H2BC5

Summary

H2BC5 (H2B clustered histone 5, HGNC:4747) is a protein-coding gene on chromosome 6p22.2, encoding Histone H2B type 1-D (P58876). Core component of nucleosome. It is a selective cancer dependency (DepMap: 34.0% of cell lines).

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-dependent histone that is a member of the histone H2B family. Two transcripts that encode the same protein have been identified for this gene, which is found in the large histone gene cluster on chromosome 6p22-p21.3.

Source: NCBI Gene 3017 — RefSeq curated summary.

At a glance

• GWAS associations: 41
• Clinical variants (ClinVar): 19 total
• Cancer dependency (DepMap): dependent in 34.0% of screened cell lines
• MANE Select transcript: NM_021063

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4747
Approved symbol	H2BC5
Name	H2B clustered histone 5
Location	6p22.2
Locus type	gene with protein product
Status	Approved
Aliases	H2B/b
Ensembl gene	ENSG00000158373
Ensembl biotype	protein_coding
OMIM	602799
Entrez	3017

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000289316, ENST00000377777, ENST00000890792, ENST00000939398, ENST00000939399

RefSeq mRNA: 2 — MANE Select: NM_021063 NM_021063, NM_138720

CCDS: CCDS4587

Canonical transcript exons

ENST00000377777 — 1 exons

Exon	Start	End
ENSE00001475093	26158122	26158607

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 98.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 409.6246 / max 6265.7454, expressed in 1818 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66479	409.6246	1818

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.56	gold quality
calcaneal tendon	UBERON:0003701	97.24	gold quality
adrenal tissue	UBERON:0018303	96.34	gold quality
mucosa of transverse colon	UBERON:0004991	95.58	gold quality
pylorus	UBERON:0001166	93.92	gold quality
lower esophagus mucosa	UBERON:0035834	93.90	gold quality
prostate gland	UBERON:0002367	93.59	gold quality
tendon	UBERON:0000043	92.83	gold quality
colonic epithelium	UBERON:0000397	92.55	gold quality
tendon of biceps brachii	UBERON:0008188	91.65	silver quality
right lobe of liver	UBERON:0001114	91.61	gold quality
heart right ventricle	UBERON:0002080	91.45	silver quality
metanephros cortex	UBERON:0010533	91.10	gold quality
ganglionic eminence	UBERON:0004023	90.74	gold quality
adult mammalian kidney	UBERON:0000082	90.65	gold quality
islet of Langerhans	UBERON:0000006	90.63	gold quality
apex of heart	UBERON:0002098	90.38	gold quality
adenohypophysis	UBERON:0002196	89.87	gold quality
bronchial epithelial cell	CL:0002328	89.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.43	gold quality
pituitary gland	UBERON:0000007	89.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.09	gold quality
vagina	UBERON:0000996	89.03	gold quality
heart left ventricle	UBERON:0002084	88.92	gold quality
cardiac ventricle	UBERON:0002082	88.70	gold quality
blood	UBERON:0000178	88.58	gold quality
monocyte	CL:0000576	88.52	gold quality
mononuclear cell	CL:0000842	88.37	gold quality
esophagus mucosa	UBERON:0002469	88.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.06	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.59

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• We report cryo-EM structures of human Dot1L bound to (1) H2BK120Ub and (2) unmodified nucleosome substrates at 3.5 A and 4.9 A, respectively. Comparison of both structures, complemented with biochemical experiments, provides critical insights into the mechanism of Dot1L stimulation by H2BK120Ub. (PMID:30981630)
• Epigenetic landscape of testis specific histone H2B variant and its influence on sperm function. (PMID:33933143)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2bc14	ENSMUSG00000114279
rattus_norvegicus	Hist1h2bo	ENSRNOG00000068034

Paralogs (21): H2BW2 (ENSG00000101812), H2BW1 (ENSG00000123569), H2BC11 (ENSG00000124635), H2BC1 (ENSG00000146047), 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-D — P58876 (reviewed: P58876)

Alternative names: H2B-clustered histone 5, HIRA-interacting protein 2, Histone H2B.1 B, Histone H2B.b

All UniProt accessions (1): P58876

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.

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.

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.

Miscellaneous. The mouse orthologous protein does not seem to exist.

Similarity. Belongs to the histone H2B family.

RefSeq proteins (2): NP_066407, NP_619790 (=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 (100 total): modified residue 91, cross-link 4, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P58876-F1	87.58	0.69

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: 321 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, REACTOME_MEIOTIC_RECOMBINATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_MEIOTIC_SYNAPSIS, FISCHER_G1_S_CELL_CYCLE, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, PATIL_LIVER_CANCER, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS

GO Biological Process (0):

GO Molecular Function (4): DNA binding (GO:0003677), structural constituent of chromatin (GO:0030527), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (6): nucleosome (GO:0000786), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), extracellular exosome (GO:0070062), chromosome (GO:0005694)

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
chromatin	2
cellular anatomical structure	2
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
extracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2BC5	PLG	P00747	866
H2BC5	H3C1	P02295	863
H2BC5	RNF20	Q5VTR2	823
H2BC5	H3-3A	P06351	797
H2BC5	H3-4	Q16695	797
H2BC5	H3-7	Q5TEC6	797
H2BC5	H3-5	Q6NXT2	797
H2BC5	H3C14	Q71DI3	797
H2BC5	H4C16	P02304	768
H2BC5	H2AC19	P20670	764
H2BC5	H2AC20	Q16777	764
H2BC5	RNF40	O75150	756
H2BC5	H4C7	Q99525	742
H2BC5	DET1	Q7L5Y6	721
H2BC5	USP22	Q9UPT9	702

IntAct

96 interactions, top by confidence:

A	B	Type	Score
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
H2AX	PPM1G	psi-mi:“MI:0914”(association)	0.730
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
YWHAZ	HSPB1	psi-mi:“MI:0914”(association)	0.680
H2AX	H2BC5	psi-mi:“MI:0915”(physical association)	0.670
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
H2AZ1	H2BC5	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	LMNA	psi-mi:“MI:0914”(association)	0.560
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
PPM1G	COPE	psi-mi:“MI:0914”(association)	0.530
H2AC20	PPM1G	psi-mi:“MI:0914”(association)	0.530
H2BC5	HNRNPK	psi-mi:“MI:0915”(physical association)	0.400
HDAC6	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
CCDC63	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
UFL1	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
H2BC5	H4C16	psi-mi:“MI:0915”(physical association)	0.400
NEMF	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
H2AC4	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
JPH2	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
NOP53	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
SHLD2	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
H2BC5	DCTN2	psi-mi:“MI:0915”(physical association)	0.400
REST	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
MYH9	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
PDCD4	H2BC5	psi-mi:“MI:0915”(physical association)	0.400
CC2D1B	H2BC5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (624): HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Reconstituted Complex), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS), HIST1H2BD (Affinity Capture-MS)

ESM2 similar proteins: O60814, P02281, P02284, P04255, P06899, P06900, P07794, P0C1H3, P0C1H4, P0C1H5, P10853, P10854, P14001, P16889, P21897, P23527, P33778, P57053, P58876, P62807, P62808, P69069, P69070, Q16778, Q27484, Q27876, Q27894, Q2M2T1, Q2PFX4, Q32L48, Q5BJA5, Q5QNW6, Q5R893, Q5RCP8, Q64475, Q64478, Q64524, Q64525, Q6PC60, Q6ZWY9

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

2 interactions.

A	Effect	B	Mechanism
SLBP	“up-regulates quantity by expression”	H2BC5	“translation regulation”
“MSL acetyltransferase”	“down-regulates activity”	H2BC5	monoubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
Packaging Of Telomere Ends	7	22.3×	3e-06
Recognition and association of DNA glycosylase with site containing an affected purine	7	20.7×	3e-06
Cleavage of the damaged purine	7	20.7×	3e-06
Condensation of Prophase Chromosomes	9	20.4×	2e-07
SIRT1 negatively regulates rRNA expression	8	19.8×	1e-06
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	7	18.7×	3e-06
Cleavage of the damaged pyrimidine	7	18.7×	3e-06
RNA Polymerase I Promoter Opening	7	18.7×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	8	22.2×	2e-06
nucleosome assembly	7	10.7×	9e-04
chromatin organization	8	8.6×	9e-04
DNA repair	8	5.5×	1e-02

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

51 predictions. Top by Δscore:

Variant	Effect	Δscore
6:26158287:GT:G	donor_gain	0.7400
6:26158303:TGCTG:T	donor_gain	0.7400
6:26158541:TTCC:T	donor_gain	0.6400
6:26158276:A:T	donor_gain	0.6300
6:26158560:G:GG	donor_gain	0.6300
6:26158304:GCTGA:G	donor_gain	0.5800
6:26158397:C:T	donor_gain	0.5200
6:26158555:GCCAA:G	donor_gain	0.5000
6:26158345:C:T	donor_gain	0.4700
6:26158525:TCACC:T	donor_gain	0.4700
6:26158551:C:G	donor_gain	0.4700
6:26158292:T:A	donor_gain	0.4500
6:26158534:ACACC:A	donor_gain	0.4500
6:26158275:G:GT	donor_gain	0.4300
6:26158546:A:AG	donor_gain	0.4300
6:26158547:G:GG	donor_gain	0.4300
6:26158559:A:G	donor_gain	0.4100
6:26158305:C:CG	donor_gain	0.4000
6:26158288:T:G	donor_gain	0.3900
6:26158245:G:GT	donor_gain	0.3800
6:26158280:C:G	donor_gain	0.3800
6:26158565:C:T	donor_gain	0.3700
6:26158289:G:GG	donor_gain	0.3400
6:26158341:A:AC	acceptor_gain	0.3400
6:26158250:G:GT	donor_gain	0.3200
6:26158250:G:T	donor_gain	0.3100
6:26158299:A:AC	acceptor_gain	0.3000
6:26158342:A:G	acceptor_gain	0.2900
6:26158326:ACC:A	acceptor_gain	0.2800
6:26158556:CCAAG:C	donor_loss	0.2800

AlphaMissense

812 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:26158306:T:C	L46P	1.000
6:26158447:G:T	R93M	1.000
6:26158448:G:C	R93S	1.000
6:26158448:G:T	R93S	1.000
6:26158449:G:A	E94K	1.000
6:26158457:G:C	Q96H	1.000
6:26158457:G:T	Q96H	1.000
6:26158461:G:C	A98P	1.000
6:26158462:C:A	A98D	1.000
6:26158471:T:C	L101P	1.000
6:26158482:G:T	G105W	1.000
6:26158483:G:A	G105E	1.000
6:26158489:T:C	L107P	1.000
6:26158496:G:C	K109N	1.000
6:26158496:G:T	K109N	1.000
6:26158499:C:A	H110Q	1.000
6:26158499:C:G	H110Q	1.000
6:26158501:C:A	A111D	1.000
6:26158512:G:C	G115R	1.000
6:26158512:G:T	G115C	1.000
6:26158513:G:A	G115D	1.000
6:26158513:G:T	G115V	1.000
6:26158520:G:C	K117N	1.000
6:26158520:G:T	K117N	1.000
6:26158312:A:C	Q48P	0.999
6:26158317:C:G	H50D	0.999
6:26158345:C:A	A59E	0.999
6:26158354:T:A	I62N	0.999
6:26158362:T:C	S65P	0.999
6:26158369:T:A	V67D	0.999

dbSNP variants (sampled 300 via entrez): RS1000015128 (6:26157852 A>C,G,T), RS1000066168 (6:26158087 C>A,G,T), RS1000279080 (6:26163531 T>C), RS1000406825 (6:26164790 C>CT), RS1000412746 (6:26169308 T>C), RS1001068147 (6:26158747 G>A,C), RS1001193179 (6:26164504 T>C,G), RS1001204765 (6:26164896 T>A), RS1001430999 (6:26170974 G>C,T), RS1002111724 (6:26159724 A>G), RS1002125041 (6:26160114 G>C), RS1002420046 (6:26159485 C>T), RS1002477465 (6:26159788 T>G), RS1002598295 (6:26157589 G>A), RS1003090955 (6:26162359 T>A)

Disease associations

OMIM: gene MIM:602799 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST004521_113	Autism spectrum disorder or schizophrenia	3.000000e-19
GCST004521_169	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_69	Autism spectrum disorder or schizophrenia	8.000000e-24
GCST004521_83	Autism spectrum disorder or schizophrenia	1.000000e-13
GCST005316_559	Intelligence (MTAG)	4.000000e-10
GCST005908_32	Height	9.000000e-18
GCST006269_1088	General cognitive ability	4.000000e-11
GCST007294_143	Body fat distribution (trunk fat ratio)	5.000000e-29
GCST007294_82	Body fat distribution (trunk fat ratio)	1.000000e-48
GCST007295_120	Body fat distribution (leg fat ratio)	2.000000e-46
GCST007295_91	Body fat distribution (leg fat ratio)	1.000000e-26
GCST010002_50	Refractive error	4.000000e-34
GCST010042_70	Asthma	6.000000e-13
GCST010141_1	Beef consumption	7.000000e-13
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
GCST010143_19	Meat-related diet	5.000000e-13
GCST010143_31	Meat-related diet	7.000000e-09
GCST010143_5	Meat-related diet	4.000000e-09
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16
GCST012226_38	Waist circumference adjusted for body mass index	3.000000e-25
GCST012226_39	Waist circumference adjusted for body mass index	4.000000e-16
GCST012226_40	Waist circumference adjusted for body mass index	2.000000e-20
GCST012226_41	Waist circumference adjusted for body mass index	1.000000e-11
GCST012227_886	Hip circumference adjusted for BMI	3.000000e-13

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004341	body fat distribution
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression, increases expression	11
Valproic Acid	increases expression, affects expression, decreases expression	5
bisphenol A	decreases expression, affects cotreatment, increases expression	3
trichostatin A	affects cotreatment, decreases expression	3
Resveratrol	decreases expression, affects cotreatment	3
Benzo(a)pyrene	increases expression	3
Estradiol	affects expression, decreases expression, affects cotreatment, increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
sodium arsenite	decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Silicon Dioxide	increases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
deoxynivalenol	increases expression	1
decabromobiphenyl ether	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
methylparaben	increases expression	1
o,p’-DDT	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	increases expression	1
periodate-oxidized adenosine	affects expression	1
ferrous chloride	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
propionic acid	decreases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1

Clinical trials (associated diseases)

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