MACROH2A1

macroH2A.1 histone, the group of H2A histones|Macro domain containing

Basic information

Region (hg38): 5:135334381-135399914

Previous symbols: [ "H2AFY" ]

Links

ENSG00000113648

∙ NCBI:9555 ∙ OMIM:610054 ∙ HGNC:4740 ∙ Uniprot:O75367 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

brachydactyly-elbow wrist dysplasia syndrome (Supportive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MACROH2A1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MACROH2A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					3 clinvar	3
missense			12 clinvar			12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	12	0	3

Variants in MACROH2A1

This is a list of pathogenic ClinVar variants found in the MACROH2A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
5-135335028-C-T	not specified	Uncertain significance (Feb 21, 2024)	3121930
5-135335067-G-T	not specified	Uncertain significance (Sep 25, 2023)	3121929
5-135335071-T-C	not specified	Uncertain significance (Jul 14, 2022)	3121928
5-135335080-C-T	not specified	Uncertain significance (Apr 11, 2023)	2513708
5-135335100-T-C	not specified	Uncertain significance (Jun 07, 2023)	2508246
5-135343265-G-A		Benign (Aug 18, 2018)	716117
5-135343347-A-G	not specified	Uncertain significance (Mar 01, 2023)	2491874
5-135343348-G-A	not specified	Uncertain significance (Oct 03, 2022)	3121934
5-135343366-C-T	not specified	Uncertain significance (Mar 01, 2024)	3121933
5-135360551-T-C		Benign (Jan 09, 2019)	799411
5-135369416-C-T	not specified	Uncertain significance (Oct 07, 2022)	3121932
5-135369417-G-A	not specified	Uncertain significance (Jan 06, 2023)	2471494
5-135369490-G-A		Benign (Jun 26, 2018)	730304
5-135369494-G-A	not specified	Uncertain significance (May 09, 2023)	2515413
5-135370028-G-A		Benign (Dec 31, 2019)	785137
5-135388947-C-T	not specified	Uncertain significance (May 20, 2024)	3292516
5-135388967-C-A	not specified	Uncertain significance (Sep 29, 2022)	3121931

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MACROH2A1	protein_coding	protein_coding	ENST00000511689	8	66015

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.737	0.262	125712	0	2	125714	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.30	84	223	0.377	0.0000132	2417
Missense in Polyphen		12	95.541	0.1256		1013
Synonymous	0.650	87	95.1	0.915	0.00000634	764
Loss of Function	2.85	2	13.1	0.152	5.53e-7	193

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.00000891	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription (PubMed:12718888, PubMed:15621527, PubMed:16428466). 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. Involved in stable X chromosome inactivation (PubMed:15897469). Inhibits the binding of transcription factors, including NF-kappa-B, and interferes with the activity of remodeling SWI/SNF complexes (PubMed:12718888, PubMed:16428466). Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin (PubMed:16428466, PubMed:16107708). {ECO:0000269|PubMed:12718888, ECO:0000269|PubMed:15621527, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16107708, ECO:0000269|PubMed:16428466}.; FUNCTION: Isoform 2: Represses SOD3 gene expression. {ECO:0000269|PubMed:23022728}.;
Pathway: Systemic lupus erythematosus - Homo sapiens (human);Necroptosis - Homo sapiens (human);Alcoholism - Homo sapiens (human);H19 action Rb-E2F1 signaling and CDK-β-catenin activity;ATF-2 transcription factor network (Consensus)

Recessive Scores

pRec: 0.212

Intolerance Scores

loftool: 0.137
rvis_EVS: -0.41
rvis_percentile_EVS: 26.23

Haploinsufficiency Scores

pHI: 0.308
hipred: Y
hipred_score: 0.728
ghis: 0.647

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.939

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low

Mouse Genome Informatics

Gene name: H2afy
Phenotype: growth/size/body region phenotype; normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; vision/eye phenotype; immune system phenotype; liver/biliary system phenotype; pigmentation phenotype;

Gene ontology

Biological process: negative regulation of transcription by RNA polymerase II;chromatin organization;nucleosome assembly;dosage compensation;regulation of lipid metabolic process;negative regulation of histone phosphorylation;positive regulation of maintenance of mitotic sister chromatid cohesion;regulation of gene expression, epigenetic;positive regulation of keratinocyte differentiation;negative regulation of gene expression, epigenetic;positive regulation of gene expression, epigenetic;negative regulation of histone H3-K4 methylation;negative regulation of histone H3-K27 methylation;regulation of chromatin silencing at rDNA;establishment of protein localization to chromatin;negative regulation of protein serine/threonine kinase activity;negative regulation of transcription of nucleolar large rRNA by RNA polymerase I;negative regulation of cell cycle G2/M phase transition;regulation of response to oxidative stress;negative regulation of protein localization to chromosome, telomeric region
Cellular component: nuclear chromosome;nuclear chromosome, telomeric region;nucleosome;nuclear chromatin;condensed chromosome;sex chromatin;Barr body;nucleus;pericentric heterochromatin;nucleolus;extracellular exosome
Molecular function: rDNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II core promoter sequence-specific DNA binding;DNA binding;protein binding;double-stranded methylated DNA binding;enzyme binding;protein kinase binding;protein serine/threonine kinase inhibitor activity;chromatin DNA binding;nucleosomal DNA binding;transcription regulatory region DNA binding;protein heterodimerization activity;promoter-specific chromatin binding