LRRC7

Chr 1AD

leucine rich repeat containing 7

Also known as: DENSIN, MRD77

NCBI Gene: 57554ENSG00000033122UniProt: Q96NW7

The LRRC7 protein is required for normal synaptic spine architecture and function, and is necessary for proper localization of DISC1 and GRM5 to postsynaptic density complexes and for both NMDA receptor-dependent and metabotropic glutamate receptor-dependent long term depression. Mutations cause autosomal dominant intellectual developmental disorder. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.157), indicating intolerance to protein-disrupting mutations.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 77MIM #621415
AD
0
Active trials
2
Pubs (1 yr)
28
P/LP submissions
11%
P/LP missense
0.16
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— LRRC7
⚡
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
28 unique Pathogenic / Likely Pathogenic· 188 VUS of 241 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 7.39
OE 0.08 (0.04–0.16)
Highly constrained

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

Missense Constraint
3.60Z-score
OE missense 0.65 (0.60–0.69)
533 obs / 824.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.08 (0.04–0.16)
0≤0.351.4
Missense OE0.65 (0.60–0.69)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 6 / 75.2Missense obs/exp: 533 / 824.2Syn Z: -0.14
DN
0.4587th %ile
GOF
0.5465th %ile
LOF
0.73top 10%

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

LOFprediction above median · LOEUF 0.16

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

241 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic1
VUS188
Likely Benign18
Benign4
27
Pathogenic
1
Likely Pathogenic
188
VUS
18
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
24
0
27
Likely Pathogenic
0
1
0
0
1
VUS
9
126
51
2
188
Likely Benign
0
5
2
11
18
Benign
0
1
0
3
4
Total101357716238

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

View in ClinVar →

Protein Context — Lollipop Plot

LRRC7 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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