H2AC14

Summary

H2AC14 (H2A clustered histone 14, HGNC:4727) is a protein-coding gene on chromosome 6p22.1, encoding Histone H2A type 1-J (Q99878). 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 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 small histone gene cluster on chromosome 6p22-p21.3.

Source: NCBI Gene 8331 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_021066

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4727
Approved symbol	H2AC14
Name	H2A clustered histone 14
Location	6p22.1
Locus type	gene with protein product
Status	Approved
Aliases	H2A/E
Ensembl gene	ENSG00000276368
Ensembl biotype	protein_coding
OMIM	602791
Entrez	8331

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000333151

RefSeq mRNA: 1 — MANE Select: NM_021066 NM_021066

CCDS: CCDS4628

Canonical transcript exons

ENST00000333151 — 1 exons

Exon	Start	End
ENSE00001611885	27814302	27814777

Expression profiles

Bgee: expression breadth broad, 97 present calls, max score 98.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 501.9736 / max 9592.1767, expressed in 1682 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72382	501.1992	1677
203927	0.7744	337

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	98.35	gold quality
adrenal tissue	UBERON:0018303	91.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.57	gold quality
bone marrow	UBERON:0002371	87.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.75	gold quality
colonic epithelium	UBERON:0000397	68.83	gold quality
calcaneal tendon	UBERON:0003701	67.12	gold quality
tonsil	UBERON:0002372	62.31	gold quality
mucosa of transverse colon	UBERON:0004991	58.84	gold quality
ganglionic eminence	UBERON:0004023	54.88	gold quality
blood	UBERON:0000178	50.84	gold quality
sural nerve	UBERON:0015488	47.63	silver quality
monocyte	CL:0000576	47.31	gold quality
lymph node	UBERON:0000029	46.47	gold quality
corpus callosum	UBERON:0002336	45.72	gold quality
leukocyte	CL:0000738	45.53	gold quality
esophagus mucosa	UBERON:0002469	45.35	gold quality
placenta	UBERON:0001987	43.96	gold quality
spleen	UBERON:0002106	43.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	42.62	gold quality
liver	UBERON:0002107	42.55	gold quality
cortical plate	UBERON:0005343	41.84	gold quality
duodenum	UBERON:0002114	41.59	gold quality
ventricular zone	UBERON:0003053	41.50	gold quality
vermiform appendix	UBERON:0001154	41.10	gold quality
lung	UBERON:0002048	40.08	gold quality
skeletal muscle tissue	UBERON:0001134	38.64	silver quality
right lobe of liver	UBERON:0001114	38.57	silver quality
stomach	UBERON:0000945	38.39	gold quality
muscle tissue	UBERON:0002385	37.61	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-56	yes	1980.75
E-CURD-84	yes	633.40
E-MTAB-10042	yes	481.92
E-MTAB-10662	yes	459.06
E-MTAB-6911	yes	442.95
E-MTAB-8894	yes	347.19
E-MTAB-7407	yes	256.50
E-MTAB-9467	yes	36.40
E-CURD-122	yes	24.31
E-ANND-3	yes	3.59

Regulation

Is transcription factor: no

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
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), H2AC6 (ENSG00000180573), 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), H2AC16 (ENSG00000276903), H2AC8 (ENSG00000277075), H2AB3 (ENSG00000277745), H2AB2 (ENSG00000277858), H2AC4 (ENSG00000278463), H2AC17 (ENSG00000278677), H2AC18 (ENSG00000288825), H2AC19 (ENSG00000288859)

Protein

Protein identifiers

Histone H2A type 1-J — Q99878 (reviewed: Q99878)

Alternative names: Histone H2A/e

All UniProt accessions (1): Q99878

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_066544* (*=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 (52 total): modified residue 36, helix 6, cross-link 3, strand 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8OL1	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99878-F1	91.94	0.81

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, 14, 14, 16, 37, 37, 37, 37, 75, 76, 96, 96, 96, 96, 96, 100, 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: 166 (showing top): REACTOME_MEIOTIC_RECOMBINATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_MEIOTIC_SYNAPSIS, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, FISCHER_DREAM_TARGETS, REACTOME_DNA_REPAIR, OCT1_B, DANG_BOUND_BY_MYC, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, REACTOME_REGULATION_OF_T_CELL_ACTIVATION_BY_CD28_FAMILY, BENPORATH_MYC_MAX_TARGETS, REACTOME_CO_INHIBITION_BY_PD_1, REACTOME_CELL_JUNCTION_ORGANIZATION

GO Biological Process (1): 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 (4): nucleosome (GO:0000786), nucleus (GO:0005634), 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
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
extracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2AC14	H1-5	P16401	582
H2AC14	NAP1L1	P55209	460
H2AC14	H2BC5	P58876	457
H2AC14	H1-4	P10412	446
H2AC14	H4C16	P02304	395
H2AC14	H2BC8	P02278	394
H2AC14	ARID2	Q68CP9	371
H2AC14	H2BC14	Q99879	371
H2AC14	OR2B2	Q9GZK3	369
H2AC14	CCNE1	P24864	363
H2AC14	IGF2	P01344	354
H2AC14	OR10A5	Q9H207	348
H2AC14	ITPRID1	Q6ZRS4	325
H2AC14	H2BC21	Q16778	313
H2AC14	TLL1	O43897	306

IntAct

78 interactions, top by confidence:

A	B	Type	Score
MED25	MED24	psi-mi:“MI:0914”(association)	0.740
PKMYT1	CCNB2	psi-mi:“MI:0914”(association)	0.730
OPG044	DDX3X	psi-mi:“MI:0914”(association)	0.730
MED10	POLR2D	psi-mi:“MI:0914”(association)	0.640
H2AC14	H2BC21	psi-mi:“MI:0915”(physical association)	0.560
H2AC14	H1-0	psi-mi:“MI:0915”(physical association)	0.560
ING4	KAT7	psi-mi:“MI:0914”(association)	0.530
MAP4K4	STRN	psi-mi:“MI:0914”(association)	0.530
MED27	POLR2D	psi-mi:“MI:0914”(association)	0.530
MSH6	PCNA	psi-mi:“MI:0914”(association)	0.530
P/V/C	KPNA3	psi-mi:“MI:0914”(association)	0.530
MKI67	ZC3H11A	psi-mi:“MI:0914”(association)	0.480
JPH2	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
H2BC20P	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
H2AC14	H2BC14	psi-mi:“MI:0915”(physical association)	0.400
H2AC14	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
H2AC14	KCND3	psi-mi:“MI:0915”(physical association)	0.400
H2AC14	H4C16	psi-mi:“MI:0915”(physical association)	0.400
H1-2	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
H3-4	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
H2AC14	H1-1	psi-mi:“MI:0915”(physical association)	0.400
H3C13	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
CPAMD8	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
CEP290	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
CTPS1	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
H1-10	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
DMXL1	H2AC14	psi-mi:“MI:0915”(physical association)	0.400
Rbm8a	GOSR1	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (230): HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-RNA), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS), HIST1H2AJ (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PP81, A0A1W2PPE2, A0A1W2PPH5, A0A1W2PPL8, A0A1W2PR64, A0A1W2PRV1, A0A3B3IU63, A4QVR2, A5DQL2, A9UMV8, F4HR03, O35216, P06898, P0C1H6, P0C5Y9, P0C5Z0, P0DW11, P0DW12, P0DW13, P0DW14, P0DW85, P35061, P48003, P49450, Q00728, Q3SZB8, Q3ZBX9, Q4IMD1, Q5M8Q2, Q5TKR9, Q64522, Q64598, Q7Z2G1, Q803H4, Q873G4, Q8BRB7, Q8BZ21, Q8CGP5, Q8IUE6, Q8R1M2

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

3 interactions.

A	Effect	B	Mechanism
SLBP	“up-regulates quantity by expression”	H2AC14	“translation regulation”
DZIP3	“up-regulates activity”	H2AC14	monoubiquitination
DCAF1	“up-regulates activity”	H2AC14	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 99 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	20.8×	2e-06
Recognition and association of DNA glycosylase with site containing an affected purine	7	19.3×	3e-06
Cleavage of the damaged purine	7	19.3×	3e-06
Replacement of protamines by nucleosomes in the male pronucleus	5	18.4×	8e-05
Inhibition of DNA recombination at telomere	8	18.2×	2e-06
DNA Damage/Telomere Stress Induced Senescence	8	17.6×	2e-06
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	7	17.4×	5e-06
Cleavage of the damaged pyrimidine	7	17.4×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	5	66.1×	3e-06
nucleosome assembly	12	19.8×	6e-10
positive regulation of transcription elongation by RNA polymerase II	5	17.7×	1e-03
RNA polymerase II preinitiation complex assembly	5	16.0×	2e-03
chromatin organization	7	8.2×	2e-03
chromatin remodeling	8	6.9×	2e-03
DNA damage response	10	6.3×	8e-04
DNA repair	8	6.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

24 predictions. Top by Δscore:

Variant	Effect	Δscore
6:27814360:AGT:A	donor_gain	0.7300
6:27814356:A:AC	donor_gain	0.7100
6:27814357:C:CC	donor_gain	0.7100
6:27814361:G:C	donor_gain	0.6800
6:27814360:A:AC	donor_gain	0.6700
6:27814627:G:A	donor_gain	0.5200
6:27814515:T:TA	donor_gain	0.4800
6:27814571:TCCAG:T	donor_gain	0.4800
6:27814572:CCAGC:C	donor_gain	0.4800
6:27814623:AGTTG:A	donor_gain	0.3400
6:27814718:C:CA	donor_gain	0.3400
6:27814358:T:C	donor_gain	0.3300
6:27814609:G:T	donor_gain	0.2900
6:27814469:T:C	donor_gain	0.2500
6:27814726:A:AC	donor_gain	0.2500
6:27814727:C:CC	donor_gain	0.2500
6:27814727:CCACG:C	donor_gain	0.2500
6:27814572:C:CA	donor_gain	0.2400
6:27814624:G:C	donor_gain	0.2400
6:27814377:CAGTT:C	donor_gain	0.2100
6:27814629:CTT:C	acceptor_gain	0.2100
6:27814630:T:TG	acceptor_gain	0.2100
6:27814666:C:CA	acceptor_gain	0.2100
6:27814667:T:A	acceptor_gain	0.2100

AlphaMissense

804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:27814469:T:A	D91V	1.000
6:27814538:C:T	G68D	1.000
6:27814569:A:G	Y58H	1.000
6:27814422:C:G	G107R	0.999
6:27814425:C:G	G106R	0.999
6:27814469:T:C	D91G	0.999
6:27814469:T:G	D91A	0.999
6:27814470:C:G	D91H	0.999
6:27814475:C:G	R89P	0.999
6:27814481:G:T	A87D	0.999
6:27814484:A:G	L86P	0.999
6:27814490:A:G	L84P	0.999
6:27814497:G:T	R82S	0.999
6:27814505:A:T	I79N	0.999
6:27814529:G:T	A71D	0.999
6:27814530:C:G	A71P	0.999
6:27814538:C:A	G68V	0.999
6:27814539:C:G	G68R	0.999
6:27814541:G:T	A67D	0.999
6:27814544:A:G	L66P	0.999
6:27814548:C:T	E65K	0.999
6:27814550:A:G	L64P	0.999
6:27814556:T:A	E62V	0.999
6:27814559:G:T	A61D	0.999
6:27814560:C:G	A61P	0.999
6:27814565:A:G	L59P	0.999
6:27814571:T:A	E57V	0.999
6:27814580:G:T	A54E	0.999
6:27814664:A:G	F26S	0.999
6:27814670:A:T	L24H	0.999

dbSNP variants (sampled 300 via entrez): RS1003588463 (6:27813983 C>T), RS1004068522 (6:27814159 C>A,G), RS1004900989 (6:27815510 G>A,C), RS1005229686 (6:27814266 G>A,C,T), RS1005576257 (6:27813956 G>A), RS1005734410 (6:27814187 A>C,G), RS1006999175 (6:27816232 A>C,T), RS1007745778 (6:27814447 C>T), RS1010579983 (6:27816046 A>C,G), RS1012373002 (6:27815793 T>A), RS1014391829 (6:27815708 C>A,T), RS1014900679 (6:27815519 TAA>T), RS1015361168 (6:27814189 C>A,T), RS1016902183 (6:27816523 G>A,C), RS1017452979 (6:27816236 C>G)

Disease associations

OMIM: gene MIM:602791 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST004521_112	Autism spectrum disorder or schizophrenia	3.000000e-26
GCST004521_115	Autism spectrum disorder or schizophrenia	3.000000e-16
GCST004521_116	Autism spectrum disorder or schizophrenia	3.000000e-16
GCST004521_166	Autism spectrum disorder or schizophrenia	4.000000e-24
GCST004521_22	Autism spectrum disorder or schizophrenia	2.000000e-11
GCST004521_23	Autism spectrum disorder or schizophrenia	2.000000e-11
GCST004521_6	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_73	Autism spectrum disorder or schizophrenia	8.000000e-11
GCST007201_367	Schizophrenia	2.000000e-21
GCST008921_6	Asthma and major depressive disorder	1.000000e-09
GCST010002_50	Refractive error	4.000000e-34
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
Doxorubicin	decreases expression	2
Oxygen	decreases expression, increases expression	2
Silicon Dioxide	increases expression	2
Smoke	decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
graphene oxide	increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
kojic acid	increases expression	1
nickel sulfate	increases expression	1
hydroquinone	decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
Sunitinib	decreases expression	1
Berberine	decreases expression	1
Cannabidiol	decreases expression	1
Dexamethasone	increases expression	1
Hydrogen Peroxide	decreases expression	1
Lucanthone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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