Table 6 A review of literature and databases on the variants of the ATP2B3 gene

NM_001001344.3(ATP2B3):c.130G > A

Missense

p.Glu44Lys

Likely Pathogenic

Spastic Ataxia

N/R^a

N/R

N/R

N/R

N/R

ClinVar (RCV001647254.1)

NM_001001344.3(ATP2B3):c.197C > T

Missense

p.Ser66Leu

Likely Pathogenic

Arthrogryposis Multiplex Congenita, Fetal Akinesia Deformation Sequence 1

N/R

N/R

N/R

N/R

N/R

ClinVar(RCV000855493.1), Pergande(2020) Genet Med 22(3) -511 [39]

NM_001001344.3(ATP2B3):c.1445G > A

Missense

p.Arg482His

Pathogenic

Cerebellar ataxia, X-linked

N/R

Yes

N/R

N/R

Generalized Hypotonia, Cerebellar Ataxia

Calì (2015) J Biol Chem 290, 16,132 [38]

NM_001001344.3(ATP2B3): c.1610G > A

Missense

p.Arg537His

Pathogenic

Abnormality of the Nervous System

N/R

N/R

N/R

N/R

N/R

Retterer (2016) Genet Med 18, 696 [40]

NM_001001344.3(ATP2B3): c.1678C > G

Missense

p.Pro560Ala

Pathogenic

Autism Spectrum Disorder

N/R

N/R

N/R

N/R

N/R

Al-Mubarak (2017) Sci Rep 7, 5679 [41]

NM_001001344.3(ATP2B3):c.2197G > A

Missense

p.Gly733Arg

Pathogenic

Cerebellar Ataxia

Yes

Yes

Yes

N/R

Psychomotor Retardation, Generalized Hypotonia, Hyporeflexia, Dysmetria and Trunk Ataxia, Exotropia and Nystagmus, Skin & Joint Hyperlaxity, Mild Dorsal Kyphosis, Structural Brain Anomalies

Vicario (2017) Biochim Biophys Acta 1863, 3303 [42]

NM_001001344.3(ATP2B3):c.2770A > G

Missense

p.Thr924Ala

Likely Pathogenic

X-linked Progressive Cerebellar Ataxia

Yes

Yes

Yes

N/R

Cognitive Impairment, Psychomotor Retardation, Inability to Walk, Limb Tremor

ClinVar (RCV001420157.1)

NM_001001344.3(ATP2B3):c.3320G > A

Missense

p.Gly1107Asp

Pathogenic /Likely Pathogenic

X-linked Progressive Cerebellar Ataxia,

N/R

N/R

N/R

N/R

N/R

Zanni (2012) Proc Natl Acad Sci U S A 109, 14,514 [43]

NM_001001344.3(ATP2B3):c.3338C > T

Missense

p.Thr1113Met

Likely Pathogenic

Epileptic Encephalopathy with Infantile Spasms

N/R

N/R

N/R

N/R

N/R

Helbig (2016) Genet Med 18, 898 [44]

NM_001001344.3(ATP2B3):c.3594G > T

Missense

p.Lys1198Asn

Pathogenic /Likely Pathogenic

X-linked progressive cerebellar ataxia

Yes

Yes

N/R

N/R

Microcephaly, Abnormal Cerebral Cortex Morphology, Hypotonia, Muscular Atrophy, Carious Teeth, Oral-Pharyngeal Dysphagia

Charng (2016) BMC Med Genomics 9, 42 [45]

NM_001001344.2(ATP2B3), c.2541C > G

Patient A

Missense

p.Asp847Glu

Likely Pathogenic

X-linked Progressive Cerebellar Ataxia

Yes

Yes

Yes

Yes

Delayed in Milestones, no Walking, Hearing Impairment, Agitation and Crying, Dysmorphic Facial Features such as Strabismus, Congenital Hypotrichosis, and Low Eyebrow, Seizure, Severe Abnormality in EEG

Current Study

Patient B