LRRFIP2

protein-coding

LRR binding FLII interacting protein 2

Gene summary

The protein encoded by this gene, along with MYD88, binds to the cytosolic tail of toll-like receptor 4 (TLR4), which results in activation of nuclear factor kappa B signaling. The ubiquitin-like protein FAT10 prevents the interaction of the encoded protein and TLR4, thereby inactivating the nuclear factor kappa B signaling pathway. In addition, this protein can downregulate the NLRP3 inflammasome by recruiting the caspase-1 inhibitor Flightless-I to the inflammasome complex. [provided by RefSeq, Jan 2017]

MANE transcript

NM_006309.4

Inheritance

—

ClinVar variants

U:98B:5

Top phenotype

Hereditary cancer-predisposing syndrome

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr3:37,052,626-37,183,689

External References & Databases

Ensembl (ENSG00000093167)

Transcript & Mutation Effects

hg38 • Region Span ~131.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRRFIP2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 88

not providedTotal: 3

Hereditary cancer-predisposing syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006309.4. 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	1 clinvar		3
missense			88 clinvar	2 clinvar	2 clinvar	92
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	98	3	2	103

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 708 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006309.4	RefSeq	NP_006300.1	27	MANE Select
ENST00000336686.9	Ensembl	ENSP00000338727.4	27	MANE Select
NM_001134369.2	RefSeq	NP_001127841.1	13	Standard
NM_001282691.1	RefSeq	NP_001269620.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
biological_process
Wnt signaling pathway

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
protein binding
LRR domain binding

Cellular Component

cellular_component

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000421307
Coding exons: 27
Length: 131064
Individuals with no LoFs: 125607
Homozygous LoFs: 0
Heterozygous LoFs: 141
Defined: 125748
p: 0.000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.713	348	387	0.898	0.0000206	4681
Missense (PolyPhen)		95	124.71	0.76176		1594
Synonymous	0.958	117	131	0.893	0.00000625	1304
Loss of Function	1.66	46	59.8	0.769	0.00000376	643

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.0010	notable
Latino/Admixed American	0.00078	0.00078	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00044	0.00044	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00056	0.00055	rare
South Asian	0.00069	0.00069	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as activator of the canonical Wnt signaling pathway, in association with DVL3, upstream of CTNNB1/beta- catenin. Positively regulates Toll-like receptor (TLR) signaling in response to agonist probably by competing with the negative FLII regulator for MYD88-binding. {ECO:0000269|PubMed:15677333, ECO:0000269|PubMed:19265123}.;

Recessive Scores

pRec: 0.0964

Intolerance Scores

LoFtool: 0.924
RVIS EVS: -0.06
RVIS percentile EVS: 48.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.810

Gene Damage Prediction

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