LRIG2

protein-coding

leucine rich repeats and immunoglobulin like domains 2, the group of I-set domain containing

Gene summary

This gene encodes a transmembrane protein containing leucine-rich repeats and immunoglobulin-like domains. The encoded protein promotes epidermal growth factor signalling, resulting in increased proliferation. Its expression in the cytoplasm of glioma cells is correlated with poor survival. Mutations in this gene can cause urofacial syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

MANE transcript

NM_014813.3

Inheritance

ClinVar variants

P:14U:163B:38

Top phenotype

Urofacial syndrome 2

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr1:113,073,198-113,132,260

External References & Databases

Ensembl (ENSG00000198799)

Transcript & Mutation Effects

hg38 • Region Span ~59.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

urofacial syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014049

Submitter: PanelApp Australia

urofacial syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014049

Submitter: Labcorp Genetics (formerly Invitae)

urofacial syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014049

Submitter: G2P

urofacial syndrome 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014049

Submitter: Ambry Genetics

Ochoa syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0000463

Submitter: Orphanet

Clinical Genomic Database (CGD)

Urofacial syndrome 2AR

Manifestation: Craniofacial; Renal

Intervention: Renal

Rationale: Individuals have been described with manifestations including low-capacity, overactive bladder, vesicoureteral reflux, hydronephrosis, urosepsis, and renal impairment, though treatment attempts (eg, with intermittent catheterization, antimuscarinic agents, and surgical bladder augmentation) were not reported as slowing slow renal failure, and dialysis was required in at least one individual; Early recognition may allow management aimed at preserving renal function

Comments: Wilms tumor has been reported in one individual

Refs: 23313374

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRIG2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 165

not providedTotal: 38

LRIG2-related disorderTotal: 22

Urofacial syndrome 2Total: 12

Global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014813.3. 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	17 clinvar	2 clinvar	21
missense		1 clinvar	152 clinvar	15 clinvar	4 clinvar	172
nonsense	1 clinvar	2 clinvar	3 clinvar			6
start loss			1 clinvar			1
frameshift	3 clinvar	3 clinvar	4 clinvar			10
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar	1 clinvar			5
Total	5	9	163	32	6	215

Highest pathogenic variant AF is 0.000011205345

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014813.3	RefSeq	NP_055628.1	18	MANE Select
ENST00000361127.6	Ensembl	ENSP00000355396.4	18	MANE Select
NM_001312686.2	RefSeq	NP_001299615.1	16	Standard
ENST00000890455.1	Ensembl	ENSP00000560514.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

sensory perception of sound
regulation of platelet-derived growth factor receptor signaling pathway
negative regulation of axon regeneration
negative regulation of membrane protein ectodomain proteolysis
innervation

Molecular Function

signaling receptor binding

Cellular Component

extracellular space
cytoplasm
plasma membrane
integral component of membrane
growth cone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361127
Coding exons: 18
Length: 59052
Individuals with no LoFs: 125617
Homozygous LoFs: 1
Heterozygous LoFs: 130
Defined: 125748
p: 0.000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.482	542	575	0.943	0.0000292	7001
Missense (PolyPhen)		98	122.51	0.79993		1563
Synonymous	-0.0610	215	214	1.01	0.0000108	2057
Loss of Function	2.10	35	51.2	0.683	0.00000279	598

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00041	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00087	0.00087	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00070	0.00069	rare
South Asian	0.00046	0.00042	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0859

Intolerance Scores

LoFtool: 0.938
RVIS EVS: -0.35
RVIS percentile EVS: 29.59

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.168

Gene Damage Prediction

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