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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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ZNF408
zinc finger protein 408
Chromosome 11 Β· 11p11.2
NCBI Gene: 79797Ensembl: ENSG00000175213.4HGNC: HGNC:20041UniProt: B4DXY4
37PubMed Papers
22Diseases
0Drugs
13Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
identical protein bindingprotein bindingnucleusRNA polymerase II cis-regulatory region sequence-specific DNA bindingFamilial exudative vitreoretinopathyretinitis pigmentosaRetinal dystrophyexudative vitreoretinopathy
✦AI Summary

ZNF408 is a zinc finger transcription factor involved in the regulation of genes critical for retinal vascular development 1. The protein functions as a DNA-binding transcription factor with RNA polymerase II-specific activity that regulates the expression of genes essential for vasculature development 2. ZNF408 mutations cause familial exudative vitreoretinopathy (FEVR), an inherited disorder characterized by abnormal retinal angiogenesis and peripheral retinal avascularity 3. Pathogenic variants in ZNF408 are inherited in an autosomal dominant manner 3. Mechanistically, the p.His455Tyr missense mutation reduces ZNF408's DNA-binding ability and disrupts the expression of genes involved in vascular development 1. In zebrafish models, znf408 mutations cause progressive retinal vascular pathology, including deficient hyaloid vessel development, ectopic vascular hyper-sprouting, and vascular leakage 4. Clinical studies demonstrate that ZNF408 variants account for a small fraction of FEVR cases, with novel missense mutations identified in Chinese cohorts 5. While ZNF408 represents a rare genetic cause of FEVR compared to LRP5 and FZD4, its identification expands the mutational spectrum of this retinal vascular disease and confirms the critical role of transcriptional regulation in retinal angiogenesis.

Sources cited
1
ZNF408 is a transcription factor whose mutations disrupt DNA-binding ability and alter expression of vasculature development genes, causing FEVR
PMID: 29982478
2
ZNF408 variants are associated with FEVR and operate in pathways affecting retinal endothelial cell function
PMID: 37947657
3
ZNF408 mutations cause autosomal dominant FEVR, a rare inherited disorder of retinal angiogenesis
PMID: 25323851
4
ZNF408 mutations in zebrafish cause progressive retinal vascular pathology including deficient vessel development and vascular leakage
PMID: 32097476
5
ZNF408 variants are detected in FEVR patients, with missense mutations causing the disease
PMID: 37684015
Disease Associationsβ“˜22
Familial exudative vitreoretinopathyOpen Targets
0.68Moderate
retinitis pigmentosaOpen Targets
0.66Moderate
Retinal dystrophyOpen Targets
0.51Moderate
exudative vitreoretinopathyOpen Targets
0.46Moderate
neurodegenerative diseaseOpen Targets
0.37Weak
ventricular fibrillationOpen Targets
0.34Weak
autosomal recessive retinitis pigmentosaOpen Targets
0.33Weak
diabetes mellitusOpen Targets
0.24Weak
lymphatic system diseaseOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
vein disorderOpen Targets
0.19Weak
open-angle glaucomaOpen Targets
0.18Weak
schizophreniaOpen Targets
0.17Weak
optic atrophyOpen Targets
0.14Weak
venous thromboembolismOpen Targets
0.12Weak
deep vein thrombosisOpen Targets
0.10Suggestive
PhlebitisOpen Targets
0.06Suggestive
ThrombophlebitisOpen Targets
0.06Suggestive
aneurysmOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
Retinitis pigmentosa 72UniProt
Vitreoretinopathy, exudative 6UniProt
Pathogenic Variants13
NM_024741.3(ZNF408):c.1363C>T (p.His455Tyr)Pathogenic
Exudative vitreoretinopathy 6|not provided|Retinal dystrophy
β˜…β˜…β˜†β˜†2025β†’ Residue 455
NM_024741.3(ZNF408):c.1621C>T (p.Arg541Cys)Pathogenic
Retinitis pigmentosa 72|Retinal dystrophy|not provided|Exudative vitreoretinopathy 6;Retinitis pigmentosa 72
β˜…β˜…β˜†β˜†2025β†’ Residue 541
NM_024741.3(ZNF408):c.653-1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_024741.3(ZNF408):c.331-2A>GPathogenic
Retinitis pigmentosa 72
β˜…β˜†β˜†β˜†2024
NM_024741.3(ZNF408):c.1219C>T (p.Arg407Trp)Likely pathogenic
Retinal dystrophy
β˜…β˜†β˜†β˜†2023β†’ Residue 407
NM_024741.3(ZNF408):c.604C>T (p.Gln202Ter)Likely pathogenic
Retinal dystrophy
β˜…β˜†β˜†β˜†2023β†’ Residue 202
NM_024741.3(ZNF408):c.111del (p.Gln38fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2021β†’ Residue 38
NM_024741.3(ZNF408):c.943C>T (p.Gln315Ter)Likely pathogenic
Exudative vitreoretinopathy 6
β˜…β˜†β˜†β˜†2019β†’ Residue 315
NM_024741.3(ZNF408):c.274G>T (p.Glu92Ter)Pathogenic
Retinal dystrophy
β˜†β˜†β˜†β˜†2021β†’ Residue 92
NM_024741.3(ZNF408):c.1996del (p.Glu666fs)Likely pathogenic
Retinal dystrophy
β˜†β˜†β˜†β˜†2020β†’ Residue 666
NM_024741.3(ZNF408):c.1697T>A (p.Leu566His)Pathogenic
Familial exudative vitreoretinopathy
β˜†β˜†β˜†β˜†2019β†’ Residue 566
NM_024741.3(ZNF408):c.653-1G>TPathogenic
Autosomal recessive retinitis pigmentosa
β˜†β˜†β˜†β˜†2017
NM_024741.3(ZNF408):c.363_364del (p.Ala122fs)Pathogenic
Retinitis pigmentosa 72
β˜†β˜†β˜†β˜†2015β†’ Residue 122
View on ClinVar β†—
Related Genes
GPATCH3Protein interaction100%RNF25Protein interaction78%ZNF212Protein interaction71%NDPProtein interaction66%FZD4Protein interaction66%TSPAN12Protein interaction66%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
89%
Ovary
48%
Heart
43%
Lung
40%
Brain
24%
Gene Interaction Network
Click a node to explore
ZNF408GPATCH3RNF25ZNF212NDPFZD4TSPAN12
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9H9D4
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.15LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.82 [0.59–1.15]
RankingsWhere ZNF408 stands among ~20K protein-coding genes
  • #10,726of 20,598
    Most Researched37
  • #2,627of 5,498
    Most Pathogenic Variants13
  • #11,915of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedZNF408
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 20301590
1.00
2
Ocular Features and Mutation Spectrum of Patients With Familial Exudative Vitreoretinopathy.
PMID: 34860240
Invest Ophthalmol Vis Sci Β· 2021
0.90
3
Mechanisms Underlying Rare Inherited Pediatric Retinal Vascular Diseases: FEVR, Norrie Disease, Persistent Fetal Vascular Syndrome.
PMID: 37947657
Cells Β· 2023
0.80
4
Genetic and clinical characteristics of ZNF408-related familial exudative vitreoretinopathy.
PMID: 37684015
J Int Med Res Β· 2023
0.70
5
Genetic Characteristics and Clinical Manifestations of Foveal Hypoplasia in Familial Exudative Vitreoretinopathy.
PMID: 38280677
Am J Ophthalmol Β· 2024
0.60