LRRC7

protein-coding

leucine rich repeat containing 7, the group of PDZ domain containing

Gene summary

Predicted to enable protein kinase binding activity. Predicted to be involved in several processes, including establishment or maintenance of epithelial cell apical/basal polarity; neurotransmitter receptor transport, endosome to postsynaptic membrane; and receptor clustering. Located in cytosol. Implicated in cocaine dependence. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001370785.2

Inheritance

ClinVar variants

P:10U:162B:31

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr1:69,567,922-70,151,945

External References & Databases

Ensembl (ENSG00000033122)

Transcript & Mutation Effects

hg38 • Region Span ~584.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRRC7 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 81

Intellectual developmental disorder, autosomal dominant 77Total: 9

LRRC7-associated obesity and neurodevelopmental disorderTotal: 2

LRRC7-associated neurodevelopmental disorderTotal: 1

Paediatric disordersTotal: 1

LRRC7-associated disorderTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001370785.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	16 clinvar	4 clinvar	22
missense	2 clinvar	1 clinvar	149 clinvar	9 clinvar	1 clinvar	162
nonsense	2 clinvar		1 clinvar			3
start loss						0
frameshift	4 clinvar		7 clinvar			11
splice donor/acceptor (+/-2bp)	1 clinvar		3 clinvar	1 clinvar		5
Total	9	1	162	26	5	203

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001370785.2	RefSeq	NP_001357714.1	27	MANE Select
ENST00000651989.2	Ensembl	ENSP00000498937.2	27	MANE Select
NM_001330635.3	RefSeq	NP_001317564.1	25	Standard
NM_001350216.3	RefSeq	NP_001337145.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

MAPK cascade
positive regulation of neuron projection development
receptor clustering
neutrophil degranulation
establishment or maintenance of epithelial cell apical/basal polarity

Molecular Function

Ras guanyl-nucleotide exchange factor activity
protein binding
ionotropic glutamate receptor binding

Cellular Component

extracellular region
cytosol
cell-cell junction
cell-cell adherens junction
ionotropic glutamate receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000035383
Coding exons: 25
Length: 583548
Individuals with no LoFs: 125644
Homozygous LoFs: 0
Heterozygous LoFs: 57
Defined: 125701
p: 0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.60	533	824	0.647	0.0000434	10118
Missense (PolyPhen)		209	400.01	0.52249		5182
Synonymous	-0.140	310	307	1.01	0.0000167	2923
Loss of Function	7.39	6	75.2	0.0798	0.00000384	910

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.00039	0.00039	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for normal synaptic spine architecture and function. Necessary for DISC1 and GRM5 localization to postsynaptic density complexes and for both N-methyl D-aspartate receptor-dependent and metabotropic glutamate receptor-dependent long term depression. {ECO:0000269|PubMed:11729199}.;

Recessive Scores

pRec: 0.128

Intolerance Scores

LoFtool: 0.209
RVIS EVS: -1.37
RVIS percentile EVS: 4.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.872

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium