BLOC1S2

protein-coding

biogenesis of lysosomal organelles complex 1 subunit 2, the group of BLOC-1 related complex subunits|Biogenesis of lysosomal organelles complex 1 subunits

Gene summary

This gene encodes a protein with multiple functions. The encoded protein has been found in association with the centrosome, shown to co-localize with gamma-tubulin, and also found to be one of the proteins in the BLOC-1 complex which functions in the formation of lysosome-related organelles. A pseudogene of this gene is located on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

MANE transcript

NM_173809.5

Inheritance

—

ClinVar variants

U:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr10:100,273,280-100,286,680

External References & Databases

Ensembl (ENSG00000196072)

Transcript & Mutation Effects

hg38 • Region Span ~13.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BLOC1S2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173809.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			10 clinvar			10
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	15	0	0	15

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173809.5	RefSeq	NP_776170.2	5	MANE Select
ENST00000370372.7	Ensembl	ENSP00000359398.2	5	MANE Select
NM_001001342.2	RefSeq	NP_001001342.1	4	Standard
NM_001282436.2	RefSeq	NP_001269365.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
bloc1s2	Danio rerio	Structure: erythroid lineage cell Quality: decreased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

bloc1s2

Danio rerio

Structure: erythroid lineage cell

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

anterograde axonal transport
extrinsic apoptotic signaling pathway via death domain receptors
endosomal transport
neuron projection development
lysosome localization

Molecular Function

protein binding
gamma-tubulin binding

Cellular Component

gamma-tubulin complex
mitochondrion
lysosomal membrane
BLOC-1 complex
BORC complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370372
Coding exons: 5
Length: 12757
Individuals with no LoFs: 125690
Homozygous LoFs: 0
Heterozygous LoFs: 49
Defined: 125739
p: 0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.00	50	74.3	0.673	0.00000330	920
Missense (PolyPhen)		3	19.947	0.1504		291
Synonymous	-1.40	38	28.5	1.33	0.00000127	257
Loss of Function	1.25	4	7.75	0.516	3.29e-7	104

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00069	0.00069	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00034	0.00034	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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 (PubMed:15102850, PubMed:17182842). 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 (By similarity). As part of the BORC complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, the BORC complex may recruit ARL8B and couple lysosomes to microtubule plus-end- directed kinesin motor (PubMed:25898167). May play a role in cell proliferation (PubMed:15381421). {ECO:0000250|UniProtKB:Q9CWG9, ECO:0000269|PubMed:15102850, ECO:0000269|PubMed:15381421, ECO:0000269|PubMed:17182842, ECO:0000269|PubMed:25898167}.;

Recessive Scores

pRec: 0.147

Intolerance Scores

LoFtool: 0.357
RVIS EVS: 0.15
RVIS percentile EVS: 64.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.435

Gene Damage Prediction

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