H2BC12

Summary

H2BC12 (H2B clustered histone 12, HGNC:13954) is a protein-coding gene on chromosome 6p22.1, encoding Histone H2B type 1-K (O60814). Core component of nucleosome.

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 encodes a replication-dependent histone that is a member of the histone H2B family. The protein encoded is an antimicrobial protein with antibacterial and antifungal activity. Two transcripts that encode the same protein have been identified for this gene, which is found in the histone microcluster on chromosome 6p21.33.

Source: NCBI Gene 85236 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 55 total — 2 pathogenic
• MANE Select transcript: NM_001312653

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13954
Approved symbol	H2BC12
Name	H2B clustered histone 12
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	H2BFAiii
Ensembl gene	ENSG00000197903
Ensembl biotype	protein_coding
OMIM	615045
Entrez	85236

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000356950, ENST00000715895, ENST00000932143, ENST00000932144

RefSeq mRNA: 2 — MANE Select: NM_001312653 NM_001312653, NM_080593

CCDS: CCDS4621

Canonical transcript exons

ENST00000356950 — 1 exons

Exon	Start	End
ENSE00004028271	27146361	27146855

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 306.6956 / max 7849.3187, expressed in 1824 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72361	306.6956	1824

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	99.46	gold quality
monocyte	CL:0000576	97.73	gold quality
blood	UBERON:0000178	97.57	gold quality
leukocyte	CL:0000738	97.37	gold quality
calcaneal tendon	UBERON:0003701	96.30	gold quality
placenta	UBERON:0001987	95.60	gold quality
mucosa of transverse colon	UBERON:0004991	95.52	gold quality
adrenal tissue	UBERON:0018303	95.37	gold quality
bone marrow	UBERON:0002371	95.23	gold quality
spleen	UBERON:0002106	95.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.84	gold quality
prostate gland	UBERON:0002367	94.53	gold quality
fallopian tube	UBERON:0003889	94.48	gold quality
right lung	UBERON:0002167	94.46	gold quality
esophagus mucosa	UBERON:0002469	94.43	gold quality
lymph node	UBERON:0000029	94.40	gold quality
right lobe of liver	UBERON:0001114	93.92	gold quality
ectocervix	UBERON:0012249	93.92	gold quality
right uterine tube	UBERON:0001302	93.82	gold quality
uterine cervix	UBERON:0000002	93.78	gold quality
right testis	UBERON:0004534	93.64	gold quality
lung	UBERON:0002048	93.53	gold quality
endocervix	UBERON:0000458	93.46	gold quality
vagina	UBERON:0000996	93.19	gold quality
left coronary artery	UBERON:0001626	93.19	gold quality
upper lobe of left lung	UBERON:0008952	93.17	gold quality
left uterine tube	UBERON:0001303	92.97	gold quality
omental fat pad	UBERON:0010414	92.95	gold quality
tonsil	UBERON:0002372	92.70	gold quality
granulocyte	CL:0000094	92.68	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.23
E-CURD-11	no	117.84
E-MTAB-7303	no	111.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting H2BC12, 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-1184	99.99	68.19	1458
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-3928-3P	97.61	66.53	1096
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-3935	96.33	66.79	797
HSA-MIR-6742-5P	96.32	64.01	869

Literature-anchored findings (GeneRIF, showing 2)

• Histone H2B antimicrobial peptides exhibit antibacterial activity and contribute to the formation of the antimicrobial barrier of the colonic epithelium (PMID:15019208)
• The physical interaction between lipin1 and eEF1A1 was further affirmed in 293T cells transfected with 6-His tagged lipin1 and hepatocyte SMMC7721 cells by protein immunoprecipitation and immunofluorescence microscopy. Lipin1 also interacted with HIST1H2BK, which was confirmed in SMMC7721 cells by protein immunoprecipitation. (PMID:30092116)

Cross-species orthologs

0 orthologs

Paralogs (21): H2BW2 (ENSG00000101812), H2BW1 (ENSG00000123569), H2BC11 (ENSG00000124635), H2BC1 (ENSG00000146047), H2BC5 (ENSG00000158373), H2BC4 (ENSG00000180596), H2BC21 (ENSG00000184678), H2BC13 (ENSG00000185130), H2BC26 (ENSG00000196890), 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-K — O60814 (reviewed: O60814)

Alternative names: HIRA-interacting protein 1

All UniProt accessions (1): O60814

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.

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 (2): NP_001299582, NP_542160 (=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 (106 total): modified residue 91, helix 4, cross-link 4, strand 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

85 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9ECP	ELECTRON MICROSCOPY	1.91
8Q3E	X-RAY DIFFRACTION	2.17
6KE9	X-RAY DIFFRACTION	2.22
8Q3X	X-RAY DIFFRACTION	2.3
2CV5	X-RAY DIFFRACTION	2.5
8Q3M	X-RAY DIFFRACTION	2.5
7XCR	ELECTRON MICROSCOPY	2.57
6L9H	X-RAY DIFFRACTION	2.6
6LE9	X-RAY DIFFRACTION	2.6
8Q36	X-RAY DIFFRACTION	2.6
7XCT	ELECTRON MICROSCOPY	2.72
8YV8	ELECTRON MICROSCOPY	3
8HR1	ELECTRON MICROSCOPY	3.02
8GRM	ELECTRON MICROSCOPY	3.05
8HQY	ELECTRON MICROSCOPY	3.05
8WG5	ELECTRON MICROSCOPY	3.05
9ZEO	ELECTRON MICROSCOPY	3.1
8IEJ	ELECTRON MICROSCOPY	3.12
9U5U	ELECTRON MICROSCOPY	3.12
6Y5E	ELECTRON MICROSCOPY	3.15
9ZEN	ELECTRON MICROSCOPY	3.17
6T79	ELECTRON MICROSCOPY	3.2
7XD1	ELECTRON MICROSCOPY	3.2
8ZJT	ELECTRON MICROSCOPY	3.2
8X7I	ELECTRON MICROSCOPY	3.27
8X7K	ELECTRON MICROSCOPY	3.27
8ZJR	ELECTRON MICROSCOPY	3.3
9D3R	ELECTRON MICROSCOPY	3.3
7YQK	ELECTRON MICROSCOPY	3.38
8X7J	ELECTRON MICROSCOPY	3.39

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60814-F1	87.60	0.66

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: 304 (showing top): REACTOME_MEIOTIC_RECOMBINATION, E2F_Q4, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, MODULE_52, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_MEIOTIC_SYNAPSIS, DORN_ADENOVIRUS_INFECTION_12HR_UP, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, CHUNG_BLISTER_CYTOTOXICITY_DN, MODULE_45

GO Biological Process (7): innate immune response in mucosa (GO:0002227), 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), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), defense response to bacterium (GO:0042742)

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), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), 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
defense response to bacterium	3
antimicrobial humoral response	2
chromatin	2
cellular anatomical structure	2
mucosal immune response	1
innate immune response	1
cell killing	1
disruption of cell in another organism	1
defense response	1
response to bacterium	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
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2BC12	H3C1	P02295	932
H2BC12	H4C16	P02304	888
H2BC12	H3C14	Q71DI3	881
H2BC12	H3-3A	P06351	880
H2BC12	H3-5	Q6NXT2	880
H2BC12	H3-4	Q16695	880
H2BC12	H3-7	Q5TEC6	880
H2BC12	PLG	P00747	876
H2BC12	RNF20	Q5VTR2	831
H2BC12	H4C7	Q99525	821
H2BC12	H2AC19	P20670	808
H2BC12	H2AC20	Q16777	795
H2BC12	RNF40	O75150	772
H2BC12	DET1	Q7L5Y6	725
H2BC12	USP22	Q9UPT9	720

IntAct

82 interactions, top by confidence:

A	B	Type	Score
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
SMARCB1	H2BC12	psi-mi:“MI:0914”(association)	0.580
H2BC12	SMARCB1	psi-mi:“MI:0915”(physical association)	0.580
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
H2AC4	H2BC12	psi-mi:“MI:0915”(physical association)	0.530
H2BC12	E7	psi-mi:“MI:0915”(physical association)	0.490
RBM45	HNRNPDL	psi-mi:“MI:0914”(association)	0.460
PPM1G	H2BC12	psi-mi:“MI:0914”(association)	0.420
PPM1G	H2BC12	psi-mi:“MI:2364”(proximity)	0.420
LANA1	H2BC12	psi-mi:“MI:0915”(physical association)	0.400
H2BC12	E7	psi-mi:“MI:0915”(physical association)	0.370
KIF11	ILVBL	psi-mi:“MI:0914”(association)	0.350
CEP170P1	PCYT1A	psi-mi:“MI:0914”(association)	0.350
Kif7	SF3B1	psi-mi:“MI:0914”(association)	0.350
CBX8	CMSS1	psi-mi:“MI:0914”(association)	0.350
PRKCD	DHX16	psi-mi:“MI:0914”(association)	0.350
CHD1L	H2BC12	psi-mi:“MI:0914”(association)	0.350
UBE3A	IGLC7	psi-mi:“MI:0914”(association)	0.350
UBE3A	TXNL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (639): HIST1H2BK (Biochemical Activity), HIST1H2BK (Biochemical Activity), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Proximity Label-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS), HIST1H2BK (Affinity Capture-MS)

ESM2 similar proteins: A1CJ09, A1D8G9, A2QY49, A3LXE6, A3LZZ1, A5DBG5, A5DJJ1, A5DWF0, L7I1W3, O60814, P02281, P02293, P02294, P04255, P04913, P06899, P0C1H3, P0C1H5, P0CO02, P0CO03, P0CT13, P10853, P23754, P37210, P48989, P78567, Q0CBD1, Q1E5N0, Q1SU99, Q27484, Q27894, Q2HH38, Q2U5A9, Q43217, Q4HTT2, Q4PEF8, Q4WWC5, Q59VP1, Q5RCP8, Q6BKW7

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”	H2BC12	“translation regulation”
“MSL acetyltransferase”	“down-regulates activity”	H2BC12	monoubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 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
Processing of Capped Intron-Containing Pre-mRNA	7	10.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	6	8.9×	7e-03
chromatin remodeling	6	7.1×	7e-03
protein phosphorylation	6	6.6×	1e-02

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2443865	NM_003495.3(H4C9):c.122G>T (p.Arg41Leu)	Pathogenic
2443866	NM_003495.3(H4C9):c.227A>G (p.His76Arg)	Pathogenic

SpliceAI

161 predictions. Top by Δscore:

Variant	Effect	Δscore
6:27139465:G:GC	acceptor_gain	0.8900
6:27139464:TG:T	acceptor_gain	0.8700
6:27139463:ATGAG:A	acceptor_gain	0.8300
6:27139464:T:G	acceptor_gain	0.7900
6:27139462:TATG:T	acceptor_gain	0.7800
6:27139463:ATGA:A	acceptor_gain	0.7800
6:27146425:G:C	donor_gain	0.7700
6:27138659:G:GT	donor_gain	0.7600
6:27146660:TCAGC:T	donor_gain	0.7600
6:27138660:A:T	donor_gain	0.7400
6:27138671:A:T	donor_gain	0.7400
6:27139464:TGAGG:T	acceptor_gain	0.7300
6:27138633:A:G	donor_gain	0.7200
6:27146424:AG:A	donor_gain	0.7000
6:27139431:C:CA	acceptor_gain	0.6900
6:27146424:AGCG:A	donor_gain	0.6900
6:27146424:A:AC	donor_gain	0.6800
6:27146420:A:AC	donor_gain	0.6600
6:27146421:C:CC	donor_gain	0.6600
6:27146659:TTCAG:T	donor_gain	0.6400
6:27139759:A:G	acceptor_gain	0.6300
6:27138616:C:T	donor_gain	0.6100
6:27146692:T:A	donor_gain	0.6100
6:27139461:CTATG:C	acceptor_gain	0.6000
6:27139463:AT:A	acceptor_gain	0.6000
6:27139403:AGC:A	acceptor_gain	0.5900
6:27139311:G:T	acceptor_gain	0.5700
6:27139151:AGAGC:A	acceptor_gain	0.5600
6:27146438:TGGTG:T	donor_gain	0.5500
6:27139463:A:AG	acceptor_gain	0.5300

AlphaMissense

813 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:27146447:C:G	A118P	1.000
6:27146448:C:A	K117N	1.000
6:27146448:C:G	K117N	1.000
6:27146455:C:T	G115D	1.000
6:27146456:C:A	G115C	1.000
6:27146456:C:G	G115R	1.000
6:27146467:G:T	A111D	1.000
6:27146469:G:C	H110Q	1.000
6:27146469:G:T	H110Q	1.000
6:27146479:A:G	L107S	1.000
6:27146485:C:A	G105V	1.000
6:27146485:C:T	G105E	1.000
6:27146486:C:A	G105W	1.000
6:27146497:A:G	L101P	1.000
6:27146519:C:T	E94K	1.000
6:27146520:C:A	R93S	1.000
6:27146520:C:G	R93S	1.000
6:27146521:C:A	R93M	1.000
6:27146521:C:G	R93T	1.000
6:27146593:T:A	D69V	1.000
6:27146662:A:G	L46P	1.000
6:27146446:G:T	A118D	0.999
6:27146450:T:C	K117E	0.999
6:27146452:G:A	T116I	0.999
6:27146455:C:A	G115V	0.999
6:27146456:C:T	G115S	0.999
6:27146459:C:T	E114K	0.999
6:27146468:C:G	A111P	0.999
6:27146470:T:C	H110R	0.999
6:27146471:G:C	H110D	0.999

dbSNP variants (sampled 300 via entrez): RS1000523775 (6:27147863 C>T), RS1000535928 (6:27144468 G>A,C,T), RS1000619674 (6:27138650 T>C,G), RS1000637352 (6:27144605 C>T), RS1001361991 (6:27148034 G>C), RS1001416528 (6:27144227 C>T), RS1001502335 (6:27147739 C>G,T), RS1001547777 (6:27145410 C>G,T), RS1001565580 (6:27148829 G>A), RS1001641087 (6:27145697 A>G), RS1002154990 (6:27139712 T>A,C,G), RS1002449964 (6:27142791 C>T), RS1003095047 (6:27145331 CACACACA>C), RS1003231886 (6:27143092 G>A), RS1003560703 (6:27147037 A>G)

Disease associations

OMIM: gene MIM:615045 | disease phenotypes: MIM:619951, MIM:617439

GenCC curated gene-disease

Mondo (2): Tessadori-Van Haaften neurodevelopmental syndrome 4 (MONDO:0031000), craniosynostosis 7 (MONDO:0044315)

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
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
GCST006940_166	Neurociticism	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
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

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	8
sodium arsenite	increases expression	4
trichostatin A	affects cotreatment, decreases expression	3
(+)-JQ1 compound	increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Fluorouracil	affects response to substance, decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Doxorubicin	affects expression, decreases expression	2
Tretinoin	decreases expression	2
1-Methyl-4-phenylpyridinium	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
OTX015	increases expression	1
bisphenol A	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
bleomycetin	decreases expression	1
potassium chromate(VI)	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
deguelin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1

Clinical trials (associated diseases)

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