ATXN10

protein-coding

ataxin 10, the group of Armadillo like helical domain containing|MicroRNA protein coding host genes

Gene summary

This gene encodes a protein that may function in neuron survival, neuron differentiation, and neuritogenesis. These roles may be carried out via activation of the mitogen-activated protein kinase cascade. Expansion of an ATTCT repeat from 9-32 copies to 800-4500 copies in an intronic region of this locus has been associated with spinocerebellar ataxia, type 10. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jul 2016]

Previous symbols:

SCA10

MANE transcript

NM_013236.4

Inheritance

ClinVar variants

U:24B:8

Top phenotype

Spinocerebellar ataxia 10

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr22:45,671,798-45,845,307

External References & Databases

Ensembl (ENSG00000130638)

Transcript & Mutation Effects

hg38 • Region Span ~173.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spinocerebellar ataxia type 10SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011330

Submitter: Orphanet

spinocerebellar ataxia type 10STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011330

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spinocerebellar ataxia 10AD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 11017075; 11506407; 15127363; 16717236; 17420323; 20301354; 20818609; 21236683; 21531163

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATXN10 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 10

Inborn genetic diseasesTotal: 10

Spinocerebellar ataxia type 10Total: 8

ATXN10-related disorderTotal: 3

not specifiedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013236.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	6 clinvar		8
missense			14 clinvar	2 clinvar		16
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	24	8	0	32

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013236.4	RefSeq	NP_037368.1	12	MANE Select
ENST00000252934.10	Ensembl	ENSP00000252934.4	12	MANE Select
NM_001167621.2	RefSeq	NP_001161093.1	11	Standard
ENST00000381061.8	Ensembl	ENSP00000370449.4	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nervous system development
neuron projection development
cilium assembly
protein homotrimerization

Molecular Function

protein binding
enzyme binding
identical protein binding

Cellular Component

extracellular space
cytoplasm
cytosol
plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252934
Coding exons: 11
Length: 173510
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.325	270	255	1.06	0.0000135	3127
Missense (PolyPhen)		79	75.702	1.0436		986
Synonymous	0.0366	100	100	0.995	0.00000537	929
Loss of Function	2.69	10	24.3	0.411	0.00000130	278

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Necessary for the survival of cerebellar neurons. Induces neuritogenesis by activating the Ras-MAP kinase pathway. May play a role in the maintenance of a critical intracellular glycosylation level and homeostasis. {ECO:0000250}.;
Disease: DISEASE: Note=Defects in ATXN1 may be a cause of nephronophthisis a chronic tubulo-interstitial nephropathy that leads to anemia, polyuria, polydipsia, isosthenuria and death in uremia. {ECO:0000269|PubMed:21565611}.;

Recessive Scores

pRec: 0.162

Intolerance Scores

LoFtool: 0.248
RVIS EVS: -1.02
RVIS percentile EVS: 7.94

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.629

Gene Damage Prediction

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