LRRC41

Chr 1

leucine rich repeat containing 41

Also known as: MUF1, PP7759

NCBI Gene: 10489 ENSG00000132128 UniProt: Q15345 OMIM: 618753

The protein functions as a substrate recognition component of an E3 ubiquitin ligase complex that targets proteins for degradation via the ubiquitin-proteasome system. Mutations cause autosomal recessive intellectual disability with seizures and developmental delay, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable identical protein binding activity. Predicted to be involved in protein ubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.18

Clinical Summary— LRRC41

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 228 VUS of 336 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.18LOEUF

pLI 1.000

Z-score 5.09

OE 0.06 (0.02–0.18)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.08Z-score

OE missense 0.61 (0.55–0.67)

300 obs / 492.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.02–0.18)

0≤0.351.4

Missense OE?0.61 (0.55–0.67)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 2 / 34.1Missense obs/exp: 300 / 492.4Syn Z: 0.87

This gene — mechanism propensity

0.2199th %ile

GOF

0.2995th %ile

LOF

0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.18

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

336 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS228

Likely Benign80

Benign2

Conflicting1

Likely Pathogenic

228

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	2	0	0	2
VUS	2	226	0	0	228
Likely Benign	0	17	1	62	80
Benign	0	0	1	1	2
Conflicting	—				1
Total	2	245	2	63	313

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

View in ClinVar →

6 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap LRRC41 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →