NRARP

protein-coding

NOTCH regulated ankyrin repeat protein, the group of Ankyrin repeat domain containing

Gene summary

Involved in Notch signaling pathway. Acts upstream of or within negative regulation of Notch signaling pathway and positive regulation of canonical Wnt signaling pathway. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001004354.3

Inheritance

—

ClinVar variants

—

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr9:137,299,631-137,302,271

External References & Databases

Ensembl (ENSG00000198435)

Transcript & Mutation Effects

hg38 • Region Span ~2.6 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 NRARP variants in ClinVar

0 Conditions Cataloged

No annotated ClinVar phenotypes.

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript . 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
synonymous
missense
nonsense
start loss
frameshift
splice donor/acceptor (+/-2bp)
Total	0	0	0	0	0

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001004354.3	RefSeq	NP_001004354.1	1	MANE Select
ENST00000356628.4	Ensembl	ENSP00000349041.2	1	MANE Select

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nrarpb	Danio rerio	Structure: intersegmental vessel Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

nrarpb

Danio rerio

Structure: intersegmental vessel

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
branching involved in blood vessel morphogenesis
positive regulation of endothelial cell proliferation
blood vessel endothelial cell proliferation involved in sprouting angiogenesis
Notch signaling pathway

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356628
Coding exons: 1
Length: 2621
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.33	14	67.9	0.206	0.00000312	734
Missense (PolyPhen)		7	42.256	0.16566		436
Synonymous	0.844	28	34.3	0.817	0.00000161	233
Loss of Function	1.03	1	2.89	0.347	1.25e-7	25

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Downstream effector of Notch signaling. Involved in the regulation of liver cancer cells self-renewal (PubMed:25985737). Involved in angiogenesis acting downstream of Notch at branch points to regulate vascular density. Proposed to integrate endothelial Notch and Wnt signaling to control stalk cell proliferation and to stablilize new endothelial connections during angiogenesis (PubMed:19154719). During somitogenesis involved in maintenance of proper somite segmentation and proper numbers of somites and vertebrae. Required for proper anterior-posterior somite patterning. Proposed to function in a negative feedback loop to destabilize Notch 1 intracellular domain (NICD) and downregulate the Notch signal, preventing expansion of the Notch signal into the anterior somite domain (By similarity). {ECO:0000250|UniProtKB:Q91ZA8, ECO:0000269|PubMed:19154719, ECO:0000269|PubMed:25985737, ECO:0000305|PubMed:25985737}.;

Recessive Scores

pRec: 0.141

Intolerance Scores

LoFtool: 0.205
RVIS EVS: 0.19
RVIS percentile EVS: 66.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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