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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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HINFP
histone H4 transcription factor
Chromosome 11 · 11q23.3
NCBI Gene: 25988Ensembl: ENSG00000172273.14HGNC: HGNC:17850UniProt: Q9BQA5
31PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
DNA RepairTranscription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
establishment of protein localizationmyoblast differentiationnegative regulation of DNA-templated transcriptionpositive regulation of DNA-templated transcriptionneurodegenerative diseaseAlzheimer diseaseParkinson diseaselysosomal storage disease
✦AI Summary

HINFP (histone H4 transcription factor) is a cell cycle-regulated transcriptional regulator essential for coordinating DNA replication with histone gene expression. HINFP functions as a transcriptional activator that promotes histone H4 gene transcription at the G1/S phase transition, working in conjunction with its cofactor NPAT in response to cyclin E/CDK2 signaling 1. This HINFP/NPAT complex operates within specialized subnuclear histone locus bodies (HLBs) to enable synchronized histone biosynthesis with DNA replication 2. Beyond histone regulation, HINFP activates transcription of DNA damage response genes ATM and PRKDC and acts as a co-activator in SREBP2-mediated PCSK9 gene expression controlling cholesterol metabolism 3. HINFP is genetically nonredundant: homozygous loss causes embryonic lethality by E6.5, with null embryos showing impaired histone H4 expression and developmental failure 1. In bladder cancer, HINFP downregulation induces senescence by inhibiting histone H1 genes, triggering DNA damage; however, the resulting senescence-associated secretory phenotype paradoxically promotes metastasis in non-senescent cells, suggesting histone deacetylase inhibitors may benefit metastatic patients 4. HINFP knockdown in retinal pigment epithelium similarly triggers histone loss, senescence, and SASP markers, linking HINFP dysfunction to age-related degeneration 5. These findings establish HINFP as a critical regulator of chr11 dynamics with implications for developmental biology, cancer progression, and aging.

Sources cited
1
HINFP/NPAT complex activates histone H4 genes at G1/S transition; homozygous HINFP knockout causes embryonic lethality by E6.5 with loss of histone H4 expression
PMID: 19590016
2
HINFP operates within histone locus bodies (HLBs) to coordinate histone gene transcription with DNA replication; complete loss disrupts HLB integrity
PMID: 29744889
3
HINFP acts as co-activator in SREBP2-mediated PCSK9 gene transcription; HINFP/NPAT/TRRAP complex facilitates histone H4 acetylation
PMID: 22288532
4
HINFP downregulation in bladder cancer inhibits H1F0 and H1FX, inducing senescence and senescence-associated secretory phenotype that promotes metastasis
PMID: 35668172
5
HINFP knockdown in retinal pigment epithelium induces histone loss, senescence, and SASP markers; HINFP is a key HLB component affected in aging
PMID: 38408164
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
Alzheimer diseaseOpen Targets
0.37Weak
Parkinson diseaseOpen Targets
0.37Weak
lysosomal storage diseaseOpen Targets
0.37Weak
multiple sclerosisOpen Targets
0.37Weak
hepatocellular carcinomaOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
urinary bladder carcinomaOpen Targets
0.01Suggestive
colorectal carcinomaOpen Targets
0.01Suggestive
age-related macular degenerationOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
Crohn's diseaseOpen Targets
0.00Suggestive
COVID-19Open Targets
0.00Suggestive
Ehlers-Danlos syndromeOpen Targets
0.00Suggestive
Huntington diseaseOpen Targets
0.00Suggestive
metabolic diseaseOpen Targets
0.00Suggestive
type 2 diabetes mellitusOpen Targets
0.00Suggestive
CirrhosisOpen Targets
0.00Suggestive
cervical carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GSCProtein interaction95%NPATProtein interaction90%HMX3Protein interaction78%TAF8Protein interaction78%LRRC57Protein interaction78%ZNF766Protein interaction73%
Tissue Expression6 tissues
Ovary
100%
Liver
86%
Lung
77%
Bone Marrow
67%
Brain
65%
Heart
55%
Gene Interaction Network
Click a node to explore
HINFPGSCNPATHMX3TAF8LRRC57ZNF766
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9BQA5
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.50Moderately Constrained
pLIⓘ
0.97Intolerant
Observed/Expected LoF0.34 [0.24–0.50]
RankingsWhere HINFP stands among ~20K protein-coding genes
  • #11,726of 20,598
    Most Researched31
  • #3,051of 17,882
    Most Constrained (LOEUF)0.50 · top quartile
Genes detectedHINFP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Downregulation of HINFP induces senescence-associated secretory phenotype to promote metastasis in a non-cell-autonomous manner in bladder cancer.
PMID: 35668172
Oncogene · 2022
1.00
2
The histone gene activator HINFP is a nonredundant cyclin E/CDK2 effector during early embryonic cell cycles.
PMID: 19590016
Proc Natl Acad Sci U S A · 2009
0.90
3
Higher order genomic organization and regulatory compartmentalization for cell cycle control at the G1/S-phase transition.
PMID: 29744889
J Cell Physiol · 2018
0.80
4
Establishment of histone gene regulation and cell cycle checkpoint control in human embryonic stem cells.
PMID: 17096384
J Cell Physiol · 2007
0.70
5
Histone deficiency and hypoacetylation in the aging retinal pigment epithelium.
PMID: 38408164
Aging Cell · 2024
0.60