LRRC4

Chr 7

leucine rich repeat containing 4

Also known as: NAG14, NGL-2

NCBI Gene: 64101ENSG00000128594UniProt: Q9HBW1

Predicted to be involved in modulation of chemical synaptic transmission and synapse organization. Predicted to act upstream of or within synapse organization. Predicted to be located in dendritic spine; excitatory synapse; and postsynaptic membrane. Predicted to be active in Schaffer collateral - CA1 synapse; glutamatergic synapse; and postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2025]

111
ClinVar variants
24
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— LRRC4
⚡
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.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 80 VUS of 111 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.17LOEUF
pLI 0.998
Z-score 3.93
OE 0.00 (0.00–0.17)
Highly constrained

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

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.
1.96Z-score
OE missense 0.72 (0.66–0.80)
287 obs / 396.8 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.0.00 (0.00–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.66–0.80)
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.1.20
0≤1.21.6
LoF obs/exp: 0 / 18.0Missense obs/exp: 287 / 396.8Syn Z: -2.09

ClinVar Variant Classifications

111 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
VUS80
Likely Benign3
Benign4
24
Pathogenic
80
VUS
3
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
0
0
0
VUS
1
73
6
0
80
Likely Benign
0
2
1
0
3
Benign
0
0
0
4
4
Total175314111

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

View in ClinVar →

Protein Context — Lollipop Plot

LRRC4 · 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
LRRC4 functions as a neuron-protective role in experimental autoimmune encephalomyelitis.
Zhang Y et al.·Mol Med
2021
Expression and clinical significance of LRRC4 in benign and malignant nasopharyngeal diseases.
Zhou XJ et al.·Genet Mol Res
2015
LRRC4 inhibits human glioblastoma cells proliferation, invasion, and proMMP-2 activation by reducing SDF-1 alpha/CXCR4-mediated ERK1/2 and Akt signaling pathways.
Wu M et al.·J Cell Biochem
2008
LRRC4 inhibits the proliferation of human glioma cells by modulating the expression of STMN1 and microtubule polymerization.
Wang R et al.·J Cell Biochem
2011
Methylated DNA in Pancreatic Juice Distinguishes Patients With Pancreatic Cancer From Controls.
Majumder S et al.·Clin Gastroenterol Hepatol
2020Cohort
Methylated DNA Markers for Sporadic Colorectal and Endometrial Cancer Are Strongly Associated with Lynch Syndrome Cancers.
Bramblet RM et al.·Cancer Prev Res (Phila)
2023
Gene-Expression Profiles in Generalized Aggressive Periodontitis: A Gene Network-Based Microarray Analysis.
Guzeldemir-Akcakanat E et al.·J Periodontol
2016
Identification of circRNA-lncRNA-miRNA-mRNA Competitive Endogenous RNA Network as Novel Prognostic Markers for Acute Myeloid Leukemia.
Cheng Y et al.·Genes (Basel)
2020
Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism.
Du Y et al.·Genet Med
2020Functional
Homozygous frameshift variant in NTNG2, encoding a synaptic cell adhesion molecule, in individuals with developmental delay, hypotonia, and autistic features.
Abu-Libdeh B et al.·Neurogenetics
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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