REV3L

protein-coding

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

Gene summary

The protein encoded by this gene represents the catalytic subunit of DNA polymerase zeta, which functions in translesion DNA synthesis. The encoded protein can be found in mitochondria, where it protects DNA from damage. Defects in this gene are a cause of Mobius syndrome. [provided by RefSeq, Jan 2017]

MANE transcript

NM_001372078.1

Inheritance

ClinVar variants

P:3U:311B:118

Top phenotype

Moebius syndrome

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr6:111,299,028-111,483,715

External References & Databases

Ensembl (ENSG00000009413)

Transcript & Mutation Effects

hg38 • Region Span ~184.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Moebius syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008006

Submitter: PanelApp Australia

Moebius syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008006

Submitter: Orphanet

Moebius syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008006

Submitter: G2P

Moebius syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0008006

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to REV3L variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 303

not providedTotal: 117

REV3L-related disorderTotal: 39

not specifiedTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Carcinoma of colonTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001372078.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	45 clinvar	15 clinvar	64
missense		1 clinvar	293 clinvar	43 clinvar	15 clinvar	352
nonsense	1 clinvar		4 clinvar			5
start loss						0
frameshift	1 clinvar		5 clinvar			6
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	2	1	311	88	30	432

Highest pathogenic variant AF is 0.000007663188

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001372078.1	RefSeq	NP_001359007.1	32	MANE Select
ENST00000368802.8	Ensembl	ENSP00000357792.3	32	MANE Select
NM_001286431.2	RefSeq	NP_001273360.1	31	Standard
NM_001286432.2	RefSeq	NP_001273361.1	31	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fanconi anemia pathway - Homo sapiens (human)
DNA Repair
Purine metabolism
Pyrimidine metabolism
Translesion synthesis by REV1

Biological Process

DNA-dependent DNA replication
error-prone translesion synthesis
nucleic acid phosphodiester bond hydrolysis

Molecular Function

nucleotide binding
DNA binding
DNA-directed DNA polymerase activity
protein binding
3'-5' exonuclease activity

Cellular Component

nucleoplasm
nucleolus
zeta DNA polymerase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358835
Coding exons: 32
Length: 184685
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125737
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.47	1315	1.59e+3	0.826	0.0000808	20622
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.195

Intolerance Scores

LoFtool: 0.218
RVIS EVS: -2.1
RVIS percentile EVS: 1.55

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.761

Gene Damage Prediction

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