H2AC6

Summary

H2AC6 (H2A clustered histone 6, HGNC:4733) is a protein-coding gene on chromosome 6p22.2, encoding Histone H2A type 1-C (Q93077). Core component of nucleosome. It is a selective cancer dependency (DepMap: 37.3% of 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 H2A family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6.

Source: NCBI Gene 8334 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 26
• Clinical variants (ClinVar): 13 total
• Cancer dependency (DepMap): dependent in 37.3% of screened cell lines
• MANE Select transcript: NM_003512

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4733
Approved symbol	H2AC6
Name	H2A clustered histone 6
Location	6p22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000180573
Ensembl biotype	protein_coding
OMIM	602794
Entrez	8334

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000314088, ENST00000377791, ENST00000602637

RefSeq mRNA: 1 — MANE Select: NM_003512 NM_003512

CCDS: CCDS4585

Canonical transcript exons

ENST00000377791 — 1 exons

Exon	Start	End
ENSE00003913950	26124172	26124690

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 516.3365 / max 11051.4524, expressed in 1827 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66476	516.3365	1827

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.19	gold quality
mononuclear cell	CL:0000842	99.04	gold quality
leukocyte	CL:0000738	98.80	gold quality
blood	UBERON:0000178	97.94	gold quality
buccal mucosa cell	CL:0002336	97.57	gold quality
lower esophagus mucosa	UBERON:0035834	96.21	gold quality
pericardium	UBERON:0002407	95.89	gold quality
jejunal mucosa	UBERON:0000399	95.03	gold quality
mucosa of transverse colon	UBERON:0004991	94.27	gold quality
cranial nerve II	UBERON:0000941	94.25	gold quality
esophagus squamous epithelium	UBERON:0006920	94.03	gold quality
granulocyte	CL:0000094	93.95	gold quality
bone marrow	UBERON:0002371	93.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.37	gold quality
prostate gland	UBERON:0002367	93.36	gold quality
bone marrow cell	CL:0002092	93.30	gold quality
epithelium of esophagus	UBERON:0001976	93.26	gold quality
choroid plexus epithelium	UBERON:0003911	93.18	gold quality
periodontal ligament	UBERON:0008266	93.01	gold quality
corpus callosum	UBERON:0002336	92.91	gold quality
corpus epididymis	UBERON:0004359	92.57	gold quality
bronchial epithelial cell	CL:0002328	92.46	gold quality
right lobe of liver	UBERON:0001114	92.38	gold quality
right adrenal gland cortex	UBERON:0035827	92.33	gold quality
spinal cord	UBERON:0002240	92.03	gold quality
amniotic fluid	UBERON:0000173	91.91	gold quality
esophagus mucosa	UBERON:0002469	91.69	gold quality
duodenum	UBERON:0002114	91.62	gold quality
right adrenal gland	UBERON:0001233	91.33	gold quality
vagina	UBERON:0000996	91.07	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-GEOD-150728	yes	5396.23
E-MTAB-7407	yes	3953.25
E-MTAB-8207	yes	2199.76
E-GEOD-131882	yes	1275.04
E-CURD-95	yes	1068.18
E-ANND-5	yes	642.05
E-GEOD-124858	yes	248.19
E-HCAD-4	yes	41.43
E-MTAB-9221	yes	22.65
E-CURD-122	yes	21.71
E-HCAD-1	yes	9.83
E-MTAB-9801	yes	9.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 37.3% of screened cell lines.

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	Hist1h2ah	ENSRNOG00000084247
drosophila_melanogaster	His2A:CG31618	FBGN0051618
drosophila_melanogaster	His2A:CG33808	FBGN0053808
drosophila_melanogaster	His2A:CG33814	FBGN0053814
drosophila_melanogaster	His2A:CG33817	FBGN0053817
drosophila_melanogaster	His2A:CG33820	FBGN0053820
drosophila_melanogaster	His2A:CG33823	FBGN0053823
drosophila_melanogaster	His2A:CG33826	FBGN0053826
drosophila_melanogaster	His2A:CG33829	FBGN0053829
drosophila_melanogaster	His2A:CG33832	FBGN0053832
drosophila_melanogaster	His2A:CG33835	FBGN0053835
drosophila_melanogaster	His2A:CG33838	FBGN0053838
drosophila_melanogaster	His2A:CG33841	FBGN0053841
drosophila_melanogaster	His2A:CG33844	FBGN0053844
drosophila_melanogaster	His2A:CG33847	FBGN0053847
drosophila_melanogaster	His2A:CG33850	FBGN0053850
drosophila_melanogaster	His2A:CG33853	FBGN0053853
drosophila_melanogaster	His2A:CG33856	FBGN0053856
drosophila_melanogaster	His2A:CG33859	FBGN0053859
drosophila_melanogaster	His2A:CG33862	FBGN0053862
drosophila_melanogaster	His2A:CG33865	FBGN0053865

Paralogs (27): MACROH2A2 (ENSG00000099284), H2AZ2 (ENSG00000105968), MACROH2A1 (ENSG00000113648), H2AZ1 (ENSG00000164032), H2AC1 (ENSG00000164508), H2AC25 (ENSG00000181218), H2AC20 (ENSG00000184260), H2AC21 (ENSG00000184270), H2AX (ENSG00000188486), H2AC13 (ENSG00000196747), H2AC11 (ENSG00000196787), H2AC7 (ENSG00000196866), H2AL3 (ENSG00000229674), H2AJ (ENSG00000246705), H2AL1Q (ENSG00000249467), H2AB1 (ENSG00000274183), H2AC12 (ENSG00000274997), H2AC15 (ENSG00000275221), H2AC14 (ENSG00000276368), H2AC16 (ENSG00000276903), H2AC8 (ENSG00000277075), H2AB3 (ENSG00000277745), H2AB2 (ENSG00000277858), H2AC4 (ENSG00000278463), H2AC17 (ENSG00000278677), H2AC18 (ENSG00000288825), H2AC19 (ENSG00000288859)

Protein

Protein identifiers

Histone H2A type 1-C — Q93077 (reviewed: Q93077)

Alternative names: H2A-clustered histone 6, Histone H2A/l

All UniProt accessions (1): Q93077

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. Deiminated on Arg-4 in granulocytes upon calcium entry. Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of ‘Lys-27’ of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers. Following DNA double-strand breaks (DSBs), it is ubiquitinated through ‘Lys-63’ linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and ‘Lys-63’-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend ‘Lys-63’-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired. H2AK119Ub and ionizing radiation-induced ‘Lys-63’-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events. Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription. Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex. Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage. 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 H2A family.

RefSeq proteins (1): NP_003503* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002119	Histone_H2A	Family
IPR007125	H2A/H2B/H3	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR032454	Histone_H2A_C	Domain
IPR032458	Histone_H2A_CS	Conserved_site

Pfam: PF00125, PF16211

UniProt features (56 total): modified residue 36, helix 5, turn 4, cross-link 3, strand 3, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
7R5R	ELECTRON MICROSCOPY	2.44
8OX0	ELECTRON MICROSCOPY	2.52
7PII	ELECTRON MICROSCOPY	2.68
7U46	ELECTRON MICROSCOPY	2.68
8OOP	ELECTRON MICROSCOPY	2.7
8OX1	ELECTRON MICROSCOPY	2.7
8OO7	ELECTRON MICROSCOPY	2.8
9EOZ	ELECTRON MICROSCOPY	3.1
7A08	ELECTRON MICROSCOPY	3.11
8OOA	ELECTRON MICROSCOPY	3.18
8X15	ELECTRON MICROSCOPY	3.2
8X19	ELECTRON MICROSCOPY	3.2
8X1C	ELECTRON MICROSCOPY	3.2
8OOS	ELECTRON MICROSCOPY	3.29
6MUP	ELECTRON MICROSCOPY	3.5
6MUO	ELECTRON MICROSCOPY	3.6
6C0W	ELECTRON MICROSCOPY	4
7Y8R	ELECTRON MICROSCOPY	4.4
9TAX	ELECTRON MICROSCOPY	4.5
6UPK	ELECTRON MICROSCOPY	4.9
6UPL	ELECTRON MICROSCOPY	7.4
7U47	ELECTRON MICROSCOPY	7.5
7U4D	ELECTRON MICROSCOPY	8.1
7YYH	ELECTRON MICROSCOPY	8.9
7YWX	ELECTRON MICROSCOPY	12
9TAY	ELECTRON MICROSCOPY	15.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q93077-F1	91.27	0.80

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 (39): 10, 10, 10, 10, 10, 14, 14, 16, 37, 37, 37, 37, 75, 76, 96, 96, 96, 96, 96, 105 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
2	blocks the inhibition of transcription by rps6ka5/msk1.

Function

Pathways and Gene Ontology

Reactome pathways

55 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-3214858	RMTs methylate histone arginines
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-5689603	UCH proteinases
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5689901	Metalloprotease DUBs
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-73728	RNA Polymerase I Promoter Opening

MSigDB gene sets: 354 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, REACTOME_MEIOTIC_RECOMBINATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, KOBAYASHI_EGFR_SIGNALING_24HR_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, REACTOME_MEIOTIC_SYNAPSIS, FISCHER_G1_S_CELL_CYCLE, CHIARETTI_T_ALL_REFRACTORY_TO_THERAPY, CHUNG_BLISTER_CYTOTOXICITY_DN, MODULE_45, CAFFAREL_RESPONSE_TO_THC_UP, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN

GO Biological Process (2): negative regulation of cell population proliferation (GO:0008285), heterochromatin formation (GO:0031507)

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 (5): nucleosome (GO:0000786), nucleus (GO:0005634), nucleoplasm (GO:0005654), extracellular exosome (GO:0070062), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Cellular Senescence	3
Chromatin modifying enzymes	3
Depyrimidination	2
Depurination	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
Epigenetic regulation of gene expression	1
Mitotic Prophase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	2
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	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
cellular anatomical structure	1
extracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1715 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2AC6	H2BC5	P58876	595
H2AC6	H2BC11	P06899	542
H2AC6	SLBP	Q14493	474
H2AC6	NEFM	P07197	422
H2AC6	H2BC8	P02278	421
H2AC6	H2BC12	O60814	415
H2AC6	H2BC26	Q8N257	414
H2AC6	HEXIM2	Q96MH2	402
H2AC6	H4C16	P02304	397
H2AC6	H1-2	P16403	397
H2AC6	MPC2	O95563	392
H2AC6	CBR3	O75828	385
H2AC6	PGAM2	P15259	374
H2AC6	NDEL1	Q9GZM8	372
H2AC6	H2BC21	Q16778	372

IntAct

46 interactions, top by confidence:

A	B	Type	Score
OPG044	DDX3X	psi-mi:“MI:0914”(association)	0.730
H2AC6	BAG6	psi-mi:“MI:0915”(physical association)	0.560
KLF11	H2AC6	psi-mi:“MI:0915”(physical association)	0.560
P/V/C	KPNA3	psi-mi:“MI:0914”(association)	0.530
MTNR1A	H2AC6	psi-mi:“MI:0915”(physical association)	0.370
ORF73	ECI2	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
RALBP1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
PRKCB	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
MYLK2		psi-mi:“MI:0914”(association)	0.350
ELK4	MYO1C	psi-mi:“MI:0914”(association)	0.350
RPS6KA3	BAG2	psi-mi:“MI:0914”(association)	0.350
PRKCB	CHEK1	psi-mi:“MI:0914”(association)	0.350
CAMK2A	SEC16A	psi-mi:“MI:0914”(association)	0.350
Aire	NOP56	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
H2AZ1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HMGA1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
NUCKS1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
NUMA1	SHANK3	psi-mi:“MI:0914”(association)	0.350
PARP1	KPNA3	psi-mi:“MI:0914”(association)	0.350

BioGRID (199): HIST1H2AC (Two-hybrid), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Two-hybrid), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-RNA), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-MS), HIST1H2AC (Affinity Capture-MS)

ESM2 similar proteins: A1A4R1, A9UMV8, C0HKE1, C0HKE2, C0HKE3, C0HKE4, C0HKE5, C0HKE6, C0HKE7, C0HKE8, C0HKE9, P02262, P02263, P02270, P04908, P06897, P0C0S8, P0C0S9, P0C169, P0C170, P0CC09, P13912, P19178, P20671, P21896, P27325, P35061, P35062, P70082, P84052, Q07135, Q16777, Q3ZBX9, Q4FZT6, Q4R3X5, Q64522, Q64523, Q64598, Q6FI13, Q6GSS7

Diamond homologs: A0A097I1R9, A0A097I2B5, A0A0D2UG83, A1A4R1, A1CJ10, A1D8G8, A3LXE7, A3LZZ0, A5DBG4, A5DJJ2, A5DWF1, A5DXC6, A9UMV8, C0HKE1, C0HKE2, C0HKE3, C0HKE4, C0HKE5, C0HKE6, C0HKE7, C0HKE8, C0HKE9, L7HZV6, O74268, P02262, P02263, P02264, P04908, P04909, P04910, P04911, P04912, P06897, P07793, P08844, P0C0S8, P0C0S9, P0C169, P0C170, P0C952

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SLBP	“up-regulates quantity by expression”	H2AC6	“translation regulation”
DZIP3	“up-regulates activity”	H2AC6	monoubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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
B-WICH complex positively regulates rRNA expression	5	17.9×	3e-03
Amyloid fiber formation	5	15.1×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
chromatin organization	6	14.5×	8e-04

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

165 predictions. Top by Δscore:

Variant	Effect	Δscore
6:26138050:TTA:T	acceptor_loss	0.9800
6:26138051:TAGG:T	acceptor_loss	0.9800
6:26138052:A:T	acceptor_loss	0.9800
6:26138053:G:GT	acceptor_loss	0.9800
6:26124619:C:T	donor_gain	0.9500
6:26138053:GGTT:G	acceptor_gain	0.9500
6:26138052:A:AG	acceptor_gain	0.9200
6:26138053:G:GG	acceptor_gain	0.9200
6:26124746:TAAG:T	donor_loss	0.9100
6:26124747:AAGG:A	donor_loss	0.9100
6:26124749:GGTAA:G	donor_loss	0.9100
6:26124750:G:C	donor_loss	0.9100
6:26124751:TAA:T	donor_loss	0.9100
6:26124728:TAG:T	donor_gain	0.8700
6:26124729:AGA:A	donor_gain	0.8700
6:26124752:AA:A	donor_loss	0.8400
6:26124536:A:AG	donor_gain	0.8200
6:26124616:G:A	donor_gain	0.8100
6:26124702:G:GT	donor_gain	0.8000
6:26124750:G:GG	donor_gain	0.7800
6:26124626:T:G	donor_gain	0.7600
6:26124629:GACAG:G	donor_loss	0.7600
6:26124630:ACAG:A	donor_loss	0.7600
6:26124631:CAG:C	donor_loss	0.7600
6:26124632:AGGTA:A	donor_loss	0.7600
6:26124633:GGT:G	donor_loss	0.7600
6:26124634:GTAT:G	donor_loss	0.7600
6:26124635:T:G	donor_loss	0.7600
6:26124636:A:T	donor_loss	0.7500
6:26124625:A:AG	donor_gain	0.7300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000511689 (6:26123136 G>A), RS1000779831 (6:26124984 A>G), RS1002014735 (6:26123329 C>A,G,T), RS1002069803 (6:26124684 C>A,T), RS1003687727 (6:26124041 T>C), RS1005123304 (6:26125076 G>A,C), RS1005964233 (6:26122406 G>A), RS1006487303 (6:26122581 C>T), RS1006601335 (6:26122866 G>A), RS1006856017 (6:26123226 C>A,G,T), RS1007860300 (6:26124030 G>A), RS1007976269 (6:26124128 C>T), RS1009423988 (6:26123453 T>C), RS1010374077 (6:26122815 T>C), RS1011396697 (6:26124481 C>T)

Disease associations

OMIM: gene MIM:602794 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST002912_2	Narcolepsy with cataplexy	1.000000e-08
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
GCST004749_62	Lung cancer in ever smokers	2.000000e-07
GCST004750_80	Squamous cell lung carcinoma	6.000000e-12
GCST005316_547	Intelligence (MTAG)	2.000000e-10
GCST007269_243	Pulse pressure	4.000000e-20
GCST007325_68	General risk tolerance (MTAG)	4.000000e-10
GCST010002_50	Refractive error	4.000000e-34
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
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16
GCST010988_353	Adult body size	8.000000e-12
GCST012227_885	Hip circumference adjusted for BMI	2.000000e-09
GCST90002394_39	Monocyte percentage of white cells	1.000000e-09
GCST90020028_926	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0005763	pulse pressure measurement
EFO:0008579	risk-taking behaviour
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression, decreases expression	7
Valproic Acid	affects cotreatment, decreases expression, increases expression	6
Air Pollutants	increases abundance, increases expression, decreases expression, affects cotreatment	5
sodium arsenite	increases expression, decreases expression, affects cotreatment	4
bisphenol A	decreases expression	3
trichostatin A	affects cotreatment, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance	3
lead acetate	decreases expression, affects cotreatment, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression, decreases expression	2
Cadmium Chloride	increases expression, affects cotreatment	2
Okadaic Acid	decreases expression	2
bisphenol F	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
propionaldehyde	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
decabromobiphenyl ether	affects expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
kojic acid	increases expression	1
3,4-dichloroaniline	increases expression	1
methylparaben	decreases expression	1
sodium bichromate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice