RIF1

replication timing regulatory factor 1, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 2:151409882-151508013

Links

ENSG00000080345 ∙ NCBI:55183 ∙ OMIM:608952 ∙ HGNC:23207 ∙ Uniprot:Q5UIP0 ∙ 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 RIF1 gene.

• Inborn genetic diseases (94 variants)
• not provided (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RIF1 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				4	2	6
missense			88	11		99
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	88	15	2

Variants in RIF1

This is a list of pathogenic ClinVar variants found in the RIF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-151410491-A-G		not specified	Uncertain significance (Jun 07, 2023)
2-151411277-A-G		not specified	Uncertain significance (Jan 24, 2023)
2-151411328-A-G		not specified	Uncertain significance (Jan 08, 2024)
2-151414829-A-G		not specified	Uncertain significance (Nov 18, 2022)
2-151414845-C-T		not specified	Uncertain significance (Jun 11, 2021)
2-151416616-C-A		not specified	Uncertain significance (Oct 25, 2023)
2-151416897-G-A		not specified	Likely benign (May 04, 2023)
2-151420284-C-A		not specified	Uncertain significance (Jan 18, 2022)
2-151420291-G-A		not specified	Uncertain significance (Jul 20, 2021)
2-151420347-A-G		not specified	Uncertain significance (Nov 21, 2023)
2-151428861-G-A		not specified	Uncertain significance (Jul 26, 2022)
2-151428862-A-G		not specified	Uncertain significance (Mar 24, 2023)
2-151428883-G-A		not specified	Uncertain significance (Mar 11, 2024)
2-151428898-A-G		not specified	Uncertain significance (Dec 15, 2021)
2-151435488-C-G		not specified	Uncertain significance (Dec 28, 2023)
2-151435488-C-T		not specified	Uncertain significance (May 27, 2022)
2-151436830-C-A		not specified	Uncertain significance (Nov 04, 2023)
2-151436887-G-T		not specified	Uncertain significance (Sep 01, 2021)
2-151436970-T-G		not specified	Uncertain significance (Feb 15, 2023)
2-151437250-A-G		not specified	Uncertain significance (Aug 02, 2021)
2-151437256-C-G		not specified	Uncertain significance (Dec 08, 2023)
2-151437256-C-T		not specified	Uncertain significance (Jun 06, 2023)
2-151437328-T-G		not specified	Uncertain significance (Feb 23, 2023)
2-151440115-A-T			Likely benign (Feb 01, 2023)
2-151440119-A-G		not specified	Uncertain significance (Apr 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RIF1	protein_coding	protein_coding	ENST00000243326	35	98131

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.07e-13	125720	0	21	125741	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.414	1270	1.23e+3	1.03	0.0000606	16238
Missense in Polyphen		242	333.04	0.72665		4396
Synonymous	-2.66	503	433	1.16	0.0000217	4659
Loss of Function	8.96	6	105	0.0571	0.00000515	1497

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000186	0.000184
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000220	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000100	0.0000967
Middle Eastern	0.000220	0.000217
South Asian	0.0000441	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)- mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity). {ECO:0000250|UniProtKB:Q6PR54, ECO:0000269|PubMed:15342490, ECO:0000269|PubMed:23333306, ECO:0000269|PubMed:28241136}.
• Pathway: Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);ATM Signaling Network in Development and Disease;DNA Repair;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair (Consensus)

Recessive Scores

• pRec: 0.0948

Intolerance Scores

• loftool: 0.489
• rvis_EVS: -1.81
• rvis_percentile_EVS: 2.18

Haploinsufficiency Scores

• pHI: 0.636
• hipred: N
• hipred_score: 0.273
• ghis: 0.619

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.929

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rif1
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; reproductive system phenotype; normal 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); hematopoietic system phenotype; embryo phenotype; immune system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;telomere maintenance;double-strand break repair via nonhomologous end joining;chromatin silencing at telomere;cellular response to DNA damage stimulus;cell cycle;stem cell population maintenance;telomere maintenance in response to DNA damage;positive regulation of isotype switching;positive regulation of histone H3-K9 methylation;cellular response to leukemia inhibitory factor;negative regulation of double-strand break repair via homologous recombination;positive regulation of double-strand break repair via nonhomologous end joining
• Cellular component: chromosome, telomeric region;nuclear chromatin;condensed chromosome;female pronucleus;male pronucleus;nucleus;nucleoplasm;cytoplasm;plasma membrane;nuclear body;nuclear membrane;site of double-strand break;spindle midzone
• Molecular function: protein binding