Enum: G2PMolecularMechanism

The mechanism of disease derived from the available evidence, following the definitions of Backwell and Marsh (PMID:35395171). These mechanisms describe a gene-disease association rather than an individual variant, so the Sequence Ontology variant terms are recorded as close mappings rather than exact meanings.

URI: valuesets:G2PMolecularMechanism

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Permissible Values

Value	Title	Description	Close Mappings
LOSS_OF_FUNCTION	loss of function	Loss-of-function variants involve a loss of the normal biological function of a protein. Often these are nonsense or frameshift mutations that introduce premature stop codons. Due to nonsense-mediated decay of the resulting mRNAs, most premature stop codons will result in no protein being produced, rather than a truncated protein. However, there are also many examples of loss-of-function variants that change the amino acid sequence and result in non-functional protein products. These mutations can cause a complete loss of function (amorphic), analogous to a protein null mutation, or only a partial loss of function (hypomorphic). May also include variants in regulatory regions.	SO:0002054
GAIN_OF_FUNCTION	gain of function	Gain-of-function variants have their phenotypic effect because the mutant protein does something different than the wild-type protein. Often, these variants cause disease by increasing protein activity (hypermorphic) or introducing a completely new function (neomorphic), but the specific molecular mechanisms underlying gain-of-function mutations can be complex. May also include variants in regulatory regions.	SO:0002053
DOMINANT_NEGATIVE	dominant negative	Dominant-negative variants involve the mutant protein directly or indirectly blocking the normal biological function of the wild-type protein (antimorphic). They can thus cause a disproportionate (>50%) loss of function, even though only half of the protein is mutated eg. heterozygous variants in COL1A1 that disrupt the triple collagen helix.	SO:0002052
UNDETERMINED_NON_LOSS_OF_FUNCTION	undetermined non-loss-of-function	Very often it is difficult to distinguish between dominant negative and gain of function, but it is clearly a non-loss-of-function mechanism (e.g. from co-expression experiments showing a damaging effect from the mutant allele).
UNDETERMINED	undetermined	Not known.

Slots

Name	Description
g2p_molecular_mechanism	The mechanism of disease derived from the available evidence

Identifier and Mapping Information

Annotations

property	value
stewards	https://www.ebi.ac.uk/gene2phenotype
publishers	https://www.ebi.ac.uk/gene2phenotype
source	https://www.ebi.ac.uk/gene2phenotype/about/terminology#molecular-mechanism-section
reference	PMID:35395171

Schema Source

from schema: https://w3id.org/valuesets

LinkML Source

name: G2PMolecularMechanism
instantiates:
- valuesets_meta:ValueSetEnumDefinition
annotations:
  stewards:
    tag: stewards
    value: https://www.ebi.ac.uk/gene2phenotype
  publishers:
    tag: publishers
    value: https://www.ebi.ac.uk/gene2phenotype
  source:
    tag: source
    value: https://www.ebi.ac.uk/gene2phenotype/about/terminology#molecular-mechanism-section
  reference:
    tag: reference
    value: PMID:35395171
description: The mechanism of disease derived from the available evidence, following
  the definitions of Backwell and Marsh (PMID:35395171). These mechanisms describe
  a gene-disease association rather than an individual variant, so the Sequence Ontology
  variant terms are recorded as close mappings rather than exact meanings.
title: G2P Molecular Mechanism
from_schema: https://w3id.org/valuesets
contributors:
- orcid:0000-0002-6601-2165
- https://github.com/anthropics/claude-code
status: STANDARD
rank: 1000
permissible_values:
  LOSS_OF_FUNCTION:
    text: LOSS_OF_FUNCTION
    description: Loss-of-function variants involve a loss of the normal biological
      function of a protein. Often these are nonsense or frameshift mutations that
      introduce premature stop codons. Due to nonsense-mediated decay of the resulting
      mRNAs, most premature stop codons will result in no protein being produced,
      rather than a truncated protein. However, there are also many examples of loss-of-function
      variants that change the amino acid sequence and result in non-functional protein
      products. These mutations can cause a complete loss of function (amorphic),
      analogous to a protein null mutation, or only a partial loss of function (hypomorphic).
      May also include variants in regulatory regions.
    title: loss of function
    aliases:
    - loss_of_function_variant
    close_mappings:
    - SO:0002054
  GAIN_OF_FUNCTION:
    text: GAIN_OF_FUNCTION
    description: Gain-of-function variants have their phenotypic effect because the
      mutant protein does something different than the wild-type protein. Often, these
      variants cause disease by increasing protein activity (hypermorphic) or introducing
      a completely new function (neomorphic), but the specific molecular mechanisms
      underlying gain-of-function mutations can be complex. May also include variants
      in regulatory regions.
    title: gain of function
    aliases:
    - gain_of_function_variant
    close_mappings:
    - SO:0002053
  DOMINANT_NEGATIVE:
    text: DOMINANT_NEGATIVE
    description: Dominant-negative variants involve the mutant protein directly or
      indirectly blocking the normal biological function of the wild-type protein
      (antimorphic). They can thus cause a disproportionate (>50%) loss of function,
      even though only half of the protein is mutated eg. heterozygous variants in
      COL1A1 that disrupt the triple collagen helix.
    title: dominant negative
    aliases:
    - antimorphic
    - dominant_negative_variant
    close_mappings:
    - SO:0002052
  UNDETERMINED_NON_LOSS_OF_FUNCTION:
    text: UNDETERMINED_NON_LOSS_OF_FUNCTION
    description: Very often it is difficult to distinguish between dominant negative
      and gain of function, but it is clearly a non-loss-of-function mechanism (e.g.
      from co-expression experiments showing a damaging effect from the mutant allele).
    title: undetermined non-loss-of-function
    aliases:
    - undetermined non-loss-of-function
  UNDETERMINED:
    text: UNDETERMINED
    description: Not known.
    title: undetermined