The protein encoded by this gene functions to recycle protein-bound biotin by cleaving biocytin (biotin-epsilon-lysine), a normal product of carboxylase degradation, resulting in regeneration of free biotin. The encoded protein has also been shown to have biotinyl transferase activity. Mutations in this gene are associated with biotinidase deficiency. Multiple transcript varian... See more...

Aliases for BTD Gene

Aliases for BTD Gene

  • Biotinidase 2 3 4 5
  • Biotinase 2 3 4
  • EC 4 50
  • EC 3.5.1 50
  • BTD 5

External Ids for BTD Gene

Previous GeneCards Identifiers for BTD Gene

  • GC03P015572
  • GC03P015619
  • GC03P015620
  • GC03P015621
  • GC03P015645

Summaries for BTD Gene

Entrez Gene Summary for BTD Gene

  • The protein encoded by this gene functions to recycle protein-bound biotin by cleaving biocytin (biotin-epsilon-lysine), a normal product of carboxylase degradation, resulting in regeneration of free biotin. The encoded protein has also been shown to have biotinyl transferase activity. Mutations in this gene are associated with biotinidase deficiency. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

GeneCards Summary for BTD Gene

BTD (Biotinidase) is a Protein Coding gene. Diseases associated with BTD include Biotinidase Deficiency and Biotin Deficiency. Among its related pathways are Metabolism of water-soluble vitamins and cofactors and Metabolism. Gene Ontology (GO) annotations related to this gene include hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds and biotin carboxylase activity. An important paralog of this gene is VNN1.

UniProtKB/Swiss-Prot Summary for BTD Gene

  • Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for BTD Gene

Genomics for BTD Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for BTD Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J015600 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 250.7 +0.4 359 3 BCLAF1 SP1 ZNF207 NCOR1 MYC ZNF600 ZNF580 ZNF592 KLF9 POLR2A HACL1 BTD HSALNG0024436 SH3BP5-AS1 CCDC174 CAPN7 NR2C2 COLQ
GH03J015623 Enhancer 0.6 Ensembl ENCODE 16.8 +23.2 23246 2 XRCC3 FOXA1 NCOA3 CBFA2T3 CCDC174 BTD SH3BP5-AS1 HACL1 NR2C2 EAF1 COLQ piR-36575-043 lnc-HACL1-2 ANKRD28
GH03J015792 Promoter/Enhancer 2.3 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 4.4 +196.3 196306 9.6 NCOR1 MYC IKZF1 ZNF600 JUND ZNF592 ZNF223 CEBPB SMAD5 SIN3A lnc-HACL1-9 ANKRD28 IMPDH1P8 EAF1 EAF1-AS1 METTL6 BTD DPH3 COLQ SH3BP5
GH03J015629 Promoter/Enhancer 1.8 FANTOM5 Ensembl ENCODE dbSUPER 5 +33.1 33146 9.5 BCLAF1 ZNF654 IKZF1 MYC JUND ZNF592 CEBPA ZIC2 YY1 BCL11A EAF1 CAPN7 COL6A4P1 COLQ HACL1 BTD SH3BP5 ANKRD28 lnc-HACL1-2 HSALNG0024440
GH03J015644 Enhancer 1 ENCODE dbSUPER 6.6 +45.9 45888 5.7 BCLAF1 SP1 JUND ZIC2 BCL11A CEBPB DEK TRIM22 MAX EP300 HSALNG0024440 CAPN7 COL6A4P1 EAF1 COLQ ANKRD28 BTD HACL1 IMPDH1P8 piR-50437-456
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around BTD on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for BTD

Top Transcription factor binding sites by QIAGEN in the BTD gene promoter:
  • GATA-1
  • GR
  • GR-alpha
  • GR-beta
  • Nkx3-1
  • Nkx3-1 v1
  • Nkx3-1 v2
  • Nkx3-1 v3
  • Nkx3-1 v4
  • Sp1

Genomic Locations for BTD Gene

Latest Assembly
121,176 bases
Plus strand

Previous Assembly
(GRCh37/hg19 by Entrez Gene)
121,165 bases
Plus strand

(GRCh37/hg19 by Ensembl)
44,482 bases
Plus strand

Genomic View for BTD Gene

Genes around BTD on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
BTD Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for BTD Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for BTD Gene

Proteins for BTD Gene

  • Protein details for BTD Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Protein Accession:
    Secondary Accessions:
    • A6NHF2
    • B2R865
    • B4DFX1
    • B4DLJ9
    • B7Z7C9
    • F8W1Q3
    • Q96EM9

    Protein attributes for BTD Gene

    543 amino acids
    Molecular mass:
    61133 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for BTD Gene


neXtProt entry for BTD Gene

Selected DME Specific Peptides for BTD Gene


Post-translational modifications for BTD Gene

  • Glycosylation at Asn119, Asn150, Asn203, Asn349, Asn402, and Asn489
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect

Antibodies for research

  • Abcam antibodies for BTD
  • Boster Bio Antibodies for BTD

Domains & Families for BTD Gene

Gene Families for BTD Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for BTD Gene

  • Nitrilase/cyanide hydratase and apolipoprotein N-acyltransferase

Suggested Antigen Peptide Sequences for BTD Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ59679, highly similar to Biotinidase (EC (A6NHF2_HUMAN)
  • cDNA FLJ51892, highly similar to Biotinidase (EC (B4DLJ9_HUMAN)
  • Biotinidase (BTD_HUMAN)

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.
  • Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.
genes like me logo Genes that share domains with BTD: view

Function for BTD Gene

Molecular function for BTD Gene

UniProtKB/Swiss-Prot Function:
Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=biotin amide + H2O = biotin + NH4(+); Xref=Rhea:RHEA:13081, ChEBI:CHEBI:15377, ChEBI:CHEBI:16615, ChEBI:CHEBI:28938, ChEBI:CHEBI:57586; EC=;.
GENATLAS Biochemistry:
biotinidase,76.5kDa,microsomal,catalyzing the recycling of biotin

Enzyme Numbers (IUBMB) for BTD Gene

Phenotypes From GWAS Catalog for BTD Gene

Gene Ontology (GO) - Molecular Function for BTD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016787 hydrolase activity IEA --
GO:0016811 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides IEA --
GO:0047708 biotinidase activity TAS --
genes like me logo Genes that share ontologies with BTD: view
genes like me logo Genes that share phenotypes with BTD: view

Human Phenotype Ontology for BTD Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for BTD Gene

MGI Knock Outs for BTD:
  • Btd Btd<tm1Bwol>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BTD

No data available for Transcription Factor Targets and HOMER Transcription for BTD Gene

Localization for BTD Gene

Subcellular locations from UniProtKB/Swiss-Prot for BTD Gene

Secreted, extracellular space.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for BTD gene
Compartment Confidence
extracellular 5
mitochondrion 4
cytoskeleton 3
lysosome 2
plasma membrane 1
peroxisome 1
nucleus 1
cytosol 1
endoplasmic reticulum 0
golgi apparatus 0

Gene Ontology (GO) - Cellular Components for BTD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA,HDA 16502470
GO:0005759 mitochondrial matrix TAS --
GO:0070062 extracellular exosome HDA 23533145
genes like me logo Genes that share ontologies with BTD: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for BTD Gene

Pathways & Interactions for BTD Gene

genes like me logo Genes that share pathways with BTD: view

Gene Ontology (GO) - Biological Process for BTD Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006768 biotin metabolic process IBA,TAS --
GO:0006807 nitrogen compound metabolic process IEA --
GO:0007417 central nervous system development TAS 7550325
genes like me logo Genes that share ontologies with BTD: view

No data available for SIGNOR curated interactions for BTD Gene

Drugs & Compounds for BTD Gene

(15) Drugs for BTD Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Biotin Approved, Investigational Nutra 70
Lysine Approved Nutra 187
Ammonia Approved Pharma 0
Water Approved Pharma 0

(14) Additional Compounds for BTD Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • (3AS-(3aalpha,4beta,6aalpha))-N(6)-(5-(hexahydro-2-oxo-1H-thieno(3,4-D)imidazol-4-yl)-1-oxopentyl)-L-lysine
  • Biotinyl-L-lysine
  • epsilon-N-Biotinyl-L-lysine
  • epsilon-N-Biotinyllysine
  • N(epsilon)-Biotinyl-L-lysine
Biotin amide
  • 5-[(3AS,6R,6ar)-2-hydroxy-1H,3ah,4H,6H,6ah-thieno[3,4-D]imidazol-6-yl]pentanimidate
genes like me logo Genes that share compounds with BTD: view

Transcripts for BTD Gene

mRNA/cDNA for BTD Gene

20 NCBI additional mRNA sequence :
25 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BTD

Alternative Splicing Database (ASD) splice patterns (SP) for BTD Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c ^ 5 ^ 6 ^ 7a · 7b · 7c · 7d ^ 8a · 8b · 8c
SP1: - - -
SP2: - - - -
SP3: - - - - - - -
SP4: - - - - -
SP5: - - - - - -
SP6: -

Relevant External Links for BTD Gene

GeneLoc Exon Structure for

Expression for BTD Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for BTD Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for BTD Gene

This gene is overexpressed in Serum (27.4), Vitreous humor (13.1), and Plasma (11.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for BTD Gene

Protein tissue co-expression partners for BTD Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for BTD

SOURCE GeneReport for Unigene cluster for BTD Gene:


Evidence on tissue expression from TISSUES for BTD Gene

  • Nervous system(4.8)
  • Kidney(4.5)
  • Liver(4.5)
  • Blood(4.4)
  • Bone marrow(4.1)
  • Thyroid gland(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for BTD Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • nervous
  • respiratory
  • skeletal muscle
  • urinary
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • eye
  • head
  • diaphragm
  • esophagus
  • lung
  • intestine
  • kidney
  • large intestine
  • liver
  • small intestine
  • spleen
  • stomach
  • blood
  • blood vessel
  • hair
  • peripheral nerve
  • peripheral nervous system
  • skin
  • white blood cell
genes like me logo Genes that share expression patterns with BTD: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for BTD Gene

Orthologs for BTD Gene

This gene was present in the common ancestor of animals.

Orthologs for BTD Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia BTD 29 30
  • 99.39 (n)
(Canis familiaris)
Mammalia BTD 29 30
  • 87.89 (n)
(Mus musculus)
Mammalia Btd 29 16 30
  • 83.46 (n)
(Bos Taurus)
Mammalia BTD 29 30
  • 82.28 (n)
(Rattus norvegicus)
Mammalia Btd 29
  • 81.28 (n)
(Ornithorhynchus anatinus)
Mammalia -- 30
  • 71 (a)
-- 30
  • 64 (a)
(Monodelphis domestica)
Mammalia BTD 30
  • 62 (a)
(Gallus gallus)
Aves BTD 29 30
  • 65.02 (n)
(Anolis carolinensis)
Reptilia BTD 30
  • 57 (a)
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia btd 29
  • 63.13 (n)
(Danio rerio)
Actinopterygii btd 29 30
  • 57.29 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta vanin-like 29 30 31
  • 46.35 (n)
CG3599 31
  • 29 (a)
Btd 30
  • 25 (a)
CG32751 30
  • 25 (a)
CG32750 30
  • 24 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010733 29
  • 45.89 (n)
Species where no ortholog for BTD was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for BTD Gene

Gene Tree for BTD (if available)
Gene Tree for BTD (if available)
Evolutionary constrained regions (ECRs) for BTD: view image
Alliance of Genome Resources:
Additional Orthologs for BTD

Paralogs for BTD Gene

Paralogs for BTD Gene

(3) SIMAP similar genes for BTD Gene using alignment to 8 proteins:

  • C9J387_HUMAN
  • F8W1Q3_HUMAN
  • L0R6D3_HUMAN
genes like me logo Genes that share paralogs with BTD: view

Variants for BTD Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for BTD Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
1003311 Uncertain Significance: Biotinidase deficiency 15,644,412(+) T/C
NM_001370658.1(BTD):c.496T>C (p.Cys166Arg)
1004892 Uncertain Significance: Biotinidase deficiency 15,644,598(+) A/C
NM_001370658.1(BTD):c.682A>C (p.Ile228Leu)
1010740 Uncertain Significance: Biotinidase deficiency 15,645,372(+) C/A
NM_001370658.1(BTD):c.1456C>A (p.Leu486Ile)
1015113 Uncertain Significance: Biotinidase deficiency 15,642,040(+) C/G
NM_001370658.1(BTD):c.382C>G (p.Arg128Gly)
1017712 Uncertain Significance: Biotinidase deficiency 15,635,693(+) G/T

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for BTD Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for BTD Gene

Variant ID Type Subtype PubMed ID
nsv979807 CNV duplication 23825009

Variation tolerance for BTD Gene

Residual Variation Intolerance Score: 79.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.60; 56.34% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for BTD Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for
Leiden Open Variation Database (LOVD)

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for BTD Gene

Disorders for BTD Gene

MalaCards: The human disease database

(36) MalaCards diseases for BTD Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
biotinidase deficiency
  • btd deficiency
biotin deficiency
  • b7 deficiency
seizure disorder
  • seizures
multiple carboxylase deficiency
  • mcd
seborrheic dermatitis
  • seborrhea
- elite association - COSMIC cancer census association via MalaCards
Search BTD in MalaCards View complete list of genes associated with diseases


  • Biotinidase deficiency (BTD deficiency) [MIM:253260]: A juvenile form of multiple carboxylase deficiency, an autosomal recessive disorder of biotin metabolism, characterized by ketoacidosis, hyperammonemia, excretion of abnormal organic acid metabolites, and dermatitis. Biotinidase deficiency is characterized by seizures, hypotonia, skin rash, alopecia, ataxia, hearing loss, and optic atrophy. If untreated, symptoms usually become progressively worse, and coma and death may occur. {ECO:0000269 PubMed:10206677, ECO:0000269 PubMed:9099842, ECO:0000269 PubMed:9654207}. Note=The disease is caused by variants affecting the gene represented in this entry.

Genatlas disease for BTD Gene

multiple carboxylase deficiency,late onset with feeding difficulties,hypotonia,seizures,lethargy, skin rash and metabolic acidosis,organic aciduria,biotinidase deficiency

Additional Disease Information for BTD

Human Genome Epidemiology Navigator
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with BTD: view

Publications for BTD Gene

  1. Human serum biotinidase. cDNA cloning, sequence, and characterization. (PMID: 7509806) Cole H … Wolf B (The Journal of biological chemistry 1994) 3 4 22 72
  2. Real time PCR assays to detect common mutations in the biotinidase gene and application of mutational analysis to newborn screening for biotinidase deficiency. (PMID: 12618081) Dobrowolski SF … Naylor EW (Molecular genetics and metabolism 2003) 3 22 40
  3. Seventeen novel mutations that cause profound biotinidase deficiency. (PMID: 12359137) Wolf B … Sykut-Cegielska J (Molecular genetics and metabolism 2002) 3 22 72
  4. Double mutation (A171T and D444H) is a common cause of profound biotinidase deficiency in children ascertained by newborn screening the the United States. Mutations in brief no. 128. Online. (PMID: 10206677) Norrgard KJ … Wolf B (Human mutation 1998) 3 4 22
  5. Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene. (PMID: 9654207) Swango KL … Wolf B (Human genetics 1998) 3 4 22

Products for BTD Gene

Sources for BTD Gene