| 2025 | 2017 | 2016 | 2015 | 2014 | 2013 | Description | |
| Base Pathways | 395 | 314 | 307 | 289 | 288 | 293 | Number of metabolic and signaling pathways, excluding super-pathways |
| Reactions | 3587 | 2887 | 2640 | 2619 | 2611 | 2582 | Number of reactions |
| Genes (including pseudogenes) | 59059 | 20830 | 20792 | 20791 | 20801 | 20892 | Number of genes |
| Polypeptides | 93431 | 20541 | 20512 | 20469 | 20480 | 20629 | Number of polypeptides |
| Protein complexes | 660 | 486 | 474 | 456 | 456 | 341 | Number of protein complexes |
| Enzymes | 3027 | 3255 | 3636 | 3250 | 3260 | 3765 | Number of enzymes |
| Transporters | 357 | 465 | 393 | 466 | 470 | 451 | Number of transporters |
| Chemical compounds | 2124 | 1929 | 1841 | 1798 | 1798 | 1657 | Number of chemical compounds |
| Citations | 105264 | 67404 | 41455 | 40753 | 40687 | 40551 | Number of citations to the scientific literature |
Released on Sep 22, 2025
With version 29.5 we introduced major revisions to the HumanCyc database. Previously, HumanCyc included only the genomic coordinates of genes but not the full sequence. Beginning with this release, the database now incorporates the complete human genome sequence.
Since the creation of HumanCyc, the quality of human genome annotation has advanced considerably, resulting in a larger set of identified genes, shifts in their genomic positions, and refined functional annotations. To reflect these improvements, we updated HumanCyc to the most recent NCBI annotation as of September 30, 2024. This update expanded the gene count from 21,083 (including 4,826 unmapped genes) to 59,059 (with only a single unmapped gene). The vast majority of the new genes are RNA genes and pseudogenes; the number of protein-encoding genes actually decreased rom 20,737 to 20,487.
A substantial effort went into reconciling differences between older and newer annotations, remapping genes to updated positions, and revising their functional descriptions as needed. Isoforms were also introduced into HumanCyc, increasing the number of polypeptides from 20,765 to 93,431. Following UniProt's convention, one isoform per protein was designated as the canonical form. A new "Isoforms tab" was added to protein pages, listing the isoforms and their exons, and enabling download of the sequence of a specified isoform.
Beyond sequence and annotation updates, HumanCyc content was further enriched. The number of base pathways increased to 395, and the number of enzymatic reactions rose from 2,958 to 3,172. For the first time, protein features were incorporated into HumanCyc from UniProt, adding 428,277 new protein features.
Released on Nov 28, 2017
Since release 20.5 we added 12 new pathways to HumanCyc and revised one pathway. We continued to expand our coverage of protein modification with two new pathways that describe protein N-glycosylation, a pathway about protein NEDDylation, and a pathway describing the hydroxylation and glycosylation of procollagen. New biosynthetic pathways were added for coenzyme A, heme a, lipoate, and UDP-α-D-glucose. Other new pathways describe the metabolism of 5-oxo-L-proline, hydrogen sulfide biosynthesis and oxidation, and two pathways about thiolation of uridine bases in tRNA.All of the entries in the UniProt human proteome set (http://www.uniprot.org/help/human_proteome) are now represented in HumanCyc. Links to the OMIM (Online Mendelian Inheritance in Man) database have been updated, and are now limited to phenotype entries. In addition, HumanCyc was also updated by propagation of new data from MetaCyc.
New Pathways
Revised pathways:
Released on Dec 17, 2016
Since the last release we have added 25 new pathways to HumanCyc. A main effort focused on glycosylation pathways, describing the biosynthesis of the ABH histo-blood group antigens, the Lewis histo-blood group antigens, and several types of glycosphingolipids, including all common gangliosides. HumanCyc was also updated by propagation of new data from MetaCyc.New Pathways
New Superpathways
Released on Jun 23, 2014
Since the last release we have added six new pathways to HumanCyc. These include a novel threonine degradation pathway in humans, an alternate lysine degradation pathway via pipecolate, carnosine and homocarnosine biosynthesis, fructose 2,6-bisphosphate metabolism and hydrogen sulfide biosynthesis. We also revised 10 existing pathways in HumanCyc, which include ubiquinol 10, taurine, asparagine and coenzyme A biosynthesis; glycine betaine, purines, β alanine, asparagine and valine degradation; and the superpathway of choline degradation to serine. HumanCyc was also updated by propagation of new data from MetaCyc.New Pathways
Revised pathways:
Released on March 24, 2014
Since the last release we have added two new pathways to HumanCyc which show an alternate biosynthetic pathway for putrescine and a superpathway to demonstrate choline degradation to L-serine. We also revised 24 existing pathways in HumanCyc.These include several degradation pathways for pyrimidines, uracil, 4-hydroxyproline, tryptophan, 2-oxobutanoate, histamine, glutamate, glycine betaine and lysine; fatty acid biosynthesis and the biosynthesis of glutamate, NAD, ornithine and L-carnitine; the mitochondrial L-carnitine shuttle, acyl carrier protein metabolism, the oxidative branch of the pentose phosphate pathway, sulfite oxidation, the GABA shunt, glutathione redox reactions I and II, folate transformations, 2-oxoglutarate decarboxylation to succinyl coA and sulfate activation. HumanCyc was also updated by propagation of new data from MetaCyc.New Pathways
Revised pathways:
Released on October 11, 2013
Since the last release we have added two new pathways to HumanCyc, which cover the salvage of tetrahydrobioterin and purine nucleotides. We also revised 10 existing pathways, which include the malate aspartate shuttle, biosynthesis of the amino acids serine and glycine and NAD salvage.New pathways:
Revised pathways:
Released on June 11, 2013
Since the last release we have added 5 new pathways to HumanCyc, all of which were imported from MetaCyc. We also revised 4 existing pathways. The new pathways cover purine nucleotide and deoxynucleotide biosynthesis and salvage. Pathway curation in HumanCyc was facilitated by importing some compounds from MetaCyc to enable computational instantiation. HumanCyc was also upgraded by propagation of relevant data updates from MetaCyc.New pathways:
Revised pathways:
Released on March 28, 2013
Since the last release we have added 17 new pathways and three super pathways to HumanCyc, most of which
were imported from MetaCyc. We also revised 5
existing pathways.
The coverage of nucleotide and nucleoside phosphorylation, biosynthesis and
degradation was significantly enhanced by the addition of several new pathways.
Other new pathways curated include the degradation of phytol, a metabolite
derived from chlorophyll, the peroxisomal β oxidation of fatty acids and the
biosynthesis of novel anti-inflammatory compounds derived from omega 3 and 6
fatty acids.
Pathway curation in HumanCyc was facilitated by importing some compounds from MetaCyc to enable computational instantiation. HumanCyc was also upgraded by propagation of relevant data updates from MetaCyc.
New pathways:
New super pathways
Revised pathways:
Released on Nov 14, 2012
We curated two new pathways in HumanCyc that describe the peroxisomal
α-oxidation of 3-methyl branched fatty acids and 2-hydroxylated
straight chain fatty acids. We also imported a pathway from MetaCyc for the
detoxification of 4-hydroxy-2-nonenal, a product of lipid peroxidation.
Several compounds were imported into HumanCyc from MetaCyc in order to allow
computational instantiation of the two new fatty acid α-oxidation
pathways, as well as the existing pathway fatty acid β-oxidation III
(unsaturated, odd number).
Also for this release, HumanCyc has also been upgraded by propagation of the
latest data updates from MetaCyc.
New pathways curated in HumanCyc:
Pathways added from MetaCyc:
Released on Feb 21, 2012
Further refinements of the HumanCyc flux-balance analysis (FBA) model, including reaction balancing, structure modifications, instantiations of compound classes and addition of reactions from MetaCyc have occurred in this version of HumanCyc.
We have also added the following pathways from MetaCyc:Released on October 17, 2011.
Further refinements of the HumanCyc flux-balance analysis (FBA) model have occurred in this version of HumanCyc. This model can be executed by downloading a configuration of the Pathway Tools software (Linux-64 version) that includes HumanCyc.
Released on June 8, 2011.
With this release we have completed the FBA modeling of HumanCyc, including reaction balancing, structure modifications, instantiations of compound classes and addition of reactions from MetaCyc.
We have also added the following human metabolic pathways from MetaCyc:Released on March 18, 2011.
For this release, we have used a number of automated Pathway Tools to analyze the reactions and pathways of HumanCyc to interrogate the completeness of the metabolic network. These efforts are carried out in conjunction with the development of a Flux Balance Analysis (FBA) modeling capability for Pathway Tools. The creation of an FBA model for HumanCyc is ongoing, and any feedback would be appreciated.
We have used the dead-end metabolite tool to identify compounds that are only reactants, or only products, of HumanCyc reactions. Such compounds are necessarily excluded from FBA models due to balance constraints. Therefore, any compounds that are truly only reactants in a metabolic network must be obligate nutrients (such as essential amino acids or vitamins) and should also have transport reactions. We have added some transport reactions of this type and will add more in future releases.
Similarly, compounds that are only products cannot be further metabolized by the metabolic network and must be listed as secreted compounds and have defined (possibly orphan) transport reactions. Many such compounds in HumanCyc are likely metabolized further by reactions that have yet to be added to the HumanCyc metabolic network. Some of these transport and enzymatic reactions have been added, and more will be resolved subsequently.
We have employed automated tools for identifying unbalanced reactions, as these will also be excluded from the FBA model. Chemical structure and stoichiometric corrections have resulted in properly balanced enzymatic reactions. More of these will be identified and resolved in future.
Preliminary results from executing the FBA analysis of the HumanCyc metabolic network have identified enzymatic reactions and pathways in the MetaCyc database that were added to HumanCyc based on analysis of the scientific literature. We have also defined reaction directions as suggested by the FBA model followed by literature research.
We have removed all legacy comments previously uploaded from locuslink, removed some deaccessioned EntrezGene links and repaired some other external links.
With this release we have added 107 new transport reactions and newly assigned more than 300 proteins to these transport activities. We have added literature citations, evidence codes and comments to many of these transport activities, and will be expanding this aspect of the HumanCyc knowledge base in the future.
We have also imported to HumanCyc more than 100 comments, literature citations and evidence codes for pathways originally curated in MetaCyc. These have been edited to focus on the Homo sapiens specific biology.
Released on October 1, 2010.
We are continuing with manual curation of the HumanCyc knowledge base of metabolic pathways. HumanCyc is still a work in progress; any constructive feedback will be greatly appreciated.
With this release we have updated the genes and proteins content of HumanCyc such that it now contains the UniProt Complete Proteome for H. sapiens. This has included an automated update of names, synonyms and functional annotation of enzymes. We have also updated UniProt and EntrezGene identifiers and external links in HumanCyc.
Additionally, we have created and curated the following pathways focused on lipid, steroid and proteoglycan metabolism. Pathways Created and Manually Curated for Version 14.5 include:
Released on June 16, 2010.
Curation of the HumanCyc knowledge base continues in conjunction with the Pharmacometabolomics Research Network (PMRN). This is a multi-year collaboration to develop tools and provide resources for the metabolomics community; to this end we have focused on curation of information from the scientific literature concerning chemical compounds and enzymes of interest to the PMRN and the larger field of metabolomics.
As a consequence of the unique capabilities of metabolomics measurements, particular emphasis will be placed on pathways of metabolism of xenobiotics, nutrients and metabolites produced by the gut Microbiome. As always, feedback and suggestions are welcome. New HumanCyc pathways for this release include:
Released on March 18, 2010.
We have recently begun a more intensive manual curation of the HumanCyc knowledge base with the intent of developing a fully curated database of human metabolic pathways. These efforts are anticipated to span years, and hence, HumanCyc is still a work in progress. Any constructive feedback will be greatly appreciated.
We have initially focused on updating the current content of HumanCyc. This has included an automated update of names and functional annotation of genes and proteins from the UniProt Complete Proteome for H. sapiens (using a version downloaded on 11/11/2009). We have also updated Ensembl identifiers in HumanCyc to reflect the latest Ensembl identifiers from version 56. We have also updated the UniProt and Ensembl external links in HumanCyc. In general, HumanCyc has undergone extensive housecleaning so as to represent the latest publicly available gene functions.
Additionally, we have developed a Pathway Tools Signaling Pathway Editor that debuts with this version; demonstration pathways have been created for MAP kinase and BMP intracellular signaling.
Pathways newly created and manually curated for Version 14.0 include:
Released on April 1, 2008.
The automated PathoLogic function to rescore pathways was run to clear out some obsolete pathways and get newly created pathways from MetaCyc. This was done with little human oversight -- just a quick visual pass to eliminate likely false positive pathways. 55 pathways were deleted from HumanCyc, and 116 new pathways (including superpathways) were imported from MetaCyc.
Released on December 15, 2006.
We have added two new human metabolic pathways and a superpathway in this release:
The new pathways expand our coverage of cholesterol biosynthesis by illustrating other biosynthetic intermediates that have been shown to occur. The pre-existing pathway was renamed cholesterol biosynthesis I. The superpathway combines these three pathways, giving an overview of some of the multiple possible routes for cholesterol biosynthesis. Descriptive comments and references have been entered for these pathways and for the respective enzyme entries comprising these pathways.
Released on September 8, 2006.
We have added two new human metabolic pathways in this release:
These pathways describe the degradation of anandamide, a member of the endocannabinoid class of signaling lipids, and the degradation of dopamine, a neurotransmitter and physiological regulator. Descriptive comments and references have been entered for these pathways and for the respective enzyme entries comprising these pathways.
Released on May 23, 2005.
We have added one new human metabolic pathway in this release:
This pathway describes the biosynthesis of cholesterol from farnesyl diphosphate in a series of 22 reactions. The biosynthesis of farnesyl diphosphate from acetyl-CoA is described in the linked mevalonate pathway in HumanCyc. The cholesterol pathway proceeds through the formation of lanosterol, followed by the series of membrane-associated reactions that lead to the formation of cholesterol. Extensive descriptive comments and references have been entered for this pathway and for the respective enzyme entries comprising this pathway.
Released on February 25, 2005.
We have added several new human metabolic pathways in this release:
The catecholamine pathway describes the biosynthesis of the neurotransmitters dopamine, norepinephrine, and epinephrine. The metabolism of xenobiotics is described in the two linked pathways of nicotine degradation, and the pathway for the degradation of the antidepressant drug bupropion, which is also used in smoking cessation therapy. Extensive descriptive comments and references have been entered for these pathways and for the respective enzyme entries comprising these pathways.
Released on March 12, 2004.
We are continuing on-going curation of new and existing human metabolic pathways. In this release, three new pathways have been added:
Extensive descriptive comments and references have been entered for these pathways and for the respective gene, enzyme and reaction entries comprising these pathways. In describing the genes that encode the enzymes and/or subunits of enzymes catalyzing steps of pathways, specific emphasis has been placed on describing sites of genetic polymorphism and their associated genotypes and/or disease associations.
Human pathways span multiple cellular and tissue compartments. The partitioning of these pathways across cellular and tissue compartments has also been described.
Released on November 4, 2003.
In this release, we have made putative functional assignments to 22 genes in HumanCyc. These functional assignments were made to fill pathway holes in the database. A pathway hole occurs when a reaction in a pathway does not have an assigned enzyme. The putative enzymes that fill these pathway holes were identified using a prediction program developed by Green and Karp and described in "A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases". Each enzymatic reaction linked to an enzyme by this program is identified by the evidence code "Computational Evidence: EV-COMP-HINF-FN-FROM-SEQ". The evidence code indicates the source of information as computationally-derived from sequence analysis with human review. The gene product field of the corresponding enzyme has also been updated to include the functional description of the reaction to which it has been linked.
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