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)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
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)