DTNBP1

Chr 6AR

dystrobrevin binding protein 1

Also known as: BLOC1S8, DBND, HPS7, My031, SDY

NCBI Gene: 84062 ENSG00000047579 UniProt: Q96EV8 OMIM: 607145

DTNBP1 encodes dysbindin, a component of the BLOC-1 complex required for biogenesis of lysosome-related organelles such as melanosomes and platelet dense granules, and plays a role in synaptic vesicle trafficking and neurotransmitter release. Mutations cause Hermansky-Pudlak syndrome type 7, an autosomal recessive disorder characterized by oculocutaneous albinism and bleeding due to platelet storage pool deficiency. The gene is extremely tolerant to loss-of-function variants in the general population (pLI nearly 0), suggesting that complete loss of function may be required for disease manifestation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that may play a role in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes. A similar protein in mouse is a component of a protein complex termed biogenesis of lysosome-related organelles complex 1 (BLOC-1), and binds to alpha- and beta-dystrobrevins, which are components of the dystrophin-associated protein complex (DPC). Mutations in this gene are associated with Hermansky-Pudlak syndrome type 7. This gene may also be associated with schizophrenia. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.981 OMIM phenotype

Clinical Summary— DTNBP1

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Gene-Disease Validity (ClinGen)

Hermansky-Pudlak syndrome 7 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

18 unique Pathogenic / Likely Pathogenic· 139 VUS of 370 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — DTNBP1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.98LOEUF

pLI 0.000

Z-score 1.62

OE 0.59 (0.37–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.24Z-score

OE missense 1.05 (0.93–1.18)

197 obs / 187.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.59 (0.37–0.98)

0≤0.351.4

Missense OE?1.05 (0.93–1.18)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 11 / 18.5Missense obs/exp: 197 / 187.6Syn Z: -1.75

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveDTNBP1-related Hermansky-Pudlak syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.76top 25%

GOF

0.75top 25%

LOF

0.2582th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

370 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic10

VUS139

Likely Benign156

Benign35

Conflicting10

Pathogenic

Likely Pathogenic

139

VUS

156

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	4	0	4	0	8
Likely Pathogenic	10	0	0	0	10
VUS	8	123	8	0	139
Likely Benign	0	7	77	72	156
Benign	1	2	29	3	35
Conflicting	—				10
Total	23	132	118	75	358

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

View in ClinVar →

23 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap DTNBP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →