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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ZNF597
zinc finger protein 597
Chromosome 16 · 16p13.3
NCBI Gene: 146434Ensembl: ENSG00000167981.7HGNC: HGNC:26573UniProt: Q96LX8
19PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsequence-specific double-stranded DNA bindingDNA-binding transcription activator activity, RNA polymerase II-specificnucleusFamilial ocular anterior segment mesenchymal dysgenesisPeters anomalyPersistent pupillary membraneX-linked intellectual disability-retinitis pigmentosa syndrome
✦AI Summary

ZNF597 is a zinc finger protein that functions as a transcriptional regulator and represents a human-specific maternally expressed imprinted gene located on chromosome 16.3 1. The gene exhibits parent-of-origin expression regulated by the ZNF597:TSS-DMR, where only the paternal allele acquires methylation during the postimplantation period 1. ZNF597 contains seven C2H2 zinc-finger motifs and shows tissue-specific expression patterns, with enrichment in brain tissue 2. The gene appears critical for early embryonic development, as homozygous knockout in mice results in embryonic lethality before cardiogenesis at embryonic day 7.5, while heterozygous mice show brain degeneration in the striatum and cingulate cortex 2. Loss of imprinting leads to ZNF597 overexpression, which has been associated with Silver-Russell syndrome-like phenotypes and hemimegalencephaly through potential modulation of mTOR signaling 13. Recent genome-wide association studies have identified ZNF597 as a novel locus potentially associated with Alzheimer's disease 4. The gene's imprinted status and expression regulation by DNA methylation appear conserved across mammalian species, including cattle 5.

Sources cited
1
ZNF597 is a human-specific maternally expressed imprinted gene regulated by ZNF597:TSS-DMR methylation
PMID: 32576657
2
ZNF597 contains seven C2H2 zinc-finger motifs and knockout studies show embryonic lethality and brain degeneration
PMID: 19968752
3
ZNF597 overexpression in somatic uniparental disomy is associated with hemimegalencephaly and mTOR signaling
PMID: 28864461
4
ZNF597 identified as a novel genetic locus associated with Alzheimer's disease
PMID: 40691194
5
ZNF597 imprinting status and DNA methylation regulation is conserved in cattle
PMID: 31874365
Disease Associationsⓘ20
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.06Suggestive
Peters anomalyOpen Targets
0.06Suggestive
Persistent pupillary membraneOpen Targets
0.06Suggestive
X-linked intellectual disability-retinitis pigmentosa syndromeOpen Targets
0.05Suggestive
iridocorneal endothelial syndromeOpen Targets
0.05Suggestive
Axenfeld anomalyOpen Targets
0.05Suggestive
Rieger anomalyOpen Targets
0.05Suggestive
spinocerebellar ataxia type 17Open Targets
0.04Suggestive
familial progressive retinal dystrophy-iris coloboma-congenital cataract syndromeOpen Targets
0.04Suggestive
posterior amorphous corneal dystrophyOpen Targets
0.04Suggestive
microphthalmia, isolated, with coloboma 7Open Targets
0.04Suggestive
spastic ataxia 10, autosomal recessiveOpen Targets
0.04Suggestive
microphthalmia, isolated, with colobomaOpen Targets
0.04Suggestive
deafnessOpen Targets
0.04Suggestive
hearing loss, autosomal recessiveOpen Targets
0.04Suggestive
Huntington diseaseOpen Targets
0.04Suggestive
CLN8 diseaseOpen Targets
0.04Suggestive
neuronal ceroid lipofuscinosis 8Open Targets
0.04Suggestive
Dravet syndromeOpen Targets
0.04Suggestive
cataract - microcornea syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NSMCE1Protein interaction100%SMC5Protein interaction84%NSMCE4AProtein interaction84%NSMCE3Protein interaction84%SMC6Protein interaction84%NSMCE2Protein interaction84%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
77%
Heart
59%
Ovary
56%
Lung
55%
Liver
45%
Gene Interaction Network
Click a node to explore
ZNF597NSMCE1SMC5NSMCE4ANSMCE3SMC6NSMCE2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96LX8
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.53LoF Tolerant
pLIⓘ
0.05Tolerant
Observed/Expected LoF0.69 [0.34–1.53]
RankingsWhere ZNF597 stands among ~20K protein-coding genes
  • #14,612of 20,598
    Most Researched19
  • #15,340of 17,882
    Most Constrained (LOEUF)1.53
Genes detectedZNF597
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Machine learning in Alzheimer's disease genetics.
PMID: 40691194
Nat Commun · 2025
1.00
2
Loss of imprinting of the human-specific imprinted gene
PMID: 32576657
J Med Genet · 2021
0.90
3
Clinical and Molecular Presentation of a Patient with Paternal Uniparental Isodisomy of Chromosome 16.
PMID: 40943441
Int J Mol Sci · 2025
0.80
4
Molecular characterization and gene disruption of a novel zinc-finger protein, HIT-4, expressed in rodent brain.
PMID: 19968752
J Neurochem · 2010
0.70
5
Environmental temperature and human epigenetic modifications: A systematic review.
PMID: 31884209
Environ Pollut · 2020
0.60