NACC1

Chr 19AD

nucleus accumbens associated 1

Also known as: BEND8, BTBD14B, BTBD30, NAC-1, NAC1, NECFM

NCBI Gene: 112939 ENSG00000160877 UniProt: Q96RE7 OMIM: 610672

The protein functions as a transcriptional repressor in neuronal cells through recruitment of histone deacetylases and is required for recruiting the proteasome from the nucleus to the cytoplasm and dendritic spines. Mutations cause autosomal dominant neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination. The gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.169), indicating intolerance to protein-truncating mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the BTB/POZ protein family. BTB/POZ proteins are involved in several cellular processes including proliferation, apoptosis and transcription regulation. The encoded protein is a transcriptional repressor that plays a role in stem cell self-renewal and pluripotency maintenance. The encoded protein also suppresses transcription of the candidate tumor suppressor Gadd45GIP1, and expression of this gene may play a role in the progression of multiple types of cancer. A pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Feb 2012]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelinationMIM #617393

Clinical highlights

Gene-disease validity (ClinGen)

NACC1-related neurodevelopmental disorder with epilepsy, cataracts and episodic irritability · ADDefinitivesufficient evidence for diagnostic panels

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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

GOF*

Mechanism· G2P