ZNF668

Chr 16AR

zinc finger protein 668

Also known as: NEDGEF

NCBI Gene: 79759ENSG00000167394UniProt: Q96K58

Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and zinc ion binding activity. Involved in DNA repair. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with poor growth, large ears, and dysmorphic faciesMIM #620194
AR
121
ClinVar variants
18
Pathogenic / LP
0.22
pLI score
0
Active trials
Clinical Summary— ZNF668
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
18 Pathogenic / Likely Pathogenic· 92 VUS of 121 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.52LOEUF
pLI 0.221
Z-score 3.14
OE 0.25 (0.13–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.35Z-score
OE missense 0.69 (0.63–0.76)
326 obs / 469.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.25 (0.13–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.63–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.94
0≤1.21.6
LoF obs/exp: 5 / 20.2Missense obs/exp: 326 / 469.4Syn Z: 0.63

ClinVar Variant Classifications

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic4
VUS92
Likely Benign7
Benign4
14
Pathogenic
4
Likely Pathogenic
92
VUS
7
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
1
0
3
0
4
VUS
1
83
8
0
92
Likely Benign
0
3
1
3
7
Benign
0
1
0
3
4
Total287266121

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF668 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies

MIM #620194

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools