PLAGL2

Chr 20

PLAG1 like zinc finger 2

Also known as: ZNF900

The protein is a zinc-finger transcription factor that binds DNA and RNA with weak transcriptional activatory activity. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and speech impairment, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.24), indicating that haploinsufficiency is likely not tolerated in the general population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
19
Pubs (1 yr)
15
P/LP submissions
0%
P/LP missense
0.24
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryPLAGL2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
15 unique Pathogenic / Likely Pathogenic· 62 VUS of 83 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 0.983
Z-score 3.25
OE 0.00 (0.000.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.11Z-score
OE missense 0.66 (0.590.74)
198 obs / 300.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.24)
00.351.4
Missense OE0.66 (0.590.74)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 0 / 12.3Missense obs/exp: 198 / 300.7Syn Z: -0.28
DN
0.4091th %ile
GOF
0.3590th %ile
LOF
0.80top 5%

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

LOFprediction above median · LOEUF 0.24

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

83 submitted variants in ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic4
VUS62
Likely Benign1
11
Pathogenic
4
Likely Pathogenic
62
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
11
0
11
Likely Pathogenic
0
0
4
0
4
VUS
0
57
5
0
62
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total05820078

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

View in ClinVar →

Protein Context — Lollipop Plot

PLAGL2 · 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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