene(s) | P-value | Study ID |
|---|---|---|---|
| Bipolar I disorder | PRSS36 | 5.0 × 10⁻⁷ | GCST008115_32 |
| Bipolar disorder | PRSS36 | 8.0 × 10⁻⁶ | GCST008103_175 |
| HDL cholesterol levels | PRSS36, NDUFA3P6 | 7.0 × 10⁻⁹ | GCST010242_340 |
Note: GWAS associations mapped to adjacent loci (PRSS36); direct FUS GWAS signals are minimal, consistent with FUS primarily causing high-penetrance monogenic disorders rather than common complex traits.