NRIP2

protein-coding

nuclear receptor interacting protein 2, the group of Peptidase family A28

Gene summary

Predicted to enable aspartic-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within Notch signaling pathway and negative regulation of transcription by RNA polymerase II. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_031474.3

Inheritance

—

ClinVar variants

U:60B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr12:2,825,348-2,835,544

External References & Databases

Ensembl (ENSG00000053702)

Transcript & Mutation Effects

hg38 • Region Span ~10.2 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 NRIP2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 63

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031474.3. 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			60 clinvar	3 clinvar		63
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	60	3	0	63

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031474.3	RefSeq	NP_113662.1	6	MANE Select
ENST00000337508.9	Ensembl	ENSP00000337501.4	6	MANE Select
ENST00000542386.1	Ensembl	ENSP00000438338.1	3	Standard
ENST00000542990.5	Ensembl	ENSP00000446283.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

aspartic-type endopeptidase activity
protein binding

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000337508
Coding exons: 6
Length: 10197
Individuals with no LoFs: 125522
Homozygous LoFs: 0
Heterozygous LoFs: 225
Defined: 125747
p: 0.000895

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.04	200	163	1.23	0.00000907	1800
Missense (PolyPhen)		55	52.377	1.0501		544
Synonymous	-0.569	75	69.0	1.09	0.00000381	582
Loss of Function	-0.0258	15	14.9	1.01	7.34e-7	150

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.00083	0.00081	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00087	0.00087	rare
Finnish	0.00046	0.00046	rare
European (Non-Finnish)	0.0013	0.0013	notable
South Asian	0.00030	0.00029	rare
Other	0.0012	0.0011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Down-regulates transcriptional activation by nuclear receptors such as NR1F2. {ECO:0000250}.;

Recessive Scores

pRec: 0.0868

Intolerance Scores

LoFtool: 0.369
RVIS EVS: -0.36
RVIS percentile EVS: 29.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.641

Gene Damage Prediction

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