U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Gene ID: 29072, updated on 2-Nov-2024

Summary

Go to the top of the page Help
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
See SETD2 in Genome Data Viewer
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_000003.12Genomic Context describing neighboring genes Neighboring gene coiled-coil domain containing 12 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:47021430-47022210 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47022211-47022991 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47026300-47027052 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19806 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14301 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19807 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47039103-47039996 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:47050749-47051546 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:47051547-47052343 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47054299-47054798 Neighboring gene neurobeachin like 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14303 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:47082829-47083038 Neighboring gene neurotrophin receptor associated death domain, pseudogene Neighboring gene mitochondrial ribosomal protein L57 pseudogene 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47108907-47109512 Neighboring gene NANOG hESC enhancer GRCh37_chr3:47125242-47125743 Neighboring gene uncharacterized LOC124906375 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:47155200-47155707 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:47155708-47156216 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14304 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14305 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14306 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14307 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19809 Neighboring gene KIF9 antisense RNA 1 Neighboring gene MPRA-validated peak4632 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:47238926-47239426 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19810 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:47301362-47302268 Neighboring gene small nucleolar RNA, C/D box 13 pseudogene 3 Neighboring gene small nucleolar RNA, C/D box 13J Neighboring gene kinesin family member 9 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:47323613-47324812 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19812 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14308 Neighboring gene kelch like family member 18 Neighboring gene Sharpr-MPRA regulatory region 13740

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • Project title: HPA RNA-seq normal tissues 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Mutation pattern and genotype-phenotype correlations of SETD2 in neurodevelopmental disorders. Chen M, et al. Eur J Med Genet, 2021 May. PMID 33766796
  2. SETD2 related overgrowth syndrome: Presentation of four new patients and review of the literature. Marzin P, et al. Am J Med Genet C Semin Med Genet, 2019 Dec. PMID 31643139
  3. SETD2 Mutation in an Aggressive Optic Nerve Glioma. Campbell AA, et al. JAMA Ophthalmol, 2020 Jan 1. PMID 31697302
  4. Mutations in SETD2 cause a novel overgrowth condition. Luscan A, et al. J Med Genet, 2014 Aug. PMID 24852293
  5. SETD2 mutation in renal clear cell carcinoma suppress autophagy via regulation of ATG12. González-Rodríguez P, et al. Cell Death Dis, 2020 Jan 27. PMID 31988284, Free PMC Article

See all (208) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. Prognostic and therapeutic roles of SETD2 in cutaneous melanoma.
    Title: Prognostic and therapeutic roles of SETD2 in cutaneous melanoma.
  3. Methyltransferase Setd2 prevents T cell-mediated autoimmune diseases via phospholipid remodeling.
    Title: Methyltransferase Setd2 prevents T cell-mediated autoimmune diseases via phospholipid remodeling.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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

Go to the top of the page Help

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

Review eQTL and phenotype association data in this region using PheGenI

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

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

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

Go to the top of the page Help
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
NP_054878.5
XP_024309255.1
XP_024309256.1
XP_024309257.1
XP_047304001.1

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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

  1. NG_032091.1 RefSeqGene

    Range
    5001..152570
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_775

mRNA and Protein(s)

  1. 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

  2. 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

  1. 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

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    47016436..47164840 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. XM_047448045.1 → XP_047304001.1  histone-lysine N-methyltransferase SETD2 isoform X1

    UniProtKB/TrEMBL
    A0A1W2PPX9

  3. 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

  4. 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

  1. XR_007095670.1 RNA Sequence

  2. XR_002959514.2 RNA Sequence

  3. XR_007095673.1 RNA Sequence

  4. XR_007095672.1 RNA Sequence

  5. XR_007095671.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. 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

  1. NM_012271.1: Suppressed sequence

    Description
    NM_012271.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9BYW2.3 GenPept UniProtKB/Swiss-Prot:Q9BYW2

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous