RFPL1

protein-coding

ret finger protein like 1, the group of Ring finger proteins

Gene summary

Predicted to enable ubiquitin protein ligase activity. Involved in negative regulation of G2/M transition of mitotic cell cycle and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_021026.2

Inheritance

—

ClinVar variants

U:53B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr22:29,438,583-29,442,455

External References & Databases

Ensembl (ENSG00000128250)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RFPL1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 55

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021026.2. 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						0
missense			53 clinvar	3 clinvar		56
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	53	3	0	56

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021026.2	RefSeq	NP_066306.2	2	MANE Select
ENST00000354373.2	Ensembl	ENSP00000346342.2	2	MANE Select
NM_001393612.1	RefSeq	NP_001380541.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell cycle
negative regulation of cell population proliferation
negative regulation of G2/M transition of mitotic cell cycle
positive regulation of proteasomal ubiquitin-dependent protein catabolic process
positive regulation of apoptotic process

Molecular Function

metal ion binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354373
Coding exons: 2
Length: 3873
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125747
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.409	167	183	0.915	0.0000105	2086
Missense (PolyPhen)		40	48.734	0.82077		643
Synonymous	-1.47	88	72.2	1.22	0.00000431	638
Loss of Function	0.515	3	4.13	0.726	1.77e-7	58

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Negatively regulates the G2-M phase transition, possibly by promoting cyclin B1/CCNB1 and CDK1 proteasomal degradation and thereby preventing their accumulation during interphase. {ECO:0000269|PubMed:20725088}.;

Intolerance Scores

LoFtool: 0.915
RVIS EVS: 1.4
RVIS percentile EVS: 94.7

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0503

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High