PRKRA

protein activator of interferon induced protein kinase EIF2AK2

Basic information

Region (hg38): 2:178431292-178451512

Links

ENSG00000180228

∙ NCBI:8575 ∙ OMIM:603424 ∙ HGNC:9438 ∙ Uniprot:O75569 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

dystonia 16 (Strong), mode of inheritance: AR
dystonia 16 (Moderate), mode of inheritance: AR
dystonia 16 (Supportive), mode of inheritance: AR
dystonia 16 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 16	AR	General	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	Neurologic	18243799; 18420150; 20408955; 22415584; 22842711; 25142429

ClinVar

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

Dystonia_16 (100 variants)
not_provided (36 variants)
Inborn_genetic_diseases (16 variants)
Dystonic_disorder (3 variants)
PRKRA-related_disorder (3 variants)
not_specified (1 variants)
Hearing_loss,_autosomal_recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKRA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003690.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	20 clinvar	1 clinvar	24
missense		3 clinvar	52 clinvar	2 clinvar	1 clinvar	58
nonsense			1 clinvar			1
start loss			1			1
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)		1 clinvar	4 clinvar			5
Total	1	4	61	22	2

Highest pathogenic variant AF is 0.000477542

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRKRA	protein_coding	protein_coding	ENST00000325748	8	20099

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.417	0.582	125504	0	244	125748	0.000971

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.58	103	159	0.648	0.00000709	2044
Missense in Polyphen		14	53.289	0.26272		703
Synonymous	0.974	46	55.2	0.833	0.00000254	570
Loss of Function	2.71	3	13.9	0.216	5.87e-7	192

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00146	0.00144
Ashkenazi Jewish	0.000403	0.000397
East Asian	0.00146	0.00141
Finnish	0.00209	0.00203
European (Non-Finnish)	0.000915	0.000897
Middle Eastern	0.00146	0.00141
South Asian	0.000829	0.000817
Other	0.000833	0.000815

dbNSFP

Source: dbNSFP

Function: FUNCTION: Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post- transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1. Promotes UBC9-p53/TP53 association and sumoylation and phosphorylation of p53/TP53 at 'Lys-386' at 'Ser-392' respectively and enhances its activity in a EIF2AK2/PKR-dependent manner (By similarity). {ECO:0000250, ECO:0000269|PubMed:10336432, ECO:0000269|PubMed:11238927, ECO:0000269|PubMed:16424907, ECO:0000269|PubMed:16982605, ECO:0000269|PubMed:17452327, ECO:0000269|PubMed:9687506}.;
Disease: DISEASE: Dystonia 16 (DYT16) [MIM:612067]: An early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features. {ECO:0000269|PubMed:18243799, ECO:0000269|PubMed:18420150}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Gene expression (Transcription);MicroRNA (miRNA) biogenesis;Small interfering RNA (siRNA) biogenesis;Ceramide signaling pathway;Gene Silencing by RNA (Consensus)

Recessive Scores

pRec: 0.178

Intolerance Scores

loftool: 0.296
rvis_EVS: 0.33
rvis_percentile_EVS: 73.11

Haploinsufficiency Scores

pHI: 0.404
hipred: Y
hipred_score: 0.744
ghis: 0.533

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: E
essential_gene_gene_trap: H
gene_indispensability_pred: N
gene_indispensability_score: 0.243

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Prkra
Phenotype: growth/size/body region phenotype; muscle phenotype; hearing/vestibular/ear phenotype; craniofacial phenotype; 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; limbs/digits/tail 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);

Gene ontology

Biological process: protein phosphorylation;immune response;negative regulation of cell population proliferation;response to virus;miRNA metabolic process;viral process;production of siRNA involved in RNA interference;pre-miRNA processing;cellular response to oxidative stress;production of miRNAs involved in gene silencing by miRNA;outer ear morphogenesis;middle ear morphogenesis;positive regulation of catalytic activity;skeletal system morphogenesis;protein stabilization;positive regulation of intrinsic apoptotic signaling pathway
Cellular component: nucleoplasm;cytoplasm;cytosol;membrane;perinuclear region of cytoplasm;RISC-loading complex
Molecular function: RNA binding;double-stranded RNA binding;protein binding;enzyme activator activity;enzyme binding;identical protein binding;protein homodimerization activity;pre-miRNA binding