​

Protein

​

Identifiers and Primary Sources

The IGVF Catalog has protein nodes collection with Ensembl Protein IDs (e.g., ENSP00000384707) as identifiers from the following GENCODE releases:

• Human: GENCODE v43
• Mouse: GENCODE vM36

Information from UniProt are also integrated as properties on each node, including UniProt IDs (e.g., P49711), protein names, and Database cross-reference (dbxref). The data was imported from the following UniProt files (downloaded in May 2024):

• Human: uniprot_sprot_human.dat.gz, uniprot_trembl_human.dat.gz
• Mouse: uniprot_sprot_rodents.dat.gz, uniprot_trembl_rodents.dat.gz

​

Additional Protein Edge Collections

​

Complexes-Proteins Edges

Data protein complexes are imported from Complex Portal at the EBI.

​

Motifs-Proteins Edges

Transcription Factor (TF) Binding Motifs represented by Position Weight Matrices (PWMs) defining the DNA binding preferences for transcription factors from HOCOMOCO v11.

​

Variants-Proteins Edges

Source	Class	Edge Description	Datasets
External	statistical assessment	Allele-specific TF binding events called from assays such as ChIP-seq	ADASTRA Bill Cipher
External	statistical assessment	Allele-specific TF binding events called SNP-SELEX	GVATdb
IGVF	prediction	Predictions of the impact of variants on binding to 223 TFs binding using SEMVAR	SEMpl
external	statsistical assessment	pQTL (Protein Quantitative Trait Loci) studies on blood plasma protein abundance levels	UK BioBank Pharma Proteomics Project

​

Protein-Protein Edges

Protein-protein interactions from BioGRID and IntAct includes direct physical interactions and functional genetic associations.

​

Coding variants

​

Identifiers and Primary Sources

The IGVF Catalog has coding variants collection using identifiers combining Ensembl Transcript ID and HGVS nomenclature for both protein and cDNA changes (e.g., HK1_ENST00000298649_p.Arg380Gly_c.1138C>G). Each coding variant is also mapped to its genomic location using standardized SPDI identifiers. The primary source is dbNSFP v5.1, which aggregates scores from dozens of functional prediction algorithms (e.g., SIFT, CADD) for all possible non-synonymous single-nucleotide variants (nsSNVs) and splice-site variants in the human genome. Additionally, predictions on coding variants functions from Mutpred2 and ESM-1v for every possible single amino acid change in human genes are imported as part of the IGVF project. As part of this import process, all possible genetic indels that could lead to each specific amino acid change were enumerated and included.

​

Coding Variant Edges

Source	Class	Edge Description	Datasets
IGVF	observed data	Variant Abundance by Massively Parallel Sequencing (VAMP-seq) uses massively parallel sequencing to measure the effects of thousands of missense variants on protein abundance for CYP2C19 and G6PD.	VAMP-seq assays
IGVF	observed data	An advanced version of VAMP-seq tailored for secreted proteins. Measures how missense variants impact secretion and post-translational modifications for coagulation factor IX (F9).	MultiSTEP assays
IGVF	prediction	Predictions for all single amino acid substitutions across all human genes.	Mutpred2
IGVF	prediction	Predictions for all single amino acid substitutions in all MANE protein sequences	ESM-1v

​

Variants-Phenotypes-Coding variants Edges

• IGVF SGE assays: CRISPR-based assays that systematically introduce and evaluate the functional impact of hundreds to thousands of variants in PALB2, CTCF, RAD51D, SFPQ, XRCC2, and BRCA2.

​

GO Terms Table

This table presents Gene Ontology (GO) terms associated with the protein, describing its functions, processes, and cellular locations.

Column Name	Description
Annotation ID	Unique identifier for the protein
Annotation Name	Protein name from UniProt
GO Term Name	The specific Gene Ontology term
Source	Origin of the GO term information
Gene Product Type	Type of gene product (e.g., protein, RNA)
Gene Product Symbol	Symbol representing the gene product
Qualifier	Additional qualifiers for the GO term (if applicable)
Organism	The organism to which this annotation applies
Evidence	Code indicating the type of evidence for this annotation
GO ID	Unique identifier for the GO term

​

TF-Binding Motif

This table shows information about transcription factor binding motifs associated with the protein. from HOCOMOCO v11.

Column	Description
Source	Origin of the motif information
Motif Name	Name of the binding motif
TF Name	Name of the transcription factor
Length	Length of the motif
Motif Source	Source of the motif data (click for more details)

​

Protein Complex

This table displays information about protein complexes that include the protein you’re viewing from EBI complex.

Column	Description
ID	Unique identifier for the complex
Name	Name of the protein complex
Alias	Alternative names for the complex
Molecules	Other molecules in the complex
Evidence Code	Code indicating the type of evidence (hover for full text)
Experimental Evidence	Details of experimental evidence
Description	Brief description of the complex (hover for full text)
Complex Assembly	Information on how the complex assembles
Complex Source	Source of the complex information
Reactome Xref	Cross-references to Reactome database
Source	Origin of the complex data (click for more details)

​

Protein-Protein Interactions Table

This table presents protein-protein interactions for this protein from Biogrid and IntAct, includes direct physical interactions or functional genetic associations.

Column	Description
Interacting Protein	The name of the interacting protein
Interaction Type	A numerical code classifying the interaction (hover for full text)
Detection Method	The specific technique used to identify the interaction (e.g., affinity chromatography technology)
Confidence (BioGRID)	A confidence score assigned by BioGRID. Higher scores generally indicate stronger supporting evidence
Confidence (IntAct)	A confidence score from the IntAct database
PMIDs	The publication(s) that reported the interaction
Source	Database source of the interaction

​

Associated Variant Table

This table shows variants that are directly associated with this protein, including pQTLs (protein quantitative trait loci) and allele-specific transcription factor binding events.

Column	Description
Variant (rsID)	The variant identifier, typically an rsID when available
Association Type	The type of association between the variant and protein
Source	Database or study source of the association
Context / Biosample	The biological context or biosample in which the association was observed
Motif	Associated transcription factor binding motif (if applicable)
P-value (-log10)	Statistical significance of the association as -log10(p-value)
Beta (pQTL)	Effect size for protein quantitative trait loci
Standard Error	Standard error of the effect estimate
Class	Classification of the variant or association
Gene	Associated gene symbol
Gene Consequence	The predicted consequence of the variant on the gene
Effect on Binding	Predicted effect on protein binding (if applicable)
Relative Binding Affinity	Relative change in binding affinity
Alt Score	Alternative allele score
Ref Score	Reference allele score

​

Related Variant Table

This table displays variants that are related to this protein through various evidence sources including pQTL and other regulatory mechanisms.

Column	Description
rsID	The variant’s reference SNP cluster ID
Chromosome	The chromosome where the variant is located
Position	The genomic position of the variant
Ref	The reference allele
Alt	The alternative allele
HGVS	Human Genome Variation Society nomenclature for the variant
Evidence Sources	The databases or studies providing evidence for this relationship
Biological Context	The biological contexts in which this relationship was observed
Max -log10(p-value)	Maximum statistical significance across all evidence sources

​

Related Genes & Protein Table

This table shows genes and proteins that are related to this protein through various biological relationships, including protein-protein interactions and regulatory networks.

Column	Description
Related Protein	Proteins that have biological relationships with this protein
Related Gene	Genes that have biological relationships with this protein
Related Entities	Other biological entities connected to this protein through various pathways