MACROH2A2

Summary

MACROH2A2 (macroH2A.2 histone, HGNC:14453) is a protein-coding gene on chromosome 10q22.1, encoding Core histone macro-H2A.2 (Q9P0M6). Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription.

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 encodes a replication-independent histone that is a member of the histone H2A family. It replaces conventional H2A histones in a subset of nucleosomes where it represses transcription and may participate in stable X chromosome inactivation.

Source: NCBI Gene 55506 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_018649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14453
Approved symbol	MACROH2A2
Name	macroH2A.2 histone
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000099284
Ensembl biotype	protein_coding
OMIM	616141
Entrez	55506

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 14 protein_coding, 10 nonsense_mediated_decay, 6 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000373255, ENST00000455786, ENST00000676608, ENST00000676609, ENST00000676683, ENST00000676692, ENST00000676699, ENST00000676896, ENST00000676923, ENST00000677255, ENST00000677268, ENST00000677373, ENST00000677507, ENST00000677557, ENST00000677659, ENST00000677881, ENST00000677894, ENST00000677954, ENST00000678178, ENST00000678191, ENST00000678195, ENST00000678214, ENST00000678425, ENST00000678503, ENST00000678523, ENST00000678526, ENST00000678586, ENST00000678682, ENST00000678762, ENST00000678931, ENST00000679230, ENST00000679292, ENST00000679349

RefSeq mRNA: 1 — MANE Select: NM_018649 NM_018649

CCDS: CCDS7296

Canonical transcript exons

ENST00000373255 — 9 exons

Exon	Start	End
ENSE00000707819	70091757	70091954
ENSE00000834297	70093735	70093845
ENSE00000834298	70095654	70095753
ENSE00001026946	70100208	70100297
ENSE00001026951	70111518	70112282
ENSE00001026952	70052846	70053000
ENSE00001459878	70075600	70075830
ENSE00002484163	70090060	70090166
ENSE00002720881	70109033	70109207

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 97.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.9894 / max 744.9926, expressed in 1523 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105372	28.8802	1495
105371	0.9164	569
105369	0.0604	8
105370	0.0582	23
105374	0.0495	35
105368	0.0166	4
105373	0.0081	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.98	gold quality
ganglionic eminence	UBERON:0004023	97.34	gold quality
embryo	UBERON:0000922	97.32	gold quality
ventricular zone	UBERON:0003053	96.81	gold quality
olfactory bulb	UBERON:0002264	96.32	silver quality
type B pancreatic cell	CL:0000169	95.87	silver quality
tongue squamous epithelium	UBERON:0006919	95.00	gold quality
colonic epithelium	UBERON:0000397	94.04	gold quality
diaphragm	UBERON:0001103	91.57	gold quality
gingival epithelium	UBERON:0001949	90.96	gold quality
cerebellar vermis	UBERON:0004720	90.25	gold quality
cervix squamous epithelium	UBERON:0006922	90.00	silver quality
squamous epithelium	UBERON:0006914	89.54	gold quality
gingiva	UBERON:0001828	88.87	gold quality
epithelial cell of pancreas	CL:0000083	88.81	silver quality
islet of Langerhans	UBERON:0000006	88.44	gold quality
epithelium of esophagus	UBERON:0001976	88.21	gold quality
hair follicle	UBERON:0002073	88.19	silver quality
cerebellar cortex	UBERON:0002129	88.02	gold quality
cerebellar hemisphere	UBERON:0002245	87.98	gold quality
esophagus squamous epithelium	UBERON:0006920	87.94	gold quality
cerebellum	UBERON:0002037	87.89	gold quality
left ventricle myocardium	UBERON:0006566	87.72	silver quality
cervix epithelium	UBERON:0004801	87.65	gold quality
smooth muscle tissue	UBERON:0001135	87.64	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.36	gold quality
uterine cervix	UBERON:0000002	87.33	gold quality
tonsil	UBERON:0002372	87.22	gold quality
mucosa of transverse colon	UBERON:0004991	86.79	gold quality
lower esophagus mucosa	UBERON:0035834	86.75	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	897.17
E-GEOD-124472	yes	469.21
E-MTAB-7407	yes	240.03
E-HCAD-10	yes	42.84
E-MTAB-8271	yes	8.30
E-ANND-3	yes	4.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting MACROH2A2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-516A-3P	99.46	67.96	1378

Literature-anchored findings (GeneRIF, showing 6)

• expression of histone macroH2A1.1 and macroH2A2 predicts lung cancer recurrence. (PMID:19648962)
• rs16927253-T and rs4746957-A alleles showed a dominant protective effect towards eyelid sagging (PMID:29654602)
• macroH2A1.1 mediates an isoform-specific effect through its ability to suppress PARP1 activity. Second, the unstructured linker region exerts an additional repressive effect that is common to all macroH2A proteins. In the absence of DNA damage, the macroH2A linker is also sufficient for rescuing heterochromatin architecture in cells deficient for macroH2A (PMID:30177554)
• LSH catalyzes ATP-driven exchange of histone variants macroH2A1 and macroH2A2. (PMID:34223906)
• Analysis of histone variant constraint and tissue expression suggests five potential novel human disease genes: H2AFY2, H2AFZ, H2AFY, H2AFV, H1F0. (PMID:35072799)
• Breast cancer malignancy is governed by regulation of the macroH2A2/TM4SF1 axis, the AKT/NF-kappaB pathway, and elevated MMP13 expression. (PMID:38251858)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	macroh2a2	ENSDARG00000087897
mus_musculus	Macroh2a2	ENSMUSG00000020086
rattus_norvegicus	Macroh2a2	ENSRNOG00000024751

Paralogs (27): 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), H2AC14 (ENSG00000276368), H2AC16 (ENSG00000276903), H2AC8 (ENSG00000277075), H2AB3 (ENSG00000277745), H2AB2 (ENSG00000277858), H2AC4 (ENSG00000278463), H2AC17 (ENSG00000278677), H2AC18 (ENSG00000288825), H2AC19 (ENSG00000288859)

Protein

Protein identifiers

Core histone macro-H2A.2 — Q9P0M6 (reviewed: Q9P0M6)

All UniProt accessions (22): Q9P0M6, A0A7I2V2N7, A0A7I2V3B3, A0A7I2V3C2, A0A7I2V3M7, A0A7I2V3R0, A0A7I2V3Z8, A0A7I2V412, A0A7I2V423, A0A7I2V4D9, A0A7I2V4W8, A0A7I2V522, A0A7I2V583, A0A7I2V5A9, A0A7I2V5G0, A0A7I2V633, A0A7I2V6E9, A0A7I2YQB9, A0A7I2YQD6, A0A7I2YQF0, A0A7I2YQR8, Q5SQT3

UniProt curated annotations — full annotation on UniProt →

Function. Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. 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. May be involved in stable X chromosome inactivation.

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.

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the histone H2A family.

RefSeq proteins (1): NP_061119* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002119	Histone_H2A	Family
IPR002589	Macro_dom	Domain
IPR007125	H2A/H2B/H3	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR021171	Core_histone_macro-H2A	Family
IPR032454	Histone_H2A_C	Domain
IPR035796	Macro_H2A	Domain
IPR043472	Macro_dom-like	Homologous_superfamily

Pfam: PF00125, PF01661, PF16211

UniProt features (22 total): strand 8, helix 5, domain 2, modified residue 2, chain 1, turn 1, region of interest 1, compositionally biased region 1, cross-link 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6FY5	X-RAY DIFFRACTION	1.65
2XD7	X-RAY DIFFRACTION	2.09

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P0M6-F1	82.71	0.63

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 (3): 7, 9, 239

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, RNGTGGGC_UNKNOWN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_KERATINOCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_EPIDERMIS_DEVELOPMENT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, CAGGTCC_MIR492, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_RRNA_TRANSCRIPTION, GOBP_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), nucleosome assembly (GO:0006334), brain development (GO:0007420), dosage compensation by inactivation of X chromosome (GO:0009048), heterochromatin formation (GO:0031507), positive regulation of keratinocyte differentiation (GO:0045618), negative regulation of gene expression, epigenetic (GO:0045814), establishment of protein localization to chromatin (GO:0071169), negative regulation of transcription of nucleolar large rRNA by RNA polymerase I (GO:1901837), chromatin organization (GO:0006325)

GO Molecular Function (7): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), structural constituent of chromatin (GO:0030527), chromatin DNA binding (GO:0031490), protein heterodimerization activity (GO:0046982), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (8): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleosome (GO:0000786), Barr body (GO:0001740), nucleus (GO:0005634), nucleoplasm (GO:0005654), extracellular exosome (GO:0070062), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
central nervous system development	1
animal organ development	1
head development	1
sex-chromosome dosage compensation	1
heterochromatin formation	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
keratinocyte differentiation	1
positive regulation of epidermal cell differentiation	1
regulation of keratinocyte differentiation	1
positive regulation of multicellular organismal process	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
establishment of protein localization to chromosome	1
negative regulation of transcription by RNA polymerase I	1
nucleolar large rRNA transcription by RNA polymerase I	1
regulation of transcription of nucleolar large rRNA by RNA polymerase I	1
cellular component organization	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
transcription cis-regulatory region binding	1
structural molecule activity	1
DNA binding	1
chromatin binding	1
protein dimerization activity	1
nucleic acid binding	1
binding	1
chromosomal region	1
chromosome	1
protein-DNA complex	1

Protein interactions and networks

STRING

1642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MACROH2A2	GDAP2	Q9NXN4	594
MACROH2A2	H3Y2	P0DPK5	509
MACROH2A2	H3Y1	P0DPK2	506
MACROH2A2	SMCHD1	A6NHR9	474
MACROH2A2	MACROD1	Q9BQ69	447
MACROH2A2	H2BC21	Q16778	434
MACROH2A2	MECP2	P51608	405
MACROH2A2	H1-0	P07305	400
MACROH2A2	PARG	Q86W56	400
MACROH2A2	CENPA	P49450	387
MACROH2A2	JARID2	Q92833	381
MACROH2A2	PARP15	Q460N3	369
MACROH2A2	H1-10	Q92522	365
MACROH2A2	RPS4X	P12631	362
MACROH2A2	OTC	P00480	353
MACROH2A2	UBA1	P22314	353

IntAct

93 interactions, top by confidence:

A	B	Type	Score
XPC	CETN3	psi-mi:“MI:0914”(association)	0.730
rep	GTF2F2	psi-mi:“MI:0914”(association)	0.730
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
FAM133A	MACROH2A2	psi-mi:“MI:0915”(physical association)	0.560
MACROH2A2	H2BC15	psi-mi:“MI:0915”(physical association)	0.560
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
MED27	POLR2D	psi-mi:“MI:0914”(association)	0.530
NUFIP1	PDE2A	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	rep	psi-mi:“MI:0915”(physical association)	0.510
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
MACROH2A2	CDC37	psi-mi:“MI:0915”(physical association)	0.400
MACROH2A2	WWP1	psi-mi:“MI:0915”(physical association)	0.370
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
TEAD2	DDX39A	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
EZH2	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
MACROH2A2	SUZ12	psi-mi:“MI:0914”(association)	0.350
COX15	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
DLST		psi-mi:“MI:0914”(association)	0.350

BioGRID (302): H2AFY2 (Affinity Capture-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Proximity Label-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Affinity Capture-MS), H2AFY2 (Synthetic Lethality), H2AFY2 (Proximity Label-MS), H2AFY (Affinity Capture-MS)

ESM2 similar proteins: A0A097I2B5, A0A097I2D0, A0A1W2PP81, A0A1W2PPE2, A0A1W2PPH5, A0A1W2PR64, A0A1W2PRV1, A6NLC8, O75367, O93327, P02276, P06898, P0DW11, P0DW12, P0DW13, P0DW14, P25469, P35066, P35067, P40284, P40287, P61830, P61831, P61833, P61836, P81196, P81198, P81201, P81202, P93354, Q00715, Q02874, Q06196, Q0U1A0, Q2HU65, Q43213, Q54LP8, Q54WG6, Q6C0C4, Q757N1

Diamond homologs: A0A0D2UG83, A1A4R1, A1CJ10, A1D8G8, A9UMV8, C0HKE1, C0HKE2, C0HKE3, C0HKE4, C0HKE5, C0HKE6, C0HKE7, C0HKE8, C0HKE9, L7HZV6, O74268, O75367, O93327, P02262, P02263, P02264, P02268, P02269, P02270, P04735, P04908, P06897, P07793, P08844, P09588, P0C0S8, P0C0S9, P0C169, P0C170, P0C952, P0C953, P0CC09, P0CN98, P0CN99, P0CT12

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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
Replacement of protamines by nucleosomes in the male pronucleus	5	20.0×	8e-05
Influenza Viral RNA Transcription and Replication	6	19.0×	2e-05
Defective pyroptosis	8	18.4×	1e-06
Influenza Infection	7	18.1×	5e-06
PRC2 methylates histones and DNA	8	17.9×	1e-06
FXIIa activates plasma kallikrein-kinin system	7	17.8×	5e-06
SIRT1 negatively regulates rRNA expression	7	17.6×	5e-06
RNA Polymerase I Promoter Opening	6	16.2×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	7	19.2×	2e-05
double-strand break repair	7	15.3×	7e-05
nucleosome assembly	10	15.1×	1e-06
cytoplasmic translation	6	11.9×	2e-03
chromatin organization	10	10.7×	1e-05
DNA repair	13	8.9×	1e-06
chromatin remodeling	8	6.3×	4e-03
DNA damage response	9	5.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1932 predictions. Top by Δscore:

Variant	Effect	Δscore
10:70052998:CAGG:C	donor_loss	1.0000
10:70053000:GGTG:G	donor_loss	1.0000
10:70053002:T:A	donor_loss	1.0000
10:70090058:A:AG	acceptor_gain	1.0000
10:70090058:AGC:A	acceptor_gain	1.0000
10:70090058:AGCG:A	acceptor_gain	1.0000
10:70090059:G:GG	acceptor_gain	1.0000
10:70090059:GCG:G	acceptor_gain	1.0000
10:70090059:GCGG:G	acceptor_gain	1.0000
10:70090059:GCGGA:G	acceptor_gain	1.0000
10:70090164:CAGG:C	donor_loss	1.0000
10:70090166:GGTA:G	donor_loss	1.0000
10:70090167:G:GC	donor_loss	1.0000
10:70090168:T:A	donor_loss	1.0000
10:70093729:C:A	acceptor_gain	1.0000
10:70093733:A:AG	acceptor_gain	1.0000
10:70093734:G:GG	acceptor_gain	1.0000
10:70093734:GTCC:G	acceptor_gain	1.0000
10:70093841:AGAAG:A	donor_loss	1.0000
10:70093843:AAGG:A	donor_loss	1.0000
10:70093844:AG:A	donor_loss	1.0000
10:70093845:GG:G	donor_loss	1.0000
10:70093846:G:T	donor_loss	1.0000
10:70093847:T:G	donor_loss	1.0000
10:70109024:A:AG	acceptor_gain	1.0000
10:70109025:T:G	acceptor_gain	1.0000
10:70109203:GGCAG:G	donor_gain	1.0000
10:70109204:GCAG:G	donor_gain	1.0000
10:70109204:GCAGG:G	donor_gain	1.0000
10:70109207:GGT:G	donor_loss	1.0000

AlphaMissense

2415 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:70075821:T:C	Y55H	1.000
10:70075825:T:C	L56P	1.000
10:70090069:T:C	L61P	1.000
10:70090075:T:C	L63S	1.000
10:70090077:G:C	A64P	1.000
10:70090078:C:A	A64D	1.000
10:70090081:G:A	G65D	1.000
10:70090114:T:A	I76K	1.000
10:70090135:T:C	L83P	1.000
10:70090141:T:A	V85D	1.000
10:70090150:A:C	D88A	1.000
10:70090150:A:G	D88G	1.000
10:70090150:A:T	D88V	1.000
10:70090159:T:C	L91P	1.000
10:70091815:T:C	L113P	1.000
10:70075725:T:C	F23L	0.999
10:70075726:T:C	F23S	0.999
10:70075727:T:A	F23L	0.999
10:70075727:T:G	F23L	0.999
10:70075798:T:A	V47D	0.999
10:70075819:A:T	E54V	0.999
10:70075822:A:G	Y55C	0.999
10:70075830:G:C	A58P	0.999
10:70090062:G:A	E59K	0.999
10:70090063:A:T	E59V	0.999
10:70090064:A:C	E59D	0.999
10:70090064:A:T	E59D	0.999
10:70090071:G:A	E62K	0.999
10:70090073:A:C	E62D	0.999
10:70090073:A:T	E62D	0.999

dbSNP variants (sampled 300 via entrez): RS1000001984 (10:70090534 T>C,G), RS1000027150 (10:70059285 T>C), RS1000056718 (10:70058923 A>G,T), RS1000089565 (10:70063074 G>T), RS1000092612 (10:70052674 T>C), RS1000246162 (10:70078790 G>A,C), RS1000274644 (10:70065382 C>T), RS1000301967 (10:70073267 A>G,T), RS1000358427 (10:70071723 A>T), RS1000528103 (10:70052476 C>T), RS1000546441 (10:70085247 G>A,T), RS1000639088 (10:70070781 C>T), RS1000757974 (10:70059894 G>T), RS1000784548 (10:70097045 T>C), RS1000813217 (10:70079145 G>C,T)

Disease associations

OMIM: gene MIM:616141 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004029_44	Angiotensin-converting enzyme inhibitor intolerance	1.000000e-07
GCST006365_1	Upper eyelid sagging severity	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005325	response to angiotensin-converting enzyme inhibitor

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	4
sodium arsenite	decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, decreases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
aristolochic acid I	decreases expression	1
ginger extract	increases abundance, decreases expression	1
TL8-506	affects cotreatment, increases expression	1
terbufos	increases methylation	1
propionic acid	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
NSC 689534	decreases expression, affects binding	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	affects expression	1
Fonofos	increases methylation	1
Ivermectin	increases expression	1
Oils, Volatile	increases abundance, decreases expression	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2K5	SEES3-1V human H2AFY2, clone1	Embryonic stem cell	Male
CVCL_A2K6	SEES3-1V human H2AFY2, clone2	Embryonic stem cell	Male
CVCL_A2K7	SEES3-1V human H2AFY2, clone3	Embryonic stem cell	Male
CVCL_D7TX	Ubigene A-549 MACROH2A2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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