RNF128

protein-coding

ring finger protein 128, the group of Ring finger proteins

Gene summary

The protein encoded by this gene is a type I transmembrane protein that localizes to the endocytic pathway. This protein contains a RING zinc-finger motif and has been shown to possess E3 ubiquitin ligase activity. Expression of this gene in retrovirally transduced T cell hybridoma significantly inhibits activation-induced IL2 and IL4 cytokine production. Induced expression of this gene was observed in anergic CD4(+) T cells, which suggested a role in the induction of anergic phenotype. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_194463.2

Inheritance

—

ClinVar variants

U:136B:6

Top phenotype

Laterality defects, autosomal dominant

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chrX:106,693,794-106,797,016

External References & Databases

Ensembl (ENSG00000133135)

Transcript & Mutation Effects

hg38 • Region Span ~103.2 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 RNF128 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 56

not providedTotal: 8

Laterality defects, autosomal dominantTotal: 2

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_194463.2. 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			17 clinvar	1 clinvar	1 clinvar	19
missense			95 clinvar	3 clinvar	1 clinvar	99
nonsense			6 clinvar			6
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			18 clinvar			18
Total	0	0	136	4	2	142

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_194463.2	RefSeq	NP_919445.1	7	MANE Select
ENST00000255499.3	Ensembl	ENSP00000255499.2	7	MANE Select
NM_024539.3	RefSeq	NP_078815.3	7	Standard
ENST00000324342.7	Ensembl	ENSP00000316127.3	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Ub-specific processing proteases
Ovarian tumor domain proteases
Deubiquitination

Biological Process

ubiquitin-dependent protein catabolic process
protein ubiquitination
protein deubiquitination
regulation of protein stability
negative regulation of cytokine biosynthetic process

Molecular Function

protein binding
metal ion binding
ubiquitin protein ligase activity

Cellular Component

late endosome
endoplasmic reticulum
Golgi apparatus
cytosol
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000255499
Coding exons: 7
Length: 103200
Individuals with no LoFs: 125737
Homozygous LoFs: 3
Heterozygous LoFs: 4
Defined: 125744
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.666	141	165	0.854	0.0000120	2752
Missense (PolyPhen)		47	64.071	0.73356		1027
Synonymous	0.707	61	68.4	0.891	0.00000512	891
Loss of Function	2.33	3	11.5	0.260	7.86e-7	208

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000083	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00015	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000026	rare
South Asian	0.000053	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: E3 ubiquitin-protein ligase that catalyzes 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains formation. Functions as an inhibitor of cytokine gene transcription. Inhibits IL2 and IL4 transcription, thereby playing an important role in the induction of the anergic phenotype, a long-term stable state of T-lymphocyte unresponsiveness to antigenic stimulation associated with the blockade of interleukin production. Ubiquitinates ARPC5 with 'Lys- 48' linkages and COR1A with 'Lys-63' linkages leading to their degradation, down-regulation of these cytosleletal components results in impaired lamellipodium formation and reduced accumulation of F-actin at the immunological synapse. Functions in the patterning of the dorsal ectoderm; sensitizes ectoderm to respond to neural-inducing signals. {ECO:0000269|PubMed:12705856, ECO:0000269|PubMed:22016387}.;

Recessive Scores

pRec: 0.161

Intolerance Scores

LoFtool: 0.651
RVIS EVS: 0.06
RVIS percentile EVS: 58.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.566

Gene Damage Prediction

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