ZNF213

Chr 16

zinc finger protein 213

Also known as: CR53, ZKSCAN21, ZSCAN53

ZNF213 encodes a C2H2 zinc finger protein that binds DNA or RNA and modulates target gene expression as a transcriptional regulator. Mutations cause autosomal dominant developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, epilepsy, and developmental delays. The gene shows minimal constraint against loss-of-function variants, with clinical manifestations primarily affecting the central nervous system.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.05
Clinical SummaryZNF213
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 86 VUS of 147 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.05LOEUF
pLI 0.000
Z-score 1.37
OE 0.67 (0.451.05)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.01Z-score
OE missense 0.84 (0.760.93)
266 obs / 316.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.451.05)
00.351.4
Missense OE0.84 (0.760.93)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 14 / 20.7Missense obs/exp: 266 / 316.7Syn Z: -0.43
DN
0.7327th %ile
GOF
0.75top 25%
LOF
0.2872th %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

147 submitted variants in ClinVar

Classification Summary

Pathogenic35
VUS86
Likely Benign11
Benign2
35
Pathogenic
86
VUS
11
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
0
0
0
VUS
0
72
14
0
86
Likely Benign
0
9
1
1
11
Benign
0
0
0
2
2
Total081503134

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF213 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC