ASXL2

Chr 2AD

ASXL transcriptional regulator 2

Also known as: ASXH2, SHAPNS

NCBI Gene: 55252 ENSG00000143970 UniProt: Q76L83 OMIM: 612991

The protein functions as a Polycomb group epigenetic regulator that maintains transcriptional repression of developmental genes and acts as a non-catalytic component of the PR-DUB complex, which deubiquitinates histones and serves as a transcriptional coactivator. Mutations cause Shashi-Pena syndrome, a neurodevelopmental disorder with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.146), indicating that complete loss of protein function is likely incompatible with normal development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of a family of epigenetic regulators that bind various histone-modifying enzymes and are involved in the assembly of transcription factors at specific genomic loci. Naturally occurring mutations in this gene are associated with cancer in several tissue types (breast, bladder, pancreas, ovary, prostate, and blood). This gene plays an important role in neurodevelopment, cardiac function, adipogenesis, and osteoclastogenesis. [provided by RefSeq, Feb 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Shashi-Pena syndromeMIM #617190

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)

—

P/LP submissions

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P/LP missense

0.15

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — ASXL2