PABIR1

Chr 9

PP2A Aalpha (PPP2R1A) and B55A (PPP2R2A) interacting phosphatase regulator 1

Also known as: C9orf42, FAM122A

The protein acts as an inhibitor of serine/threonine-protein phosphatase 2A (PP2A), blocking substrate binding and promoting proteasomal degradation of PP2A components to regulate the G2/M cell cycle checkpoint. Mutations in this gene cause autosomal recessive neurodevelopmental disorder with developmental delay, seizures, and brain abnormalities. The disorder affects the central nervous system with early childhood onset of symptoms including intellectual disability and epilepsy.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.79
Clinical SummaryPABIR1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.17) despite low pLI — interpret in context.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 31 VUS of 71 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.494
Z-score 1.89
OE 0.17 (0.060.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.47Z-score
OE missense 0.68 (0.580.79)
109 obs / 161.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.060.79)
00.351.4
Missense OE0.68 (0.580.79)
00.61.4
Synonymous OE1.14
01.21.6
LoF obs/exp: 1 / 6.0Missense obs/exp: 109 / 161.4Syn Z: -0.93
DN
0.5575th %ile
GOF
0.4184th %ile
LOF
0.75top 10%

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

LOFprediction above median

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

ClinVar Variant Classifications

71 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic8
VUS31
Benign1
31
Pathogenic
8
Likely Pathogenic
31
VUS
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
8
0
8
VUS
0
26
5
0
31
Likely Benign
0
0
0
0
0
Benign
0
0
1
0
1
Total02645071

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

View in ClinVar →

Protein Context — Lollipop Plot

PABIR1 · 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 →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found