Table of Contents
Overview
HVCN1, a voltage-gated proton channel, has been identified as recurrently mutated in follicular lymphoma and mutations also appear in some DLBCL.[chapuyMolecularSubtypesDiffuse2018] HVCN1 mutations disrupt its normal function, affecting B-cell receptor (BCR) signaling pathways.[chapuyMolecularSubtypesDiffuse2018] This gene has some recurrent sites of mutations (hot spots) but the function of these mutations is not well understood. The mutation pattern in DLBCL and FL implies the preferential accumulation of inactivating mutations.
Relevance tier by entity
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Mutation incidence in large patient cohorts (GAMBL reanalysis)
DLBCL
| Entity | Collection | N | mutated | Incidence | 95% CI |
|---|---|---|---|---|---|
| DLBCL | GAMBL without Reddy | 1,089 | 26 | 0.0239 | [0.0148,0.0329] |
| DLBCL | GAMBL with Reddy | 2,088 | 49 | 0.0235 | [0.017,0.03] |
| DLBCL | BC | 231 | 6 | 0.0260 | [0.0055,0.0465] |
| DLBCL | Dana-Farber | 303 | 11 | 0.0363 | [0.0152,0.0574] |
| DLBCL | NCI | 470 | 9 | 0.0191 | [0.0068,0.0315] |
| DLBCL | Reddy | 999 | 23 | 0.0230 | [0.0137,0.0323] |
| DLBCL | DLBCL_ICGC | 85 | 0 | 0.0012 | [0,0.0085] |
FL
| pathology | Collection | N | mutated | Incidence | CI |
|---|---|---|---|---|---|
| FL | GAMBL without Crouch | 642 | 35 | 0.0545 | [0.037,0.0721] |
| FL | GAMBL with Crouch | 1,189 | 35 | 0.0294 | [0.0198,0.039] |
| FL | BC | 379 | 27 | 0.0712 | [0.0453,0.0971] |
| FL | Kalmbach | 164 | 7 | 0.0427 | [0.0117,0.0736] |
| FL | Crouch | 547 | 0 | 0.0002 | [0,0.0013] |
| FL | FL_ICGC | 99 | 1 | 0.0101 | [0,0.0298] |
Mutation pattern and selective pressure estimates
| Entity | Missense dN/dS | Nonsense dN/dS | Q value |
|---|---|---|---|
| BL | 2.0412 | 0.0000 | 1 |
| FL | 7.8092 | 77.0744 | 0 |
| DLBCL | 2.9468 | 18.3010 | 0 |
HVCN1 Hotspots
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr12 | 111099150 | T>G | Y42S |
| chr12 | 111099150 | T>C | Y42C |
| chr12 | 111099142 | A>T | W45R |
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Expression
History
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timeline
title Publication timing
2017-01-26 : Krysiak : FL
References
1.
Krysiak K, Gomez F, White BS, Matlock M, Miller
CA, Trani L, Fronick CC, Fulton RS, Kreisel F, Cashen AF, Carson KR,
Berrien-Elliott MM, Bartlett NL, Griffith M, Griffith OL, Fehniger TA.
Recurrent somatic mutations affecting B-cell
receptor signaling pathway genes in follicular lymphoma. Blood. 2017 Jan
26;129(4):473–483. PMCID: PMC5270390