RFPL2

protein-coding

ret finger protein like 2, 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 active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001394555.1

Inheritance

—

ClinVar variants

U:70B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.21

Max pathogenic AF

—

Genomic locus

chr22:32,190,435-32,205,073

External References & Databases

Ensembl (ENSG00000128253)

Transcript & Mutation Effects

hg38 • Region Span ~14.6 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 RFPL2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394555.1. 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			69 clinvar	6 clinvar		75
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	70	6	0	76

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394555.1	RefSeq	NP_001381484.1	4	MANE Select
ENST00000652607.2	Ensembl	ENSP00000498332.1	4	MANE Select
NM_001098527.3	RefSeq	NP_001091997.2	4	Standard
NM_001159545.3	RefSeq	NP_001153017.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Molecular Function

metal ion binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000400237
Coding exons: 4
Length: 14297
Individuals with no LoFs: 125519
Homozygous LoFs: 2
Heterozygous LoFs: 227
Defined: 125748
p: 0.000911

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.00517	222	222	0.999	0.0000128	2460
Missense (PolyPhen)		55	60.581	0.90787		782
Synonymous	-0.788	94	84.8	1.11	0.00000498	758
Loss of Function	-0.525	9	7.45	1.21	3.14e-7	98

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00042	0.00037	rare
Latino/Admixed American	0.00051	0.00049	rare
Ashkenazi Jewish	0.011	0.011	notable
East Asian	0.00057	0.00054	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00057	0.00056	rare
South Asian	0.00060	0.00056	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Intolerance Scores

LoFtool: 0.915
RVIS EVS: 1.35
RVIS percentile EVS: 94.4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0301

Gene Damage Prediction

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