FABP2

Chr 4

fatty acid binding protein 2

Also known as: FABPI, I-FABP

The protein encoded by FABP2 is an intracellular fatty acid-binding protein that transports long-chain fatty acids and their acyl-CoA esters within cells, participates in triglyceride-rich lipoprotein synthesis, and functions as a lipid sensor for energy homeostasis. This gene is not well-established as a cause of pediatric neurogenetic disease, as it shows tolerance to loss-of-function variants (pLI = 0.005, LOEUF = 1.5) and primarily functions in intestinal fatty acid metabolism rather than neurological pathways.

Summary from RefSeq, UniProt
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4
Active trials
42
Pubs (1 yr)
22
P/LP submissions
0%
P/LP missense
1.50
LOEUF
DN
Mechanism· predicted
Clinical SummaryFABP2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 21 VUS of 73 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.50LOEUF
pLI 0.005
Z-score 0.73
OE 0.68 (0.331.50)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.71Z-score
OE missense 0.76 (0.610.95)
52 obs / 68.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.331.50)
00.351.4
Missense OE0.76 (0.610.95)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 4 / 5.9Missense obs/exp: 52 / 68.6Syn Z: 0.13
DN
0.75top 25%
GOF
0.5367th %ile
LOF
0.2580th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

73 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS21
Likely Benign5
Benign24
20
Pathogenic
2
Likely Pathogenic
21
VUS
5
Likely Benign
24
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
2
0
2
VUS
0
17
4
0
21
Likely Benign
0
2
2
1
5
Benign
0
1
21
2
24
Total02049372

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

View in ClinVar →

Protein Context — Lollipop Plot

FABP2 · protein map & ClinVar variants

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

Clinical Literature
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