NRIP2

Chr 12

nuclear receptor interacting protein 2

Also known as: NIX1

NRIP2 encodes a protein that down-regulates transcriptional activation by nuclear receptors and is predicted to have aspartic-type endopeptidase activity involved in proteolysis and Notch signaling. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and spasticity. This gene shows strong constraint against loss-of-function variants, indicating intolerance to haploinsufficiency.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
63
P/LP submissions
0%
P/LP missense
1.54
LOEUF
Mechanism
Clinical SummaryNRIP2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
63 unique Pathogenic / Likely Pathogenic· 65 VUS of 134 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.54LOEUF
pLI 0.000
Z-score -0.03
OE 1.01 (0.671.54)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.04Z-score
OE missense 1.23 (1.091.38)
200 obs / 162.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.01 (0.671.54)
00.351.4
Missense OE1.23 (1.091.38)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 15 / 14.9Missense obs/exp: 200 / 162.7Syn Z: -0.57

ClinVar Variant Classifications

134 submitted variants in ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic3
VUS65
Likely Benign4
60
Pathogenic
3
Likely Pathogenic
65
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
0
3
0
3
VUS
0
60
5
0
65
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total063690132

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

View in ClinVar →

Protein Context — Lollipop Plot

NRIP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC