SETD5
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
SETD5 (HGNC:25566) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
SET domain containing 5
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
FLJ10707, SETD5A
%HI
12.88(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.38(Read more about gnomAD LOEUF score)
Cytoband
3p25.3
Genomic Coordinates
GRCh37/hg19: chr3:9439299-9519838 NCBI Ensembl UCSC
GRCh38/hg38: chr3:9397615-9478154 NCBI Ensembl UCSC
MANE Select Transcript
NM_001080517.3 ENST00000402198.7 (Read more about MANE Select)
Function
Chromatin regulator required for brain development: acts as a regulator of RNA elongation rate, thereby regulating neural stem cell (NSC) proliferation and synaptic transmission. May act by mediating trimethylation of 'Lys-36' of histone H3 (H3K36me3), which is essential to allow on-time RNA elongation dynamics. Also monomethylates 'Lys-9' of histone H3 (H3K9me1) in vitro. The relevance of histone methyltransferase activity is however subject to discussion. {ECO:0000250|UniProtKB:Q5XJV7}. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-32743
ClinGen Curation ID:
CCID:007832
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
11/06/2014

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency Monarch
HI Evidence:
  • PUBMED: 25138099
    Kuechler et al. (2014) performed whole exome sequencing (trio analysis) on a cohort of 301 patients with intellectual disability and identified de novo intragenic variants in SET domain-containing 5 (SETD5) in two unrelated female patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splite-donor site. Both intragenic variants were shown to undergo nonsense mediated decay, consistent with a loss-of-function and haploinsufficiency. Genomic microarray analysis of the same cohort identified additional de novo nonfocal microdeletions encompassing the SETD5 gene in 4 unrelated patients (6 total). In addition to ID, all patients with SETD5 alterations in this study were reported to have similar facial dysmorphisms.
  • PUBMED: 24680889
    Grozeva et al. (2014) sequenced a cohort of 996 patients with moderate to severe ID by a targeted NGS approach and identified 7 unrelated male patients with de novo heterozygous frameshift or truncating mutations in SETD5. This reference was also reviewed in OMIM (see http://www.omim.org/entry/615743).
HI Evidence Comments:
Heterozygous loss-of-function mutations and deletions affecting SETD5 have been identified in multiple unrelated patients with ID and similar facial features. Additional reports of deletions encompassing SETD5 include Pinto et al., 2014 (PMID 24768552), Peltekova et al., 2012 (PMID 22903836) and Kellogg et al., 2013 (PMID 23613140).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000003.11) (NC_000003.12)