BTD

biotinidase, the group of Vanin family

Basic information

Region (hg38): 3:15601340-15722311

Links

ENSG00000169814 ∙ NCBI:686 ∙ OMIM:609019 ∙ HGNC:1122 ∙ Uniprot:P43251 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Biotinidase deficiency	AR	Biochemical	Individuals 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 bioavailability	Allergy/Immunology/Infectious; Biochemical; Dermatologic; Neurologic; Ophthalmologic	4103667; 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 (518 variants)
• not provided (142 variants)
• Inborn genetic diseases (62 variants)
• not specified (43 variants)
• BTD-related condition (5 variants)
• Intellectual disability (4 variants)
• Global developmental delay (1 variants)
• Cryptorchidism;Generalized hypotonia;Macrocephaly;Global developmental delay (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	121	1	124
missense	24	47	138	5		214
nonsense	13	17				30
start loss						0
frameshift	24	29				53
inframe indel		3	5			8
splice donor/acceptor (+/-2bp)	3	8	1			12
splice region	1	2	3	14		20
non coding		2	42	17	10	71
Total	64	106	188	143	11

Highest pathogenic variant AF is 0.000151

Variants in BTD

This is a list of pathogenic ClinVar variants found in the BTD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-15601412-T-C		not specified	Uncertain significance (Jan 26, 2023)
3-15601449-G-C		not specified	Uncertain significance (Aug 02, 2021)
3-15601452-A-C		not specified	Uncertain significance (Sep 14, 2022)
3-15601456-T-C		not specified	Uncertain significance (May 31, 2023)
3-15601536-A-G			Benign (Jun 26, 2018)
3-15601668-G-A			Benign (Jul 27, 2018)
3-15601713-G-C			Likely benign (Aug 20, 2019)
3-15601743-G-T			Uncertain significance (Aug 06, 2022)
3-15601763-C-T		Biotinidase deficiency	Conflicting classifications of pathogenicity (Apr 01, 2020)
3-15601806-C-T		Biotinidase deficiency	Uncertain significance (Jun 14, 2016)
3-15601817-C-T		Biotinidase deficiency • not specified	Benign/Likely benign (Dec 07, 2017)
3-15601824-G-T		Biotinidase deficiency	Uncertain significance (Jun 14, 2016)
3-15601837-G-A		Biotinidase deficiency	Uncertain significance (Dec 27, 2016)
3-15601846-G-T		Biotinidase deficiency	Uncertain significance (Jun 14, 2016)
3-15601851-A-G		Biotinidase deficiency	Uncertain significance (Jun 05, 2018)
3-15601852-T-A		Biotinidase deficiency	Uncertain significance (Apr 23, 2022)
3-15601852-T-C		Biotinidase deficiency	Uncertain significance (May 29, 2018)
3-15601853-G-A		Biotinidase deficiency	Uncertain significance (Nov 27, 2017)
3-15601860-G-T		Biotinidase deficiency	Uncertain significance (Jul 31, 2022)
3-15601865-T-C		Biotinidase deficiency	Likely benign (Dec 14, 2023)
3-15601866-A-T		Biotinidase deficiency	Uncertain significance (Aug 13, 2020)
3-15601873-G-A		Biotinidase deficiency	Uncertain significance (May 04, 2022)
3-15601881-C-G		Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
3-15601883-C-T		Biotinidase deficiency	Likely benign (Jan 06, 2020)
3-15601887-A-T		Biotinidase deficiency	Likely pathogenic (Jan 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BTD	protein_coding	protein_coding	ENST00000303498	4	44482

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.50e-7	0.398	125687	0	61	125748	0.000243

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.525	320	295	1.09	0.0000160	3608
Missense in Polyphen		114	98.904	1.1526		1193
Synonymous	-0.576	124	116	1.07	0.00000690	1057
Loss of Function	0.698	12	14.9	0.805	6.53e-7	199

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000177	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000264	0.000185
Middle Eastern	0.000544	0.000544
South Asian	0.00137	0.000817
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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