BLOC1S5

Chr 6AR

biogenesis of lysosomal organelles complex 1 subunit 5

Also known as: BLOS5, HPS11, MU, MUTED

NCBI Gene: 63915ENSG00000188428UniProt: Q8TDH9

This gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenesis of organelles such as melanosomes and platelet-dense granules. A mouse model for Hermansky-Pudlak Syndrome is mutated in the murine version of this gene. Alternative splicing results in multiple transcript variants. Read-through transcription exists between this gene and the upstream EEF1E1 (eukaryotic translation elongation factor 1 epsilon 1) gene, as well as with the downstream TXNDC5 (thioredoxin domain containing 5) gene. [provided by RefSeq, Dec 2010]

Primary Disease Associations & Inheritance

Hermansky-Pudlak syndrome 11MIM #619172
AR
85
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BLOC1S5
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Gene-Disease Validity (ClinGen)
Hermansky-Pudlak syndrome 11 · 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.
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ClinVar Variants
37 Pathogenic / Likely Pathogenic· 39 VUS of 85 total submissions

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.
1.81LOEUF
pLI 0.000
Z-score -0.57
OE 1.19 (0.76–1.81)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.25Z-score
OE missense 1.07 (0.92–1.25)
109 obs / 101.9 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.1.19 (0.76–1.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.07 (0.92–1.25)
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.1.06
0≤1.21.6
LoF obs/exp: 12 / 10.1Missense obs/exp: 109 / 101.9Syn Z: -0.27

ClinVar Variant Classifications

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic6
VUS39
Likely Benign8
Benign1
31
Pathogenic
6
Likely Pathogenic
39
VUS
8
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
29
0
31
Likely Pathogenic
2
0
4
0
6
VUS
0
38
1
0
39
Likely Benign
0
6
0
2
8
Benign
0
0
1
0
1
Total34535285

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

View in ClinVar →

Protein Context — Lollipop Plot

BLOC1S5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hermansky-Pudlak syndrome 11

MIM #619172

Molecular basis of disorder known

Autosomal recessive
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GeneReview available — BLOC1S5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Novel Likely Pathogenic Variant in the BLOC1S5 Gene Associated with Hermansky-Pudlak Syndrome Type 11 and an Overview of Human BLOC-1 Deficiencies.
Boeckelmann D et al.·Cells
2021Review
A novel BLOC1S5-related HPS-11 patient and zebrafish with bloc1s5 disruption.
Zhong Z et al.·Pigment Cell Melanoma Res
2021Functional
BLOC1S5 pathogenic variants cause a new type of Hermansky-Pudlak syndrome.
Pennamen P et al.·Genet Med
2020
Diagnostic and prognostic biomarkers associated with histotype in advanced epithelial ovarian cancer.
Ittner E et al.·Sci Rep
2025
Expanding the phenotype associated with interstitial 6p25.1p24.3 microdeletion: a new case and review of the literature.
Tassano E et al.·J Genet
2021Review
The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma.
Chang C et al.·Nat Commun
2022
Novel variants in the BLOC1S3 gene in patients presenting a mild form of Hermansky-Pudlak syndrome.
Pennamen P et al.·Pigment Cell Melanoma Res
2021Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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