NRTN

protein-coding

neurturin, the group of GDNF family ligands

Gene summary

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein signals through the RET receptor tyrosine kinase and a GPI-linked coreceptor, and promotes survival of neuronal populations. A neurturin mutation has been described in a family with Hirschsprung Disease. [provided by RefSeq, Aug 2016]

MANE transcript

NM_004558.5

Inheritance

—

ClinVar variants

U:45B:12

Top phenotype

NRTN-related disorder

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr19:5,805,067-5,828,324

External References & Databases

Ensembl (ENSG00000171119)

Transcript & Mutation Effects

hg38 • Region Span ~23.3 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 NRTN variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 50

NRTN-related disorderTotal: 7

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004558.5. 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	9 clinvar	1 clinvar	11
missense			43 clinvar	2 clinvar		45
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	45	11	1	57

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004558.5	RefSeq	NP_004549.1	2	MANE Select
ENST00000303212.3	Ensembl	ENSP00000302648.1	2	MANE Select
ENST00000879152.1	Ensembl	ENSP00000549211.1	2	Standard
ENST00000879152.2	Ensembl	ENSP00000549211.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Developmental Biology
Signal Transduction
RAF/MAP kinase cascade
MAPK1/MAPK3 signaling
MAPK family signaling cascades

Biological Process

MAPK cascade
neural crest cell migration
transmembrane receptor protein tyrosine kinase signaling pathway
nervous system development
axon guidance

Molecular Function

Ras guanyl-nucleotide exchange factor activity
signaling receptor binding
growth factor activity

Cellular Component

extracellular region
axon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000303212
Coding exons: 2
Length: 4523
Individuals with no LoFs: 123767
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 123770
p: 0.0000121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.679	68	85.7	0.794	0.00000536	1145
Missense (PolyPhen)		30	38.41	0.78104		578
Synonymous	0.833	34	40.8	0.834	0.00000232	477
Loss of Function	1.12	3	5.95	0.504	3.94e-7	60

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
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)	0.0000089	0.0000089	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Supports the survival of sympathetic neurons in culture. May regulate the development and maintenance of the CNS. Might control the size of non-neuronal cell population such as haemopoietic cells.;
Disease: DISEASE: Note=Genetic variations in NRTN may contribute to Hirschsprung disease, in association with mutations of RET gene, and possibly mutations in other loci. Hirschsprung disease is a disorder of neural crest development is characterized by the absence of intramural ganglion cells in the hindgut, often resulting in intestinal obstruction. {ECO:0000269|PubMed:9700200}.;

Recessive Scores

pRec: 0.210

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.607

Gene Damage Prediction

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