DTNBP1

Summary

DTNBP1 (dystrobrevin binding protein 1, HGNC:17328) is a protein-coding gene on chromosome 6p22.3, encoding Dysbindin (Q96EV8). Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes.

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.

Source: NCBI Gene 84062 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Hermansky-Pudlak syndrome 7 (Definitive, ClinGen)
• GWAS associations: 9
• Clinical variants (ClinVar): 376 total — 8 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 15
• MANE Select transcript: NM_032122

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17328
Approved symbol	DTNBP1
Name	dystrobrevin binding protein 1
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	Dysbindin, My031, HPS7, DBND, BLOC1S8
Ensembl gene	ENSG00000047579
Ensembl biotype	protein_coding
OMIM	607145
Entrez	84062

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

ENST00000338950, ENST00000344537, ENST00000355917, ENST00000462989, ENST00000506844, ENST00000509674, ENST00000510395, ENST00000511762, ENST00000513680, ENST00000514651, ENST00000515875, ENST00000622898, ENST00000857317, ENST00000857318, ENST00000857319, ENST00000931310

RefSeq mRNA: 5 — MANE Select: NM_032122 NM_001271667, NM_001271668, NM_001271669, NM_032122, NM_183040

CCDS: CCDS4534, CCDS4535, CCDS75404, CCDS75405

Canonical transcript exons

ENST00000344537 — 10 exons

Exon	Start	End
ENSE00002058689	15662814	15663028
ENSE00003519119	15533240	15533395
ENSE00003553299	15637744	15637804
ENSE00003560128	15593059	15593081
ENSE00003582684	15651313	15651363
ENSE00003606106	15627343	15627475
ENSE00003658117	15652087	15652140
ENSE00003664789	15615267	15615399
ENSE00003689691	15524526	15524669
ENSE00003902408	15522807	15523219

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 96.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1006 / max 215.2900, expressed in 1707 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71938	5.5434	1670
71937	0.7904	445
71931	0.7792	94
71936	0.5351	265
71932	0.1993	76
71928	0.0744	28
71927	0.0672	26
203883	0.0509	23
71935	0.0427	18
71930	0.0180	5

Top tissues by expression

252 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.60	gold quality
nucleus accumbens	UBERON:0001882	96.53	gold quality
putamen	UBERON:0001874	95.25	gold quality
medial globus pallidus	UBERON:0002477	94.34	gold quality
caudate nucleus	UBERON:0001873	94.06	gold quality
hypothalamus	UBERON:0001898	93.59	gold quality
amygdala	UBERON:0001876	93.41	gold quality
globus pallidus	UBERON:0001875	93.24	gold quality
anterior cingulate cortex	UBERON:0009835	93.23	gold quality
substantia nigra	UBERON:0002038	92.22	gold quality
prefrontal cortex	UBERON:0000451	92.13	gold quality
left ventricle myocardium	UBERON:0006566	92.05	silver quality
midbrain	UBERON:0001891	91.85	gold quality
right frontal lobe	UBERON:0002810	91.80	gold quality
tibial artery	UBERON:0007610	91.49	gold quality
popliteal artery	UBERON:0002250	91.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.32	gold quality
lateral globus pallidus	UBERON:0002476	91.28	gold quality
mucosa of stomach	UBERON:0001199	91.19	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.02	gold quality
oocyte	CL:0000023	90.96	gold quality
ileal mucosa	UBERON:0000331	90.92	gold quality
superior vestibular nucleus	UBERON:0007227	90.86	gold quality
temporal lobe	UBERON:0001871	90.62	gold quality
frontal cortex	UBERON:0001870	90.57	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.54	gold quality
neocortex	UBERON:0001950	90.50	gold quality
aorta	UBERON:0000947	90.46	gold quality
secondary oocyte	CL:0000655	90.42	gold quality
lymph node	UBERON:0000029	90.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting DTNBP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-342-3P	96.44	67.48	1344

Literature-anchored findings (GeneRIF, showing 40)

• In mouse, dysbindin binds to alpha- and beta-dystrobrevin in muscle and brain. (PMID:11316798)
• single-nucleotide polymorphisms within the gene DTNBP1 (dystrobrevin-binding protein 1, or dysbindin) are strongly associated with schizophrenia (PMID:12098102)
• Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families (PMID:12474144)
• No evidence for association of dysbindin gene (DTNBP1) with schizophrenia in Irish population-based study (PMID:12591580)
• single high-risk haplotype was identified that showed a significant association with schizophrenia (PMID:12808430)
• genetic variation in the dysbindin gene is particularly involved in the development of schizophrenia in cases with a familial loading of the disease (PMID:14618545)
• DTNBP1 is a susceptibility gene for schizophrenia; Association with educational achievement may suggest protection mediated by IQ (PMID:15066891)
• These results provide strong support for DTNBP1 as a susceptibility gene for schizophrenia; however, different haplotypes seem to be associated in different studies. (PMID:15121479)
• DTNBP1 is implicated in susceptibility to schizophrenia. (PMID:15124015)
• DNTB1 is reduced in intrinsic, glutamatergic terminals of the hippocampus in schizophrenia. (PMID:15124027)
• Two highly significant peaks of haplotype sharing were found: one for psychotic patients with any diagnosis at the location of dysbindin, the other peak for patients with schizophrenia on chromosome 1p36. (PMID:15211634)
• Analysis showed no evidence for association to schizophrenia across five tested DTNBP1 loci. (PMID:15248869)
• Dysbindin appears to have novel neuronal functions. (PMID:15345706)
• the DTNBP1 gene plays a role in the genetic etiology of schizophrenia. (PMID:15362017)
• in the DTNBP1 gene confers susceptibility to schizophrenia through reduced expression (PMID:15917270)
• Based on data from a Chinese population, results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia. (PMID:16044171)
• No biased transmission towards schizophrenia was detected by haplotype analysis using TRANSMIT (PMID:16133786)
• DTNBP1 gene is associated with childhood onset psychosis. (PMID:16283082)
• this is the first report on a role of DTNBP1 gene variation for prefrontal brain function at a systemic neurophysiological level in healthy humans (PMID:16407900)
• DTNBP1 genetic variation influences human intelligence. (PMID:16415041)
• results suggest that dysbindin assembled into BLOC-1 is not a physiological binding partner of the dystrobrevins, likely due to engagement of its dystrobrevin-binding region in interactions with other subunits (PMID:16448387)
• the increased risk for schizophrenia associated with dysbindin may be partly mediated by its influence on pre-frontal function (PMID:16930638)
• results demonstrate that snapin is a binding partner of dysbindin-1 in vitro and in the brain; both dysbindin-1 and snapin are concentrated in tissue enriched in synaptic vesicle membranes and less commonly in postsynaptic densities (PMID:16980328)
• association studies are inconsistent with regard to the identity of the disease-associated haplotype at DTNBP1 in schizophrenia (PMID:17033966)
• study of possible association between DTNBP1 gene variants & bipolar I disorder; observed significant protective association of haplotype A-C-G-T-A (all SNPs, P = 0.00016) & particularly G-T-A (the last three SNP, P = 0.00007) within variants investigated (PMID:17192893)
• These preliminary results are compatible with the view that DTNBP1 is a susceptibility factor for schizophrenia, and is associated with worse psychopathology. (PMID:17290445)
• might exert gene-specific modulating effects on schizophrenia endophenotypes at the population level (PMID:17336946)
• study found no significant association between schizophrenia and DTNBP1 either through single locus or haplotype analyses (PMID:17407805)
• These results may provide further support for an association between the dysbindin gene (DTNBP1) and schizophrenia. (PMID:17408693)
• SNPs in the DTNBP1 genes were not significantly associated in any schizophrenia subtype. (PMID:17410640)
• our results suggest that DTNBP1 may contribute more to bipolar I disorder than bipolar II disorder or schizoaffective disorder. (PMID:17433541)
• There is evidence for an association of schizophrenia with SNPs at the 3’ end of DTNBP1 in the samples studied. (PMID:17476109)
• Our genetic evidence suggests that DTNBP1 is involved in psychotic liability not only for schizophrenia but also for other psychotic disorders, including substance-induced psychosis. (PMID:17555717)
• Only a weak association of one single nucleotide polymorphism in DTNBP1 with schizophrenia, which is not significant. (PMID:17604607)
• We investigated P1 performance, a component of early visual processing on which both patients and their relatives show deficits, in carriers and noncarriers of a known dysbindin risk haplotype. (PMID:17945199)
• Our results indicate that previously reported dysbindin-1 protein reductions may be due in part to decreased dysbindin-1 mRNA and that reduced dysbindin-1 may contribute to hippocampal formation synaptic pathology in schizophrenia. (PMID:17961984)
• Risk alleles in DTNBP1 compromise the ability of biogenesis of lysosome-related organelles complex 1 (BLOC-1) to traffic dopamine D2 receptor DRD2 toward degradation, but has little effect on DRD1 trafficking. (PMID:17989303)
• risk variation at the dysbindin gene may contribute to a more prototypical schizophrenia presentation with less severe excitement/manic symptoms and more negative symptoms. (PMID:18162312)
• Study found genome-wide significant evidence for linkage at the DTNBP1 locus on chromosome 6p22, in addition, evidence for linkage of DTNBP1 expression to chromosome 8p, a locus that exerts a trans-acting effect on DTNBP1 expression was observed. (PMID:18182443)
• RNA expression was lower in SZ than in controls before (-28%; p=0.02) and after (-30%; p=0.01) olanzapine stimulation. (PMID:18234478)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dtnbp1a	ENSDARG00000055115
danio_rerio	dtnbp1b	ENSDARG00000055206
mus_musculus	Dtnbp1	ENSMUSG00000057531
rattus_norvegicus	Dtnbp1	ENSRNOG00000048719
drosophila_melanogaster	Dysb	FBGN0036819
caenorhabditis_elegans	dsbn-1	WBGENE00013697

Paralogs (2): DBNDD1 (ENSG00000003249), DBNDD2 (ENSG00000244274)

Protein

Protein identifiers

Dysbindin — Q96EV8 (reviewed: Q96EV8)

Alternative names: Biogenesis of lysosome-related organelles complex 1 subunit 8, Dysbindin-1, Dystrobrevin-binding protein 1, Hermansky-Pudlak syndrome 7 protein

All UniProt accessions (10): A0A087WYP9, A0A0S2Z5U8, A6NFV8, D6RAR7, D6RAX1, D6RB80, D6RCT8, D6RID1, D6RJC6, Q96EV8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Associates with the BLOC-2 complex to facilitate the transport of TYRP1 independent of AP-3 function. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. Plays a role in the regulation of cell surface exposure of DRD2. May play a role in actin cytoskeleton reorganization and neurite outgrowth. May modulate MAPK8 phosphorylation. Appears to promote neuronal transmission and viability through regulating the expression of SNAP25 and SYN1, modulating PI3-kinase-Akt signaling and influencing glutamatergic release. Regulates the expression of SYN1 through binding to its promoter. Modulates prefrontal cortical activity via the dopamine/D2 pathway.

Subunit / interactions. Interacts (via its coiled coil domain) with KXD1. Interacts with CMYA5, PI4K2 and RNF151. Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) composed of at least BLOC1S1, BLOC1S2, BLOC1S3, BLOC1S4, BLOC1S5, BLOC1S6, DTNBP1/BLOC1S7 and SNAPIN/BLOC1S8. Interacts directly in the complex with BLOC1S5, BLOC1S6 and SNAPIN/BLOC1S8. The BLOC-1 complex associates with the AP-3 protein complex and membrane protein cargos. This BLOC-1 complex also associates with the BLOC-2 complex in endosomes. Binds to DTNA and DTNB but may not be a physiological binding partner. Interacts (isoform 1 and isoform 2 only) with the DNA-dependent protein kinase complex DNA-PK; the interaction phosphorylates DTNBP1 in vitro. Interacts directly in this complex with XRCC5 and XRCC6. Interacts with AP3M1, AP3B2 and TRIM32. Interacts with XPO1; the interaction exports DTNBP1 out of the nucleus.

Subcellular location. Cytoplasm. Cytoplasmic vesicle membrane. Endosome membrane. Melanosome membrane. Postsynaptic density. Endoplasmic reticulum. Nucleus Cytoplasm. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Postsynaptic cell membrane.

Tissue specificity. Detected in brain, in neurons and in neuropil. Isoform 1 is expressed in the cerebral cortex, and hippocampal frontal (HF). Specific expression in the posterior half of the superior temporal gyrus (pSTG). Higher expression of isoform 2 and 3 in the HF than in the pSTG while isoform 1 shows no difference in expression in these areas. In the HF, detected in dentate gyrus (DG) and in pyramidal cells of hippocampus CA2 and CA3 (at protein level). Expressed in all principal neuronal populations of the HF, namely pyramidal neurons in the subiculum and CA1-3, granule cells in the dense cell layer of the DG (DGg), and polymorph cells in the hilus of the DG (DGh). Maximal levels in CA2, CA3, and DGh. Isoform 2 not expressed in the cerebral cortex.

Post-translational modifications. Ubiquitinated by TRIM32. Ubiquitination leads to DTNBP1 degradation. Isoforms 1 and 2 highly phosphorylated by PRKDC in vitro. Isoform 3 only weakly phosphorylated by PRKDC in vitro.

Disease relevance. Hermansky-Pudlak syndrome 7 (HPS7) [MIM:614076] A form of Hermansky-Pudlak syndrome, a genetically heterogeneous autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. The disease is caused by variants affecting the gene represented in this entry. Defects in DTNBP1 are associated with susceptibility to schizophrenia, a mental disorder characterized by a breakdown of thought processes and by poor emotional responsiveness. Genetic mutations lead to alterations in the glutamatergic transmission in the brain and modified Akt signaling. Protein levels and expression are reduced in nerve terminals of the hippocampus and there is an increased release of glutamate in schizophrenic patients. Levels of isoform 1 are reduced in the pSTG, but not in HF, by about 48% in 92% of schizophrenic patients. In the HF, there is an average of 33% reduction in synaptic expression of isoform 2 in 67% of cases, and of isoform 3, an average reduction of 35% in 80% of cases. In the dorsolateral prefrontal cortex (DLPFC), significant reductions in levels of isoform 3 are observed about 71% of schizophrenic patients showed an average reduction of this isoform of about 60%.

Miscellaneous. Major isoform. May be due to intron retention.

Similarity. Belongs to the dysbindin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96EV8-1	1, Dysbindin 1-A	yes
Q96EV8-2	2
Q96EV8-3	3, Dysbindin 1-B

RefSeq proteins (5): NP_001258596, NP_001258597, NP_001258598, NP_115498, NP_898861 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007531	Dysbindin	Family

Pfam: PF04440

UniProt features (17 total): modified residue 4, region of interest 2, splice variant 2, sequence variant 2, mutagenesis site 2, chain 1, sequence conflict 1, coiled-coil region 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EV8-F1	75.92	0.44

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 11, 316, 321, 349

Mutagenesis-validated functional residues (2):

Position	Phenotype
215	reduced interaction with ap3m1.
243–256	abolishes cytoplasmic location. increased expression of syn1.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-432722	Golgi Associated Vesicle Biogenesis

MSigDB gene sets: 346 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_NEGATIVE_REGULATION_OF_DENDRITIC_SPINE_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_GLUTAMATE_SECRETION, GOBP_COGNITION, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_BEHAVIOR, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_VESICLE_LOCALIZATION, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC

GO Biological Process (23): kidney development (GO:0001822), positive regulation of neurotransmitter secretion (GO:0001956), positive regulation of receptor internalization (GO:0002092), blood coagulation (GO:0007596), memory (GO:0007613), anterograde axonal transport (GO:0008089), regulation of signal transduction (GO:0009966), positive regulation of gene expression (GO:0010628), regulation of dopamine secretion (GO:0014059), actin cytoskeleton organization (GO:0030036), neuron projection development (GO:0031175), melanosome organization (GO:0032438), anterograde synaptic vesicle transport (GO:0048490), neuron projection morphogenesis (GO:0048812), dendrite morphogenesis (GO:0048813), retina development in camera-type eye (GO:0060041), platelet dense granule organization (GO:0060155), regulation of dopamine receptor signaling pathway (GO:0060159), cilium assembly (GO:0060271), negative regulation of dendritic spine morphogenesis (GO:0061002), positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization (GO:0061646), protein transmembrane transport (GO:0071806), regulation of synaptic vesicle exocytosis (GO:2000300)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (31): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), postsynaptic density (GO:0014069), microtubule cytoskeleton (GO:0015630), sarcoplasm (GO:0016528), axon (GO:0030424), growth cone (GO:0030426), midbody (GO:0030496), synaptic vesicle membrane (GO:0030672), BLOC-1 complex (GO:0031083), melanosome membrane (GO:0033162), sarcolemma (GO:0042383), neuron projection (GO:0043005), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), postsynaptic membrane (GO:0045211), Schaffer collateral - CA1 synapse (GO:0098685), hippocampal mossy fiber to CA3 synapse (GO:0098686), glutamatergic synapse (GO:0098978), axon cytoplasm (GO:1904115), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), asymmetric synapse (GO:0032279), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
trans-Golgi Network Vesicle Budding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
postsynapse	2
animal organ development	1
renal system development	1
neurotransmitter secretion	1
regulation of neurotransmitter secretion	1
positive regulation of synaptic transmission	1
positive regulation of neurotransmitter transport	1
positive regulation of secretion by cell	1
regulation of receptor internalization	1
receptor internalization	1
positive regulation of receptor-mediated endocytosis	1
hemostasis	1
wound healing	1
coagulation	1
learning or memory	1
axonal transport	1
axon cytoplasm	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
dopamine secretion	1
regulation of catecholamine secretion	1
cytoskeleton organization	1
actin filament-based process	1
neuron development	1
plasma membrane bounded cell projection organization	1
pigment granule organization	1
anterograde axonal transport	1
synaptic vesicle transport along microtubule	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
dendrite development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1

Protein interactions and networks

STRING

984 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DTNBP1	SNAPIN	O95295	998
DTNBP1	BLOC1S3	Q6QNY0	998
DTNBP1	BLOC1S6	Q9UL45	997
DTNBP1	BLOC1S2	Q6QNY1	996
DTNBP1	BLOC1S1	P78537	993
DTNBP1	DISC1	Q9NRI5	953
DTNBP1	HPS5	Q9UPZ3	947
DTNBP1	HPS6	Q86YV9	941
DTNBP1	HPS3	Q969F9	926
DTNBP1	HPS4	Q9NQG7	903
DTNBP1	DTNB	O60941	874
DTNBP1	DAOA	P59103	866
DTNBP1	CMYA5	Q8N3K9	840
DTNBP1	COMT	P21964	820
DTNBP1	BLOC1S5	Q8TDH9	781

IntAct

168 interactions, top by confidence:

A	B	Type	Score
RAD51B	RAD51C	psi-mi:“MI:0914”(association)	0.940
SNAPIN	DTNBP1	psi-mi:“MI:0915”(physical association)	0.900
DTNBP1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.900
DTNBP1	SNAPIN	psi-mi:“MI:0914”(association)	0.900
DTNBP1	BLOC1S6	psi-mi:“MI:0915”(physical association)	0.860
BLOC1S6	DTNBP1	psi-mi:“MI:0915”(physical association)	0.860
BLOC1S2	SNAPIN	psi-mi:“MI:0914”(association)	0.830
BLOC1S2	SNAPIN	psi-mi:“MI:0915”(physical association)	0.830
BLOC1S1	SNAPIN	psi-mi:“MI:0915”(physical association)	0.810
OSBPL9	VAPB	psi-mi:“MI:0914”(association)	0.790
BLOC1S5	DTNBP1	psi-mi:“MI:0915”(physical association)	0.770
DTNBP1	TXLNB	psi-mi:“MI:0915”(physical association)	0.700
TXLNB	DTNBP1	psi-mi:“MI:0915”(physical association)	0.700
DTNBP1	BRK1	psi-mi:“MI:0915”(physical association)	0.670
BRK1	DTNBP1	psi-mi:“MI:0915”(physical association)	0.670
SNX7	SNX4	psi-mi:“MI:0914”(association)	0.670
DTNBP1	IFT20	psi-mi:“MI:0915”(physical association)	0.640
IFT20	DTNBP1	psi-mi:“MI:0915”(physical association)	0.640
BLOC1S6	SNAPIN	psi-mi:“MI:0914”(association)	0.640
COG7	ILVBL	psi-mi:“MI:0914”(association)	0.640
VMA8	DTNBP1	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (349): DTNBP1 (Two-hybrid), DTNBP1 (Two-hybrid), DTNBP1 (Two-hybrid), DTNBP1 (Two-hybrid), DTNBP1 (Two-hybrid), DTNBP1 (Two-hybrid), DTNBP1 (Two-hybrid), DTNBP1 (Two-hybrid), DTNBP1 (Two-hybrid), DTNBP1 (Two-hybrid), IFT20 (Two-hybrid), HAUS1 (Two-hybrid), TXLNB (Two-hybrid), CCDC153 (Two-hybrid), P4HA3 (Two-hybrid)

ESM2 similar proteins: A6QQV9, A8E4X8, A9ZLX4, D4AB98, O15259, O75901, O88480, O88869, P97817, Q13625, Q155Q3, Q1JPG0, Q28C41, Q2HJA5, Q3B7M3, Q4V8Y7, Q571B6, Q5M834, Q5U465, Q5XI03, Q5ZKM0, Q6NVC9, Q6PCG6, Q6TYB5, Q7TNY7, Q7ZWE6, Q80TI1, Q86XL3, Q86Z20, Q8BFU3, Q8BZI0, Q8CFW7, Q8CG79, Q8K342, Q8K3I4, Q8N9B5, Q8NAN2, Q8NFW9, Q8TED9, Q8TF30

Diamond homologs: A6H7B4, Q2HJA5, Q5M831, Q5M834, Q5ZKM0, Q6DJE5, Q7ZWE6, Q91WZ8, Q96EV8, Q9CZ00, Q9H9R9, Q9BQY9, Q9CRD4

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
DTNBP1	“form complex”	BLOC-1	binding
DTNBP1	“up-regulates activity”	WASF2	binding
DTNBP1	“up-regulates activity”	ABI1	binding
TRIM32	“down-regulates quantity”	DTNBP1	ubiquitination
VRK2	“down-regulates quantity by destabilization”	DTNBP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
trans-Golgi Network Vesicle Budding	6	22.4×	1e-04
Golgi Associated Vesicle Biogenesis	5	14.7×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
anterograde synaptic vesicle transport	7	75.4×	8e-10
melanosome organization	7	49.3×	1e-08
anterograde axonal transport	7	44.2×	2e-08
lysosome localization	6	34.4×	2e-06
neuron projection development	8	10.6×	7e-05
protein transport	10	4.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

376 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	7
Uncertain significance	145
Likely benign	148
Benign	35

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1421143	NM_032122.5(DTNBP1):c.164del (p.Tyr55fs)	Pathogenic
1433981	NM_032122.5(DTNBP1):c.93del (p.Lys31_Val32insTer)	Pathogenic
1448584	NC_000006.11:g.(?15487538)(15533626_?)del	Pathogenic
162098	NM_032122.5(DTNBP1):c.177G>A (p.Trp59Ter)	Pathogenic
2427022	NC_000006.11:g.(?15523206)(16146982_?)del	Pathogenic
2427023	NC_000006.11:g.(?15637955)(15638055_?)del	Pathogenic
2702268	NC_000006.12:g.15593076TCCT[1]	Pathogenic
3432	NM_032122.5(DTNBP1):c.307C>T (p.Gln103Ter)	Pathogenic
1480225	NM_032122.5(DTNBP1):c.161+2T>G	Likely pathogenic
1698876	NM_032122.5(DTNBP1):c.872T>G (p.Leu291Ter)	Likely pathogenic
1968264	NM_032122.5(DTNBP1):c.512-2A>C	Likely pathogenic
2634805	NM_032122.5(DTNBP1):c.1011_1014dup (p.Arg339Ter)	Likely pathogenic
3347607	NM_032122.5(DTNBP1):c.390del (p.Asn130fs)	Likely pathogenic
4081356	NM_032122.5(DTNBP1):c.502dup (p.Thr168fs)	Likely pathogenic
4773137	NM_032122.5(DTNBP1):c.668-2A>C	Likely pathogenic

SpliceAI

2449 predictions. Top by Δscore:

Variant	Effect	Δscore
6:15524666:GGCT:G	acceptor_gain	1.0000
6:15524668:CTCTG:C	acceptor_loss	1.0000
6:15524669:TCT:T	acceptor_loss	1.0000
6:15524669:TCTGC:T	acceptor_gain	1.0000
6:15524670:C:CC	acceptor_gain	1.0000
6:15524670:CTG:C	acceptor_loss	1.0000
6:15524676:A:AC	acceptor_gain	1.0000
6:15524676:A:C	acceptor_gain	1.0000
6:15524682:C:CT	acceptor_gain	1.0000
6:15524683:A:T	acceptor_gain	1.0000
6:15524685:C:CT	acceptor_gain	1.0000
6:15533279:A:AC	donor_gain	1.0000
6:15533280:C:CC	donor_gain	1.0000
6:15533280:CTG:C	donor_gain	1.0000
6:15533305:T:TA	donor_gain	1.0000
6:15533391:TTCAG:T	acceptor_gain	1.0000
6:15533392:TCAG:T	acceptor_gain	1.0000
6:15533393:CAG:C	acceptor_gain	1.0000
6:15533393:CAGC:C	acceptor_gain	1.0000
6:15533394:AG:A	acceptor_gain	1.0000
6:15533396:C:CC	acceptor_gain	1.0000
6:15584159:A:C	donor_gain	1.0000
6:15615262:CTCA:C	donor_loss	1.0000
6:15615263:TCA:T	donor_loss	1.0000
6:15615264:CA:C	donor_loss	1.0000
6:15615266:CCT:C	donor_gain	1.0000
6:15615400:C:CC	acceptor_gain	1.0000
6:15627339:TTA:T	donor_loss	1.0000
6:15627340:TA:T	donor_loss	1.0000
6:15627341:A:AC	donor_gain	1.0000

AlphaMissense

2309 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:15533298:G:C	F203L	0.997
6:15533298:G:T	F203L	0.997
6:15533300:A:G	F203L	0.997
6:15533323:C:G	R195P	0.997
6:15637791:A:G	W59R	0.997
6:15637791:A:T	W59R	0.997
6:15533303:C:G	A202P	0.996
6:15615360:A:G	L132P	0.996
6:15524572:G:C	F255L	0.995
6:15524572:G:T	F255L	0.995
6:15524574:A:G	F255L	0.995
6:15533299:A:G	F203S	0.995
6:15524573:A:G	F255S	0.994
6:15533279:A:C	Y210D	0.994
6:15615351:A:G	L135P	0.993
6:15627408:A:G	L97P	0.993
6:15637789:C:A	W59C	0.993
6:15637789:C:G	W59C	0.993
6:15524573:A:C	F255C	0.992
6:15662844:A:G	L9P	0.992
6:15524656:G:C	S227R	0.991
6:15524656:G:T	S227R	0.991
6:15524658:T:G	S227R	0.991
6:15533278:T:G	Y210S	0.991
6:15627396:A:G	L101P	0.991
6:15662854:G:T	R6S	0.991
6:15533299:A:C	F203C	0.990
6:15533310:A:C	F199L	0.990
6:15533310:A:T	F199L	0.990
6:15533312:A:G	F199L	0.990

dbSNP variants (sampled 300 via entrez): RS1000001165 (6:15655869 A>G), RS1000004771 (6:15617707 C>T), RS1000005106 (6:15606635 T>A,C), RS1000052868 (6:15543654 T>C), RS1000053384 (6:15559269 A>T), RS1000083934 (6:15559125 A>C), RS1000110208 (6:15613082 T>A,C), RS1000126136 (6:15646205 CCAA>C), RS1000144550 (6:15633800 AAAAC>A), RS1000166221 (6:15644953 C>A,T), RS1000189203 (6:15603285 A>G), RS1000224664 (6:15651987 C>A), RS1000272073 (6:15599436 G>A), RS1000283212 (6:15609424 A>G), RS1000292078 (6:15550534 T>C)

Disease associations

OMIM: gene MIM:607145 | disease phenotypes: MIM:614076, MIM:203300, MIM:178500

GenCC curated gene-disease

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 7	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Hermansky-Pudlak syndrome 7	Definitive	AR

Mondo (3): Hermansky-Pudlak syndrome 7 (MONDO:0013559), Hermansky-Pudlak syndrome (MONDO:0019312), interstitial lung disease 2 (MONDO:0800497)

Orphanet (4): Hermansky-Pudlak syndrome due to BLOC-1 deficiency (Orphanet:231531), Hermansky-Pudlak syndrome (Orphanet:79430), Idiopathic pulmonary fibrosis (Orphanet:2032), Acute interstitial pneumonia (Orphanet:79126)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000421	Epistaxis
HP:0000505	Visual impairment
HP:0000639	Nystagmus
HP:0000978	Bruising susceptibility
HP:0001022	Albinism
HP:0001107	Ocular albinism
HP:0001934	Persistent bleeding after trauma
HP:0003010	Prolonged bleeding time
HP:0003540	Impaired platelet aggregation
HP:0006298	Prolonged bleeding after dental extraction
HP:0007663	Reduced visual acuity
HP:0011463	Childhood onset
HP:0011891	Post-partum hemorrhage

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004483_1	Multiple myeloma	1.000000e-08
GCST007100_3	Asthma exacerbations in inhaled corticosteroid treatment	7.000000e-06
GCST007100_5	Asthma exacerbations in inhaled corticosteroid treatment	3.000000e-06
GCST007157_3	Corneal astigmatism	4.000000e-06
GCST007159_18	Corneal astigmatism	3.000000e-06
GCST008872_9	Squamous cell carcinoma	1.000000e-08
GCST012490_374	Femur bone mineral density x serum urate levels interaction	3.000000e-08
GCST90011900_140	Serum alkaline phosphatase levels	3.000000e-12
GCST90013406_170	Liver enzyme levels (alkaline phosphatase)	4.000000e-18

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007614	asthma exacerbation measurement
EFO:1002040	Corneal astigmatism
EFO:0004531	urate measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D022861	Hermanski-Pudlak Syndrome	C11.270.040.545.400; C15.378.100.100.515; C15.378.100.685.400; C15.378.140.735.400; C15.378.463.735.400; C16.320.099.515; C16.320.290.040.100.400; C16.320.565.100.102.100.400; C16.320.850.080.100.400; C17.800.621.440.102.100.400; C17.800.827.080.100.400; C18.452.648.100.102.100.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2619538	Toxicity	3	methamphetamine	Psychotic Disorder
rs3213207	Toxicity	3	methamphetamine	Psychotic Disorder
rs742105	Efficacy	3	clozapine	Schizophrenia
rs760761	Efficacy	3	citalopram	Major Depressive Disorder
rs909706	Efficacy	3	haloperidol	Schizophrenia

PharmGKB variants

9 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs742105	DTNBP1	3	2.50	1	clozapine
rs760761	DTNBP1	3	0.00	1	citalopram
rs909706	DTNBP1	3	0.00	1	haloperidol
rs1011313	DTNBP1		0.00	0
rs2005976	DTNBP1		0.00	0
rs2619522	DTNBP1		0.00	0
rs2619538	DTNBP1	3	0.00	1	methamphetamine
rs2619539	DTNBP1		0.00	0
rs3213207	DTNBP1	3	2.75	1	methamphetamine

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	4
trichostatin A	affects cotreatment, decreases expression	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
ethylene dichloride	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Clozapine	increases response to substance, affects response to substance	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Haloperidol	increases response to substance, affects response to substance	1
Methyl Methanesulfonate	increases expression	1
Rotenone	decreases expression	1
Cyclosporine	increases expression	1
Asbestos, Serpentine	increases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1MD	HyCyte PANC-1 KO-hDTNBP1	Cancer cell line	Male
CVCL_F1NG	HyCyte BxPC-3 KO-hDTNBP1	Cancer cell line	Female

Clinical trials (associated diseases)

8 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04193592	PHASE2	UNKNOWN	Efficacy and Safety of Pirfenidone Treatment in HPS-ILD
NCT00467831	PHASE1/PHASE2	TERMINATED	Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
NCT00001456	Not specified	RECRUITING	Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome
NCT00084305	Not specified	ACTIVE_NOT_RECRUITING	Analysis of Specimens From Individuals With Pulmonary Fibrosis
NCT01417520	Not specified	COMPLETED	Clinical and Pathophysiological Investigations Into Erdheim Chester Disease
NCT02368340	Not specified	COMPLETED	A Longitudinal Study of Hermansky-Pudlak Syndrome Pulmonary Fibrosis
NCT06372353	Not specified	COMPLETED	The Effect Of Baduanjin Exercises In Patients With Idiopathic Pulmonary Fibrosis
NCT06644144	Not specified	RECRUITING	P4O2 ILD Extension