REV3L

REV3 like, DNA directed polymerase zeta catalytic subunit, the group of DNA polymerases

Basic information

Region (hg38): 6:111299027-111483715

Links

ENSG00000009413 ∙ NCBI:5980 ∙ OMIM:602776 ∙ HGNC:9968 ∙ Uniprot:O60673 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Mobius syndrome (Limited), mode of inheritance: Unknown
• Mobius syndrome (Supportive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the REV3L gene.

• not provided (112 variants)
• Inborn genetic diseases (78 variants)
• not specified (2 variants)
• Carcinoma of colon (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the REV3L 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				33	15	48
missense		1	69	26	17	113
nonsense			2			2
start loss						0
frameshift	1		1			2
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)						0
splice region				3	5	8
non coding				5	1	6
Total	1	1	73	65	33

Variants in REV3L

This is a list of pathogenic ClinVar variants found in the REV3L region.

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

Position	Type	Phenotype	Significance	ClinVar
6-111300067-A-C		Inborn genetic diseases	Uncertain significance (Aug 30, 2022)
6-111300067-A-G			Likely benign (Dec 01, 2022)
6-111300131-A-G		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
6-111307394-C-G		REV3L-related disorder	Benign (Jun 07, 2019)
6-111307396-G-A		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
6-111307423-C-T		REV3L-related disorder	Benign (Jun 07, 2019)
6-111307491-T-C		Inborn genetic diseases	Uncertain significance (Apr 27, 2022)
6-111307505-A-G		REV3L-related disorder	Benign (Dec 31, 2019)
6-111307507-A-G		Inborn genetic diseases	Uncertain significance (Apr 10, 2023)
6-111307513-A-C			Likely benign (Feb 07, 2018)
6-111307527-C-T			Benign (Mar 29, 2018)
6-111307543-T-A		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
6-111307547-C-T		REV3L-related disorder	Likely benign (Dec 30, 2019)
6-111307568-G-T		REV3L-related disorder	Benign (Dec 31, 2019)
6-111309957-G-A		REV3L-related disorder	Likely benign (Mar 25, 2019)
6-111310038-T-C		Inborn genetic diseases	Uncertain significance (Jan 24, 2024)
6-111310051-T-C			Likely benign (Aug 07, 2018)
6-111310090-C-T		REV3L-related disorder	Likely benign (Aug 29, 2019)
6-111310105-C-T		REV3L-related disorder	Benign (Dec 31, 2019)
6-111310106-G-A			Likely benign (Mar 29, 2018)
6-111313342-T-G		REV3L-related disorder	Benign (Dec 31, 2019)
6-111313380-C-G		Inborn genetic diseases	Uncertain significance (May 27, 2022)
6-111313415-G-C		Inborn genetic diseases	Uncertain significance (Nov 22, 2023)
6-111313489-C-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 22, 2021)
6-111315258-T-C			Likely benign (Jun 01, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
REV3L	protein_coding	protein_coding	ENST00000358835	32	184685

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.05e-16	125715	0	22	125737	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.47	1315	1.59e+3	0.826	0.0000808	20622
Missense in Polyphen		329	566.28	0.58099		7303
Synonymous	0.556	544	561	0.970	0.0000278	5956
Loss of Function	10.0	9	135	0.0669	0.00000765	1720

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000153	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000143	0.000139
European (Non-Finnish)	0.000110	0.000105
Middle Eastern	0.000109	0.000109
South Asian	0.0000333	0.0000327
Other	0.000175	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of the DNA polymerase zeta complex, an error-prone polymerase specialized in translesion DNA synthesis (TLS). Lacks an intrinsic 3'-5' exonuclease activity and thus has no proofreading function. {ECO:0000269|PubMed:24449906}.
• Pathway: Fanconi anemia pathway - Homo sapiens (human);DNA Repair;Purine metabolism;Pyrimidine metabolism;Translesion synthesis by REV1;Translesion synthesis by POLK;Translesion synthesis by POLI;Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template;DNA Damage Bypass (Consensus)

Recessive Scores

• pRec: 0.195

Intolerance Scores

• loftool: 0.218
• rvis_EVS: -2.1
• rvis_percentile_EVS: 1.55

Haploinsufficiency Scores

• pHI: 0.860
• hipred: Y
• hipred_score: 0.783
• ghis: 0.592

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.761

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rev3l
• 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); immune system phenotype; embryo 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: DNA-dependent DNA replication;error-prone translesion synthesis;nucleic acid phosphodiester bond hydrolysis
• Cellular component: nucleoplasm;nucleolus;zeta DNA polymerase complex
• Molecular function: nucleotide binding;DNA binding;DNA-directed DNA polymerase activity;protein binding;3'-5' exonuclease activity;metal ion binding;4 iron, 4 sulfur cluster binding