DTNBP1

Chr 6AR

dystrobrevin binding protein 1

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

NCBI Gene: 84062ENSG00000047579UniProt: Q96EV8

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]

Primary Disease Associations & Inheritance

Hermansky-Pudlak syndrome 7MIM #614076
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— DTNBP1
🧬
Gene-Disease Validity (ClinGen)
Hermansky-Pudlak syndrome 7 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.98LOEUF
pLI 0.000
Z-score 1.62
OE 0.59 (0.37–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.24Z-score
OE missense 1.05 (0.93–1.18)
197 obs / 187.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.37–0.98)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.93–1.18)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.26
0≤1.21.6
LoF obs/exp: 11 / 18.5Missense obs/exp: 197 / 187.6Syn Z: -1.75

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DTNBP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DTNBP1-related Hermansky-Pudlak syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
EyeSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hermansky-Pudlak syndrome 7

MIM #614076

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DTNBP1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The diagnostic yield, candidate genes, and pitfalls for a genetic study of intellectual disability in 118 middle eastern families.
Al-Kasbi G et al.·Sci Rep
2022
Dopaminergic signalling and behavioural alterations by Comt-Dtnbp1 genetic interaction and their clinical relevance.
Managò F et al.·Br J Pharmacol
2023
Meta-analysis of genetic variation in DTNBP1 and general cognitive ability.
Zhang JP et al.·Biol Psychiatry
2010Meta-analysis
Is the dysbindin gene (DTNBP1) a susceptibility gene for schizophrenia?
Williams NM et al.·Schizophr Bull
2005Review
Objective to identify and verify the regulatory mechanism of DTNBP1 as a prognostic marker for hepatocellular carcinoma.
Cheng X et al.·Sci Rep
2022Functional
COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors.
Correa DD et al.·Neuro Oncol
2016Cohort
Unraveling Hermansky-Pudlak syndrome type 7: a case report and comprehensive literature review on the identification of DTNBP1 variants.
Rodrigues R et al.·Ophthalmic Genet
2024Review
Evaluating historical candidate genes for schizophrenia.
Farrell MS et al.·Mol Psychiatry
2015Review
Clinical and molecular genetics of psychotic depression.
Domschke K·Schizophr Bull
2013Review
Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia.
Cheah SY et al.·Eur Psychiatry
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools