ZNF335

Chr 20AR

zinc finger protein 335

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

NCBI Gene: 63925ENSG00000198026UniProt: Q9H4Z2

The protein encoded by this gene enhances transcriptional activation by ligand-bound nuclear hormone receptors. However, it does this not by direct interaction with the receptor, but by direct interaction with the nuclear hormone receptor transcriptional coactivator NRC. The encoded protein may function by altering local chromatin structure. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Microcephaly 10, primary, autosomal recessiveMIM #615095
AR
0
Active trials
31
Pathogenic / LP
544
ClinVar variants
4
Pubs (1 yr)
0.5
Missense Z
0.50
LOEUF
Clinical Summary— ZNF335
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 245 VUS of 544 total submissions

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

544 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic13
VUS245
Likely Benign201
Benign39
Conflicting28
18
Pathogenic
13
Likely Pathogenic
245
VUS
201
Likely Benign
39
Benign
28
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
4
11
0
18
Likely Pathogenic
9
1
3
0
13
VUS
1
230
11
3
245
Likely Benign
0
19
68
114
201
Benign
0
4
24
11
39
Conflicting
—28
Total13258117128544

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

View in ClinVar →

ZNF335 · protein map & ClinVar variants

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

Gene2Phenotype Curations

ZNF335-related microcephaly, epilepsy, cerebral and/or cerebellar atrophy and short stature

strong
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantsplice donor variantmissense variantinframe deletionintron variant

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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