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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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ZFX
zinc finger protein X-linked
Chromosome X Β· Xp22.11
NCBI Gene: 7543Ensembl: ENSG00000005889.17HGNC: HGNC:12869UniProt: P17010
73PubMed Papers
21Diseases
0Drugs
11Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription activator activity, RNA polymerase II-specificchromatinpositive regulation of transcription by RNA polymerase IIintellectual developmental disorder, X-linked, syndromic 37neoplasmhepatocellular carcinomatriple-negative breast cancer
✦AI Summary

ZFX is a zinc finger transcription factor located on chromosome X.11 that encodes a DNA-binding protein with 13 zinc fingers structurally similar to its Y-chromosome X ZFY 1. ZFX functions as a transcriptional activator that binds to CpG island promoters and regulates gene expression through recruitment of histone modification complexes; reduction of ZFX increases RNA polymerase II pausing at target promoters and decreases histone H4 acetylation 2. Notably, ZFX escapes X-inactivation and modulates autosomal gene expression broadly, with its effects on approximately 21% of expressed genes in lymphoblastoid cells and fibroblasts being comparable to those of the Y chrX's ZFY 3. Pathogenic ZFX variants cause X-linked intellectual developmental disorder, syndromic 37, characterized by developmental delay, behavioral abnormalities, hypotonia, and distinctive facial features including thickened eyebrows, external eye abnormalities, and ear abnormalities 4. Missense variants in the DNA-binding domain alter transcriptional activity of target genes, while truncation variants produce more severe phenotypes 4. Additional clinical associations include hyperparathyroidism and increased tumor risk in affected families 4. ZFX variants have also been identified as potential candidates in nonobstructive azoospermia, suggesting involvement in male reproductive development 5.

Sources cited
1
ZFX is structurally similar to ZFY, encodes 13 zinc fingers, and escapes X-inactivation
PMID: 2500252
2
ZFX binds CpG island promoters, recruits H4 acetylation complexes, and regulates transcriptional elongation
PMID: 38726870
3
ZFX and ZFY modulate autosomal gene expression affecting ~21% of expressed genes
PMID: 38190107
4
ZFX variants cause X-linked intellectual disability with distinctive facial features, behavioral abnormalities, and association with hyperparathyroidism and tumors
PMID: 38325380
5
ZFX variants identified as candidate genes in nonobstructive azoospermia
PMID: 36017582
Disease Associationsβ“˜21
intellectual developmental disorder, X-linked, syndromic 37Open Targets
0.63Moderate
neoplasmOpen Targets
0.10Suggestive
hepatocellular carcinomaOpen Targets
0.10Suggestive
triple-negative breast cancerOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
chronic myelogenous leukemiaOpen Targets
0.08Suggestive
osteoarthritisOpen Targets
0.08Suggestive
renal cell carcinomaOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.07Suggestive
azoospermiaOpen Targets
0.06Suggestive
gliomaOpen Targets
0.06Suggestive
osteosarcomaOpen Targets
0.06Suggestive
cancerOpen Targets
0.06Suggestive
spermatogenic failure 8Open Targets
0.05Suggestive
familial primary pulmonary hypoplasiaOpen Targets
0.05Suggestive
spermatogenic failure 12Open Targets
0.05Suggestive
partial chromosome Y deletionOpen Targets
0.05Suggestive
spermatogenic failure 51Open Targets
0.05Suggestive
spermatogenic failure 54Open Targets
0.05Suggestive
Intellectual developmental disorder, X-linked, syndromic 37UniProt
Pathogenic Variants11
NM_003410.4(ZFX):c.2321A>G (p.Tyr774Cys)Pathogenic
Intellectual developmental disorder, X-linked, syndromic 37|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 774
NM_003410.4(ZFX):c.1763_1764del (p.Ser588fs)Pathogenic
Intellectual developmental disorder, X-linked, syndromic 37
β˜…β˜†β˜†β˜†2026β†’ Residue 588
NM_003410.4(ZFX):c.2363C>G (p.Pro788Arg)Likely pathogenic
Intellectual developmental disorder, X-linked, syndromic 37
β˜…β˜†β˜†β˜†2025β†’ Residue 788
NM_003410.4(ZFX):c.458T>G (p.Val153Gly)Likely pathogenic
Intellectual developmental disorder, X-linked, syndromic 37
β˜…β˜†β˜†β˜†2025β†’ Residue 153
NM_003410.4(ZFX):c.2312C>T (p.Thr771Met)Pathogenic
Intellectual developmental disorder, X-linked, syndromic 37|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 771
NM_003410.4(ZFX):c.529dup (p.Ser177fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 177
NM_003410.4(ZFX):c.1996_1997del (p.Met666fs)Pathogenic
Intellectual developmental disorder, X-linked, syndromic 37
β˜…β˜†β˜†β˜†2024β†’ Residue 666
NM_003410.4(ZFX):c.2360G>A (p.Arg787Lys)Likely pathogenic
Intellectual developmental disorder, X-linked, syndromic 37
β˜…β˜†β˜†β˜†2024β†’ Residue 787
NM_003410.4(ZFX):c.115_116del (p.Val39fs)Pathogenic
Intellectual developmental disorder, X-linked, syndromic 37
β˜†β˜†β˜†β˜†2024β†’ Residue 39
NM_003410.4(ZFX):c.1319dup (p.Leu440fs)Pathogenic
Intellectual developmental disorder, X-linked, syndromic 37
β˜†β˜†β˜†β˜†2024β†’ Residue 440
NM_003410.4(ZFX):c.2357G>A (p.Arg786Gln)Pathogenic
Intellectual developmental disorder, X-linked, syndromic 37
β˜†β˜†β˜†β˜†2024β†’ Residue 786
View on ClinVar β†—
Related Genes
USP9YProtein interaction100%KDM5DProtein interaction97%UTYProtein interaction96%MYCProtein interaction93%E2F1Protein interaction90%MYCNProtein interaction88%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
77%
Heart
61%
Liver
43%
Lung
42%
Brain
41%
Gene Interaction Network
Click a node to explore
ZFXUSP9YKDM5DUTYMYCE2F1MYCN
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P17010
View on AlphaFold β†—
RankingsWhere ZFX stands among ~20K protein-coding genes
  • #6,525of 20,598
    Most Researched73
  • #2,761of 5,498
    Most Pathogenic Variants11
Genes detectedZFX
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Accuracy of Intraoral Scanners: A Systematic Review of Influencing Factors.
PMID: 29989757
Eur J Prosthodont Restor Dent Β· 2018
1.00
2
The human Y and inactive X chromosomes similarly modulate autosomal gene expression.
PMID: 38190107
Cell Genom Β· 2024
0.90
3
Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt.
PMID: 38325380
Am J Hum Genet Β· 2024
0.80
4
Chromosomal localization of ZFX--a human gene that escapes X inactivation--and its murine homologs.
PMID: 1970799
Genomics Β· 1990
0.70
5
The human Y and inactive X chromosomes similarly modulate autosomal gene expression.
PMID: 37333288
bioRxiv Β· 2023
0.60