Enum: G2PMolecularMechanismSynopsis

A more detailed description of the molecular mechanism of a G2P gene-disease association, following the definitions of Backwell and Marsh (PMID:35395171). A synopsis refines the higher-level molecular mechanism; more than one synopsis may apply to a single gene-disease association.

URI: valuesets:G2PMolecularMechanismSynopsis

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Permissible Values

Value	Title	Description	Parent Mechanism
DESTABILISING_LOF	destabilising LOF	A process whereby a missense change destabilises the protein structure resulting in loss of function.	LOSS_OF_FUNCTION
INTERACTION_DISRUPTING_LOF	interaction-disrupting LOF	A process whereby a variant allele disrupts interaction resulting in loss of function, for example a change in an interaction site.	LOSS_OF_FUNCTION
LOSS_OF_ACTIVITY_LOF	loss of activity LOF	A process whereby a variant allele disrupts activity resulting in loss of function, for example a change in an active site.	LOSS_OF_FUNCTION
LOF_DUE_TO_PROTEIN_MISLOCALISATION	LOF due to protein mislocalisation	A loss of function caused by mislocalisation of a protein, rather than direct disruption of its structure or function.	LOSS_OF_FUNCTION
ASSEMBLY_MEDIATED_DOMINANT_NEGATIVE	assembly-mediated dominant negative	A protein change which does not prevent coassembly into a complex with wild-type subunits but results in poisoning the activity of the hybrid complex, causing a disproportionate loss of function.	DOMINANT_NEGATIVE
COMPETITIVE_DOMINANT_NEGATIVE	competitive dominant-negative	A process whereby the novel protein disrupts specific interactions by competing with wild-type protein, thus having a dominant-negative effect.	DOMINANT_NEGATIVE
ASSEMBLY_MEDIATED_GOF	assembly-mediated GOF	A process whereby incorporation of a mutant subunit into a protein complex leads to a gain of function, for example through constitutive activation of a channel.	GAIN_OF_FUNCTION
LOCAL_LOF_LEADING_TO_OVERALL_GOF	local LOF leading to overall GOF	A gain of function caused by the localised loss of a specific function within a protein, for example binding of a regulatory domain is disrupted but enzymatic activity is retained.	GAIN_OF_FUNCTION
AGGREGATION	aggregation	A process by which the variant allele causes aggregation usually causing toxic gain of function, for example misfolded proteins self-assembling into large aggregates or RNA binding protein gelation.	GAIN_OF_FUNCTION
OTHER_GOF	other GOF	A gain of function process other than local loss of function or assembly mediated, for example a mutation in an active site which changes histone binding causing a novel function.	GAIN_OF_FUNCTION

Slots

Name	Description
g2p_molecular_mechanism_synopsis	A more detailed description of the molecular mechanism of disease

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#mechanism-synopsis-section
reference	PMID:35395171

Schema Source

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

LinkML Source

name: G2PMolecularMechanismSynopsis
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#mechanism-synopsis-section
  reference:
    tag: reference
    value: PMID:35395171
description: A more detailed description of the molecular mechanism of a G2P gene-disease
  association, following the definitions of Backwell and Marsh (PMID:35395171). A
  synopsis refines the higher-level molecular mechanism; more than one synopsis may
  apply to a single gene-disease association.
title: G2P Molecular Mechanism Synopsis
from_schema: https://w3id.org/valuesets
contributors:
- orcid:0000-0002-6601-2165
- https://github.com/anthropics/claude-code
status: STANDARD
rank: 1000
permissible_values:
  DESTABILISING_LOF:
    text: DESTABILISING_LOF
    description: A process whereby a missense change destabilises the protein structure
      resulting in loss of function.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: LOSS_OF_FUNCTION
    title: destabilising LOF
  INTERACTION_DISRUPTING_LOF:
    text: INTERACTION_DISRUPTING_LOF
    description: A process whereby a variant allele disrupts interaction resulting
      in loss of function, for example a change in an interaction site.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: LOSS_OF_FUNCTION
    title: interaction-disrupting LOF
  LOSS_OF_ACTIVITY_LOF:
    text: LOSS_OF_ACTIVITY_LOF
    description: A process whereby a variant allele disrupts activity resulting in
      loss of function, for example a change in an active site.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: LOSS_OF_FUNCTION
    title: loss of activity LOF
  LOF_DUE_TO_PROTEIN_MISLOCALISATION:
    text: LOF_DUE_TO_PROTEIN_MISLOCALISATION
    description: A loss of function caused by mislocalisation of a protein, rather
      than direct disruption of its structure or function.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: LOSS_OF_FUNCTION
    title: LOF due to protein mislocalisation
  ASSEMBLY_MEDIATED_DOMINANT_NEGATIVE:
    text: ASSEMBLY_MEDIATED_DOMINANT_NEGATIVE
    description: A protein change which does not prevent coassembly into a complex
      with wild-type subunits but results in poisoning the activity of the hybrid
      complex, causing a disproportionate loss of function.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: DOMINANT_NEGATIVE
    title: assembly-mediated dominant negative
  COMPETITIVE_DOMINANT_NEGATIVE:
    text: COMPETITIVE_DOMINANT_NEGATIVE
    description: A process whereby the novel protein disrupts specific interactions
      by competing with wild-type protein, thus having a dominant-negative effect.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: DOMINANT_NEGATIVE
    title: competitive dominant-negative
  ASSEMBLY_MEDIATED_GOF:
    text: ASSEMBLY_MEDIATED_GOF
    description: A process whereby incorporation of a mutant subunit into a protein
      complex leads to a gain of function, for example through constitutive activation
      of a channel.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: GAIN_OF_FUNCTION
    title: assembly-mediated GOF
  LOCAL_LOF_LEADING_TO_OVERALL_GOF:
    text: LOCAL_LOF_LEADING_TO_OVERALL_GOF
    description: A gain of function caused by the localised loss of a specific function
      within a protein, for example binding of a regulatory domain is disrupted but
      enzymatic activity is retained.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: GAIN_OF_FUNCTION
    title: local LOF leading to overall GOF
  AGGREGATION:
    text: AGGREGATION
    description: A process by which the variant allele causes aggregation usually
      causing toxic gain of function, for example misfolded proteins self-assembling
      into large aggregates or RNA binding protein gelation.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: GAIN_OF_FUNCTION
    title: aggregation
  OTHER_GOF:
    text: OTHER_GOF
    description: A gain of function process other than local loss of function or assembly
      mediated, for example a mutation in an active site which changes histone binding
      causing a novel function.
    annotations:
      parent_mechanism:
        tag: parent_mechanism
        value: GAIN_OF_FUNCTION
    title: other GOF