Function Constraint

Definition and Information Model

Warning

This data class is at a draft maturity level and may change significantly in future releases. Maturity levels are described in the GKS Maturity Model.

Computational Definition

A classification of the protein functional consequence that characterizes members of this categorical variant.

Information Model

Some FunctionConstraint attributes are inherited from Constraint.

Field	Flags	Type	Limits	Description
type		string	1..1	MUST be “FunctionConstraint”
functionConsequence		MappableConcept	1..1	The functional consequence of members of this categorical variant, as defined by an external ontology. We recommend using one of the defined terms from The Sequence Ontology. See Implementation Guidance for more details.
description		string	0..1	A free-text description of the function change.

Examples

The following are example implementations of FunctionConstraint:

NRAS functionally normal variants

      {
         "type": "FunctionConstraint",
         "functionConsequence": {
            "id": "SO:0002219",
            "name": "functionally normal",
            "primaryCoding": {
               "id": "SO:0002219",
               "name": "functionally_normal",
               "system": "http://www.sequenceontology.org",
               "code": "SO:0002219",
               "iris": [
                  "http://www.sequenceontology.org/browser/current_release/term/SO:0002219"
               ]
            }
         },
         "description": "Function consequence described as functionally normal using Sequence Ontology."
      }

BRCA2 loss of function variants

      {
         "type": "FunctionConstraint",
         "functionConsequence": {
            "id": "SO:0002054",
            "name": "loss of function",
            "primaryCoding": {
               "id": "SO:0002054",
               "name": "loss_of_function_variant",
               "system": "http://www.sequenceontology.org",
               "code": "SO:0002054",
               "iris": [
                  "http://www.sequenceontology.org/browser/current_release/term/SO:0002054"
               ]
            }
         },
         "description": "Function consequence described as loss of function using Sequence Ontology."
      }

PIK3CA p.R38H

      {
         "type": "FunctionConstraint",
         "functionConsequence": {
            "id": "SO:0002053",
            "name": "gain of function",
            "primaryCoding": {
               "id": "SO:0002053",
               "name": "gain_of_function",
               "system": "http://www.sequenceontology.org",
               "code": "SO:0002053",
               "iris": [
                  "http://www.sequenceontology.org/browser/current_release/term/SO:0002053"
               ]
            }
         },
         "description": "Function consequence described as gain of function using Sequence Ontology."
      }

Implementation Guidance

The functionConsequence attribute is a MappableConcept, meaning that it should be represented using an externally defined ontology term. We recommend using one of the following defined terms from The Sequence Ontology:

• dominant negative variant (SO:0002052 - dominant_negative_variant): A variant where the mutated gene product adversely affects the other (wild type) gene product.

• functionally normal (SO:0002219 - functionally_normal): A sequence variant in which the function of a gene product is retained with respect to a reference.

• gain of function (SO:0002053 - gain_of_function_variant): A sequence variant whereby new or enhanced function is conferred on the gene product.

• loss of function (SO:0002054 - loss_of_function_variant): A sequence variant whereby the gene product has diminished or abolished function.

• loss of heterozygosity (SO:0001786 - loss_of_heterozygosity): A functional variant whereby the sequence alteration causes a loss of function of one allele of a gene.

• polypeptide partial loss of function (SO:0001561 - polypeptide_partial_loss_of_function): A sequence variant that causes some but not all loss of polypeptide function with respect to a reference sequence.