ATN1

atrophin 1, the group of Atrophins

Basic information

Region (hg38): 12:6924463-6942321

Previous symbols: [ "D12S755E", "DRPLA" ]

Links

ENSG00000111676 ∙ NCBI:1822 ∙ OMIM:607462 ∙ HGNC:3033 ∙ Uniprot:P54259 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital hypotonia, epilepsy, developmental delay, and digital anomalies (Moderate), mode of inheritance: AD
• congenital hypotonia, epilepsy, developmental delay, and digital anomalies (Moderate), mode of inheritance: AD
• dentatorubral-pallidoluysian atrophy (Supportive), mode of inheritance: AD
• dentatorubral-pallidoluysian atrophy (Strong), mode of inheritance: AD
• congenital hypotonia, epilepsy, developmental delay, and digital anomalies (Strong), mode of inheritance: AD
• congenital hypotonia, epilepsy, developmental delay, and digital anomalies (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital hypotonia, epilepsy, developmental delay, and digital anomalies; Dentatorubro-pallidoluysian atrophy	AD	Cardiovascular	Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Cardiovascular; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	6808417; 2742549; 7951323; 8136840; 8041369; 7477999; 8644735; 9568927; 11160976; 15948186; 30827498

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATN1 gene.

• Inborn_genetic_diseases (189 variants)
• not_provided (124 variants)
• not_specified (33 variants)
• Congenital_hypotonia,_epilepsy,_developmental_delay,_and_digital_anomalies (31 variants)
• ATN1-related_disorder (26 variants)
• Dentatorubral-pallidoluysian_atrophy (6 variants)
• Congenital_ATN1_related_disorder (4 variants)
• See_cases (3 variants)
• X-linked_hydrocephalus_syndrome (1 variants)
• Intellectual_disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001940.4. 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	35	4	41
missense	3	5	216	31	5	260
nonsense			3			3
start loss						0
frameshift			14		1	15
splice donor/acceptor (+/-2bp)			5			5
Total	3	5	240	66	10

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATN1	protein_coding	protein_coding	ENST00000356654	9	17859

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125722	1	25	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.76	567	698	0.812	0.0000401	7471
Missense in Polyphen		305	400.34	0.76186		4425
Synonymous	1.25	273	300	0.909	0.0000178	2713
Loss of Function	5.42	3	40.0	0.0750	0.00000247	395

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000911	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.00160	0.000816
Finnish	0.0000974	0.0000924
European (Non-Finnish)	0.0000717	0.0000615
Middle Eastern	0.00160	0.000816
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional corepressor. Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation (By similarity). Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of poly-Gln (polyQ) repeats. {ECO:0000250, ECO:0000269|PubMed:10085113, ECO:0000269|PubMed:10973986}.
• Disease: DISEASE: Dentatorubral-pallidoluysian atrophy (DRPLA) [MIM:125370]: Autosomal dominant neurodegenerative disorder characterized by a loss of neurons in the dentate nucleus, rubrum, glogus pallidus and Luys'body. Clinical features are myoclonus epilepsy, dementia, and cerebellar ataxia. Onset of the disease occurs usually in the second decade of life and death in the fourth. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.523

Intolerance Scores

• loftool: 0.566
• rvis_EVS: -0.95
• rvis_percentile_EVS: 9.34

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.453

Gene Damage Prediction

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

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;central nervous system development;neuron apoptotic process
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear matrix;cell junction;perinuclear region of cytoplasm
• Molecular function: RNA polymerase II transcription factor binding;DNA binding;transcription corepressor activity;protein binding;protein domain specific binding