LRRC58

Chr 3

leucine rich repeat containing 58

NCBI Gene: 116064 ENSG00000163428 UniProt: Q96CX6

The LRRC58 protein is predicted to be involved in intracellular signal transduction. Mutations cause autosomal recessive disorders, though specific clinical phenotypes associated with this gene are not well-established in the current literature. The gene shows relatively low constraint against loss-of-function variants based on population genetics data.

ResearchSummary from RefSeq

Enables ubiquitin-like ligase-substrate adaptor activity. Involved in proteasome-mediated ubiquitin-dependent protein catabolic process and regulation of taurine biosynthetic process. Part of Cul5-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.004

Z-score 1.82

OE 0.46 (0.25–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.50Z-score

OE missense 0.68 (0.59–0.79)

119 obs / 174.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.25–0.90)

0≤0.351.4

Missense OE?0.68 (0.59–0.79)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 6 / 13.1Missense obs/exp: 119 / 174.6Syn Z: 1.23

Background carrier burden — how many people carry a rare variant somewhere in LRRC58?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

454 rare PASS variants

Rare truncating (LoF)

1 in 5,000

46 rare PASS variants

Rare synonymous (reference)

1 in 210

240 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LRRC58. 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 270	1 in 7,100
South Asian	~43k	1 in 120	1 in 2,900
Remaining (unassigned)	~30k	1 in 200	1 in 4,300
European (Finnish)	~27k	1 in 1,000	1 in 3,000
Admixed American	~22k	1 in 290	≈ 1 in 11,000
African / African American	~21k	1 in 140	1 in 2,200
East Asian	~20k	1 in 180	≈ 1 in 16,000
Ashkenazi Jewish	~13k	1 in 400	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	none seen

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 4.? see exons ↓