ZNF335

Chr 20AR

zinc finger protein 335

Also known as: MCPH10, NIF-1, NIF1, NIF2

NCBI Gene: 63925ENSG00000198026UniProt: Q9H4Z2OMIM: 610827

The protein is a component of histone methyltransferase complexes that enhances ligand-dependent transcriptional activation by nuclear hormone receptors and plays an important role in neural progenitor cell proliferation and self-renewal through regulation of genes involved in brain development. Mutations cause microcephaly 10, primary, autosomal recessive, which presents with congenital microcephaly. The gene is highly constrained against loss-of-function variation (LOEUF 0.501), reflecting its critical role in neurodevelopment.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.501 OMIM phenotype
Clinical Summary— ZNF335
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.000
Z-score 4.83
OE 0.35 (0.25–0.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.55Z-score
OE missense 0.95 (0.89–1.00)
795 obs / 839.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.25–0.50)
0≤0.351.4
Missense OE0.95 (0.89–1.00)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 23 / 65.0Missense obs/exp: 795 / 839.8Syn Z: -0.63

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

ZNF335 · 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

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Compound heterozygous ZNF335 variants in a patient with microcephaly, refractory epilepsy, and severe developmental delay: A case report and literature review.
Yamoto K et al.·Congenit Anom (Kyoto)
2025Review
Participant-derived cell line transcriptomic analyses and mouse studies reveal a role for ZNF335 in plasma cholesterol statin response.
Theusch E et al.·Genome Med
2024Open AccessFunctional
Novel biallelic ZNF335 variant causing primary microcephaly: A case report and radiological review.
Patel DD et al.·Am J Med Genet A
2024Review
Possible effect of OAS1 and TMPRSS6 but not DPP4 and ZNF335 polymorphisms on COVID-19 severity in the Czech population.
Hubáček JA et al.·Cent Eur J Public Health
2023
Primary and Secondary Microcephaly, Global Developmental Delay, and Seizure in Two Siblings Caused by a Novel Missense Variant in the ZNF335 Gene.
Tavasoli AR et al.·J Mol Neurosci
2022
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients