NSD2

Chr 4

nuclear receptor binding SET domain protein 2

Also known as: KMT3F, KMT3G, MMSET, RAUST, REIIBP, TRX5, WHS, WHSC1

NCBI Gene: 7468 ENSG00000109685 UniProt: O96028

The protein encoded by this gene is a histone methyltransferase that contains PWWP, HMG box, SET, and PHD domains and functions in chromatin modification during early development. Loss-of-function mutations cause Rauch-Steindl syndrome through an autosomal dominant inheritance pattern. The gene is also located within the Wolf-Hirschhorn syndrome critical region on chromosome 4p16.3 and contributes to the malformation phenotype seen with deletions of this chromosomal region.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that contains four domains present in other developmental proteins: a PWWP domain, an HMG box, a SET domain, and a PHD-type zinc finger. It is expressed ubiquitously in early development. Wolf-Hirschhorn syndrome (WHS) is a malformation syndrome associated with a hemizygous deletion of the distal short arm of chromosome 4. This gene maps to the 165 kb WHS critical region and has also been involved in the chromosomal translocation t(4;14)(p16.3;q32.3) in multiple myelomas. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. Some transcript variants are nonsense-mediated mRNA (NMD) decay candidates, hence not represented as reference sequences. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtRauch-Steindl syndrome

Clinical highlights

Gene-disease validity (ClinGen)

syndromic intellectual disability · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.12

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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