H2BC11

Summary

H2BC11 (H2B clustered histone 11, HGNC:4761) is a protein-coding gene on chromosome 6p22.1, encoding Histone H2B type 1-J (P06899). Core component of nucleosome. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

Histones are basic nuclear proteins that are responsible for the 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 H2B family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the histone microcluster on chromosome 6p21.33.

Source: NCBI Gene 8970 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 25 total
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_021058

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4761
Approved symbol	H2BC11
Name	H2B clustered histone 11
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	H2B/r
Ensembl gene	ENSG00000124635
Ensembl biotype	protein_coding
OMIM	615044
Entrez	8970

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000339812, ENST00000606923, ENST00000607124, ENST00000939860

RefSeq mRNA: 1 — MANE Select: NM_021058 NM_021058

CCDS: CCDS4618

Canonical transcript exons

ENST00000339812 — 1 exons

Exon	Start	End
ENSE00002255833	27132316	27132795

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 98.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 246.8781 / max 6879.1525, expressed in 1813 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72355	246.8781	1813

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	98.73	gold quality
monocyte	CL:0000576	95.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.39	gold quality
calcaneal tendon	UBERON:0003701	95.28	gold quality
leukocyte	CL:0000738	94.51	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.45	gold quality
left testis	UBERON:0004533	93.15	gold quality
right testis	UBERON:0004534	93.09	gold quality
testis	UBERON:0000473	92.57	gold quality
adrenal tissue	UBERON:0018303	92.38	gold quality
blood	UBERON:0000178	89.87	gold quality
bone marrow	UBERON:0002371	87.18	gold quality
granulocyte	CL:0000094	83.13	gold quality
lower esophagus mucosa	UBERON:0035834	81.99	gold quality
corpus callosum	UBERON:0002336	80.58	gold quality
tonsil	UBERON:0002372	80.39	gold quality
colonic epithelium	UBERON:0000397	79.88	gold quality
mucosa of transverse colon	UBERON:0004991	78.25	gold quality
vagina	UBERON:0000996	78.11	gold quality
spleen	UBERON:0002106	77.99	gold quality
right lung	UBERON:0002167	77.73	gold quality
esophagus mucosa	UBERON:0002469	76.23	gold quality
gastrocnemius	UBERON:0001388	76.12	gold quality
muscle of leg	UBERON:0001383	75.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	75.97	gold quality
spinal cord	UBERON:0002240	75.74	gold quality
prostate gland	UBERON:0002367	74.39	gold quality
lung	UBERON:0002048	74.37	gold quality
uterine cervix	UBERON:0000002	74.29	gold quality
skeletal muscle tissue	UBERON:0001134	73.24	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	21.36
E-ANND-3	yes	7.76
E-HCAD-1	yes	5.56
E-GEOD-124858	no	12.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F4, EZH2, HEY1, POU2F1, POU2F2, PPARA, TP53

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• Histone H2A and H2B antimicrobial peptides exhibit antibacterial activity and endotoxin-neutralizing activity in the placenta. (PMID:11859126)
• The genes HIST1H2BJ, PRSS16, and PGBD1 were not associated with Japanese patients with schizophrenia. (PMID:22488895)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2bc21	ENSMUSG00000068854
rattus_norvegicus		ENSRNOG00000075829

Paralogs (21): H2BW2 (ENSG00000101812), H2BW1 (ENSG00000123569), H2BC1 (ENSG00000146047), H2BC5 (ENSG00000158373), H2BC4 (ENSG00000180596), H2BC21 (ENSG00000184678), H2BC13 (ENSG00000185130), H2BC26 (ENSG00000196890), H2BC12 (ENSG00000197903), H2BC18 (ENSG00000203814), H2BC15 (ENSG00000233822), H2BC12L (ENSG00000234289), H2BC14 (ENSG00000273703), H2BC8 (ENSG00000273802), H2BC6 (ENSG00000274290), H2BC17 (ENSG00000274641), H2BC9 (ENSG00000275713), H2BC3 (ENSG00000276410), H2BC7 (ENSG00000277224), H2BC10 (ENSG00000278588), H2BK1 (ENSG00000285480)

Protein

Protein identifiers

Histone H2B type 1-J — P06899 (reviewed: P06899)

Alternative names: Histone H2B.1, Histone H2B.r

All UniProt accessions (2): P06899, U3KPT8

UniProt curated annotations — full annotation on UniProt →

Function. Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.

Subunit / interactions. The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Heterodimer H2BC11 and H2AZ1 interacts with VPS72 (via N-terminal domain).

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 ‘Lys-4’ (H3K4me) and ‘Lys-79’ (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 ‘Lys-4’ and ‘Lys-79’ methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons. Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription. Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination. GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes. ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage. H2BS6ADPr promotes recruitment of CHD1L. Mono-ADP-ribosylated on Glu-3 (H2BE2ADPr) by PARP3 in response to single-strand breaks. Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes. Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes. Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.

Similarity. Belongs to the histone H2B family.

RefSeq proteins (1): NP_066402* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000558	Histone_H2B	Family
IPR007125	H2A/H2B/H3	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR055333	HISTONE_H2B_site	Conserved_site

Pfam: PF00125

UniProt features (109 total): modified residue 91, helix 4, cross-link 4, strand 3, initiator methionine 1, chain 1, sequence conflict 1, turn 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

304 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4CAY	X-RAY DIFFRACTION	1.48
7VZ4	ELECTRON MICROSCOPY	1.89
8I17	X-RAY DIFFRACTION	1.98
5B0Z	X-RAY DIFFRACTION	1.99
5Y0D	X-RAY DIFFRACTION	1.99
6IPU	X-RAY DIFFRACTION	1.99
9INC	X-RAY DIFFRACTION	2.01
5Y0C	X-RAY DIFFRACTION	2.09
6JOU	X-RAY DIFFRACTION	2.17
5X7X	X-RAY DIFFRACTION	2.18
5AV6	X-RAY DIFFRACTION	2.2
5AV8	X-RAY DIFFRACTION	2.2
5AV9	X-RAY DIFFRACTION	2.2
5B31	X-RAY DIFFRACTION	2.2
6K1K	X-RAY DIFFRACTION	2.2
6KVD	X-RAY DIFFRACTION	2.21
6IQ4	X-RAY DIFFRACTION	2.25
6JXD	X-RAY DIFFRACTION	2.25
8KB5	ELECTRON MICROSCOPY	2.26
5B32	X-RAY DIFFRACTION	2.35
8JLB	ELECTRON MICROSCOPY	2.36
8YBJ	ELECTRON MICROSCOPY	2.38
3AZG	X-RAY DIFFRACTION	2.4
5AV5	X-RAY DIFFRACTION	2.4
5AVB	X-RAY DIFFRACTION	2.4
5AVC	X-RAY DIFFRACTION	2.4
6JR1	X-RAY DIFFRACTION	2.4
5Z30	X-RAY DIFFRACTION	2.45
8JLD	ELECTRON MICROSCOPY	2.48
8VG1	ELECTRON MICROSCOPY	2.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06899-F1	85.70	0.71

Antibody-complex structures (SAbDab): 8 — 6E0C, 6E0P, 7K5X, 7K5Y, 7K60, 7K61, 7K63, 8VFX

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 (95): 6, 6, 6, 6, 7, 12, 12, 12, 12, 12, 12, 13, 13, 13, 15, 16, 16, 16, 16, 17 …

Glycosylation sites (1): 113

Function

Pathways and Gene Ontology

Reactome pathways

58 pathways

ID	Pathway
R-HSA-110328	Recognition and association of DNA glycosylase with site containing an affected pyrimidine
R-HSA-110329	Cleavage of the damaged pyrimidine
R-HSA-110330	Recognition and association of DNA glycosylase with site containing an affected purine
R-HSA-110331	Cleavage of the damaged purine
R-HSA-1221632	Meiotic synapsis
R-HSA-171306	Packaging Of Telomere Ends
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-212300	PRC2 methylates histones and DNA
R-HSA-2299718	Condensation of Prophase Chromosomes
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-3214815	HDACs deacetylate histones
R-HSA-3214847	HATs acetylate histones
R-HSA-427359	SIRT1 negatively regulates rRNA expression
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-5334118	DNA methylation
R-HSA-5578749	Transcriptional regulation by small RNAs
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-5625886	Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-68616	Assembly of the ORC complex at the origin of replication
R-HSA-69473	G2/M DNA damage checkpoint

MSigDB gene sets: 284 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, REACTOME_MEIOTIC_RECOMBINATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_MEIOTIC_SYNAPSIS, GOBP_RESPONSE_TO_PEPTIDE, ENK_UV_RESPONSE_KERATINOCYTE_UP, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_NEGATIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP

GO Biological Process (11): innate immune response in mucosa (GO:0002227), chromatin organization (GO:0006325), nucleosome assembly (GO:0006334), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), antibacterial humoral response (GO:0019731), killing of cells of another organism (GO:0031640), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), protein localization to CENP-A containing chromatin (GO:0061644), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), defense response to bacterium (GO:0042742)

GO Molecular Function (5): lipopolysaccharide binding (GO:0001530), DNA binding (GO:0003677), structural constituent of chromatin (GO:0030527), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (8): nucleosome (GO:0000786), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), CENP-A containing nucleosome (GO:0043505), chromosome (GO:0005694), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Cellular Senescence	3
Depyrimidination	2
Depurination	2
Epigenetic regulation of gene expression	2
Chromatin modifying enzymes	2
Negative epigenetic regulation of rRNA expression	2
Positive epigenetic regulation of rRNA expression	2
Meiosis	1
Telomere Maintenance	1
Pre-NOTCH Expression and Processing	1
TCF dependent signaling in response to WNT	1
Mitotic Prophase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response to bacterium	3
antimicrobial humoral response	2
chromatin	2
cellular anatomical structure	2
mucosal immune response	1
innate immune response	1
cellular component organization	1
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
cell killing	1
disruption of cell in another organism	1
protein localization to chromatin	1
protein localization to chromosome, centromeric region	1
defense response	1
response to bacterium	1
lipid binding	1
carbohydrate derivative binding	1
nucleic acid binding	1
structural molecule activity	1
protein dimerization activity	1
binding	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nucleosome	1
CENP-A containing chromatin	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2420 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2BC11	PLG	P00747	874
H2BC11	RNF20	Q5VTR2	836
H2BC11	H3C1	P02295	816
H2BC11	H3C14	Q71DI3	809
H2BC11	H3-7	Q5TEC6	809
H2BC11	H3-3A	P06351	808
H2BC11	H3-5	Q6NXT2	808
H2BC11	H3-4	Q16695	808
H2BC11	RNF40	O75150	772
H2BC11	H2AC19	P20670	762
H2BC11	H2AC20	Q16777	756
H2BC11	H4C16	P02304	747
H2BC11	H4C7	Q99525	744
H2BC11	DET1	Q7L5Y6	725
H2BC11	USP22	Q9UPT9	722

IntAct

109 interactions, top by confidence:

A	B	Type	Score
H2AC4	H2BC11	psi-mi:“MI:0915”(physical association)	0.850
H2AC4	H2BC11	psi-mi:“MI:0407”(direct interaction)	0.850
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
H2AC18	PPM1G	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
ERBB2	HAX1	psi-mi:“MI:0914”(association)	0.530
		psi-mi:“MI:0915”(physical association)	0.500
ACTR5	H2AC4	psi-mi:“MI:0915”(physical association)	0.460
ACTR5	H2AC4	psi-mi:“MI:0914”(association)	0.460
ANP32E	H2BC11	psi-mi:“MI:0407”(direct interaction)	0.440
PPM1G	H2BC12	psi-mi:“MI:0914”(association)	0.420
PPM1G	H2BC12	psi-mi:“MI:2364”(proximity)	0.420
H2BC11	TLX3	psi-mi:“MI:0915”(physical association)	0.370
JMJD6	H2BC11	psi-mi:“MI:0915”(physical association)	0.370
CREB1	NFIX	psi-mi:“MI:0914”(association)	0.350

BioGRID (400): HIST1H2BJ (Affinity Capture-MS), HIST1H2BJ (Affinity Capture-MS), HIST1H2BJ (Affinity Capture-MS), HIST1H2BJ (Affinity Capture-MS), HIST1H2BJ (Affinity Capture-MS), HIST1H2BJ (Affinity Capture-MS), HIST1H2BJ (Affinity Capture-MS), HIST1H2BJ (Biochemical Activity), PARP9 (Affinity Capture-Western), DTX3L (Affinity Capture-Western), STAT1 (Affinity Capture-Western), HIST1H2BJ (Affinity Capture-Western), FGA (Affinity Capture-MS), FGB (Affinity Capture-MS), FGG (Affinity Capture-MS)

ESM2 similar proteins: A1CJ09, A1D8G9, A2QY49, A3LXE6, A3LZZ1, A5DBG5, A5DJJ1, A5DWF0, L7I1W3, P02281, P02293, P02294, P04255, P04913, P06899, P0C1H5, P0CO02, P0CO03, P0CT13, P10853, P23754, P37210, P48989, P78567, Q0CBD1, Q1E5N0, Q1SU99, Q27484, Q27876, Q27894, Q2HH38, Q2U5A9, Q43217, Q4HTT2, Q4PEF8, Q4WWC5, Q59VP1, Q5RCP8, Q6BKW7, Q6BRG2

Diamond homologs: A0A2R8Y619, A2WKT1, A2WKT4, A2WWU2, A2XF66, A2YWI3, A3AGM4, O22582, O60814, O65819, P02281, P02283, P02284, P02285, P02286, P02287, P02288, P02289, P02290, P04255, P06145, P06899, P06900, P07794, P07795, P0C1H3, P0C1H4, P0C1H5, P10853, P10854, P14001, P16888, P16889, P16890, P17271, P19374, P21897, P23527, P27326, P27807

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
H2BC11	“form complex”	“Nucleosome_H3.3 variant”	binding
SLBP	“up-regulates quantity by expression”	H2BC11	“translation regulation”
“MSL acetyltransferase”	“down-regulates activity”	H2BC11	monoubiquitination
H2BC11	“form complex”	“CENP-A nucleosome”	binding
H2BC11	“form complex”	“Nucleosome_H2A.Z.2 variant”	binding
H2BC11	“form complex”	“Nucleosome_H2A.Z.1 variant”	binding
H2BC11	“form complex”	“Nucleosome_H3.1 variant”	binding
H2BC11	“form complex”	“Nucleosome_H3.1t variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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
Transcriptional regulation of granulopoiesis	11	19.2×	6e-09
ChAHP complex assembly	6	15.3×	2e-04
Packaging Of Telomere Ends	5	15.2×	8e-04
SIRT1 negatively regulates rRNA expression	6	14.2×	3e-04
Recognition and association of DNA glycosylase with site containing an affected purine	5	14.2×	9e-04
Cleavage of the damaged purine	5	14.2×	9e-04
Inhibition of DNA recombination at telomere	6	14.0×	3e-04
Regulation of PD-L1(CD274) transcription	9	13.6×	6e-06

GO biological processes:

GO term	Partners	Fold	FDR
mRNA transcription by RNA polymerase II	5	18.6×	2e-03
heterochromatin formation	6	17.2×	7e-04
positive regulation of miRNA transcription	5	16.3×	2e-03
response to ethanol	7	11.5×	9e-04
nucleosome assembly	6	9.5×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

409 predictions. Top by Δscore:

Variant	Effect	Δscore
6:27132365:A:AC	donor_gain	1.0000
6:27132366:C:CC	donor_gain	1.0000
6:27132376:A:AC	donor_gain	1.0000
6:27132376:AG:A	donor_gain	1.0000
6:27132376:AGCG:A	donor_gain	1.0000
6:27132377:G:C	donor_gain	1.0000
6:27126459:CCAC:C	acceptor_gain	0.9900
6:27126460:CACC:C	acceptor_gain	0.9900
6:27132361:ACT:A	donor_loss	0.9900
6:27132362:C:G	donor_loss	0.9900
6:27132362:CTCA:C	donor_gain	0.9900
6:27132363:TCACT:T	donor_loss	0.9900
6:27132364:CA:C	donor_loss	0.9900
6:27132365:AC:A	donor_loss	0.9900
6:27132366:CT:C	donor_gain	0.9900
6:27132366:CTG:C	donor_gain	0.9900
6:27132372:A:AC	donor_gain	0.9900
6:27132373:C:CC	donor_gain	0.9900
6:27132390:TGGTG:T	donor_gain	0.9900
6:27132403:AGTAC:A	donor_gain	0.9900
6:27126460:CAC:C	acceptor_gain	0.9800
6:27126460:CACCT:C	acceptor_loss	0.9800
6:27126461:ACC:A	acceptor_loss	0.9800
6:27126463:C:CC	acceptor_gain	0.9800
6:27126463:CT:C	acceptor_loss	0.9800
6:27126464:T:G	acceptor_loss	0.9800
6:27127401:CCTT:C	acceptor_gain	0.9800
6:27127400:CCCTT:C	acceptor_gain	0.9700
6:27127412:C:CT	acceptor_gain	0.9700
6:27127413:A:T	acceptor_gain	0.9700

AlphaMissense

814 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:27132400:C:A	K117N	1.000
6:27132400:C:G	K117N	1.000
6:27132407:C:A	G115V	1.000
6:27132407:C:T	G115D	1.000
6:27132408:C:A	G115C	1.000
6:27132408:C:G	G115R	1.000
6:27132419:G:T	A111D	1.000
6:27132431:A:C	L107W	1.000
6:27132431:A:G	L107S	1.000
6:27132437:C:A	G105V	1.000
6:27132437:C:T	G105E	1.000
6:27132438:C:A	G105W	1.000
6:27132449:A:G	L101P	1.000
6:27132458:G:T	A98D	1.000
6:27132459:C:G	A98P	1.000
6:27132463:C:A	Q96H	1.000
6:27132463:C:G	Q96H	1.000
6:27132471:C:T	E94K	1.000
6:27132472:C:A	R93S	1.000
6:27132472:C:G	R93S	1.000
6:27132473:C:A	R93M	1.000
6:27132519:C:G	A78P	1.000
6:27132545:T:A	D69V	1.000
6:27132608:T:G	Q48P	1.000
6:27132614:A:G	L46P	1.000
6:27132395:A:T	V119D	0.999
6:27132398:G:T	A118D	0.999
6:27132399:C:G	A118P	0.999
6:27132402:T:C	K117E	0.999
6:27132404:G:A	T116I	0.999

dbSNP variants (sampled 300 via entrez): RS1000107163 (6:27131958 G>A), RS1001283944 (6:27133597 C>T), RS1001313399 (6:27133468 T>C), RS1002289581 (6:27134532 T>C), RS1002319247 (6:27134237 A>C), RS1004388343 (6:27134226 A>G), RS1004761593 (6:27134472 T>G), RS1005075620 (6:27132276 C>T), RS1006198827 (6:27133752 A>G), RS1006537220 (6:27131999 G>A,C), RS1006766102 (6:27132233 CA>C,CAA), RS1007849734 (6:27133891 G>A,T), RS1008207013 (6:27132727 A>G), RS1008298911 (6:27132812 G>A), RS1008424451 (6:27133744 A>G)

Disease associations

OMIM: gene MIM:615044 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000301_13	Iron status biomarkers	1.000000e-08
GCST000433_1	Schizophrenia	1.000000e-08
GCST004521_113	Autism spectrum disorder or schizophrenia	3.000000e-19
GCST004521_116	Autism spectrum disorder or schizophrenia	3.000000e-16
GCST004521_166	Autism spectrum disorder or schizophrenia	4.000000e-24
GCST004521_208	Autism spectrum disorder or schizophrenia	5.000000e-17
GCST004521_215	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_286	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST004521_57	Autism spectrum disorder or schizophrenia	1.000000e-20
GCST004521_69	Autism spectrum disorder or schizophrenia	8.000000e-24
GCST004571_23	Iron status biomarkers (total iron binding capacity)	2.000000e-08
GCST004572_4	Iron status biomarkers (transferrin saturation)	2.000000e-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
GCST010142_74	Fish- and plant-related diet	9.000000e-09
GCST010142_82	Fish- and plant-related diet	3.000000e-08
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16
GCST90016674_5	Liver iron content	2.000000e-135

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004461	iron biomarker measurement
EFO:0006334	total iron binding capacity
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects binding, increases reaction, decreases expression	6
(+)-JQ1 compound	increases expression	5
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression	4
Benzo(a)pyrene	increases expression, decreases methylation	3
bisphenol A	decreases expression, increases expression	2
Acetaminophen	increases expression	2
Doxorubicin	affects expression	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
UF010 compound	increases acetylation	1
OTX015	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
trichostatin A	affects expression	1
thallium sulfate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ferrous chloride	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
homosalate	affects cotreatment, increases expression	1
obeticholic acid	decreases expression	1
abrine	increases expression	1
Poly(amidoamine)	increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
Leflunomide	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1

Cellosaurus cell lines

30 cell lines: 17 cancer cell line, 10 embryonic stem cell, 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_1D62	HeLa Kyoto EGFP-LaminA/H2B-mCherry	Cancer cell line	Female
CVCL_1D63	HeLa Kyoto EGFP-H2B	Cancer cell line	Female
CVCL_1D65	HeLa Kyoto Mad2-LAP/H2B-mCherry	Cancer cell line	Female
CVCL_A2AY	YUMMER1.7 H2B-GFP5	Cancer cell line	Male
CVCL_A5NJ	H7-H2B-RFP	Embryonic stem cell	Female
CVCL_A5NK	H14-H2B-RFP	Embryonic stem cell	Male
CVCL_A5NL	HUES 17-H2B-RFP	Embryonic stem cell	Male
CVCL_A7QQ	U2OS EGFP-H2B	Cancer cell line	Female
CVCL_C4SE	CCMB-Me-14-STGG-A1	Embryonic stem cell	Male
CVCL_E7GG	H9 NR4A2-eGFP	Embryonic stem cell	Female

Clinical trials (associated diseases)

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