YEATS2

protein-coding

YEATS domain containing 2, the group of YEATS domain containing|ATAC complex

Gene summary

Summary: The protein encoded by this gene is a scaffolding subunit of the ATAC complex, which is a complex with acetyltransferase activity on histones H3 and H4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

MANE transcript

NM_018023.5

Inheritance

ClinVar variants

U:213B:34

Top phenotype

Epilepsy, myoclonic, familial adult, 4

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr3:183,697,797-183,812,624

External References & Databases

Ensembl (ENSG00000163872)

Transcript & Mutation Effects

hg38 • Region Span ~114.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epilepsy, familial adult myoclonic, 4LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014055

Submitter: PanelApp Australia

benign adult familial myoclonic epilepsySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019448

Submitter: Orphanet

Clinical Genomic Database (CGD)

Epilepsy, myoclonic, familial adult, 4AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: Reported variants have involved intronic repeat expansions

Refs: 22713812; 31539032

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to YEATS2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 211

not providedTotal: 22

Epilepsy, familial adult myoclonic, 4Total: 13

YEATS2-related disorderTotal: 6

Benign adult familial myoclonic epilepsyTotal: 1

Breast ductal adenocarcinomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018023.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	19 clinvar	1 clinvar	26
missense			194 clinvar	14 clinvar		208
nonsense			4 clinvar			4
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	213	33	1	247

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 71 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018023.5	RefSeq	NP_060493.3	30	MANE Select
ENST00000305135.10	Ensembl	ENSP00000306983.5	30	MANE Select
NM_001351369.2	RefSeq	NP_001338298.1	30	Standard
NM_001351370.2	RefSeq	NP_001338299.1	30	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Chromatin modifying enzymes
HATs acetylate histones
Chromatin organization

Biological Process

negative regulation of transcription by RNA polymerase II
histone H3 acetylation
negative regulation of transcription, DNA-templated

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
protein binding
TBP-class protein binding
histone binding
modification-dependent protein binding

Cellular Component

Ada2/Gcn5/Ada3 transcription activator complex
mitotic spindle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000305135
Coding exons: 30
Length: 114808
Individuals with no LoFs: 124737
Homozygous LoFs: 0
Heterozygous LoFs: 60
Defined: 124797
p: 0.000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.972	695	771	0.902	0.0000405	9124
Missense (PolyPhen)		155	200.45	0.77325		2447
Synonymous	1.04	276	299	0.924	0.0000176	2935
Loss of Function	6.56	13	73.9	0.176	0.00000397	860

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00052	0.00052	rare
Latino/Admixed American	0.00041	0.00041	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00017	rare
Finnish	0.00046	0.00046	rare
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0	0.0	absent
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. YEATS2 specifically recognizes and binds histone H3 crotonylated at 'Lys-27' (H3K27cr) (PubMed:27103431). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:27103431). {ECO:0000269|PubMed:18838386, ECO:0000269|PubMed:19103755, ECO:0000269|PubMed:27103431}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.402
RVIS EVS: -1.08
RVIS percentile EVS: 7.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.244

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High