RPN1

Chr 3

ribophorin I

Also known as: OST1, RBPH1

NCBI Gene: 6184 ENSG00000163902 UniProt: P04843 OMIM: 180470

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.47

Clinical Summary— RPN1

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

📋

ClinVar Variants

57 VUS of 99 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.239

Z-score 3.51

OE 0.24 (0.13–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.74Z-score

OE missense 0.89 (0.81–0.98)

305 obs / 343.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.13–0.47)

0≤0.351.4

Missense OE?0.89 (0.81–0.98)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 6 / 24.9Missense obs/exp: 305 / 343.4Syn Z: -0.08

This gene — mechanism propensity

0.6551th %ile

GOF

0.4776th %ile

LOF

0.3453th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

VUS57

Likely Benign2

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	57	0	0	57
Likely Benign	2	0	0	2
Benign	1	1	2	4
Total	60	1	2	63

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

13 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap RPN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →