BORCS5

Chr 12

BLOC-1 related complex subunit 5

Also known as: LOH12CR1, LOH1CR12, NDOABA2

NCBI Gene: 118426 ENSG00000165714 UniProt: Q969J3 OMIM: 616598

The BORCS5 protein is part of the BORC complex that regulates lysosome movement and localization by recruiting motor proteins to transport lysosomes along microtubules to the cell periphery. Mutations in BORCS5 cause autosomal recessive neurodegeneration with brain iron accumulation, typically presenting in childhood with progressive movement disorders and cognitive decline. The gene shows relatively low constraint to loss-of-function variation (pLI 0.001, LOEUF 1.13).

OMIM ResearchSummary from RefSeq, UniProt

Involved in lysosome localization and organelle transport along microtubule. Located in cytoplasmic side of lysosomal membrane and plus-end kinesin complex. Part of BORC complex. Implicated in colorectal adenocarcinoma. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodegeneration, infantile-onset, with optic atrophy and structural brain abnormalities 2MIM #621704

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neurodegeneration, infantile-onset, with optic atrophy and structural brain abnormalities 2; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.13

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.001

Z-score 1.29

OE 0.57 (0.31–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.26Z-score

OE missense 0.93 (0.80–1.09)

113 obs / 121.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.31–1.13)

0≤0.351.4

Missense OE?0.93 (0.80–1.09)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 6 / 10.5Missense obs/exp: 113 / 121.0Syn Z: -1.16

Background carrier burden — how many people carry a rare variant somewhere in BORCS5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

260 rare PASS variants

Rare truncating (LoF)

1 in 4,700

37 rare PASS variants

Rare synonymous (reference)

1 in 470

120 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BORCS5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 340	1 in 7,100
South Asian	~43k	1 in 150	1 in 1,000
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 14,000
European (Finnish)	~27k	1 in 810	≈ 1 in 13,000
Admixed American	~22k	1 in 260	≈ 1 in 22,000
African / African American	~21k	1 in 200	1 in 2,500
East Asian	~20k	1 in 190	≈ 1 in 6,600
Ashkenazi Jewish	~13k	1 in 470	none seen
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓