RNF103

protein-coding

ring finger protein 103, the group of Ring finger proteins

Gene summary

The protein encoded by this gene contains a RING-H2 finger, a motif known to be involved in protein-protein and protein-DNA interactions. This gene is highly expressed in normal cerebellum, but not in the cerebral cortex. The expression of the rat counterpart in the frontal cortex and hippocampus was shown to be induced by elctroconvulsive treatment (ECT) as well as chronic antidepressant treatment, suggesting that this gene may be a molecular target for ECT and antidepressants. The protein is a ubiquitin ligase that functions in the endoplasmic reticulum-associated degradation pathway. Alternative splicing of this gene results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream CHMP3 (charged multivesicular body protein 3) gene. [provided by RefSeq, Oct 2011]

Previous symbols:

ZFP103

MANE transcript

NM_005667.4

Inheritance

—

ClinVar variants

U:88B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr2:86,603,398-86,623,866

External References & Databases

Ensembl (ENSG00000239305)

Transcript & Mutation Effects

hg38 • Region Span ~20.5 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 RNF103 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 90

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005667.4. 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			88 clinvar	2 clinvar		90
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	88	2	0	90

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005667.4	RefSeq	NP_005658.1	4	MANE Select
ENST00000237455.5	Ensembl	ENSP00000237455.4	4	MANE Select
NM_001198951.1	RefSeq	NP_001185880.1	5	Standard
NM_001198952.2	RefSeq	NP_001185881.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

ER Quality Control Compartment (ERQC)
Calnexin/calreticulin cycle
Post-translational protein modification
Metabolism of proteins
Asparagine N-linked glycosylation

Biological Process

central nervous system development
protein ubiquitination
ubiquitin-dependent ERAD pathway
endoplasmic reticulum mannose trimming

Molecular Function

ubiquitin-protein transferase activity
protein binding
metal ion binding
ubiquitin protein ligase activity

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane
endoplasmic reticulum quality control compartment

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000237455
Coding exons: 4
Length: 20474
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.836	315	360	0.876	0.0000177	4521
Missense (PolyPhen)		109	148.57	0.73365		1873
Synonymous	-0.706	143	133	1.08	0.00000656	1260
Loss of Function	4.17	5	29.4	0.170	0.00000159	354

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as an E2-dependent E3 ubiquitin-protein ligase, probably involved in the ER-associated protein degradation pathway. {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:18675248}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.249
RVIS EVS: -0.15
RVIS percentile EVS: 42.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.882

Gene Damage Prediction

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