SETD6

protein-coding

SET domain containing 6, protein lysine methyltransferase, the group of SET domain containing

Gene summary

This gene encodes a methyltransferase that adds a methyl group to the histone H2AZ, which is involved in nuclear receptor-dependent transcription. The protein also interacts with several endogenous proteins which are involved in nuclear hormone receptor signaling. A related pseudogene is located on chromosome 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

MANE transcript

NM_001160305.4

Inheritance

—

ClinVar variants

U:85B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.17

Max pathogenic AF

—

Genomic locus

chr16:58,515,479-58,523,842

External References & Databases

Ensembl (ENSG00000103037)

Transcript & Mutation Effects

hg38 • Region Span ~8.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

colorectal cancerLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0005575

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SETD6 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 84

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001160305.4. 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		2
missense			81 clinvar	4 clinvar		85
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	85	5	0	90

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001160305.4	RefSeq	NP_001153777.1	8	MANE Select
ENST00000219315.9	Ensembl	ENSP00000219315.5	8	MANE Select
NM_024860.3	RefSeq	NP_079136.2	9	Standard
ENST00000310682.6	Ensembl	ENSP00000310082.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Histone Modifications
PKMTs methylate histone lysines
Chromatin modifying enzymes
Chromatin organization

Biological Process

peptidyl-lysine monomethylation
stem cell population maintenance
negative regulation of NF-kappaB transcription factor activity
histone lysine methylation
stem cell differentiation

Molecular Function

protein binding
protein-lysine N-methyltransferase activity
NF-kappaB binding

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000219315
Coding exons: 8
Length: 5049
Individuals with no LoFs: 125296
Homozygous LoFs: 1
Heterozygous LoFs: 451
Defined: 125748
p: 0.00180

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.390	270	253	1.07	0.0000133	3003
Missense (PolyPhen)		91	79.469	1.1451		980
Synonymous	-2.11	131	104	1.26	0.00000566	946
Loss of Function	-0.744	25	21.3	1.17	9.07e-7	246

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.0013	0.0012	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0037	0.0034	notable
Finnish	0.00039	0.00032	rare
European (Non-Finnish)	0.0024	0.0024	notable
South Asian	0.0013	0.0012	notable
Other	0.0041	0.0041	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protein-lysine N-methyltransferase. Monomethylates 'Lys- 310' of the RELA subunit of NF-kappa-B complex, leading to down- regulate NF-kappa-B transcription factor activity (PubMed:21131967). Monomethylates 'Lys-8' of H2AZ (H2AZK8me1) (PubMed:23324626). Required for the maintenance of embryonic stem cell self-renewal (By similarity). {ECO:0000250|UniProtKB:Q9CWY3, ECO:0000269|PubMed:21131967, ECO:0000269|PubMed:23324626}.;

Intolerance Scores

LoFtool: 0.737
RVIS EVS: 0.13
RVIS percentile EVS: 63.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.809

Gene Damage Prediction

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