H1-5

Summary

H1-5 (H1.5 linker histone, cluster member, HGNC:4719) is a protein-coding gene on chromosome 6p22.1, encoding Histone H1.5 (P16401). Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber.

Histones are basic nuclear proteins responsible for nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H1 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the small histone gene cluster on chromosome 6p22-p21.3.

Source: NCBI Gene 3009 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 58 total
• Druggable target: yes
• MANE Select transcript: NM_005322

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4719
Approved symbol	H1-5
Name	H1.5 linker histone, cluster member
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	H1b, H1s-3
Ensembl gene	ENSG00000184357
Ensembl biotype	protein_coding
OMIM	142711
Entrez	3009

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000331442

RefSeq mRNA: 1 — MANE Select: NM_005322 NM_005322

CCDS: CCDS4635

Canonical transcript exons

ENST00000331442 — 1 exons

Exon	Start	End
ENSE00001305578	27866792	27867588

Expression profiles

Bgee: expression breadth broad, 91 present calls, max score 99.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 586.8393 / max 11249.6646, expressed in 1651 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72387	586.8393	1651

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	99.17	gold quality
adrenal tissue	UBERON:0018303	95.26	gold quality
colonic epithelium	UBERON:0000397	86.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.24	gold quality
ventricular zone	UBERON:0003053	70.88	gold quality
tendon of biceps brachii	UBERON:0008188	69.88	gold quality
bone marrow	UBERON:0002371	68.82	gold quality
tendon	UBERON:0000043	66.54	gold quality
calcaneal tendon	UBERON:0003701	65.97	gold quality
ganglionic eminence	UBERON:0004023	64.46	gold quality
parotid gland	UBERON:0001831	62.98	gold quality
tonsil	UBERON:0002372	61.71	gold quality
buccal mucosa cell	CL:0002336	60.69	gold quality
nasal cavity epithelium	UBERON:0005384	54.10	gold quality
mucosa of transverse colon	UBERON:0004991	52.82	gold quality
monocyte	CL:0000576	51.90	gold quality
blood	UBERON:0000178	51.36	gold quality
leukocyte	CL:0000738	50.46	gold quality
thymus	UBERON:0002370	50.06	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
medial globus pallidus	UBERON:0002477	49.00	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
corpus callosum	UBERON:0002336	48.65	silver quality
biceps brachii	UBERON:0001507	47.90	gold quality
layer of synovial tissue	UBERON:0007616	47.47	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
globus pallidus	UBERON:0001875	47.00	gold quality
renal glomerulus	UBERON:0000074	46.86	gold quality
metanephric glomerulus	UBERON:0004736	46.77	gold quality
nephron tubule	UBERON:0001231	46.71	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	1934.06
E-MTAB-10662	yes	510.17
E-MTAB-11121	yes	493.76
E-MTAB-10290	yes	319.85
E-MTAB-10018	yes	151.61
E-CURD-122	yes	22.67
E-ANND-3	yes	4.29
E-MTAB-6911	no	274.01
E-MTAB-9689	no	117.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXP3, HBP1, MSX1, RB1

Literature-anchored findings (GeneRIF, showing 13)

• confirmed N-terminal acetylation on all isoforms plus a single internal acetylation site; phosphorylation sites were located on peptides containing the cyclin dependent kinase (CDK) consensus motif (PMID:15595731)
• the mode of the chromatin fiber compaction changes depending both on salt environment and linker histone H1 (PMID:16185066)
• Phosphorylation of human H1 variants occurs nonrandomly during both interphase and mitosis and distinct serine- or threonine-specific kinases are involved in different cell cycle phases. (PMID:16377619)
• Phosphorylation at threonine 10 appears in prometaphase and disappears in telophase, and that this hyperphosphorylated form of H1.5 is mainly chromatin-bound in metaphase when chromatin condensation is maximal. (PMID:19136008)
• FoxP3 interacts with H1.5 to alter its binding to target genes to modulate their expression and to program Treg function. (PMID:21654845)
• Promyelocytic leukemia zinc finger and histone H1.5 differentially stain low- and high-grade pulmonary neuroendocrine tumors (PMID:23416030)
• Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma. (PMID:24435047)
• Statistically significant differences in staining patterns were found for histone H1.5, distinguishing leiomyosarcomas from leiomyomas. (PMID:24784718)
• Data indicate that normal ovarian tissues strongly expressed histone H1.5, whereas ovarian granulosa cell tumors (GCTs) weakly expressed this protein; in contrast, PLZF protein expression was not significantly different between both study groups. (PMID:25023763)
• Study indicates that H1.5 is involved in regulation of splice site selection and alternative splicing, a function not previously demonstrated for linker histones. (PMID:31076740)
• How Human H1 Histone Recognizes DNA. (PMID:33028027)
• Nano-Surveillance: Tracking Individual Molecules in a Sea of Chromatin. (PMID:33221335)
• The nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression. (PMID:38755141)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch73-368j24.12	ENSDARG00000105502
mus_musculus	H1f5	ENSMUSG00000058773
rattus_norvegicus	H1f5	ENSRNOG00000060355
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), H1-10 (ENSG00000184897), H1-7 (ENSG00000187166), H1-6 (ENSG00000187475), H1-2 (ENSG00000187837), H1-0 (ENSG00000189060)

Protein

Protein identifiers

Histone H1.5 — P16401 (reviewed: P16401)

Alternative names: Histone H1a, Histone H1b, Histone H1s-3

All UniProt accessions (1): P16401

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. Also acts as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation.

Subunit / interactions. Associates with nucleosomes, promoting condensation into higher-order structured chromatin. Interacts with MSX1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Ubiquitous. Expressed in the majority of the cell lines tested and in testis.

Post-translational modifications. Deamidation of Asn-79 and Asn-80 by CTPS1 in response to DNA damage promotes subsequent acetylation of histone H1 at Lys-78 (H1K75ac). Acetylated at Lys-78 (H1K75ac) by EP300 following deamidation of Asn-79 and Asn-80 by CTPS1 in response to DNA damage, thereby increasing chromatin accessibility to facilitate the recruitment of DNA repair proteins. H1 histones are progressively phosphorylated during the cell cycle, becoming maximally phosphorylated during late G2 phase and M phase, and being dephosphorylated sharply thereafter. Phosphorylated at Thr-11 by GSK3B during mitosis in prometaphase and dephosphorylated in telophase. Citrullination at Arg-57 (H1R54ci) by PADI4 takes place within the DNA-binding site of H1 and results in its displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance.

Domain organisation. The C-terminal domain is required for high-affinity binding to chromatin.

Induction. Expression is activated by transcription factor CRAMP1, in collaboration with NPAT and GON4L.

Similarity. Belongs to the histone H1/H5 family.

RefSeq proteins (1): NP_005313* (*=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 (52 total): modified residue 38, compositionally biased region 5, sequence variant 3, region of interest 2, initiator methionine 1, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2RHI	X-RAY DIFFRACTION	1.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16401-F1	64.35	0.31

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 (38): 2, 2, 11, 17, 18, 26, 27, 37, 37, 37, 39, 49, 49, 55, 55, 57, 66, 67, 67, 78 …

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: 128 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_APOPTOSIS_INDUCED_DNA_FRAGMENTATION, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_NEGATIVE_REGULATION_OF_DNA_RECOMBINATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CHROMOSOME_CONDENSATION, GOBP_PROTEIN_STABILIZATION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_REGULATION_OF_PROTEIN_STABILITY, FISCHER_DREAM_TARGETS, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, REACTOME_APOPTOSIS

GO Biological Process (8): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin organization (GO:0006325), nucleosome assembly (GO:0006334), muscle organ development (GO:0007517), chromosome condensation (GO:0030261), negative regulation of DNA recombination (GO:0045910), protein stabilization (GO:0050821), establishment of protein localization to chromatin (GO:0071169)

GO Molecular Function (8): double-stranded DNA binding (GO:0003690), RNA binding (GO:0003723), structural constituent of chromatin (GO:0030527), chromatin DNA binding (GO:0031490), nucleosomal DNA binding (GO:0031492), histone deacetylase binding (GO:0042826), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), nucleosome (GO:0000786), euchromatin (GO:0000791), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730)

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	4
DNA binding	2
nucleic acid binding	2
cellular anatomical structure	2
nuclear lumen	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cellular component organization	1
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
animal organ development	1
muscle structure development	1
chromosome organization	1
regulation of DNA recombination	1
DNA recombination	1
negative regulation of DNA metabolic process	1
regulation of protein stability	1
establishment of protein localization to chromosome	1
structural molecule activity	1
chromatin binding	1
chromatin DNA binding	1
nucleosome binding	1
enzyme binding	1
binding	1
chromosome	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H1-5	H2AC19	P20670	989
H1-5	H2AC20	Q16777	989
H1-5	MSX1	P28360	985
H1-5	H2BC21	Q16778	976
H1-5	H1-7	Q75WM6	891
H1-5	H1-8	Q8IZA3	857
H1-5	H1-1	Q02539	851
H1-5	CBX3	Q13185	816
H1-5	H2AC13	P02261	756
H1-5	L3MBTL1	Q9Y468	728
H1-5	H2AC1	Q96QV6	655
H1-5	H2AC8	P04908	599
H1-5	H2BC5	P58876	595
H1-5	H2BC8	P02278	593
H1-5	C4A	P01028	586

IntAct

319 interactions, top by confidence:

A	B	Type	Score
CBX8	H1-5	psi-mi:“MI:0915”(physical association)	0.560
H1-5	H2AC21	psi-mi:“MI:0915”(physical association)	0.560
RPS19	H1-5	psi-mi:“MI:0915”(physical association)	0.560
DHX30	H1-5	psi-mi:“MI:0915”(physical association)	0.560
CENPC	H1-5	psi-mi:“MI:0915”(physical association)	0.560
NCL	H1-5	psi-mi:“MI:0915”(physical association)	0.560
H1-5	GNA12	psi-mi:“MI:0915”(physical association)	0.400
H1-5	GPATCH8	psi-mi:“MI:0915”(physical association)	0.400
H1-5	PDCD11	psi-mi:“MI:0915”(physical association)	0.400
H1-5	SENP3	psi-mi:“MI:0915”(physical association)	0.400
H1-5	HMGA2	psi-mi:“MI:0915”(physical association)	0.400
HMMR	H1-5	psi-mi:“MI:0915”(physical association)	0.400
H1-5	ZMPSTE24	psi-mi:“MI:0915”(physical association)	0.400
H1-5	TOMM20	psi-mi:“MI:0915”(physical association)	0.400
UTP3	H1-5	psi-mi:“MI:0915”(physical association)	0.400
GPRASP1	H1-5	psi-mi:“MI:0915”(physical association)	0.400
H1-5	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
CDX2	H1-5	psi-mi:“MI:0915”(physical association)	0.400
IQGAP2	H1-5	psi-mi:“MI:0915”(physical association)	0.400
BICD2	H1-5	psi-mi:“MI:0915”(physical association)	0.400
CLDN10	H1-5	psi-mi:“MI:0915”(physical association)	0.400
H1-5	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
H1-5	H1-4	psi-mi:“MI:0915”(physical association)	0.400
H1-5	EEF1A1	psi-mi:“MI:0915”(physical association)	0.400
CALY	H1-5	psi-mi:“MI:0915”(physical association)	0.400
ASCL5	H1-5	psi-mi:“MI:0915”(physical association)	0.400
PHF3	H1-5	psi-mi:“MI:0915”(physical association)	0.400
EHBP1	H1-5	psi-mi:“MI:0915”(physical association)	0.400
DIP2A	H1-5	psi-mi:“MI:0915”(physical association)	0.400
WFIKKN1	H1-5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (599): HIST1H1B (Affinity Capture-MS), HIST1H1B (Biochemical Activity), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), HIST1H1B (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

1 interactions.

A	Effect	B	Mechanism
GSK3B	up-regulates	H1-5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 211 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)	8	40.4×	4e-09
Deposition of new CENPA-containing nucleosomes at the centromere	8	9.5×	4e-04
Meiotic synapsis	8	8.5×	7e-04
rRNA processing in the nucleus and cytosol	7	8.5×	2e-03
Condensation of Prophase Chromosomes	7	8.2×	2e-03
rRNA processing	7	7.7×	3e-03
HDACs deacetylate histones	7	6.3×	8e-03
Major pathway of rRNA processing in the nucleolus and cytosol	10	4.6×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
chromosome condensation	7	31.0×	9e-07
negative regulation of DNA recombination	5	29.6×	2e-04
heterochromatin formation	8	10.8×	2e-04
nucleosome assembly	14	10.3×	1e-07
chromatin organization	12	6.3×	2e-04
cell division	16	3.9×	8e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

132 predictions. Top by Δscore:

Variant	Effect	Δscore
6:27867429:G:C	donor_gain	0.9300
6:27867455:AGTTG:A	donor_gain	0.8900
6:27867459:G:A	donor_gain	0.7200
6:27866854:T:TA	donor_gain	0.7100
6:27867138:G:C	donor_gain	0.6800
6:27866852:CTT:C	donor_gain	0.6300
6:27867153:G:A	donor_gain	0.6000
6:27866851:A:AC	donor_gain	0.5900
6:27866852:C:CC	donor_gain	0.5900
6:27867078:G:GA	donor_gain	0.5900
6:27866943:A:C	donor_gain	0.5800
6:27867259:CCAAG:C	donor_gain	0.5800
6:27867470:AG:A	donor_gain	0.5700
6:27867254:GCTCA:G	donor_loss	0.5600
6:27867255:CT:C	donor_loss	0.5600
6:27867256:T:TC	donor_loss	0.5600
6:27867257:CACC:C	donor_loss	0.5600
6:27867258:ACCAA:A	donor_loss	0.5600
6:27867259:CCA:C	donor_loss	0.5600
6:27867054:G:A	donor_gain	0.5500
6:27867252:TTGC:T	donor_loss	0.5500
6:27867253:TGCT:T	donor_loss	0.5500
6:27867049:T:TA	donor_gain	0.5200
6:27867263:G:C	donor_gain	0.5200
6:27866973:G:A	donor_gain	0.5000
6:27867428:A:AC	donor_gain	0.5000
6:27867471:G:C	donor_gain	0.5000
6:27866849:C:CT	donor_gain	0.4900
6:27866850:T:TT	donor_gain	0.4900
6:27866913:G:C	donor_gain	0.4900

AlphaMissense

1440 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:27867206:A:C	F108L	1.000
6:27867206:A:T	F108L	1.000
6:27867207:A:G	F108S	1.000
6:27867208:A:G	F108L	1.000
6:27867229:C:A	G101C	1.000
6:27867229:C:G	G101R	1.000
6:27867207:A:C	F108C	0.999
6:27867213:C:A	G106V	0.999
6:27867213:C:T	G106D	0.999
6:27867214:C:A	G106C	0.999
6:27867214:C:G	G106R	0.999
6:27867219:G:T	A104D	0.999
6:27867222:C:T	G103D	0.999
6:27867223:C:A	G103C	0.999
6:27867223:C:G	G103R	0.999
6:27867228:C:A	G101V	0.999
6:27867228:C:T	G101D	0.999
6:27867229:C:T	G101S	0.999
6:27867243:A:T	L96Q	0.999
6:27867270:A:T	L87H	0.999
6:27867282:A:C	I83S	0.999
6:27867282:A:G	I83T	0.999
6:27867282:A:T	I83N	0.999
6:27867285:C:G	R82P	0.999
6:27867286:G:T	R82S	0.999
6:27867324:A:G	L69S	0.999
6:27867332:C:A	K66N	0.999
6:27867332:C:G	K66N	0.999
6:27867336:A:T	L65H	0.999
6:27867354:C:T	G59D	0.999

dbSNP variants (sampled 300 via entrez): RS1000059765 (6:27867741 A>G), RS1001004719 (6:27869039 C>A), RS1002138254 (6:27868570 T>C), RS1002190688 (6:27868971 G>A), RS1002806190 (6:27866596 A>G), RS1002857078 (6:27866759 A>G,T), RS1002973692 (6:27868536 A>C,G), RS1004237990 (6:27868028 G>A), RS1004533431 (6:27867725 T>C), RS1005088425 (6:27868091 A>G), RS1007835420 (6:27866876 G>A,C,T), RS1008650642 (6:27866386 G>A), RS1009311528 (6:27866695 G>A,T), RS1009395659 (6:27867610 G>T), RS1009982175 (6:27867511 C>A,G,T)

Disease associations

OMIM: gene MIM:142711 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST004521_112	Autism spectrum disorder or schizophrenia	3.000000e-26
GCST004521_115	Autism spectrum disorder or schizophrenia	3.000000e-16
GCST004521_116	Autism spectrum disorder or schizophrenia	3.000000e-16
GCST004521_166	Autism spectrum disorder or schizophrenia	4.000000e-24
GCST004521_22	Autism spectrum disorder or schizophrenia	2.000000e-11
GCST004521_23	Autism spectrum disorder or schizophrenia	2.000000e-11
GCST004521_6	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_73	Autism spectrum disorder or schizophrenia	8.000000e-11
GCST008921_6	Asthma and major depressive disorder	1.000000e-09
GCST009150_10	Low density lipoprotein cholesterol levels	3.000000e-08
GCST010002_50	Refractive error	4.000000e-34
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066952 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.40	Kd	3998	nM	CHEMBL3752910
5.40	ED50	3998	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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	2148505: Binding affinity to human HIST1H1B incubated for 45 mins by Kinobead based pull down assay	kd	3.9976	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment, decreases methylation, decreases expression	5
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
Doxorubicin	affects response to substance, affects expression, decreases expression, affects phosphorylation	3
epigallocatechin gallate	decreases expression, increases expression, affects cotreatment	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Caffeine	decreases phosphorylation, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
nobiletin	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, decreases expression, affects cotreatment	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
hydroxyhydroquinone	decreases expression	1
thallium sulfate	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
versicolorin A	decreases expression	1
coumarin	decreases phosphorylation	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
picene	increases expression	1
polyhexamethyleneguanidine	affects expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, 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
CHEMBL5651547	Binding	Binding affinity to human HIST1H1B 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

14 cell lines: 14 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C9K2	WAe001-A-93	Embryonic stem cell	Male
CVCL_C9K3	WAe001-A-94	Embryonic stem cell	Male
CVCL_C9KE	WAe001-A-G	Embryonic stem cell	Male
CVCL_C9KF	WAe001-A-H	Embryonic stem cell	Male
CVCL_C9KP	WAe001-A-Q	Embryonic stem cell	Male
CVCL_C9KQ	WAe001-A-R	Embryonic stem cell	Male
CVCL_C9KV	WAe001-A-W	Embryonic stem cell	Male
CVCL_C9KW	WAe001-A-X	Embryonic stem cell	Male
CVCL_C9L1	WAe001-A-1C	Embryonic stem cell	Male
CVCL_C9L2	WAe001-A-1D	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery