LRRFIP1

Chr 2

LRR binding FLII interacting protein 1

Also known as: FLAP-1, FLAP1, FLIIAP1, GCF-2, GCF2, HUFI-1, TRIP

The LRRFIP1 protein functions as a transcriptional repressor that binds to GC-rich DNA sequences and regulates expression of genes including TNF, EGFR, and PDGFA, while also positively regulating Toll-like receptor signaling pathways. Mutations in LRRFIP1 cause autosomal recessive neurodevelopmental disorder with seizures and brain atrophy, typically presenting in early childhood. The gene shows tolerance to loss-of-function variants (pLI 0.02, LOEUF 0.68), consistent with the recessive inheritance pattern observed clinically.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
10
Pubs (1 yr)
80
P/LP submissions
0%
P/LP missense
0.68
LOEUF
Mechanism
Clinical SummaryLRRFIP1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
78 unique Pathogenic / Likely Pathogenic· 143 VUS of 267 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.020
Z-score 2.55
OE 0.34 (0.190.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.35Z-score
OE missense 1.05 (0.971.13)
465 obs / 444.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.34 (0.190.68)
00.351.4
Missense OE1.05 (0.971.13)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 6 / 17.5Missense obs/exp: 465 / 444.4Syn Z: 0.04

ClinVar Variant Classifications

267 submitted variants in ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic1
VUS143
Likely Benign8
Benign1
77
Pathogenic
1
Likely Pathogenic
143
VUS
8
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
77
0
77
Likely Pathogenic
0
0
1
0
1
VUS
0
131
12
0
143
Likely Benign
0
4
0
4
8
Benign
0
0
0
1
1
Total0135905230

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

View in ClinVar →

Protein Context — Lollipop Plot

LRRFIP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →