NSD1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- NSD1 (HGNC:14234) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- nuclear receptor binding SET domain protein 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- STO
- Alias symbols
- ARA267, FLJ22263, KMT3B
- %HI
- 29.19(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.14(Read more about gnomAD LOEUF score)
- Cytoband
- 5q35.3
- Genomic Coordinates
-
GRCh37/hg19: chr5:176560016-176727214 NCBI Ensembl UCSC GRCh38/hg38: chr5:177131798-177300213 NCBI Ensembl UCSC - MANE Select Transcript
- NM_022455.5 ENST00000439151.7 (Read more about MANE Select)
- Function
- Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. {ECO:0000269|PubMed:21196496}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-2889
ClinGen Curation ID:
CCID:007579
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency
(3)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Related Links:
Last Evaluated:
07/27/2020
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- Sotos Syndrome Monarch
HI Evidence:
-
PUBMED:
11896389
Kurotaki et al. (2002) identified 4 different de novo point mutations of NSD1 in 4 of 38 patients with Sotos syndrome. They included a nonsense mutation (1310C->G) in exon 5 which predicted to lead to a truncation of NSD1, and a one-base deletion (3536delA) in exon 5 which leads to a truncation mutation. Also included were a one-base insertion (5998insT) in exon 19 which leads to a truncation mutation, and a base substitution (6151+1G->A) at the splice donor site in intron 20 which confirmed to skip exon 20 and resulting in a truncated protein.
-
PUBMED:
17565729
Saugier-Veber et al. (2007) detected intragenic NSD1 mutations in 83 Sotos syndrome patients by Quantitative Multiplex PCR. Two cases were familial (child-mother). There were 35 nonsense mutations (21 confirmed de novo), 26 frameshift mutations (16 confirmed de novo), 15 missense mutations (10 confirmed de novo), two in-frame deletions (both confirmed de novo), and three splice-site mutations (all confirmed de novo). A total of 48 mutations were novel.
-
PUBMED:
23190751
Sohn et al. 2013 studied 18 patients with Sotos syndrome. Seven of them had NSD1 intragenic variants; two had de novo frameshift variants, one with de novo splice site variant, and three patients with de novo nonsense variants.
HI Evidence Comments:
Loss of NSD1 has been associated with Sotos syndrome (see GeneReviews for additional information). Additional literature evidence includes (but is not limited to): PMIDs 16140999, 19596467, 21677396, 23341071, and 30755392.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
To date, there have been no focal duplications of NSD1, therefore, the gene has a triplosensitivity score of 0. However, duplications of a larger region including this gene have been observed in individuals with what has been described as a "reversed" Sotos Syndrome phenotype. Please see the related region curation "5q35 recurrent (Sotos syndrome) region (includes NSD1) (ISCA-37425) for a full description of the evidence supporting triplosensitivity of this region.
Genomic View
Select assembly:
(NC_000005.9)
(NC_000005.10)