GeneBe

SETD7

protein-coding

SET domain containing 7, histone lysine methyltransferase, the group of SET domain containing|Lysine methyltransferases

Gene summary

Enables histone H3 methyltransferase activity; p53 binding activity; and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine dimethylation and peptidyl-lysine monomethylation. Acts upstream of or within DNA damage response and heterochromatin organization. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_030648.4

Inheritance

—

ClinVar variants

U:33B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr4:139,495,941-139,606,699

External References & Databases

Ensembl (ENSG00000145391)NCBI Gene (80854)OMIM (606594)HGNC:30412GenCCUniProt (Q8WTS6)AlphaFoldClinVar (SETD7)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~110.8 kb
Loading mutation effect viewer...

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 SETD7 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 29
not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030648.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
 1
missense
30
clinvar
 30
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total00330134
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_030648.4RefSeqNP_085151.18MANE Select
ENST00000274031.8EnsemblENSP00000274031.38MANE Select
NM_001306199.2RefSeqNP_001293128.18Standard
NM_001306200.2RefSeqNP_001293129.13Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
setd7Danio rerio

Structure: heart

Quality: linear

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Lysine degradation - Homo sapiens (human)
  • FoxO signaling pathway - Homo sapiens (human)
  • Carnitine Synthesis
  • Histone Modifications
  • PKMTs methylate histone lysines

Biological Process

  • chromatin organization
  • cellular response to DNA damage stimulus
  • peptidyl-lysine monomethylation
  • peptidyl-lysine dimethylation
  • histone lysine methylation

Molecular Function

  • p53 binding
  • chromatin binding
  • protein binding
  • protein-lysine N-methyltransferase activity
  • histone-lysine N-methyltransferase activity

Cellular Component

  • nucleoplasm
  • chromosome
  • nucleolus

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000274031
Coding exons
8
Length
110759
Individuals with no LoFs
125718
Homozygous LoFs
0
Heterozygous LoFs
29
Defined
125747
p
0.000115
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.661432110.6790.00001122403
Missense (PolyPhen)4676.3620.60239812
Synonymous-0.2298582.41.030.00000506687
Loss of Function2.38717.80.3938.12e-7229

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000320.000029rare
Ashkenazi Jewish0.00170.0017notable
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000970.000097rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation. {ECO:0000269|PubMed:12540855, ECO:0000269|PubMed:12588998, ECO:0000269|PubMed:15099517, ECO:0000269|PubMed:15525938, ECO:0000269|PubMed:16141209, ECO:0000269|PubMed:17108971}.;

Recessive Scores

pRec
0.156

Intolerance Scores

LoFtool
0.273
RVIS EVS
0.08
RVIS percentile EVS
60.31

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.987

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
Feedback | API | MCP | Annotate VCF | Sitemap | About | Privacy & Terms
For research and educational, non-commercial use only. Not for clinical or diagnostic use. GeneBe does not provide medical advice. Data use for AI modeling is prohibited: if used, the cost is $0.001 per byte of downloaded uncompressed data.