FNIP2

Chr 4

folliculin interacting protein 2

Also known as: FNIPL, MAPO1

The protein functions as a binding partner of folliculin (FLCN) that regulates cellular responses to amino acid availability through mTORC1 signaling and acts as a co-chaperone for HSP90, inhibiting its ATPase activity to activate client proteins. Mutations cause neurodevelopmental disorders with intellectual disability and epilepsy, typically with early childhood onset. This gene is highly constrained against loss-of-function variants (pLI ~1.0, LOEUF 0.13) and follows autosomal recessive inheritance.

Summary from RefSeq, UniProt
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0
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.13
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryFNIP2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 6.18
OE 0.04 (0.020.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.28Z-score
OE missense 0.85 (0.790.92)
517 obs / 605.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.04 (0.020.13)
00.351.4
Missense OE0.85 (0.790.92)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 2 / 48.5Missense obs/exp: 517 / 605.6Syn Z: 0.65
DN
0.3097th %ile
GOF
0.4974th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.13

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FNIP2 · 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.

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Clinical Literature
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