DTNBP1

dystrobrevin binding protein 1, the group of Biogenesis of lysosomal organelles complex 1 subunits

Basic information

Region (hg38): 6:15522806-15663058

Links

ENSG00000047579 ∙ NCBI:84062 ∙ OMIM:607145 ∙ HGNC:17328 ∙ Uniprot:Q96EV8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Hermansky-Pudlak syndrome 7 (Strong), mode of inheritance: AR
• Hermansky-Pudlak syndrome 7 (Definitive), mode of inheritance: AR
• Hermansky-Pudlak syndrome 7 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hermansky-Pudlak syndrome 7	AR	Allergy/Immunology/Infectious; Dermatologic; Hematologic; Ophthalmologic	Prevention and treatment of bleeding episodes (eg, with DDAVP or platelet/RBC transfusions) can be effective, and aspirin-containing products should be avoided; Skin surveillance and protection can be beneficial; Surveillance related to ophthalmologic and other manifestations has been recommended in all individuals with HPS	Allergy/Immunology/Infectious; Dermatologic; Gastrointestinal; Hematologic; Ophthalmologic	12923531; 20301464; 23364359

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DTNBP1 gene.

• not provided (223 variants)
• not specified (24 variants)
• Inborn genetic diseases (19 variants)
• Hermansky-Pudlak syndrome 7 (9 variants)
• Hermansky-Pudlak syndrome (7 variants)
• DTNBP1-related condition (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DTNBP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				36	3	39
missense			91	4	3	98
nonsense	1	3	1			5
start loss						0
frameshift	4	1	4			9
inframe indel			4			4
splice donor/acceptor (+/-2bp)		2			1	3
splice region			6	10	3	19
non coding			3	36	23	62
Total	5	6	103	76	30

Highest pathogenic variant AF is 0.0000131

Variants in DTNBP1

This is a list of pathogenic ClinVar variants found in the DTNBP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-15522822-C-CTT		Hermansky-Pudlak syndrome	Uncertain significance (Jun 14, 2016)
6-15522870-T-C			Benign (Jul 09, 2018)
6-15522921-C-T			Likely benign (Jul 05, 2018)
6-15522982-T-C			Uncertain significance (Jul 05, 2022)
6-15522983-C-T			Uncertain significance (Oct 24, 2022)
6-15522987-G-A			Likely benign (Nov 29, 2022)
6-15522997-C-T			Uncertain significance (Dec 26, 2022)
6-15523002-C-T			Likely benign (Nov 06, 2023)
6-15523003-G-A			Uncertain significance (Sep 19, 2022)
6-15523007-T-A			Uncertain significance (Jul 31, 2022)
6-15523010-CCT-C		not specified • Hermansky-Pudlak syndrome 7	Uncertain significance (Jan 15, 2024)
6-15523010-CCTCT-C		Hermansky-Pudlak syndrome 7 • Hermansky-Pudlak syndrome	Conflicting classifications of pathogenicity (Mar 14, 2022)
6-15523011-C-G		Inborn genetic diseases	Uncertain significance (Dec 23, 2022)
6-15523011-CT-GC			Uncertain significance (Oct 17, 2022)
6-15523012-T-C		Inborn genetic diseases	Uncertain significance (Dec 23, 2022)
6-15523016-T-TGTCA		DTNBP1-related disorder	Likely pathogenic (May 10, 2023)
6-15523022-T-C			Uncertain significance (Jul 26, 2022)
6-15523025-G-A			Uncertain significance (Dec 30, 2023)
6-15523033-G-GC			Uncertain significance (Sep 26, 2021)
6-15523040-C-T			Uncertain significance (Aug 20, 2021)
6-15523056-TTCC-T			Uncertain significance (Jul 26, 2022)
6-15523056-T-TTCC			Uncertain significance (Jun 28, 2022)
6-15523064-C-T			Uncertain significance (Jun 15, 2021)
6-15523065-A-C		Inborn genetic diseases	Uncertain significance (Dec 11, 2023)
6-15523067-C-T		Inborn genetic diseases	Uncertain significance (Dec 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DTNBP1	protein_coding	protein_coding	ENST00000344537	10	140258

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000684	0.908	125659	1	88	125748	0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.244	197	188	1.05	0.0000102	2299
Missense in Polyphen		64	63.305	1.011		814
Synonymous	-1.75	95	75.6	1.26	0.00000457	639
Loss of Function	1.62	11	18.5	0.594	8.77e-7	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00133	0.00132
Ashkenazi Jewish	0.00	0.00
East Asian	0.000233	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000176	0.000176
Middle Eastern	0.000233	0.000217
South Asian	0.00101	0.000588
Other	0.00147	0.00130

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:15345706, ECO:0000269|PubMed:16837549, ECO:0000269|PubMed:17182842, ECO:0000269|PubMed:17989303, ECO:0000269|PubMed:19094965, ECO:0000269|PubMed:20180862, ECO:0000269|PubMed:20921223}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:12923531}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=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 (PubMed:15345706). Protein levels and expression are reduced in nerve terminals of the hippocampus and there is an increased release of glutamate in schizophrenic patients (PubMed:15124027). 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% (PubMed:19617633). {ECO:0000269|PubMed:15124027, ECO:0000269|PubMed:15345706, ECO:0000269|PubMed:19617633}.
• Pathway: Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking (Consensus)

Recessive Scores

• pRec: 0.289

Intolerance Scores

• loftool: 0.933
• rvis_EVS: 0.67
• rvis_percentile_EVS: 84.61

Haploinsufficiency Scores

• pHI: 0.110
• hipred: N
• hipred_score: 0.290
• ghis: 0.432

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dtnbp1
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; pigmentation phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; immune system phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: dtnbp1a
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: positive regulation of neurotransmitter secretion;blood coagulation;anterograde axonal transport;positive regulation of gene expression;regulation of dopamine secretion;neuron projection development;actin cytoskeleton reorganization;negative regulation of protein binding;melanosome organization;regulation of JUN kinase activity;anterograde synaptic vesicle transport;neuron projection morphogenesis;dendrite morphogenesis;platelet dense granule organization;regulation of dopamine receptor signaling pathway;negative regulation of protein serine/threonine kinase activity;regulation of synaptic vesicle exocytosis
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum membrane;cytosol;endosome membrane;postsynaptic density;microtubule cytoskeleton;sarcoplasm;cell junction;axon;growth cone;midbody;synaptic vesicle membrane;BLOC-1 complex;melanosome membrane;sarcolemma;neuron projection;dendritic spine;postsynaptic membrane;Schaffer collateral - CA1 synapse;hippocampal mossy fiber to CA3 synapse;glutamatergic synapse;axon cytoplasm
• Molecular function: protein binding