ZNF48

Chr 16

zinc finger protein 48

This protein functions as a transcriptional regulator that binds to identical proteins and is predicted to regulate RNA polymerase II transcription in the nucleus. ZNF48 mutations cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and developmental regression. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.69), suggesting some intolerance to complete protein loss.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.69
Clinical SummaryZNF48
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.007
Z-score 2.56
OE 0.37 (0.210.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.27Z-score
OE missense 0.82 (0.750.90)
333 obs / 405.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.210.69)
00.351.4
Missense OE0.82 (0.750.90)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 7 / 19.1Missense obs/exp: 333 / 405.2Syn Z: 0.72
DN
0.6552th %ile
GOF
0.6736th %ile
LOF
0.4431th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ZNF48 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found