RBX1

protein-coding

ring-box 1, the group of SCF complex core subunits|Ring finger proteins

Gene summary

This locus encodes a RING finger-like domain-containing protein. The encoded protein interacts with cullin proteins and likely plays a role in ubiquitination processes necessary for cell cycle progression. This protein may also affect protein turnover. Related pseudogenes exist on chromosomes 2 and 5.[provided by RefSeq, Sep 2010]

MANE transcript

NM_014248.4

Inheritance

—

ClinVar variants

U:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr22:40,951,347-40,973,309

External References & Databases

Ensembl (ENSG00000100387)

Transcript & Mutation Effects

hg38 • Region Span ~22.0 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 RBX1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014248.4. 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						0
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	3	0	0	3

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 41 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014248.4	RefSeq	NP_055063.1	5	MANE Select
ENST00000216225.9	Ensembl	ENSP00000216225.8	5	MANE Select
ENST00000872142.1	Ensembl	ENSP00000542201.1	5	Standard
ENST00000872142.2	Ensembl	ENSP00000542201.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Nucleotide excision repair - Homo sapiens (human)
Circadian rhythm - Homo sapiens (human)
TGF-beta signaling pathway - Homo sapiens (human)
Renal cell carcinoma - Homo sapiens (human)
Cell cycle - Homo sapiens (human)

Biological Process

MAPK cascade
protein polyubiquitination
nucleotide-excision repair, DNA damage recognition
transcription-coupled nucleotide-excision repair
nucleotide-excision repair, preincision complex stabilization

Molecular Function

ubiquitin-protein transferase activity
protein binding
transcription factor binding
zinc ion binding
NEDD8 transferase activity

Cellular Component

nucleus
nucleoplasm
cytosol
SCF ubiquitin ligase complex
VCB complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216225
Coding exons: 5
Length: 21963
Individuals with no LoFs: 125688
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125689
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.38	11	65.1	0.169	0.00000326	727
Missense (PolyPhen)		3	26.155	0.1147		257
Synonymous	-0.266	25	23.4	1.07	0.00000128	183
Loss of Function	2.82	0	9.26	0.00	5.93e-7	83

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin ligase component of multiple cullin-RING- based E3 ubiquitin-protein ligase (CRLs) complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription- coupled nucleotide excision repair (PubMed:10230407, PubMed:10579999, PubMed:15983046, PubMed:16678110, PubMed:19112177, PubMed:19679664, PubMed:23455478, PubMed:27565346, PubMed:29769719, PubMed:11961546, PubMed:22748924). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (PubMed:27565346). The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Recruits the E2 ubiquitin-conjugating enzyme CDC34 to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and CUL3, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. {ECO:0000269|PubMed:10230407, ECO:0000269|PubMed:10579999, ECO:0000269|PubMed:11027288, ECO:0000269|PubMed:11961546, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:16751180, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19112177, ECO:0000269|PubMed:19679664, ECO:0000269|PubMed:22748924, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:29769719}.;

Recessive Scores

pRec: 0.174

Intolerance Scores

RVIS EVS: 0.08
RVIS percentile EVS: 59.43

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.973