SETD2 SET domain containing 2, histone lysine methyltransferase [Homo sapiens (human)] - Gene

Summary

Official Symbol: SETD2provided by HGNC
Official Full Name: SET domain containing 2, histone lysine methyltransferaseprovided by HGNC
Primary source: HGNC:HGNC:18420
See related: Ensembl:ENSG00000181555 MIM:612778; AllianceGenome:HGNC:18420
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LLS; HYPB; SET2; HIF-1; HIP-1; KMT3A; MRD70; RAPAS; HBP231; HSPC069; p231HBP
Summary: Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein belonging to a class of huntingtin interacting proteins characterized by WW motifs. This protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II. [provided by RefSeq, Aug 2008]
Expression: Ubiquitous expression in bone marrow (RPKM 11.9), testis (RPKM 11.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.31

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (47016436..47164840, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (47032799..47180480, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (47057926..47205603, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Regulation of SETD2 maintains immune regulatory function in macrophages to suppress airway allergy.
Title: Regulation of SETD2 maintains immune regulatory function in macrophages to suppress airway allergy.
Prognostic and therapeutic roles of SETD2 in cutaneous melanoma.
Title: Prognostic and therapeutic roles of SETD2 in cutaneous melanoma.
Methyltransferase Setd2 prevents T cell-mediated autoimmune diseases via phospholipid remodeling.
Title: Methyltransferase Setd2 prevents T cell-mediated autoimmune diseases via phospholipid remodeling.
Morphological characteristics of SETD2-mutated locally advanced clear cell renal cell carcinoma: Comparison with BAP1-mutated clear cell renal cell carcinoma.
Title: Morphological characteristics of SETD2-mutated locally advanced clear cell renal cell carcinoma: Comparison with BAP1-mutated clear cell renal cell carcinoma.
SETD2 mutations do not contribute to clonal fitness in response to chemotherapy in childhood B cell acute lymphoblastic leukemia.
Title: SETD2 mutations do not contribute to clonal fitness in response to chemotherapy in childhood B cell acute lymphoblastic leukemia.
SETD2 loss in renal epithelial cells drives epithelial-to-mesenchymal transition in a TGF-beta-independent manner.
Title: SETD2 loss in renal epithelial cells drives epithelial-to-mesenchymal transition in a TGF-β-independent manner.
Effects of SETD2 on telomere length and malignant transformation property of Met-5A after one-month crocidolite exposure.
Title: Effects of SETD2 on telomere length and malignant transformation property of Met-5A after one-month crocidolite exposure.
SETD2 deficiency promotes renal fibrosis through the TGF-beta/Smad signalling pathway in the absence of VHL.
Title: SETD2 deficiency promotes renal fibrosis through the TGF-β/Smad signalling pathway in the absence of VHL.
Loss of SETD2 aggravates colorectal cancer progression caused by SMAD4 deletion through the RAS/ERK signalling pathway.
Title: Loss of SETD2 aggravates colorectal cancer progression caused by SMAD4 deletion through the RAS/ERK signalling pathway.
Epigenotype-genotype-phenotype correlations in SETD1A and SETD2 chromatin disorders.
Title: Epigenotype-genotype-phenotype correlations in SETD1A and SETD2 chromatin disorders.

Submit: New GeneRIF Correction See all GeneRIFs (125)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Intellectual developmental disorder, autosomal dominant 70 MedGen: C5774271 OMIM: 620157 GeneReviews: SETD2 Neurodevelopmental Disorders	not available
Luscan-Lumish syndrome MedGen: C4085873 OMIM: 616831 GeneReviews: SETD2 Neurodevelopmental Disorders	Compare labs
Rabin-Pappas syndrome MedGen: C5774269 OMIM: 620155 GeneReviews: SETD2 Neurodevelopmental Disorders	not available

Copy number response

Description
Copy number response Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2022-03-08) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2022-03-08) ClinGen Genome Curation Page

EBI GWAS Catalog

Description
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G10736 (e-PCR)
- UniSTS:26711

SHGC-34751 (e-PCR)
- UniSTS:62807

RH45910 (e-PCR)
- UniSTS:68991

D3S4066 (e-PCR)
- UniSTS:59036

SHGC-76906 (e-PCR)
- UniSTS:6858

D20S994 (e-PCR)
- UniSTS:154613

Clone Names

FLJ16420, FLJ22472, FLJ23184, FLJ45883, FLJ46217, KIAA1732

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables alpha-tubulin binding	IDA Inferred from Direct Assay more info	PubMed
enables histone H3 methyltransferase activity	TAS Traceable Author Statement more info
enables histone H3K36 methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables histone H3K36 methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K36 methyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone H3K36 trimethyltransferase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-lysine N-methyltransferase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in cell migration involved in vasculogenesis	IEA Inferred from Electronic Annotation more info
involved_in coronary vasculature morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in defense response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in embryonic cranial skeleton morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic placenta morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in endodermal cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in forebrain development	IEA Inferred from Electronic Annotation more info
involved_in mesoderm morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in microtubule cytoskeleton organization involved in mitosis	IDA Inferred from Direct Assay more info	PubMed
involved_in mismatch repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in morphogenesis of a branching structure	IEA Inferred from Electronic Annotation more info
involved_in neural tube closure	IEA Inferred from Electronic Annotation more info
involved_in nucleosome organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-lysine trimethylation	IDA Inferred from Direct Assay more info	PubMed
involved_in pericardium development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of autophagy	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interferon-alpha production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ossification	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of cytokinesis	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of double-strand break repair via homologous recombination	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of gene expression	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of mRNA export from nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein localization to chromatin	IDA Inferred from Direct Assay more info	PubMed
involved_in response to alkaloid	IEA Inferred from Electronic Annotation more info
involved_in response to metal ion	IEA Inferred from Electronic Annotation more info
involved_in response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
involved_in response to type I interferon	IDA Inferred from Direct Assay more info	PubMed
involved_in stem cell development	IEA Inferred from Electronic Annotation more info
involved_in stem cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in transcription elongation by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in chromosome	IBA Inferred from Biological aspect of Ancestor more info
located_in chromosome	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytoplasm	IC Inferred by Curator more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: histone-lysine N-methyltransferase SETD2

Names: huntingtin interacting protein 1; huntingtin yeast partner B; huntingtin-interacting protein B; lysine N-methyltransferase 3A; protein-lysine N-methyltransferase SETD2

NP_001336299.1

EC 2.1.1.359

NP_054878.5

EC 2.1.1.359

XP_024309255.1

EC 2.1.1.359

XP_024309256.1

EC 2.1.1.359

XP_024309257.1

EC 2.1.1.359

XP_047304001.1

EC 2.1.1.359

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_032091.1 RefSeqGene

Range

5001..152570

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_775

mRNA and Protein(s)

NM_001349370.3 → NP_001336299.1 histone-lysine N-methyltransferase SETD2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AC094020, AC127430

Consensus CDS

CCDS93261.1

UniProtKB/TrEMBL

A0A1W2PPX9, A0A8I5KV15

Related

ENSP00000491413.2, ENST00000638947.2

Conserved Domains (6) summary

pfam05279
Location:1896 → 2079

Asp-B-Hydro_N; Aspartyl beta-hydroxylase N-terminal region

smart00570
Location:1451 → 1505

AWS; associated with SET domains

smart00317
Location:1506 → 1629

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

smart00508
Location:1630 → 1646

PostSET; Cysteine-rich motif following a subset of SET domains

pfam00397
Location:2347 → 2376

WW; WW domain

pfam08236
Location:2425 → 2512

SRI; SRI (Set2 Rpb1 interacting) domain
NM_014159.7 → NP_054878.5 histone-lysine N-methyltransferase SETD2 isoform 1

See identical proteins and their annotated locations for NP_054878.5

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC094020, AC127430, AI671342, AK127782, AY576987, BC117162, BX649110, DA800082

Consensus CDS

CCDS2749.2

UniProtKB/Swiss-Prot

O75397, O75405, Q17RW8, Q5BKS9, Q5QGN2, Q69YI5, Q6IN64, Q6ZN53, Q6ZS25, Q8N3R0, Q8TCN0, Q9BYW2, Q9C0D1, Q9H696, Q9NZW9

UniProtKB/TrEMBL

A0A8I5KV15

Related

ENSP00000386759.3, ENST00000409792.4

Conserved Domains (6) summary

pfam05279
Location:1940 → 2123

Asp-B-Hydro_N; Aspartyl beta-hydroxylase N-terminal region

smart00570
Location:1495 → 1549

AWS; associated with SET domains

smart00317
Location:1550 → 1673

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

smart00508
Location:1674 → 1690

PostSET; Cysteine-rich motif following a subset of SET domains

pfam00397
Location:2391 → 2420

WW; WW domain

pfam08236
Location:2469 → 2548

SRI; SRI (Set2 Rpb1 interacting) domain

RNA

NR_146158.3 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC094020, AC127430

Related

ENST00000431180.5

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

47016436..47164840 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024453487.2 → XP_024309255.1 histone-lysine N-methyltransferase SETD2 isoform X3

UniProtKB/TrEMBL

A0A8I5KV15

Related

ENSP00000509568.1, ENST00000685005.1

Conserved Domains (6) summary

pfam05279
Location:1851 → 2034

Asp-B-Hydro_N; Aspartyl beta-hydroxylase N-terminal region

smart00570
Location:1451 → 1505

AWS; associated with SET domains

smart00317
Location:1506 → 1629

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

smart00508
Location:1630 → 1646

PostSET; Cysteine-rich motif following a subset of SET domains

pfam00397
Location:2302 → 2331

WW; WW domain

pfam08236
Location:2380 → 2467

SRI; SRI (Set2 Rpb1 interacting) domain
XM_047448045.1 → XP_047304001.1 histone-lysine N-methyltransferase SETD2 isoform X1

UniProtKB/TrEMBL

A0A1W2PPX9
XM_024453488.2 → XP_024309256.1 histone-lysine N-methyltransferase SETD2 isoform X2

UniProtKB/TrEMBL

A0A8I5KV15

Conserved Domains (5) summary

pfam05279
Location:1796 → 1979

Asp-B-Hydro_N; Aspartyl beta-hydroxylase N-terminal region

smart00570
Location:1451 → 1505

AWS; associated with SET domains

smart00508
Location:1530 → 1546

PostSET; Cysteine-rich motif following a subset of SET domains

pfam00397
Location:2247 → 2276

WW; WW domain

pfam08236
Location:2325 → 2412

SRI; SRI (Set2 Rpb1 interacting) domain
XM_024453489.1 → XP_024309257.1 histone-lysine N-methyltransferase SETD2 isoform X4

UniProtKB/TrEMBL

H7BXT4

Conserved Domains (2) summary

smart00570
Location:1451 → 1505

AWS; associated with SET domains

smart00317
Location:1506 → 1595

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

RNA

XR_007095670.1 RNA Sequence
XR_002959514.2 RNA Sequence
XR_007095673.1 RNA Sequence
XR_007095672.1 RNA Sequence
XR_007095671.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

47032799..47180480 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_012271.1: Suppressed sequence

Description

NM_012271.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.