LRRFIP1

protein-coding

LRR binding FLII interacting protein 1

Gene summary

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and protein homodimerization activity. Involved in negative regulation of transcription by RNA polymerase II. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001137550.2

Inheritance

—

ClinVar variants

U:66B:2

Top phenotype

Myoepithelial tumor

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr2:237,627,587-237,813,682

External References & Databases

Ensembl (ENSG00000124831)

Transcript & Mutation Effects

hg38 • Region Span ~186.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRRFIP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 137

not providedTotal: 7

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001137550.2. 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	1 clinvar	1 clinvar	4
missense			57 clinvar			57
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	66	1	1	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 357 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001137550.2	RefSeq	NP_001131022.1	24	MANE Select
ENST00000308482.14	Ensembl	ENSP00000310109.9	24	MANE Select
NM_001137551.2	RefSeq	NP_001131023.1	12	Standard
NM_001137552.2	RefSeq	NP_001131024.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Disease
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production
Innate Immune System
Immune System
Signaling by FGFR in disease

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of transcription by RNA polymerase II
positive regulation of type I interferon production
negative regulation of transcription, DNA-templated
positive regulation of NF-kappaB transcription factor activity

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription repressor activity, RNA polymerase II-specific
DNA binding
double-stranded RNA binding

Cellular Component

nucleus
cytoplasm
cytosol
cytoskeleton
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392000
Coding exons: 11
Length: 186107
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125747
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.348	465	444	1.05	0.0000240	5355
Missense (PolyPhen)		133	137.92	0.96432		1639
Synonymous	0.0408	170	171	0.996	0.0000104	1468
Loss of Function	2.55	6	17.5	0.342	7.40e-7	234

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00012	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor which preferentially binds to the GC-rich consensus sequence (5'-AGCCCCCGGCG-3') and may regulate expression of TNF, EGFR and PDGFA. May control smooth muscle cells proliferation following artery injury through PDGFA repression. May also bind double-stranded RNA. 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:10364563, ECO:0000269|PubMed:14522076, ECO:0000269|PubMed:16199883, ECO:0000269|PubMed:19265123, ECO:0000269|PubMed:9705290}.;

Recessive Scores

pRec: 0.0898

Intolerance Scores

LoFtool: 0.827
RVIS EVS: 0.61
RVIS percentile EVS: 82.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.947

Gene Damage Prediction

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