ATCAY

protein-coding

ATCAY kinesin light chain interacting caytaxin, the group of BCH domain containing

Gene summary

This gene encodes a neuron-restricted protein that contains a CRAL-TRIO motif common to proteins that bind small lipophilic molecules. Mutations in this gene are associated with cerebellar ataxia, Cayman type. [provided by RefSeq, Jul 2008]

MANE transcript

NM_033064.5

Inheritance

ClinVar variants

P:3U:76B:24

Top phenotype

Ataxia, cerebellar, Cayman type

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr19:3,879,864-3,928,082

External References & Databases

Ensembl (ENSG00000167654)

Transcript & Mutation Effects

hg38 • Region Span ~48.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Cayman type cerebellar ataxiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011025

Submitter: Orphanet

Cayman type cerebellar ataxiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011025

Submitter: Labcorp Genetics (formerly Invitae)

Cayman type cerebellar ataxiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011025

Submitter: Ambry Genetics

Cayman type cerebellar ataxiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011025

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Ataxia, cerebellar, Cayman typeAR

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: 14556008

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATCAY variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 58

not providedTotal: 43

Cayman type cerebellar ataxiaTotal: 38

not specifiedTotal: 18

ATCAY-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033064.5. 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			5 clinvar	22 clinvar	1 clinvar	28
missense	1 clinvar		70 clinvar	1 clinvar		72
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	3	0	76	23	1	103

Highest pathogenic variant AF is 6.8619016e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033064.5	RefSeq	NP_149053.1	12	MANE Select
ENST00000450849.7	Ensembl	ENSP00000390941.1	12	MANE Select
ENST00000597739.1	Ensembl	ENSP00000472263.1	4	Standard
ENST00000598136.5	Ensembl	ENSP00000471731.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
atcaya	Danio rerio	Structure: motor neuron Quality: decreased length abnormal

Gene / Model

Organism

Observed Phenotype

atcaya

Danio rerio

Structure: motor neuron

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

polyphosphate catabolic process
apoptotic process
neuron projection development
regulation of protein localization
mitochondrion distribution

Molecular Function

exopolyphosphatase activity
protein binding
kinesin binding
WW domain binding

Cellular Component

cytoplasm
mitochondrion
cell junction
axon
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000450849
Coding exons: 12
Length: 48216
Individuals with no LoFs: 124629
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 124635
p: 0.0000241

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.61	185	258	0.718	0.0000178	2451
Missense (PolyPhen)		64	110.22	0.58063		1023
Synonymous	-0.414	116	110	1.05	0.00000892	692
Loss of Function	3.38	4	20.5	0.195	8.77e-7	234

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.000019	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions in the development of neural tissues, particularly the postnatal maturation of the cerebellar cortex. May play a role in neurotransmission through regulation of glutaminase/GLS, an enzyme responsible for the production in neurons of the glutamate neurotransmitter. Alternatively, may regulate the localization of mitochondria within axons and dendrites. {ECO:0000269|PubMed:16899818}.;
Disease: DISEASE: Cerebellar ataxia, cayman type (ATCAY) [MIM:601238]: Found in a population isolate on Grand Cayman Island and causes a marked psychomotor retardation and prominent nonprogressive cerebellar dysfunction including nystagmus, intention tremor, dysarthria, and wide-based ataxic gait. Hypotonia is present from early childhood. {ECO:0000269|PubMed:14556008}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.406
RVIS EVS: -0.54
RVIS percentile EVS: 20.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.152

Gene Damage Prediction

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