Updated November 9, 2007
- mutations, natural or introduced, that result in partial or complete impairment or alteration of the function of that gene
- polymorphism or allelic variation (including where no allele is designated wild-type or mutant)
- any procedure that disturbs the expression or function of the gene, including RNAi, anti-sense RNAs, antibody depletion, or the use of any molecule or experimental condition that may disturb or affect the normal functioning of the gene, including: inhibitors, blockers, modifiers, any type of antagonists, temperature jumps, changes in pH or ionic strength.
- overexpression or ectopic expression of wild-type or mutant gene that results in aberrant behavior of the system or aberrant expression where the resulting mutant phenotype is used to make a judgment about the normal activity of that gene product.
The IMP evidence code covers those cases when the function, process or cellular localization of a gene product is inferred based on differences in the function, process, or cellular localization between two different alleles of the corresponding gene. The IMP code is used for cases where one allele may be designated 'wild-type' and another as 'mutant'. It is also used in cases where allelic variation occurs naturally and no specific allele is designated as wild-type or mutant. Caution should be used when making annotations from gain-of-function mutations as it may be difficult to infer a gene's normal function from a gain of function mutation, although it is sometimes possible.
For transfection experiments or other experiments where a gene from one organism or tissue is put into a system that is not its normal environment, the annotator should use the author's intent and interpretation of the experiment as a guide as to whether IMP or IDA is appropriate. When the author is comparing differences between alleles, regardless of the simplicity or complexity of the assay, IMP is appropriate. When the author is using an expression system as a way to investigate the normal function of a gene product, IDA is appropriate. Examples where the IMP code should be used
- use of an inhibitor of a gene product's activity in order to see the effect of absence, or significant depletion, of that gene product. For example, an experiment using baicalein to inhibit the activity of 12-LOX in a murine bladder cancer cell line inhibits cell proliferation in a concentration dependent manner (see PMID:15161019) results in an annotation to the GO term cell proliferation using the IMP evidence code for the 12-LOX gene.
- transfection into a cell line, overexpression, or extopic expression of a gene where the effects of various alleles of a gene are compared to each other or to wild-type. For this type of experiment, annotate using IMP.
- In situations where a mutation in gene A provides information about the function, process, or component of gene B do not use IGI. Use IMP evidence code and use column-16 or the Annotation Extension column to provide additional data. For example, if a mutation in gene A causes a mislocalization of gene B, gene A is annotated to protein localization using IMP and the gene B identifier is added to the Annotation Extension column with the appropriate relationship.
Examples where the IMP code should not be used
- mutation in gene B provides information about gene A being annotated. For this type of experiment, use the IGI code.
- complementation of a mutation in one organism by a gene from a different organism.
- Transfections into a cell line, overexpression, or ectopic expression of a gene when the expression system used is considered to be an assay system to address basic, normal functions of gene product even if it would not normally be expressed in that cell type or location. If the experiments were conducted to assess the normal function of the gene and the assay system is believed to reproduce this function, i.e., the authors would consider their experiment to be a direct assay, and not a comparison between various alleles of a gene, then the IDA code should be used. This is in contrast with a situation where overexpression affects the function or expression of the gene and that difference from normal is used to make an inference about the normal function; in this case use the IMP evidence code.
Usage of the With column for IMP We recommend making a "with" entry in the with/from column when using this evidence code to indicate the identifier for the allele in which the phenotype was observed. When multiple entries are placed in the with/from field, they are separated by pipes. Example for how the with/from column should be filled in
- The mouse gene product Actc1 (actin, alpha, cardiac ; MGI:87905), has a GO annotation to muscle thin filament assembly ; GO:0030240, inferred from mutant phenotype, IMP of MGI:2180072 (symbol: Actc1tm1Jll; name: targeted mutation 1, James Lessard), from PMID:9114002. MGI:2180072 is entered in the with/from column for this annotation.