BTD

Chr 3AR

biotinidase

NCBI Gene: 686 ENSG00000169814 UniProt: P43251 OMIM: 609019

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Biotinidase deficiencyMIM #253260

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

131

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.30

LOEUF

LOF

Mechanism· G2P

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GeneReview available — BTD

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.30LOEUF

pLI 0.000

Z-score 0.70

OE 0.81 (0.52–1.30)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.53Z-score

OE missense 1.09 (0.99–1.19)

320 obs / 294.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.81 (0.52–1.30)

0≤0.351.4

Missense OE?1.09 (0.99–1.19)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 12 / 14.9Missense obs/exp: 320 / 294.6Syn Z: -0.58

Background carrier burden — how many people carry a rare variant somewhere in BTD?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 52

822 rare PASS variants

Rare truncating (LoF)

1 in 420

124 rare PASS variants

Rare synonymous (reference)

1 in 99

303 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BTD. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 67	1 in 480
South Asian	~43k	1 in 44	1 in 230
Remaining (unassigned)	~30k	1 in 60	1 in 630
European (Finnish)	~27k	1 in 400	≈ 1 in 8,900
Admixed American	~22k	1 in 68	1 in 360
African / African American	~21k	1 in 57	1 in 590
East Asian	~20k	1 in 63	1 in 790
Ashkenazi Jewish	~13k	1 in 540	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 85	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓