BTD

biotinidase, the group of Vanin family

Basic information

Region (hg38): 3:15601341-15722311

Links

ENSG00000169814NCBI:686OMIM:609019HGNC:1122Uniprot:P43251AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • biotinidase deficiency (Definitive), mode of inheritance: AR
  • biotinidase deficiency (Definitive), mode of inheritance: AR
  • biotinidase deficiency (Strong), mode of inheritance: AR
  • biotinidase deficiency (Definitive), mode of inheritance: AR
  • biotinidase deficiency (Supportive), mode of inheritance: AR
  • Leigh syndrome (Moderate), mode of inheritance: AR
  • biotinidase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Biotinidase deficiencyARBiochemicalIndividuals with severe biotinidase deficiency can present with a range of neurologic, visual, and dermatologic anomalies, which are typically not reversible after manifesting, and medical management (with oral biotin) is indicated and can prevent sequelae if instituted early; Raw eggs should be avoided due to resultant decreased biotin bioavailabilityAllergy/Immunology/Infectious; Biochemical; Dermatologic; Neurologic; Ophthalmologic4103667; 917614; 88555; 99258; 7436398; 6790844; 6135889; 6137736; 6848914; 3930842; 3926500; 4000223; 4073853; 196050; 2502673; 2515386; 2109151; 1729884; 8283357; 7550325; 9396567; 9375914; 9654207; 15776412; 7550325; 11313766; 17382128; 21752405; 20301497; 21696988; 21907891; 22378278; 22241090

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BTD gene.

  • Biotinidase_deficiency (626 variants)
  • not_provided (155 variants)
  • not_specified (69 variants)
  • Inborn_genetic_diseases (60 variants)
  • BTD-related_disorder (26 variants)
  • Intellectual_disability (4 variants)
  • Global_developmental_delay (2 variants)
  • Generalized_hypotonia (1 variants)
  • Cryptorchidism (1 variants)
  • Possible_mitochondrial_disorder_-_nuclear_genes (1 variants)
  • Macrocephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BTD gene is commonly pathogenic or not. These statistics are base on transcript: NM_001370658.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
163
clinvar
1
clinvar
167
missense
30
clinvar
123
clinvar
173
clinvar
11
clinvar
337
nonsense
20
clinvar
19
clinvar
1
clinvar
40
start loss
1
1
frameshift
33
clinvar
47
clinvar
80
splice donor/acceptor (+/-2bp)
3
clinvar
11
clinvar
1
clinvar
15
Total 86 202 177 174 1

Highest pathogenic variant AF is 0.000952165

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BTDprotein_codingprotein_codingENST00000303498 444482
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.50e-70.3981256870611257480.000243
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.5253202951.090.00001603608
Missense in Polyphen11498.9041.15261193
Synonymous-0.5761241161.070.000006901057
Loss of Function0.6981214.90.8056.53e-7199

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001770.000177
Ashkenazi Jewish0.000.00
East Asian0.0005440.000544
Finnish0.00004620.0000462
European (Non-Finnish)0.0002640.000185
Middle Eastern0.0005440.000544
South Asian0.001370.000817
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation.;
Disease
DISEASE: 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 mutations affecting the gene represented in this entry.;
Pathway
Vitamin digestion and absorption - Homo sapiens (human);Biotin metabolism - Homo sapiens (human);Biotin Metabolism;Multiple carboxylase deficiency, neonatal or early onset form;Biotinidase Deficiency;Biotin transport and metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;Vitamin H (biotin) metabolism (Consensus)

Recessive Scores

pRec
0.236

Intolerance Scores

loftool
0.126
rvis_EVS
0.02
rvis_percentile_EVS
55.76

Haploinsufficiency Scores

pHI
0.0625
hipred
N
hipred_score
0.199
ghis
0.469

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.879

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Btd
Phenotype
growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; vision/eye phenotype; renal/urinary system phenotype; skeleton phenotype;

Gene ontology

Biological process
biotin metabolic process;central nervous system development
Cellular component
extracellular region;extracellular space;mitochondrial matrix;extracellular exosome
Molecular function
biotinidase activity