SPOP

Chr 17

speckle type BTB/POZ protein

Also known as: BTBD32, NEDMACE, NEDMIDF, NSDVS1, NSDVS2, TEF2

NCBI Gene: 8405 ENSG00000121067 UniProt: O43791

The SPOP protein functions as a component of a cullin-RING-based E3 ubiquitin ligase complex that targets specific proteins for degradation or regulation, playing essential roles in transcriptional regulation, DNA replication, and cell proliferation. Mutations cause Nabais Sa-de Vries syndrome types 1 and 2 with autosomal dominant inheritance. This gene is highly constrained against loss-of-function variation in the population, indicating that such mutations are likely to have significant clinical consequences.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that may modulate the transcriptional repression activities of death-associated protein 6 (DAXX), which interacts with histone deacetylase, core histones, and other histone-associated proteins. In mouse, the encoded protein binds to the putative leucine zipper domain of macroH2A1.2, a variant H2A histone that is enriched on inactivated X chromosomes. The BTB/POZ domain of this protein has been shown in other proteins to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes. Alternative splicing of this gene results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNabais Sa-de Vries syndrome 1

UniProtNabais Sa-de Vries syndrome 2

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder with microcephaly and dysmorphic facies · ADModerateconsider for supplementary testing2 gene-disease associations curated in total

Interpreting a novel variant

Gain of function is the curated mechanism (Gene2Phenotype), so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

123

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.14

LOEUF· LoF intol.

Multiple*

Mechanism· G2P

Some data sources returned errors (1)