DTX1
Overview
Mutations in the DTX1 gene, which encodes the E3 ubiquitin ligase Deltex 1, have been identified in various B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). DTX1 is one of a number of genes affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. DTX1 functions as a negative regulator of the Notch signaling pathway. Some DTX1 mutations impair its function, thereby dysregulating Notch signaling, which is crucial for normal B-cell development and function.
Relevance tier by entity
| Entity | Tier | Description |
|---|---|---|
| BL | 2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous |
| DLBCL | 1-a | aSHM target and high-confidence DLBCL gene |
| FL | 1-a | aSHM target and high-confidence FL gene |
Mutation incidence in large patient cohorts (GAMBL reanalysis)
| Entity | source | frequency (%) |
|---|---|---|
| DLBCL | GAMBL genomes | 10.71 |
| DLBCL | Schmitz cohort | 13.62 |
| DLBCL | Reddy cohort | 5.91 |
| DLBCL | Chapuy cohort | 11.54 |
| FL | GAMBL genomes | 5.54 |
| BL | GAMBL genomes+capture | 5.54 |
| BL | Thomas cohort | 5.90 |
| BL | Panea cohort | 8.90 |
Mutation pattern and selective pressure estimates
| Entity | aSHM | Significant selection | dN/dS (missense) | dN/dS (nonsense) |
|---|---|---|---|---|
| DLBCL | Yes | Yes | 2.228 | 4.244 |
| FL | Yes | No | 6.305 | 0.000 |
| BL | Yes | No | 5.556 | 14.253 |
aSHM regions
| chr_name | hg19_start | hg19_end | region | regulatory_comment |
|---|---|---|---|---|
| chr12 | 113492311 | 113497546 | TSS | NA |
[!NOTE] First described in BL in 2019 by Panea RI. First described in DLBCL in 2018 by Schmitz R
## DTX1 Hotspots
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr12 | 113496076 | G>A | V27M |
| chr12 | 113496081 | G>A | W28* |
| chr12 | 113496082 | G>A | E29K |
| chr12 | 113496083 | A>G | E29G |
| chr12 | 113496085 | T>G | W30G |
| chr12 | 113496087 | G>A | W30* |
| chr12 | 113496089 | T>A | L31Q |
| chr12 | 113496089 | T>C | L31P |
| chr12 | 113496096 | G>C | E33D |
| chr12 | 113496097 | C>T | H34Y |
| chr12 | 113496112 | C>T | P39S |
| chr12 | 113496115 | T>C | Y40H |
| chr12 | 113496116 | A>C | Y40S |
| chr12 | 113496116 | A>G | Y40C |
| chr12 | 113496117 | C>G | Y40* |
| chr12 | 113496121 | G>C | A42P |
| chr12 | 113496130 | T>A | C45S |
| chr12 | 113496132 | C>A | C45* |
| chr12 | 113496133 | C>T | H46Y |
| chr12 | 113496135 | C>A | H46Q |
| chr12 | 113496139 | A>T | I48F |
| chr12 | 113496140 | T>A | I48N |
| chr12 | 113496141 | T>G | I48M |
| chr12 | 113496148 | G>A | V51M |
| chr12 | 113496155 | A>T | K53M |
| chr12 | 113496156 | G>C | K53N |
| chr12 | 113496159 | G>C | E54D |
| chr12 | 113496162 | CG>AA | DA55ET |
| chr12 | 113496170 | G>A | G58D |
| chr12 | 113496173 | C>A | S59Y |
| chr12 | 113496173 | C>T | S59F |
| chr12 | 113496175 | G>A | V60M |
| chr12 | 113496191 | T>C | V65A |
| chr12 | 113496191 | T>G | V65G |
| chr12 | 113496196 | G>A | A67T |
| chr12 | 113496197 | C>T | A67V |
| chr12 | 113496201 | G>C | Q68H |
| chr12 | 113496202 | C>T | L69F |
| chr12 | 113496205 | G>C | V70L |
| chr12 | 113496208 | C>G | P71A |
| chr12 | 113496208 | C>T | P71S |
| chr12 | 113496210 | CT>TC | Y72H |
| chr12 | 113496212 | A>G | Y72C |
| chr12 | 113496213 | C>A | Y72* |
View coding variants in ProteinPaint hg19 or hg38
View all variants in GenomePaint hg19 or hg38
References
- de Miranda NF, Georgiou K, Chen L, Wu C, Gao Z, Zaravinos A, Lisboa S, Enblad G, Teixeira MR, Zeng Y, Peng R, Pan-Hammarström Q. Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients. Blood. 2014 Oct 16;124(16):2544-53. doi: 10.1182/blood-2013-12-546309. Epub 2014 Aug 29. PMID: 25171927; PMCID: PMC4199956.
Citing
If you use the information or data from this site, please cite
Krysta Coyle, Kostiantyn Dreval, Daniel Hodson and Ryan D. Morin. Audit of B-cell cancer genes. Blood Adv (2025) 9 (8): 2019–2031.
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