RPN1

protein-coding

ribophorin I, the group of Oligosaccharyltransferase complex subunits

Gene summary

This gene encodes a type I integral membrane protein found only in the rough endoplasmic reticulum. The encoded protein is part of an N-oligosaccharyl transferase complex that links high mannose oligosaccharides to asparagine residues found in the Asn-X-Ser/Thr consensus motif of nascent polypeptide chains. This protein forms part of the regulatory subunit of the 26S proteasome and may mediate binding of ubiquitin-like domains to this proteasome. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002950.4

Inheritance

—

ClinVar variants

U:75B:5

Top phenotype

Hereditary breast ovarian cancer syndrome

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr3:128,619,969-128,681,075

External References & Databases

Ensembl (ENSG00000163902)

Transcript & Mutation Effects

hg38 • Region Span ~61.1 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 RPN1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 5

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002950.4. 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			7 clinvar		2 clinvar	9
missense			63 clinvar	2 clinvar	1 clinvar	66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	75	2	3	80

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002950.4	RefSeq	NP_002941.1	10	MANE Select
ENST00000296255.8	Ensembl	ENSP00000296255.3	10	MANE Select
ENST00000476931.1	Ensembl	ENSP00000419384.1	3	Standard
ENST00000497289.5	Ensembl	ENSP00000417529.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein processing in endoplasmic reticulum - Homo sapiens (human)
N-Glycan biosynthesis - Homo sapiens (human)
Proteasome Degradation
proteasome complex
SRP-dependent cotranslational protein targeting to membrane

Biological Process

cellular protein modification process
protein N-linked glycosylation via asparagine

Molecular Function

RNA binding
dolichyl-diphosphooligosaccharide-protein glycotransferase activity
protein binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
rough endoplasmic reticulum
cytosol
oligosaccharyltransferase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296255
Coding exons: 10
Length: 61102
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.736	305	343	0.888	0.0000188	3939
Missense (PolyPhen)		80	103.91	0.76986		1243
Synonymous	-0.0772	141	140	1.01	0.00000750	1243
Loss of Function	3.51	6	24.9	0.241	0.00000121	310

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000070	0.000070	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential subunit of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. {ECO:0000250|UniProtKB:E2RQ08, ECO:0000250|UniProtKB:Q9GMB0, ECO:0000305}.;

Recessive Scores

pRec: 0.321

Intolerance Scores

LoFtool: 0.101
RVIS EVS: -0.02
RVIS percentile EVS: 52.09

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.867

Gene Damage Prediction

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