ZNF213

Chr 16

zinc finger protein 213

Also known as: CR53, ZKSCAN21, ZSCAN53

NCBI Gene: 7760 ENSG00000085644 OMIM: 608387

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.

OMIM ResearchSummary from RefSeq, UniProt

C2H2 zinc finger proteins, such as ZNF213, have bipartite structures in which one domain binds DNA or RNA and the other modulates target gene expression.[supplied by OMIM, Apr 2004]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.05

Clinical Summary— ZNF213

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

66 VUS of 89 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.37

OE 0.67 (0.45–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.01Z-score

OE missense 0.84 (0.76–0.93)

266 obs / 316.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.67 (0.45–1.05)

0≤0.351.4

Missense OE?0.84 (0.76–0.93)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 14 / 20.7Missense obs/exp: 266 / 316.7Syn Z: -0.43

This gene — mechanism propensity

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

89 submitted variants in ClinVar

ClinVar

Classification Summary

VUS66

Likely Benign10

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	66	0	66
Likely Benign	9	1	10
Benign	0	0	0
Total	75	1	76

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

View in ClinVar →

4 pathogenic / likely-pathogenic (of 11) ClinVar copy-number / structural variants overlap ZNF213 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →