NACC1

nucleus accumbens associated 1, the group of BTB domain containing|BEN domain containing

Basic information

Region (hg38): 19:13116862-13141147

Previous symbols: [ "BTBD14B" ]

Links

ENSG00000160877 ∙ NCBI:112939 ∙ OMIM:610672 ∙ HGNC:20967 ∙ Uniprot:Q96RE7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (Strong), mode of inheritance: AD
• NACC1-related neurodevelopmental disorder with epilepsy, cataracts and episodic irritability (Definitive), mode of inheritance: AD
• neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (NECFM)	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic; Ophthalmologic	28132692

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NACC1 gene.

• not_provided (439 variants)
• Inborn_genetic_diseases (38 variants)
• NACC1-related_disorder (31 variants)
• Neurodevelopmental_disorder_with_epilepsy,_cataracts,_feeding_difficulties,_and_delayed_brain_myelination (18 variants)
• not_specified (6 variants)
• Neurodevelopmental_disorder (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NACC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000052876.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	162	17	181
missense	1	7	158	25	32	223
nonsense			6			6
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)						0
Total	1	7	167	187	49

Highest pathogenic variant AF is 0.00000205227

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NACC1	protein_coding	protein_coding	ENST00000292431	5	23039

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00237	124497	0	2	124499	0.00000803

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.17	143	368	0.389	0.0000256	3426
Missense in Polyphen		20	108.89	0.18367		1063
Synonymous	0.347	166	172	0.966	0.0000140	1062
Loss of Function	3.90	0	17.7	0.00	8.45e-7	189

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000545
Finnish	0.00	0.00
European (Non-Finnish)	0.0000104	0.00000890
Middle Eastern	0.0000545	0.0000545
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Functions as a transcriptional repressor. Seems to function as a transcriptional corepressor in neuronal cells through recruitment of HDAC3 and HDAC4. Contributes to tumor progression, and tumor cell proliferation and survival. This may be mediated at least in part through repressing transcriptional activity of GADD45GIP1. Required for recruiting the proteasome from the nucleus to the cytoplasm and dendritic spines. {ECO:0000269|PubMed:17130457, ECO:0000269|PubMed:17804717}.

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.0304
• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.82

Haploinsufficiency Scores

• pHI: 0.163
• hipred: Y
• hipred_score: 0.572
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.675

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nacc1
• Phenotype: reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: positive regulation of cell population proliferation;negative regulation of transcription, DNA-templated;protein homooligomerization
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear body;cell junction;intracellular membrane-bounded organelle