External Sources

Source Version
Ensembl 74
UniProt 2013_11

NECTAR Statistics

Disease and Function Enrichment
Feature Gene Number of
Amino Acid Replacements Variants
CA_BIND 229 38,793 43,836
ZN_FING 1,691 1,545,884 1,752,388
DNA_BIND 564 295,505 332,464
NP_BIND 1,629 173,276 193,072
ACT_SITE 2,002 22,933 26,170
METAL 1,247 40,323 46,067
BINDING 1,627 29,667 33,666
MOD_RES 6,966 191,901 220,695
LIPID 617 6,046 6,860
CARBOHYD 4,154 115,066 131,548
DISULFID 2,916 228,128 260,716
CROSSLNK 456 6,911 7,905
HUMSAVAR 1,987 132,954 146,971
COSMIC 16,774 2,579,124 2,856,551
HGMD-PUBLIC 2,831 284,895 319,496
ClinVar 2,198 79,113 88,092
features related with function and disease
Paralogue Enrichment
Paralogue Annotations Sources of Reported Annotations
Amino Acids Gene Amino Acids Gene
914,935 13,587 447,735 13,085

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Amongst various types of genetic mutations, non-synonymous mutations (e.g. nonsense or missense mutations) are of special interest as they can change the function of a protein by replacing native amino acid type, which could possibly cause diseases such as cystic fibrosis, sickle-cell anemia and cancer. In theory, the same single amino acid replacement (i.e. phenotype) could be generated by different genetic alleles (i.e. genotype) because there can be multiple codons encoding the same amino acid (aka. codon degeneracy).

For instance, variants in the myosin regulatory light chain (MYL2) including c.52T>C (p.Phe18Leu) have been reported to cause familial hypertrophic cardiomyopathy. Three alleles could equally substitute phenylalanine to leucine (c.54C>G, c.54C>A, and c.52T>C), although only one of them (c.52T>C) has been previously reported. Other alleles can also substitute this conserved phenylalanine to isoleucine (c.52T>A), valine (c.52T>G), tyrosine (c.53T>A), cysteine (c.53T>G), or serine (c.53T>C). Therefore phenotype associated with c.52C>T may be relevant in interpreting other alternative missense variants affecting the same codon.

We developed NECTAR based on this observation. It starts with known non-synonymous mutations responsible for diseases and expands to archive possible non-synonymous alleles at the same codon which can equally substitute the native amino acid. Read the main paper here.

What NECTAR provides

Disease mutation: You can browse disease-related non-synonymous mutations from a gene of your interest. There are 19,559 genes in NECTAR of which 17,270 genes have at least one non-synonymous disease mutations either from following four databases: HGMD-PUBLIC, UniProt, COSMIC, or ClinVar. [example].

Function annotations: The UniProt provides high quality resource of protein sequence and functional information. Especially 'sequence feature' records can be harnessed to interprete the effects of non-synonymous mutations on their occurrences. NECTAR archives functional amino acid resiudes and their possible non-synonymous mutations from the following 12 functional features. [example].

Paralogue annotations: It is equally interesting to investigate the effect of non-synonymous variants at the equivalent amino acid positions between close homologues. NECTAR identifies functionally equivalent amino acid residues in evolutionarily-related proteins (paralogues) and where appropriate transfers annotations between them [example]

Enriched annotations: Known non-synonymous disease mutations are extended to include the same or possible amino acid replacement at the same codon where the original mutations are reported. Using Ensembl API, mutations are mapped to Ensembl human genome coordinate, transcripts and proteins with enriched annotations such as 'variation consequence types' and 'protein function predictions'.

GBrowse: Disease variants, function annotations, and paralogue annotations are graphically visualized and highlighted at the amino acid reisude level of Ensembl (or UniProt) protein sequence by using Generic Genome Browser. [example]

DAS: NECTAR is a DAS server, which provides a XML-based web service to distribute annotations through the web. [Database Source Name(DSN) of NECTAR] [example]

FTP: Download (or mirror) NECTAR from here

Annotation on the fly: Upload your own VCF and have it annotated as demonstrated above. Plus have a VEP result at the same time.