Biotinidase recycles protein-bound biotin by cleaving biocytin to regenerate free biotin and also functions as a biotinyl transferase. Mutations cause biotinidase deficiency, an autosomal recessive disorder that impairs biotin recycling and can lead to metabolic dysfunction. Loss-of-function mutations result in reduced enzyme activity, preventing adequate biotin availability for essential carboxylase enzymes.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.301 OMIM phenotype
Clinical SummaryBTD
🧬
Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
79 unique Pathogenic / Likely Pathogenic· 221 VUS of 400 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — BTD
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.30LOEUF
pLI 0.000
Z-score 0.70
OE 0.81 (0.521.30)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.53Z-score
OE missense 1.09 (0.991.19)
320 obs / 294.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.81 (0.521.30)
00.351.4
Missense OE1.09 (0.991.19)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 12 / 14.9Missense obs/exp: 320 / 294.6Syn Z: -0.58

ClinVar Variant Classifications

400 submitted variants in ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic47
VUS221
Likely Benign56
Benign6
Conflicting7
32
Pathogenic
47
Likely Pathogenic
221
VUS
56
Likely Benign
6
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
8
12
0
32
Likely Pathogenic
26
20
1
0
47
VUS
1
201
19
0
221
Likely Benign
0
2
19
35
56
Benign
1
0
5
0
6
Conflicting
7
Total402315635369

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BTD · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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