PPFIBP1

Chr 12AR

PPFIB scaffold protein 1

Also known as: L2, NEDSMBA, SGT2, hSGT2, hSgt2p

The protein encoded by PPFIBP1 is a member of the liprin family that acts as a scaffold for recruiting and anchoring LAR family tyrosine phosphatases and may regulate focal adhesion disassembly. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.751), suggesting some tolerance to functional disruption.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 0.751 OMIM phenotype
Clinical SummaryPPFIBP1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.75LOEUF
pLI 0.000
Z-score 3.15
OE 0.57 (0.430.75)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.75Z-score
OE missense 0.91 (0.840.98)
482 obs / 530.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.430.75)
00.351.4
Missense OE0.91 (0.840.98)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 35 / 61.8Missense obs/exp: 482 / 530.3Syn Z: 0.92
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongPPFIBP1-related neurodevelopmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7229th %ile
GOF
0.6053th %ile
LOF
0.4234th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PPFIBP1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →