SPEN

Chr 1AD

spen family transcriptional repressor

Also known as: HIAA0929, MINT, RATARS, RBM15C, SHARP

NCBI Gene: 23013 ENSG00000065526 UniProt: Q96T58 OMIM: 613484

This gene encodes a transcriptional repressor that regulates key developmental pathways including Notch signaling and serves as a nuclear matrix platform organizing transcriptional responses. Mutations cause Radio-Tartaglia syndrome, an autosomal dominant disorder characterized by intellectual disability, distinctive facial features, and skeletal abnormalities. The gene is highly constrained against loss-of-function variation (pLI=1, LOEUF=0.071), indicating that complete loss of protein function is likely incompatible with normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other corepressor proteins. This domain also permits interaction with members of the NuRD complex, a nucleosome remodeling protein complex that contains deacetylase activity. In addition, this repressor contains several RNA recognition motifs that confer binding to a steroid receptor RNA coactivator; this binding can modulate the activity of both liganded and nonliganded steroid receptors. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Radio-Tartaglia syndromeMIM #619312

Clinical highlights

Gene-disease validity (ClinGen)

Radio-Tartaglia syndrome · 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)

—

P/LP submissions

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P/LP missense

0.07

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — SPEN