PABIR1

Chr 9

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

Also known as: C9orf42, FAM122A

NCBI Gene: 116224ENSG00000187866UniProt: Q96E09

Enables protein phosphatase 2A binding activity and protein serine/threonine phosphatase inhibitor activity. Involved in mitotic G2/M transition checkpoint; positive regulation of cell growth; and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Jul 2025]

71
ClinVar variants
39
Pathogenic / LP
0.49
pLI score
0
Active trials
Clinical Summary— PABIR1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.17) despite low pLI — interpret in context.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 31 VUS of 71 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.79LOEUF
pLI 0.494
Z-score 1.89
OE 0.17 (0.06–0.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.47Z-score
OE missense 0.68 (0.58–0.79)
109 obs / 161.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.06–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.58–0.79)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 1 / 6.0Missense obs/exp: 109 / 161.4Syn Z: -0.93

ClinVar Variant Classifications

71 submitted variants in ClinVar

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress.
Li F et al.·Mol Cell
2020
Cryo-EM structures of PP2A:B55-FAM122A and PP2A:B55-ARPP19.
Padi SKR et al.·Nature
2024
FAM122A ensures cell cycle interphase progression and checkpoint control by inhibiting B55α/PP2A through helical motifs.
Wasserman JS et al.·Nat Commun
2024
FAM122A Inhibits Erythroid Differentiation through GATA1.
Chen J et al.·Stem Cell Reports
2020
FAM122A maintains DNA stability possibly through the regulation of topoisomerase IIα expression.
Wang YQ et al.·Exp Cell Res
2020
FAM122A is required for hematopoietic stem cell function.
Liu MH et al.·Leukemia
2021
FAM122A, a new endogenous inhibitor of protein phosphatase 2A.
Fan L et al.·Oncotarget
2016
FAM122A supports the growth of hepatocellular carcinoma cells and its deletion enhances Doxorubicin-induced cytotoxicity.
Zhou Y et al.·Exp Cell Res
2020
FAM122A promotes acute myeloid leukemia cell growth through inhibiting PP2A activity and sustaining MYC expression.
Liu MH et al.·Haematologica
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools