ZNF248

Chr 10

zinc finger protein 248

Also known as: bA162G10.3

The protein functions as a DNA-binding transcription factor that regulates RNA polymerase II-mediated gene transcription in the nucleus. Mutations in this gene cause autosomal recessive intellectual disability with seizures and brain malformations, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.485), suggesting some intolerance to complete protein loss.

Summary from RefSeq, UniProt
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0
Active trials
1
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.48
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryZNF248
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.326
Z-score 3.32
OE 0.23 (0.120.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.48Z-score
OE missense 0.92 (0.831.02)
268 obs / 291.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.120.48)
00.351.4
Missense OE0.92 (0.831.02)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 5 / 21.7Missense obs/exp: 268 / 291.2Syn Z: 0.68
DN
0.78top 25%
GOF
0.75top 25%
LOF
0.3746th %ile

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

DNprediction above median
GOFprediction 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

ZNF248 · 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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