LRRC46

Chr 17

leucine rich repeat containing 46

NCBI Gene: 90506UniProt: Q96FV0

Predicted to be involved in sperm flagellum assembly. Predicted to act upstream of or within maintenance of cell number; single fertilization; and sperm flagellum assembly. Predicted to be active in sperm midpiece. [provided by Alliance of Genome Resources, Apr 2025]

0
Active trials
54
ClinVar variants
8
Pathogenic / LP
0.9
Missense Z
0.92
LOEUF
5
Pubs (2 yr)
Clinical Summary— LRRC46
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 41 VUS of 54 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

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.
0.92LOEUF
pLI 0.001
Z-score 1.79
OE 0.49 (0.28–0.92)
Tolerant

Typical tolerance to LoF variation

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.
0.85Z-score
OE missense 0.82 (0.72–0.94)
148 obs / 180.3 exp
Tolerant

Mild missense constraint

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.0.49 (0.28–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.72–0.94)
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.0.85
0≤1.21.6
LoF obs/exp: 7 / 14.3Missense obs/exp: 148 / 180.3Syn Z: 1.03

ClinVar Variant Classifications

54 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS41
Likely Benign5
7
Pathogenic
1
Likely Pathogenic
41
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
38
3
0
41
Likely Benign
0
5
0
0
5
Benign
0
0
0
0
0
Total04311054

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

View in ClinVar →

Protein Context — Lollipop Plot

LRRC46 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
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 ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
CCDC181 is required for sperm flagellum biogenesis and male fertility in mice
Zhang XJ et al.·Zool Res
2024
Whole Transcriptome Sequencing and Differential Analysis of Testes in Pre- and Post-Sexual Maturity Bactrian Camels (Camelus bactrianus).
Chang X et al.·Biology (Basel)
2025
Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population
Kim BH et al.·Front Aging Neurosci
2023
Identification of immunogenic HLA-A*02:01 epitopes associated with HCC for immunotherapy development
Maino A et al.·Hepatol Commun
2025
An intrauterine genomic classifier reliably delineates the location of nonviable pregnancies.
Lentscher JA et al.·Fertil Steril
2021
Genetic Regulation of Cytokine Response in Patients with Acute Community-Acquired Pneumonia
Kühnapfel A et al.·Genes (Basel)
2022Cohort
Function of manchette and intra-manchette transport in spermatogenesis and male fertility
Gao T et al.·Cell Commun Signal
2025
CDKN2A-mediated molecular subtypes characterize the hallmarks of tumor microenvironment and guide precision medicine in triple-negative breast cancer
Cheng T et al.·Front Immunol
2022
Top 8 full-text resultsSearch PubTator3 ↗

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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients