NSD1

This gene encodes a protein containing a SET domain, 2 LXXLL motifs, 3 nuclear translocation signals (NLSs), 4 plant homeodomain (PHD) finger regions, and a proline-rich region. The encoded protein enhances androgen receptor (AR) transactivation, and this enhancement can be increased further in the presence of other androgen receptor associated coregulators. This protein may act as a nucleus-localized, basic transcriptional factor and also as a bifunctional transcriptional regulator. Mutations of this gene have been associated with Sotos syndrome and Weaver syndrome. One version of childhood acute myeloid leukemia is the result of a cryptic translocation with the breakpoints occurring within nuclear receptor-binding Su-var, enhancer of zeste, and trithorax domain protein 1 on chromosome 5 and nucleoporin, 98-kd on chromosome 11. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq]

Full Name

nuclear receptor binding SET domain protein 1

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.

Biological Process

Chromatin organizationIEA:UniProtKB-KW
Histone methylationISS:UniProtKB
Negative regulation of transcription by RNA polymerase IIISS:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of histone H3-K36 methylationManual Assertion Based On ExperimentIMP:MGI
Regulation of peptidyl-serine phosphorylationManual Assertion Based On ExperimentIMP:MGI
Regulation of RNA polymerase II regulatory region sequence-specific DNA bindingManual Assertion Based On ExperimentIMP:MGI
Regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

Nucleus
Chromosome

Involvement in disease

Sotos syndrome 1 (SOTOS1):
A childhood overgrowth syndrome characterized by pre- and postnatal overgrowth, developmental delay, mental retardation, advanced bone age, and abnormal craniofacial morphology including macrodolichocephaly with frontal bossing, frontoparietal sparseness of hair, apparent hypertelorism, downslanting palpebral fissures, and facial flushing. Common oral findings include: premature eruption of teeth; high, arched palate; pointed chin and, more rarely, prognathism.
Beckwith-Wiedemann syndrome (BWS):
A disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors.