NSD1

Protein identityUniProt · HPA

UniProt accession

Q96L73

Gene

NSD1

Ensembl

ENSG00000165671

Chromosome

5

Canonical length

2696 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Plasma membrane

OverviewNCBI Gene

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. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Sep 2018]

Canonical amino-acid sequenceUniProt

2696 residues, UniProt reviewed canonical sequence.

>Q96L73|NSD1
     1  MDQTCELPRR NCLLPFSNPV NLDAPEDKDS PFGNGQSNFS EPLNGCTMQL STVSGTSQNA
    61  YGQDSPSCYI PLRRLQDLAS MINVEYLNGS ADGSESFQDP EKSDSRAQTP IVCTSLSPGG
   121  PTALAMKQEP SCNNSPELQV KVTKTIKNGF LHFENFTCVD DADVDSEMDP EQPVTEDESI
   181  EEIFEETQTN ATCNYETKSE NGVKVAMGSE QDSTPESRHG AVKSPFLPLA PQTETQKNKQ
   241  RNEVDGSNEK AALLPAPFSL GDTNITIEEQ LNSINLSFQD DPDSSTSTLG NMLELPGTSS
   301  SSTSQELPFC QPKKKSTPLK YEVGDLIWAK FKRRPWWPCR ICSDPLINTH SKMKVSNRRP
   361  YRQYYVEAFG DPSERAWVAG KAIVMFEGRH QFEELPVLRR RGKQKEKGYR HKVPQKILSK
   421  WEASVGLAEQ YDVPKGSKNR KCIPGSIKLD SEEDMPFEDC TNDPESEHDL LLNGCLKSLA
   481  FDSEHSADEK EKPCAKSRAR KSSDNPKRTS VKKGHIQFEA HKDERRGKIP ENLGLNFISG
   541  DISDTQASNE LSRIANSLTG SNTAPGSFLF SSCGKNTAKK EFETSNGDSL LGLPEGALIS
   601  KCSREKNKPQ RSLVCGSKVK LCYIGAGDEE KRSDSISICT TSDDGSSDLD PIEHSSESDN
   661  SVLEIPDAFD RTENMLSMQK NEKIKYSRFA ATNTRVKAKQ KPLISNSHTD HLMGCTKSAE
   721  PGTETSQVNL SDLKASTLVH KPQSDFTNDA LSPKFNLSSS ISSENSLIKG GAANQALLHS
   781  KSKQPKFRSI KCKHKENPVM AEPPVINEEC SLKCCSSDTK GSPLASISKS GKVDGLKLLN
   841  NMHEKTRDSS DIETAVVKHV LSELKELSYR SLGEDVSDSG TSKPSKPLLF SSASSQNHIP
   901  IEPDYKFSTL LMMLKDMHDS KTKEQRLMTA QNLVSYRSPG RGDCSTNSPV GVSKVLVSGG
   961  STHNSEKKGD GTQNSANPSP SGGDSALSGE LSASLPGLLS DKRDLPASGK SRSDCVTRRN
  1021  CGRSKPSSKL RDAFSAQMVK NTVNRKALKT ERKRKLNQLP SVTLDAVLQG DRERGGSLRG
  1081  GAEDPSKEDP LQIMGHLTSE DGDHFSDVHF DSKVKQSDPG KISEKGLSFE NGKGPELDSV
  1141  MNSENDELNG VNQVVPKKRW QRLNQRRTKP RKRMNRFKEK ENSECAFRVL LPSDPVQEGR
  1201  DEFPEHRTPS ASILEEPLTE QNHADCLDSA GPRLNVCDKS SASIGDMEKE PGIPSLTPQA
  1261  ELPEPAVRSE KKRLRKPSKW LLEYTEEYDQ IFAPKKKQKK VQEQVHKVSS RCEEESLLAR
  1321  GRSSAQNKQV DENSLISTKE EPPVLEREAP FLEGPLAQSE LGGGHAELPQ LTLSVPVAPE
  1381  VSPRPALESE ELLVKTPGNY ESKRQRKPTK KLLESNDLDP GFMPKKGDLG LSKKCYEAGH
  1441  LENGITESCA TSYSKDFGGG TTKIFDKPRK RKRQRHAAAK MQCKKVKNDD SSKEIPGSEG
  1501  ELMPHRTATS PKETVEEGVE HDPGMPASKK MQGERGGGAA LKENVCQNCE KLGELLLCEA
  1561  QCCGAFHLEC LGLTEMPRGK FICNECRTGI HTCFVCKQSG EDVKRCLLPL CGKFYHEECV
  1621  QKYPPTVMQN KGFRCSLHIC ITCHAANPAN VSASKGRLMR CVRCPVAYHA NDFCLAAGSK
  1681  ILASNSIICP NHFTPRRGCR NHEHVNVSWC FVCSEGGSLL CCDSCPAAFH RECLNIDIPE
  1741  GNWYCNDCKA GKKPHYREIV WVKVGRYRWW PAEICHPRAV PSNIDKMRHD VGEFPVLFFG
  1801  SNDYLWTHQA RVFPYMEGDV SSKDKMGKGV DGTYKKALQE AAARFEELKA QKELRQLQED
  1861  RKNDKKPPPY KHIKVNRPIG RVQIFTADLS EIPRCNCKAT DENPCGIDSE CINRMLLYEC
  1921  HPTVCPAGGR CQNQCFSKRQ YPEVEIFRTL QRGWGLRTKT DIKKGEFVNE YVGELIDEEE
  1981  CRARIRYAQE HDITNFYMLT LDKDRIIDAG PKGNYARFMN HCCQPNCETQ KWSVNGDTRV
  2041  GLFALSDIKA GTELTFNYNL ECLGNGKTVC KCGAPNCSGF LGVRPKNQPI ATEEKSKKFK
  2101  KKQQGKRRTQ GEITKEREDE CFSCGDAGQL VSCKKPGCPK VYHADCLNLT KRPAGKWECP
  2161  WHQCDICGKE AASFCEMCPS SFCKQHREGM LFISKLDGRL SCTEHDPCGP NPLEPGEIRE
  2221  YVPPPVPLPP GPSTHLAEQS TGMAAQAPKM SDKPPADTNQ MLSLSKKALA GTCQRPLLPE
  2281  RPLERTDSRP QPLDKVRDLA GSGTKSQSLV SSQRPLDRPP AVAGPRPQLS DKPSPVTSPS
  2341  SSPSVRSQPL ERPLGTADPR LDKSIGAASP RPQSLEKTSV PTGLRLPPPD RLLITSSPKP
  2401  QTSDRPTDKP HASLSQRLPP PEKVLSAVVQ TLVAKEKALR PVDQNTQSKN RAALVMDLID
  2461  LTPRQKERAA SPHQVTPQAD EKMPVLESSS WPASKGLGHM PRAVEKGCVS DPLQTSGKAA
  2521  APSEDPWQAV KSLTQARLLS QPPAKAFLYE PTTQASGRAS AGAEQTPGPL SQSPGLVKQA
  2581  KQMVGGQQLP ALAAKSGQSF RSLGKAPASL PTEEKKLVTT EQSPWALGKA SSRAGLWPIV
  2641  AGQTLAQSCW SAGSTQTLAQ TCWSLGRGQD PKPEQNTLPA LNQAPSSHKC AESEQK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NSD1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.56

Highest tissue expression

29 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NSD1.

Disease | AllUniProt

Conditions NSD1 is implicated in, by any mechanism.

• Sotos syndrome (SOTOS) MIM:117550
• Beckwith-Wiedemann syndrome (BWS) MIM:130650

Disease | GeneticClinVar

717 pathogenic / likely-pathogenic of 2,716 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Sotos syndrome
• Inborn genetic diseases
• Beckwith-Wiedemann syndrome
• NSD1-related disorder
• See cases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.1

gnomAD pLI

1

gnomAD missense Z

3.41

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• methylation
• negative regulation of transcription by RNA polymerase II
• positive regulation of DNA-templated transcription
• regulation of DNA-templated transcription
• regulation of peptidyl-serine phosphorylation
• regulation of RNA polymerase II regulatory region sequence-specific DNA binding

Molecular functions

• chromatin binding
• histone H3 methyltransferase activity
• histone H3K36 dimethyltransferase activity
• histone H3K36 methyltransferase activity
• histone H4K20 methyltransferase activity
• nuclear androgen receptor binding
• nuclear estrogen receptor binding
• nuclear retinoic acid receptor binding
• nuclear retinoid X receptor binding
• nuclear thyroid hormone receptor binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• transcription coregulator activity
• transcription corepressor activity
• zinc ion binding

Cellular components

• chromatin
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• PWWP domain
• SET domain
• Zinc finger, PHD-type
• Post-SET domain
• AWS domain
• Zinc finger, FYVE/PHD-type
• Zinc finger, RING/FYVE/PHD-type
• Zinc finger, PHD-type, conserved site
• Zinc finger, PHD-finger
• NSD, Cys-His rich domain
• SET domain superfamily
• Histone-lysine N-methyltransferase NSD1 / NSD2, first PHD finger
• SET2 Histone-Lysine N-Methyltransferase
• Histone-lysine N-methyltransferase NSD-like, variant PHD zinc finger
• Histone-lysine N-methyltransferase NSD-like, PHD zinc finger
• Histone-lysine N-methyltransferase NSD-like, PHD zinc finger 1
• PHD-finger
• PWWP domain
• SET domain
• AWS domain
• NSD Cys-His rich domain
• Histone-lysine N-methyltransferase NSD-like, PHD zinc finger
• Histone-lysine N-methyltransferase NSD-like, variant PHD zinc finger
• Histone-lysine N-methyltransferase NSD-like, PHD zinc finger 1
• Nuclear receptor-binding SET domain-containing protein 1, second PWWP domain
• Nuclear receptor-binding SET domain-containing protein 1, second PHD finger
• Nuclear receptor-binding SET domain-containing protein 1, third PHD finger
• Nuclear receptor-binding SET domain-containing protein 1, fourth PHD finger
• Nuclear receptor-binding SET domain-containing protein 1, fifth PHD finger
• Nuclear receptor-binding SET domain-containing protein 1, SET domain

KeywordsUniProt

• Activator
• Chromatin regulator
• Chromosomal rearrangement
• Chromosome
• Isopeptide bond
• Metal-binding
• Methyltransferase
• Nucleus
• Phosphoprotein
• Proto-oncogene
• Repeat
• Repressor
• S-adenosyl-L-methionine
• Transcription
• Transcription regulation
• Transferase
• Ubl conjugation
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of NSD1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• THRA
• ZNF496
• H2BC21