RFPL3

protein-coding

ret finger protein like 3, the group of Ring finger proteins

Gene summary

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response and regulation of gene expression. Predicted to be located in nucleus. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001098535.1

Inheritance

—

ClinVar variants

U:66B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.6

Max pathogenic AF

—

Genomic locus

chr22:32,354,885-32,361,161

External References & Databases

Ensembl (ENSG00000128276)

Transcript & Mutation Effects

hg38 • Region Span ~6.3 kb

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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 RFPL3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 69

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001098535.1. 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						0
missense			66 clinvar	6 clinvar		72
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	66	6	0	72

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001098535.1	RefSeq	NP_001092005.1	2	MANE Select
ENST00000249007.4	Ensembl	ENSP00000249007.4	2	MANE Select
NM_006604.2	RefSeq	NP_006595.1	2	Standard
ENST00000397468.5	Ensembl	ENSP00000380609.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

protein binding
metal ion binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000249007
Coding exons: 2
Length: 6277
Individuals with no LoFs: 125676
Homozygous LoFs: 0
Heterozygous LoFs: 72
Defined: 125748
p: 0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.435	198	182	1.09	0.0000106	2062
Missense (PolyPhen)		54	51.331	1.052		662
Synonymous	-1.37	87	72.2	1.20	0.00000431	641
Loss of Function	-1.07	6	3.75	1.60	1.58e-7	55

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0015	0.0015	notable
Latino/Admixed American	0.00066	0.00067	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.000097	0.000097	rare
South Asian	0.000099	0.000098	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: (Microbial infection) Stimulates the activity of Human Immunodeficiency Virus 1/HIV-1 pre-integration complex. {ECO:0000269|PubMed:25107902}.;

Intolerance Scores

LoFtool: 0.828
RVIS EVS: 0.69
RVIS percentile EVS: 85.18

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.000120

Gene Damage Prediction

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