RNF123

protein-coding

ring finger protein 123, the group of Armadillo like helical domain containing|Ring finger proteins

Gene summary

The protein encoded by this gene contains a C-terminal RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions, and an N-terminal SPRY domain. This protein displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor 1B which is also known as p27 or KIP1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

MANE transcript

NM_022064.5

Inheritance

—

ClinVar variants

U:223B:11

Top phenotype

Hypertrophic cardiomyopathy

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr3:49,689,538-49,721,529

External References & Databases

Ensembl (ENSG00000164068)

Transcript & Mutation Effects

hg38 • Region Span ~32.0 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 RNF123 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 301

not providedTotal: 18

Hypertrophic cardiomyopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022064.5. 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			2 clinvar	5 clinvar	1 clinvar	8
missense			212 clinvar	3 clinvar	2 clinvar	217
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	223	8	3	234

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022064.5	RefSeq	NP_071347.2	38	MANE Select
ENST00000327697.11	Ensembl	ENSP00000328287.6	38	MANE Select
ENST00000432042.5	Ensembl	ENSP00000392443.1	21	Standard
ENST00000433785.1	Ensembl	ENSP00000416156.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Immune System
Adaptive Immune System
Antigen processing: Ubiquitination & Proteasome degradation

Biological Process

protein ubiquitination
protein deubiquitination
proteolysis involved in cellular protein catabolic process

Molecular Function

ubiquitin-protein transferase activity
metal ion binding

Cellular Component

cytoplasm
cytosol
nuclear membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327697
Coding exons: 38
Length: 32031
Individuals with no LoFs: 125693
Homozygous LoFs: 0
Heterozygous LoFs: 55
Defined: 125748
p: 0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.65	672	804	0.836	0.0000521	8466
Missense (PolyPhen)		196	276.82	0.70805		2914
Synonymous	0.360	318	326	0.975	0.0000199	2669
Loss of Function	5.57	22	73.5	0.299	0.00000342	826

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.00038	0.00032	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalytic subunit of the KPC complex that acts as E3 ubiquitin-protein ligase. Required for poly-ubiquitination and proteasome-mediated degradation of CDKN1B during G1 phase of the cell cycle. {ECO:0000269|PubMed:15531880, ECO:0000269|PubMed:16227581}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.604
RVIS EVS: -1.12
RVIS percentile EVS: 6.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.518

Gene Damage Prediction

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