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

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.

• Congenital hypotonia, epilepsy, developmental delay, and digital anomalies (2 variants)
• ATN1-related disorder (1 variants)
• not provided (1 variants)
• Congenital ATN1 related disorder (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	20	3	24
missense	1	1	105	16	3	126
nonsense						0
start loss						0
frameshift			6			6
inframe indel	1	2	11	10	2	26
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	2	3	124	46	8

Variants in ATN1

This is a list of pathogenic ClinVar variants found in the ATN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-6931128-A-G			Uncertain significance (Sep 05, 2022)
12-6934234-C-T		ATN1-related disorder	Likely benign (Nov 16, 2019)
12-6934273-G-A		Inborn genetic diseases	Uncertain significance (Mar 18, 2024)
12-6934294-A-C		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
12-6934472-G-A		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
12-6934510-G-A		Inborn genetic diseases	Uncertain significance (Aug 26, 2022)
12-6934553-A-G		Inborn genetic diseases	Likely benign (Feb 17, 2023)
12-6934564-A-C		Inborn genetic diseases	Uncertain significance (Jun 11, 2024)
12-6935548-A-G		Inborn genetic diseases	Uncertain significance (Mar 21, 2022)
12-6935562-C-A		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
12-6935624-C-T		ATN1-related disorder	Likely benign (Dec 01, 2023)
12-6935675-C-T		not specified	Conflicting classifications of pathogenicity (Jul 01, 2024)
12-6935695-ATGACTCTGACTCATC-A		Congenital hypotonia, epilepsy, developmental delay, and digital anomalies	Uncertain significance (Apr 04, 2024)
12-6935734-C-G		not specified	Uncertain significance (Jun 17, 2024)
12-6935734-C-T			Uncertain significance (Oct 10, 2022)
12-6935752-C-G		Inborn genetic diseases	Uncertain significance (Sep 12, 2023)
12-6935763-C-G		Inborn genetic diseases	Uncertain significance (Oct 02, 2023)
12-6935779-C-T		Inborn genetic diseases	Likely benign (Feb 26, 2024)
12-6935780-G-A		ATN1-related disorder	Benign (Jul 22, 2021)
12-6935797-G-A		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
12-6935803-C-T		Inborn genetic diseases • ATN1-related disorder	Likely benign (May 27, 2022)
12-6935815-T-G		Inborn genetic diseases	Uncertain significance (Dec 12, 2022)
12-6935820-C-G			Uncertain significance (Jun 01, 2019)
12-6935843-T-C			Likely benign (Jun 01, 2024)
12-6935861-G-A		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)

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
1.00	0.0000795	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

Haploinsufficiency Scores

• pHI: 0.489
• hipred: Y
• hipred_score: 0.711
• ghis: 0.517

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

Mouse Genome Informatics

• Gene name: Atn1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); normal phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

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