PER1

period circadian regulator 1, the group of PAS domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 17:8140471-8156506

Previous symbols: [ "PER" ]

Links

ENSG00000179094 ∙ NCBI:5187 ∙ OMIM:602260 ∙ HGNC:8845 ∙ Uniprot:O15534 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PER1 gene.

• Inborn genetic diseases (53 variants)
• not provided (29 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PER1 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				10	8	18
missense			51	7	1	59
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding				1	2	3
Total	0	0	51	18	11

Variants in PER1

This is a list of pathogenic ClinVar variants found in the PER1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-8141102-G-A		not specified	Uncertain significance (Jul 14, 2021)
17-8141118-T-C		not specified	Likely benign (Jun 06, 2023)
17-8141125-T-C			Benign (Jun 06, 2018)
17-8141141-G-A		not specified	Uncertain significance (Jun 26, 2023)
17-8141166-T-C		not specified	Uncertain significance (Mar 01, 2024)
17-8141188-G-A			Likely benign (May 24, 2018)
17-8141233-G-C			Benign (Jun 05, 2018)
17-8141851-T-A		not specified	Uncertain significance (Oct 06, 2022)
17-8141884-G-C		not specified	Uncertain significance (Jun 29, 2022)
17-8142288-T-C			Likely benign (Apr 30, 2018)
17-8142383-C-T		not specified	Likely benign (Jul 20, 2022)
17-8142392-C-G		not specified	Uncertain significance (Mar 06, 2023)
17-8142640-G-A			Benign (Aug 28, 2018)
17-8142775-G-T		not specified	Uncertain significance (Jan 23, 2023)
17-8142813-T-C		not specified	Uncertain significance (Feb 06, 2024)
17-8142828-A-T		not specified	Uncertain significance (Sep 01, 2021)
17-8142829-C-T			Benign/Likely benign (Dec 01, 2022)
17-8143314-G-A			Benign (Jun 26, 2018)
17-8143357-C-T			Benign (Jun 12, 2018)
17-8143408-C-A		not specified	Uncertain significance (Apr 17, 2023)
17-8143436-G-A		not specified	Uncertain significance (Jun 10, 2022)
17-8143460-C-G		not specified	Likely benign (Feb 26, 2024)
17-8143516-G-A		not specified	Uncertain significance (Jan 23, 2023)
17-8143586-T-C		not specified	Uncertain significance (Jan 10, 2022)
17-8143604-C-T		not specified	Likely benign (Sep 27, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PER1	protein_coding	protein_coding	ENST00000317276	22	16035

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000293	1.00	125708	0	40	125748	0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.198	751	766	0.980	0.0000489	8141
Missense in Polyphen		312	359.36	0.86822		3933
Synonymous	-2.99	391	323	1.21	0.0000207	2801
Loss of Function	4.73	17	54.8	0.310	0.00000307	591

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000243	0.000242
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000234	0.000220
Middle Eastern	0.000163	0.000163
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time- keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/ARNTL target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by ARNTL:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the MAPK14/p38 and MAPK8/JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK- ARNTL/BMAL1 induced transcription of BHLHE40/DEC1. {ECO:0000269|PubMed:24005054}.
• Pathway: Circadian rhythm - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Circadian Clock;Melatonin metabolism and effects;BMAL1-CLOCK,NPAS2 activates circadian gene expression;Exercise-induced Circadian Regulation;Circadian Clock;Circadian rhythm pathway (Consensus)

Recessive Scores

• pRec: 0.229

Intolerance Scores

• loftool: 0.550
• rvis_EVS: -1.89
• rvis_percentile_EVS: 1.98

Haploinsufficiency Scores

• pHI: 0.819
• hipred: Y
• hipred_score: 0.694
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.976

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Per1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; renal/urinary system 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); 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); reproductive system phenotype; hematopoietic system phenotype

Zebrafish Information Network

• Gene name: per1b
• Affected structure: caudal tuberculum
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of sodium ion transport;circadian rhythm;response to light stimulus;entrainment of circadian clock;posttranscriptional regulation of gene expression;circadian regulation of gene expression;regulation of hair cycle;regulation of circadian rhythm;negative regulation of I-kappaB kinase/NF-kappaB signaling;entrainment of circadian clock by photoperiod;histone H3 acetylation;histone H4 acetylation;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;negative regulation of JNK cascade;response to cAMP;histone H3 deacetylation;circadian regulation of translation;regulation of cytokine production involved in inflammatory response;regulation of p38MAPK cascade;negative regulation of glucocorticoid receptor signaling pathway
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;transcription corepressor binding;protein binding;transcription factor binding;kinase binding;chromatin DNA binding;ubiquitin protein ligase binding;E-box binding