SPEN
  • 1
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
SPEN (HGNC:17575) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
spen family transcriptional repressor
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
KIAA0929, MINT, SHARP, RBM15C
%HI
5.51(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.09(Read more about gnomAD LOEUF score)
Cytoband
1p36.21-p36.13
Genomic Coordinates
GRCh37/hg19: chr1:16174202-16266951 NCBI Ensembl UCSC
GRCh38/hg38: chr1:15847707-15940456 NCBI Ensembl UCSC
MANE Select Transcript
NM_015001.3 ENST00000375759.8 (Read more about MANE Select)
Function
May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2- mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-15891
ClinGen Curation ID:
CCID:007930
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Little Evidence for Haploinsufficiency (1)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
03/27/2019

Haploinsufficiency (HI) Score Details

HI Score:
1
HI Evidence Strength:
Little Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • Complex Neurodevelopmental Disorder Monarch
HI Evidence:
  • PUBMED: 25363768
    Iossifov et al. reported a de novo frameshift variant c.3028_3029insA/p.D1011Gfs*11 in an ASD patient
  • PUBMED: 27525107
    Yuen et al. reported a de novo nonsense variant c.5392C>T/p.Q1798* in an ASD patient.
  • PUBMED: 28135719
    DDD study reported two de novo LOF variants (c.6958_6962del5 /p.K2320Gfs*37 and c.7503G>A/p.W2501*) in patients with developmental disorder.
HI Evidence Comments:
Coe et al. (2018 PMID: 30559488) summarised the de novo variants in SPEN (as one of DD genes) previously reported/detected in three above mentioned papers among patients with developmental disorders by trio exome sequencing. There are a total of four likely gene disruption (LGD) variants and four missense variants so far reported. All de novo variants are listed in http://denovo-db.gs.washington.edu/denovo-db/. Given the high genetic heterogeneity and relatively non-specific nature of this phenotype (ie. ASD/ID/DD), the dosage score for HI is 1. De novo SPEN variants reported in the Krupp 2017 and Stessman 2017 papers are likely from the same individuals due to overlapping cohorts, and are not double counted. Additionally, none of the 4 de novo variants appear in gnomAD.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
At this time, no whole-gene duplications of SPEN have been reported.

Genomic View

Select assembly: (NC_000001.10) (NC_000001.11)