SUV39H1

protein-coding

SUV39H1 histone lysine methyltransferase, the group of SET domain containing|eNoSC complex|Lysine methyltransferases

Gene summary

This gene encodes an evolutionarily-conserved protein containing an N-terminal chromodomain and a C-terminal SET domain. The encoded protein is a histone methyltransferase that trimethylates lysine 9 of histone H3, which results in transcriptional gene silencing. Loss of function of this gene disrupts heterochromatin formation and may cause chromosome instability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Previous symbols:

SUV39H

MANE transcript

NM_003173.4

Inheritance

—

ClinVar variants

U:26B:2

Top phenotype

Ependymoma

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:48,695,554-48,709,016

External References & Databases

Ensembl (ENSG00000101945)

Transcript & Mutation Effects

hg38 • Region Span ~13.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SUV39H1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 15

not providedTotal: 2

EpendymomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003173.4. 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			1 clinvar	1 clinvar	1 clinvar	3
missense			22 clinvar			22
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	26	1	1	28

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003173.4	RefSeq	NP_003164.1	6	MANE Select
ENST00000376687.4	Ensembl	ENSP00000365877.4	6	MANE Select
NM_001282166.2	RefSeq	NP_001269095.1	6	Standard
ENST00000337852.10	Ensembl	ENSP00000337976.6	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
suv39h1a	Danio rerio	Structure: exocrine pancreas Quality: undifferentiated abnormal

Gene / Model

Organism

Observed Phenotype

suv39h1a

Danio rerio

Structure: exocrine pancreas

Quality: undifferentiated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysine degradation - Homo sapiens (human)
Histone Modifications
Retinoblastoma (RB) in Cancer
Simplified Interaction Map Between LOXL4 and Oxidative Stress Pathway
SIRT1 negatively regulates rRNA expression

Biological Process

negative regulation of transcription by RNA polymerase II
chromatin silencing at rDNA
chromatin organization
rRNA processing
cellular response to DNA damage stimulus

Molecular Function

transcription regulatory region sequence-specific DNA binding
chromatin binding
protein binding
zinc ion binding
S-adenosylmethionine-dependent methyltransferase activity

Cellular Component

chromosome, centromeric region
heterochromatin
condensed nuclear chromosome
nucleus
nuclear lamina

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376687
Coding exons: 6
Length: 13459
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.49	65	206	0.316	0.0000199	2686
Missense (PolyPhen)		10	63.008	0.15871		881
Synonymous	0.642	70	77.2	0.907	0.00000693	807
Loss of Function	3.43	0	13.7	0.00	0.00000107	218

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys- 9' as substrate. Also weakly methylates histone H1 (in vitro). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone- modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation. {ECO:0000269|PubMed:14765126, ECO:0000269|PubMed:16449642, ECO:0000269|PubMed:16818776, ECO:0000269|PubMed:16858404, ECO:0000269|PubMed:18004385, ECO:0000269|PubMed:18485871}.;

Recessive Scores

pRec: 0.221

Intolerance Scores

RVIS EVS: -0.21
RVIS percentile EVS: 38.28

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.915

Gene Damage Prediction

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