NRIP1

protein-coding

nuclear receptor interacting protein 1

Gene summary

Nuclear receptor interacting protein 1 (NRIP1) is a nuclear protein that specifically interacts with the hormone-dependent activation domain AF2 of nuclear receptors. Also known as RIP140, this protein modulates transcriptional activity of the estrogen receptor. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003489.4

Inheritance

ClinVar variants

P:3U:245B:110

Top phenotype

Congenital anomalies of the kidney and urinary tract 3

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr21:14,961,235-15,065,936

External References & Databases

Ensembl (ENSG00000180530)

Transcript & Mutation Effects

hg38 • Region Span ~104.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital anomalies of kidney and urinary tract 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032646

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Congenital anomalies of the kidney and urinary tract 3AD

Manifestation: Neurologic; Renal

Intervention: Renal

Rationale: Evidence or clinical applicability is unclear

Refs: 21743468; 28381549

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NRIP1 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 188

Inborn genetic diseasesTotal: 176

NRIP1-related disorderTotal: 58

Congenital anomalies of kidney and urinary tract 3Total: 20

not specifiedTotal: 10

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Congenital anomaly of kidney and urinary tractTotal: 1

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003489.4. 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			1 clinvar	60 clinvar	10 clinvar	71
missense		1 clinvar	237 clinvar	28 clinvar	11 clinvar	277
nonsense		1 clinvar	2 clinvar			3
start loss						0
frameshift	1 clinvar		5 clinvar	1 clinvar		7
splice donor/acceptor (+/-2bp)						0
Total	1	2	245	89	21	358

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003489.4	RefSeq	NP_003480.2	1	MANE Select
ENST00000318948.7	Ensembl	ENSP00000327213.4	1	MANE Select
NM_001439275.1	RefSeq	NP_001426204.1	1	Standard
NM_001439276.1	RefSeq	NP_001426205.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Adipogenesis
Aryl Hydrocarbon Receptor
Pregnane X Receptor pathway
Vitamin D Receptor Pathway
Nuclear Receptors Meta-Pathway

Biological Process

negative regulation of transcription by RNA polymerase II
ovarian follicle rupture
circadian rhythm
lipid storage
androgen receptor signaling pathway

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
transcription coactivator activity
transcription corepressor activity
protein binding
estrogen receptor binding

Cellular Component

histone deacetylase complex
nuclear chromatin
nucleus
nucleoplasm
nucleolus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000400202
Coding exons: 1
Length: 103766
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125736
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.460	610	579	1.05	0.0000277	7665
Missense (PolyPhen)		198	201.32	0.98353		2754
Synonymous	-1.07	240	220	1.09	0.0000112	2226
Loss of Function	4.66	4	32.8	0.122	0.00000177	465

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000097	0.000079	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1. Also modulates transcriptional repression by nuclear hormone receptors. Positive regulator of the circadian clock gene expression: stimulates transcription of ARNTL/BMAL1, CLOCK and CRY1 by acting as a coactivator for RORA and RORC. {ECO:0000269|PubMed:10364267, ECO:0000269|PubMed:11509661, ECO:0000269|PubMed:11518808, ECO:0000269|PubMed:12554755, ECO:0000269|PubMed:15060175, ECO:0000269|PubMed:21628546, ECO:0000269|PubMed:7641693}.;

Recessive Scores

pRec: 0.199

Intolerance Scores

LoFtool: 0.0754
RVIS EVS: 1.39
RVIS percentile EVS: 94.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.112

Gene Damage Prediction

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