LRRC7

Chr 1

leucine rich repeat containing 7

Also known as: DENSIN, MRD77

NCBI Gene: 57554 ENSG00000033122 UniProt: 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.

ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable protein kinase binding activity. Predicted to be involved in several processes, including establishment or maintenance of epithelial cell apical/basal polarity; positive regulation of neuron projection development; and protein localization to membrane. Located in several cellular components, including centrosome; cytosol; and nucleoplasm. Implicated in cocaine dependence. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.16

Clinical Summary— LRRC7

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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

11 unique Pathogenic / Likely Pathogenic· 187 VUS of 223 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.08 (0.04–0.16)

0≤0.351.4

Missense OE?0.65 (0.60–0.69)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 6 / 75.2Missense obs/exp: 533 / 824.2Syn Z: -0.14

This gene — mechanism propensity

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 · 18% of P/LP variants are LoF · 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

223 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10

Likely Pathogenic1

VUS187

Likely Benign17

Benign5

Conflicting1

Pathogenic

Likely Pathogenic

187

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	2	6	0	10
Likely Pathogenic	0	1	0	0	1
VUS	11	128	46	2	187
Likely Benign	0	5	0	12	17
Benign	0	1	0	4	5
Conflicting	—				1
Total	13	137	52	18	221

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap LRRC7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →