H1-0

Summary

H1-0 (H1.0 linker histone, HGNC:4714) is a protein-coding gene on chromosome 22q13.1, encoding Histone H1.0 (P07305). Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber.

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a replication-independent histone that is a member of the histone H1 family.

Source: NCBI Gene 3005 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 27 total
• Druggable target: yes
• MANE Select transcript: NM_005318

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4714
Approved symbol	H1-0
Name	H1.0 linker histone
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	H1.0
Ensembl gene	ENSG00000189060
Ensembl biotype	protein_coding
OMIM	142708
Entrez	3005

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000340857

RefSeq mRNA: 1 — MANE Select: NM_005318 NM_005318

CCDS: CCDS13956

Canonical transcript exons

ENST00000340857 — 1 exons

Exon	Start	End
ENSE00001388277	37805229	37807432

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 87.1681 / max 1287.3262, expressed in 1718 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192194	83.5217	1713
192196	1.2583	766
192197	1.1474	667
192195	0.6617	444
192193	0.5789	318

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.70	gold quality
ganglionic eminence	UBERON:0004023	99.58	gold quality
cortical plate	UBERON:0005343	99.21	gold quality
embryo	UBERON:0000922	99.05	gold quality
lower esophagus mucosa	UBERON:0035834	98.82	gold quality
skin of leg	UBERON:0001511	98.69	gold quality
skin of abdomen	UBERON:0001416	98.56	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.35	gold quality
right uterine tube	UBERON:0001302	98.33	gold quality
islet of Langerhans	UBERON:0000006	98.31	gold quality
ectocervix	UBERON:0012249	98.27	gold quality
esophagus mucosa	UBERON:0002469	98.06	gold quality
mucosa of transverse colon	UBERON:0004991	98.05	gold quality
left uterine tube	UBERON:0001303	98.03	gold quality
transverse colon	UBERON:0001157	97.92	gold quality
minor salivary gland	UBERON:0001830	97.91	gold quality
zone of skin	UBERON:0000014	97.83	gold quality
rectum	UBERON:0001052	97.81	gold quality
right lobe of thyroid gland	UBERON:0001119	97.69	gold quality
descending thoracic aorta	UBERON:0002345	97.61	gold quality
esophagus	UBERON:0001043	97.49	gold quality
body of stomach	UBERON:0001161	97.49	gold quality
endocervix	UBERON:0000458	97.40	gold quality
mouth mucosa	UBERON:0003729	97.40	gold quality
vagina	UBERON:0000996	97.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.33	gold quality
body of pancreas	UBERON:0001150	97.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.32	gold quality
right ovary	UBERON:0002118	97.25	gold quality
gastrocnemius	UBERON:0001388	97.20	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	711.18
E-CURD-112	yes	66.61
E-HCAD-10	yes	39.69
E-MTAB-6678	yes	6.41
E-MTAB-2983	no	520.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HBP1

miRNA regulators (miRDB)

50 targeting H1-0, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-6770-5P	98.97	66.76	1853

Literature-anchored findings (GeneRIF, showing 13)

• nuclear transport of H1 histones requires a heterodimeric nuclear import receptor (PMID:12080050)
• H1(0)histone may be an important factor in normal DC differentiation. Tumor-derived factors may inhibit DC differentiation by affecting H1(0) expression. (PMID:12149419)
• The N-terminal domain contributes toward the differential chromatin binding affinity, whereas the C-terminal domain contributes toward distinct nucleosomal interface of isotypes H10 and H1c. (PMID:22334665)
• H1.X moves more rapidly than other linker histones in vivo Domain swapping between H1.0 and H1.X suggests that the globular domain (GD) and C-terminal domain (CTD) of H1.X independently contribute to the dynamic behavior of H1.X. (PMID:27528617)
• this study shows that dynamic epigenetic states defined by the linker histone H1.0 determine which cells within a tumor can sustain the long-term cancer growth. (PMID:27708074)
• Histone H1 acetylation at lysine 85 (H1K85) mutation leads to genomic instability and decreased cell survival upon DNA damage. (PMID:29982688)
• Measure the binding affinity for the prothymosin-alpha (ProTalpha)-H1.0 complex using isothermal titration calorimetry and report a KD value of (4.6 +/- 0.5) x 10(-7) M. In addition, we show that ProTalpha facilitates the formation of the H1.0-nucleosome complex in vitro. (PMID:30430826)
• Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture. (PMID:33299181)
• Linker histone defines structure and self-association behaviour of the 177 bp human chromatosome. (PMID:33432055)
• The Dynamic Influence of Linker Histone Saturation within the Poly-Nucleosome Array. (PMID:33667509)
• Structure, dynamics, and stability of the globular domain of human linker histone H1.0 and the role of positive charges. (PMID:35066947)
• Analysis of histone variant constraint and tissue expression suggests five potential novel human disease genes: H2AFY2, H2AFZ, H2AFY, H2AFV, H1F0. (PMID:35072799)
• Unchanged PCNA and DNMT1 dynamics during replication in DNA ligase I-deficient cells but abnormal chromatin levels of non-replicative histone H1. (PMID:36928068)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	h1-0	ENSDARG00000038559
mus_musculus	H1f0	ENSMUSG00000096210
rattus_norvegicus	H1f0	ENSRNOG00000076993
caenorhabditis_elegans		WBGENE00001853
caenorhabditis_elegans		WBGENE00001854
caenorhabditis_elegans		WBGENE00001855
caenorhabditis_elegans	hil-5	WBGENE00001856
caenorhabditis_elegans		WBGENE00001857

Paralogs (9): H1-3 (ENSG00000124575), H1-1 (ENSG00000124610), H1-4 (ENSG00000168298), H1-8 (ENSG00000178804), H1-5 (ENSG00000184357), H1-10 (ENSG00000184897), H1-7 (ENSG00000187166), H1-6 (ENSG00000187475), H1-2 (ENSG00000187837)

Protein

Protein identifiers

Histone H1.0 — P07305 (reviewed: P07305)

Alternative names: Histone H1’, Histone H1(0)

All UniProt accessions (1): P07305

UniProt curated annotations — full annotation on UniProt →

Function. Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers and promote formation of the H3K27me3 mark by the PRC2/EED-EZH2 complex. The histones H1.0 are found in cells that are in terminal stages of differentiation or that have low rates of cell division.

Subunit / interactions. Associates with nucleosomes, promoting condensation into higher-order structured chromatin.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Post-translational modifications. Phosphorylated on Ser-17 in RNA edited version. ADP-ribosylated on Ser-104 in response to DNA damage.

Induction. Both the unedited and the RNA edited versions are induced by butyrate (at protein level). Only RNA edited version is induced by DTT, vinblastine or TNF (at protein level).

Similarity. Belongs to the histone H1/H5 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P07305-1	1	yes
P07305-2	2

RefSeq proteins (1): NP_005309* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005818	Histone_H1/H5_H15	Domain
IPR005819	H1/H5	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00538

UniProt features (26 total): modified residue 10, helix 3, chain 2, strand 2, region of interest 2, compositionally biased region 2, initiator methionine 1, splice variant 1, sequence variant 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
7COW	X-RAY DIFFRACTION	2.86
7K5X	ELECTRON MICROSCOPY	2.93
6LAB	X-RAY DIFFRACTION	3.2
7XX6	X-RAY DIFFRACTION	3.39
6LA8	X-RAY DIFFRACTION	3.4
7XVL	X-RAY DIFFRACTION	3.51
6LA9	X-RAY DIFFRACTION	3.7
6LA2	X-RAY DIFFRACTION	3.89
8TB9	ELECTRON MICROSCOPY	4
9IPU	ELECTRON MICROSCOPY	4.3
7DBP	ELECTRON MICROSCOPY	4.5
6N88	ELECTRON MICROSCOPY	6.2
9QEJ	ELECTRON MICROSCOPY	6.2
6N89	ELECTRON MICROSCOPY	7.5
9QF0	ELECTRON MICROSCOPY	7.5
6HQ1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07305-F1	68.87	0.36

Antibody-complex structures (SAbDab): 1 — 7K5X

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (10): 4, 12, 40, 42, 52, 73, 104, 148, 1, 2

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-140342	Apoptosis induced DNA fragmentation
R-HSA-2559584	Formation of Senescence-Associated Heterochromatin Foci (SAHF)

MSigDB gene sets: 323 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_APOPTOSIS_INDUCED_DNA_FRAGMENTATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, HOFMANN_CELL_LYMPHOMA_UP, SP3_Q3, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DITTMER_PTHLH_TARGETS_UP, AP2_Q3, GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_DN, GOBP_CHROMOSOME_CONDENSATION, CAGCTG_AP4_Q5, GOLDRATH_ANTIGEN_RESPONSE

GO Biological Process (5): nucleosome assembly (GO:0006334), chromosome condensation (GO:0030261), heterochromatin formation (GO:0031507), negative regulation of DNA recombination (GO:0045910), positive regulation of transcription regulatory region DNA binding (GO:2000679)

GO Molecular Function (9): minor groove of adenine-thymine-rich DNA binding (GO:0003680), double-stranded DNA binding (GO:0003690), RNA binding (GO:0003723), structural constituent of chromatin (GO:0030527), chromatin DNA binding (GO:0031490), nucleosome binding (GO:0031491), nucleosomal DNA binding (GO:0031492), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (10): chromatin (GO:0000785), nucleosome (GO:0000786), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), actin cytoskeleton (GO:0015629), nuclear body (GO:0016604), transcription repressor complex (GO:0017053), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Apoptotic execution phase	1
DNA Damage/Telomere Stress Induced Senescence	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	3
DNA binding	2
nucleic acid binding	2
chromatin binding	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
intracellular membraneless organelle	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
chromosome organization	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
regulation of DNA recombination	1
DNA recombination	1
negative regulation of DNA metabolic process	1
transcription cis-regulatory region binding	1
positive regulation of DNA binding	1
regulation of transcription regulatory region DNA binding	1
DNA secondary structure binding	1
structural molecule activity	1
protein-containing complex binding	1
chromatin DNA binding	1
nucleosome binding	1
binding	1
chromosome	1
protein-DNA complex	1
nuclear lumen	1
cytoplasm	1
endomembrane system	1
cytoskeleton	1
nucleoplasm	1
transcription regulator complex	1

Protein interactions and networks

STRING

2390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H1-0	H2AC20	Q16777	995
H1-0	H2AC19	P20670	995
H1-0	H2BC21	Q16778	994
H1-0	PTMA	P06454	991
H1-0	RNF168	Q8IYW5	950
H1-0	NASP	P49321	853
H1-0	CCNL2	Q96S94	826
H1-0	NUCLEOLIN	P19338	821
H1-0	CDK1	P06493	820
H1-0	H1-7	Q75WM6	813
H1-0	DFFB	O76075	813
H1-0	H1-8	Q8IZA3	803
H1-0	CDK5	Q00535	793
H1-0	CDK2	P24941	783
H1-0	H3C1	P02295	742

IntAct

165 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
MED25	MED24	psi-mi:“MI:0914”(association)	0.740
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
YWHAZ	HSPB1	psi-mi:“MI:0914”(association)	0.680
H1-0	H2BC21	psi-mi:“MI:0915”(physical association)	0.560
H2AC21	H1-0	psi-mi:“MI:0915”(physical association)	0.560
H2AC14	H1-0	psi-mi:“MI:0915”(physical association)	0.560
H1-0	RAD51B	psi-mi:“MI:0407”(direct interaction)	0.560
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
N	RBM47	psi-mi:“MI:0914”(association)	0.530
MED27	POLR2D	psi-mi:“MI:0914”(association)	0.530
E1	H1-0	psi-mi:“MI:0915”(physical association)	0.520
MKI67	ZC3H11A	psi-mi:“MI:0914”(association)	0.480
CDK2	H1-0	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RNF168	H1-0	psi-mi:“MI:0407”(direct interaction)	0.440
H1-0		psi-mi:“MI:0407”(direct interaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
FGFBP1	H1-0	psi-mi:“MI:0915”(physical association)	0.400
H1-0	ERICH6B	psi-mi:“MI:0915”(physical association)	0.400
H1-5	H1-0	psi-mi:“MI:0915”(physical association)	0.400
PRKAR1B	H1-0	psi-mi:“MI:0915”(physical association)	0.400
H1-0	H1-2	psi-mi:“MI:0915”(physical association)	0.400
H1-0	H1-4	psi-mi:“MI:0915”(physical association)	0.400
GLCE	H1-0	psi-mi:“MI:0915”(physical association)	0.400
MED12	H1-0	psi-mi:“MI:0915”(physical association)	0.400
HAUS6	H1-0	psi-mi:“MI:0915”(physical association)	0.400
SARS1	H1-0	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (322): H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS), H1F0 (Biochemical Activity), H1F0 (Biochemical Activity), H1F0 (Reconstituted Complex), H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS), H1F0 (Affinity Capture-MS)

ESM2 similar proteins: A7MAZ5, D3ZBN0, D4A3K5, G3N131, P02251, P02252, P02253, P02254, P06350, P06893, P07305, P08284, P08285, P08286, P08287, P08288, P09426, P09987, P10412, P15796, P15864, P15865, P15866, P15867, P15870, P16401, P16402, P16403, P21895, P22844, P22845, P23444, P27806, P35060, P40262, P40263, P40264, P40265, P40266, P40275

Diamond homologs: A7MAZ5, D3ZBN0, D3ZZW6, D4A3K5, G3N131, O01833, O16277, P02251, P02252, P02253, P02254, P02255, P02256, P02257, P02258, P02259, P06144, P06348, P06349, P06350, P06513, P06892, P06893, P06894, P07305, P07796, P08284, P08285, P08286, P08287, P08288, P09426, P09987, P10412, P10922, P15796, P15864, P15865, P15866, P15867

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 153 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of Senescence-Associated Heterochromatin Foci (SAHF)	5	29.2×	2e-04
Downstream signal transduction	5	16.6×	8e-04
Condensation of Prophase Chromosomes	8	10.9×	2e-04
Signaling by SCF-KIT	5	10.8×	3e-03
Packaging Of Telomere Ends	5	9.6×	4e-03
Recognition and association of DNA glycosylase with site containing an affected purine	5	8.9×	6e-03
Cleavage of the damaged purine	5	8.9×	6e-03
Transcriptional regulation by small RNAs	7	8.8×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	7	12.9×	3e-04
positive regulation of transcription elongation by RNA polymerase II	5	10.9×	8e-03
nucleosome assembly	9	9.2×	3e-04
Ras protein signal transduction	6	8.9×	6e-03
chromatin organization	9	6.5×	2e-03
endocytosis	9	6.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

27 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

27 predictions. Top by Δscore:

Variant	Effect	Δscore
22:37806134:G:GT	donor_gain	0.5100
22:37806181:A:G	donor_gain	0.4100
22:37806123:G:GT	donor_gain	0.3500
22:37805697:G:GT	donor_gain	0.2900
22:37805890:A:T	donor_gain	0.2900
22:37806177:G:GG	donor_gain	0.2700
22:37805720:AGGTG:A	donor_gain	0.2600
22:37805889:GAAG:G	donor_gain	0.2600
22:37805897:C:G	donor_gain	0.2500
22:37805882:A:T	donor_gain	0.2400
22:37805717:ACAAG:A	donor_loss	0.2100
22:37805718:CAAG:C	donor_loss	0.2100
22:37805719:AAGGT:A	donor_loss	0.2100
22:37805720:AG:A	donor_loss	0.2100
22:37805721:GG:G	donor_loss	0.2100
22:37805722:G:GG	donor_loss	0.2100
22:37805723:T:A	donor_loss	0.2100
22:37806176:T:G	donor_gain	0.2100
22:37805722:GTGG:G	donor_gain	0.2000
22:37805850:G:GT	donor_gain	0.2000
22:37805888:AGAAG:A	donor_loss	0.2000
22:37805890:AAG:A	donor_loss	0.2000
22:37805891:AGGTA:A	donor_loss	0.2000
22:37805892:GGT:G	donor_loss	0.2000
22:37805893:G:C	donor_loss	0.2000
22:37805894:T:A	donor_loss	0.2000
22:37806205:T:A	acceptor_gain	0.2000

AlphaMissense

1251 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:37805786:T:A	L81H	1.000
22:37805800:G:A	G86R	1.000
22:37805800:G:C	G86R	1.000
22:37805800:G:T	G86W	1.000
22:37805801:G:A	G86E	1.000
22:37805807:G:A	G88E	1.000
22:37805815:G:T	G91W	1.000
22:37805816:G:A	G91E	1.000
22:37805821:T:C	F93L	1.000
22:37805822:T:C	F93S	1.000
22:37805823:C:A	F93L	1.000
22:37805823:C:G	F93L	1.000
22:37805626:T:C	Y28H	0.999
22:37805627:A:G	Y28C	0.999
22:37805636:T:C	M31T	0.999
22:37805637:G:A	M31I	0.999
22:37805637:G:C	M31I	0.999
22:37805637:G:T	M31I	0.999
22:37805639:T:A	I32N	0.999
22:37805647:G:C	A35P	0.999
22:37805648:C:A	A35D	0.999
22:37805674:G:C	G44R	0.999
22:37805675:G:A	G44D	0.999
22:37805683:C:A	R47S	0.999
22:37805684:G:C	R47P	0.999
22:37805689:T:C	S49P	0.999
22:37805693:T:A	I50N	0.999
22:37805693:T:G	I50S	0.999
22:37805705:T:A	I54N	0.999
22:37805749:A:G	K69E	0.999

dbSNP variants (sampled 300 via entrez): RS1000345223 (22:37807542 A>G), RS1001381384 (22:37805276 AGAGGCAGAGGCAGAGCCC>A), RS1001838698 (22:37807020 C>T), RS1002567107 (22:37804272 C>A,T), RS1002781131 (22:37807028 G>A,T), RS1002794176 (22:37807279 C>G), RS1003621182 (22:37805267 GGCA>G), RS1003914493 (22:37805419 G>A,T), RS1003959686 (22:37807363 T>C), RS1004240361 (22:37805721 G>A,C,T), RS1004386983 (22:37807762 C>G), RS1005132057 (22:37803390 T>C), RS1005148197 (22:37803644 G>A,C), RS1005911865 (22:37804684 C>T), RS1006140784 (22:37804768 G>C)

Disease associations

OMIM: gene MIM:142708 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005580_263	Intraocular pressure	3.000000e-10
GCST005580_270	Intraocular pressure	5.000000e-10
GCST009724_107	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-16
GCST010703_11	Brain morphology (MOSTest)	9.000000e-10
GCST90002403_702	Red blood cell count	3.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004346	neuroimaging measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3707465 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

Binding affinities (BindingDB)

5 measured of 6 human assays (7 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-one	KI	1.9 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
2-methyl-4-(4-methylpiperazin-1-yl)-10H-thieno[2,3-b][1,5]benzodiazepine	KI	4 nM
8-Chloro-11-(4-methyl-piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine(Clopazine)	KI	9.6 nM	US-8598119: Methods and compositions for sleep disorders and other disorders
7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one	EC50	1880 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.12	Kd	753.4	nM	CHEMBL3752910
6.12	ED50	753.4	nM	CHEMBL3752910
5.89	Kd	1289	nM	CHEMBL5653589
5.89	ED50	1289	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148479: Binding affinity to human H1F0 incubated for 45 mins by Kinobead based pull down assay	kd	0.7534	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148479: Binding affinity to human H1F0 incubated for 45 mins by Kinobead based pull down assay	kd	1.2888	uM

CTD chemical–gene interactions

84 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
bisphenol A	increases expression, affects cotreatment	3
(+)-JQ1 compound	increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
deoxynivalenol	increases expression	2
trichostatin A	increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
cobaltous chloride	decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
belinostat	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
methylselenic acid	affects expression	1
potassium perchlorate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	decreases expression	1
cupric chloride	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651521	Binding	Binding affinity to human H1F0 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

15 cell lines: 14 embryonic stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1C7	Abcam A-431 H1-0 KO	Cancer cell line	Female
CVCL_C9JS	WAe001-A-83	Embryonic stem cell	Male
CVCL_C9JU	WAe001-A-85	Embryonic stem cell	Male
CVCL_C9K4	WAe001-A-96	Embryonic stem cell	Male
CVCL_C9K5	WAe001-A-97	Embryonic stem cell	Male
CVCL_C9KG	WAe001-A-I	Embryonic stem cell	Male
CVCL_C9KH	WAe001-A-J	Embryonic stem cell	Male
CVCL_C9KI	WAe001-A-K	Embryonic stem cell	Male
CVCL_C9KJ	WAe001-A-L	Embryonic stem cell	Male
CVCL_C9KK	WAe001-A-M	Embryonic stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.