PLAGL1

Chr 6

PLAG1 like zinc finger 1

Also known as: LOT1, ZAC, ZAC1

This gene encodes a zinc finger transcriptional activator that suppresses cell growth and is subject to paternal imprinting. Mutations cause transient neonatal diabetes mellitus, which typically presents in the first weeks of life and often resolves by 18 months of age. The gene is highly constrained against loss-of-function variants, and the condition follows an imprinted inheritance pattern with preferential expression from the paternal allele.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.26
Clinical SummaryPLAGL1
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.
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ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 56 VUS of 104 total submissions
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GeneReview available — PLAGL1
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.976
Z-score 3.14
OE 0.00 (0.000.26)
Highly constrained

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

Missense Constraint
1.30Z-score
OE missense 0.77 (0.690.87)
198 obs / 256.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.26)
00.351.4
Missense OE0.77 (0.690.87)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 0 / 11.5Missense obs/exp: 198 / 256.5Syn Z: 0.19
DN
0.4983th %ile
GOF
0.4677th %ile
LOF
0.74top 10%

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

LOFprediction above median · LOEUF 0.26

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

104 submitted variants in ClinVar

Classification Summary

Pathogenic18
VUS56
Likely Benign11
Benign11
18
Pathogenic
56
VUS
11
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
0
0
0
VUS
0
55
1
0
56
Likely Benign
0
5
0
6
11
Benign
0
4
1
6
11
Total064201296

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

View in ClinVar →

Protein Context — Lollipop Plot

PLAGL1 · 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.

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Clinical Literature
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