ZNF142

Chr 2AR

zinc finger protein 142

Also known as: HA4654, NEDISHM, pHZ-49

NCBI Gene: 7701ENSG00000115568UniProt: P52746

The protein encoded by this gene belongs to the Kruppel family of C2H2-type zinc finger proteins. It contains 31 C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with impaired speech and hyperkinetic movementsMIM #618425
AR
518
ClinVar variants
71
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ZNF142
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
71 Pathogenic / Likely Pathogenic· 342 VUS of 518 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.79LOEUF
pLI 0.000
Z-score 2.84
OE 0.59 (0.45–0.79)
Tolerant

Typical tolerance to LoF variation

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.
0.24Z-score
OE missense 0.98 (0.93–1.03)
962 obs / 983.3 exp
Tolerant

Mild missense constraint

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.0.59 (0.45–0.79)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.93–1.03)
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.0.97
0≤1.21.6
LoF obs/exp: 34 / 57.2Missense obs/exp: 962 / 983.3Syn Z: 0.51

ClinVar Variant Classifications

518 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic24
VUS342
Likely Benign77
Benign22
Conflicting6
47
Pathogenic
24
Likely Pathogenic
342
VUS
77
Likely Benign
22
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
34
0
47
Likely Pathogenic
12
3
9
0
24
VUS
1
335
6
0
342
Likely Benign
0
38
1
38
77
Benign
0
7
8
7
22
Conflicting
—6
Total263835845518

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF142 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ZNF142-related neurodevelopmental disorder

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with impaired speech and hyperkinetic movements

MIM #618425

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
ZNF142 mutation causes neurodevelopmental disorder with speech impairment and seizures: Novel variants and literature review.
Kamal N et al.·Eur J Med Genet
2022Review
A deleterious frameshift insertion mutation in the ZNF142 gene leads to intellectual developmental disorder with impaired speech in three affected siblings: Clinical features and literature review.
Mir A et al.·Mol Genet Genomic Med
2023Review
Biallelic loss-of-function variants in ZNF142 are associated with a robust DNA methylation signature affecting a limited number of genomic loci.
Hildonen M et al.·Eur J Hum Genet
2025
Recent genetic advances in early-onset dystonia.
Steel D et al.·Curr Opin Neurol
2020Review
Vitamin D-binding protein deficiency: an underrecognized Mendelian disorder of vitamin D metabolism.
Al Masseri Z et al.·Hum Genet
2024Case report
A case report of a patient with neurodevelopmental disorder with impaired speech and hyperkinetic movements: A biallelic variant in the ZNF142 gene.
Kaya D et al.·Am J Med Genet A
2024Case report
Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder.
Christensen MB et al.·Clin Genet
2022
[Clinical features and molecular pathogenesis of neurodevelopmental disorder with impaired speech and hyperkinetic movements associated with ZNF142 gene variants].
Xu Y et al.·Zhonghua Er Ke Za Zhi
2025Case report
ZNF142 mutation causes sex-dependent neurologic disorder.
Proskorovski-Ohayon R et al.·J Med Genet
2024
Routine Diagnostics Confirm Novel Neurodevelopmental Disorders.
Jauss RT et al.·Genes (Basel)
2022
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