NRDC

protein-coding

nardilysin convertase, the group of M16 metallopeptidases|MicroRNA protein coding host genes

Gene summary

This gene encodes a zinc-dependent endopeptidase that cleaves peptide substrates at the N-terminus of arginine residues in dibasic moieties and is a member of the peptidase M16 family. This protein interacts with heparin-binding EGF-like growth factor and plays a role in cell migration and proliferation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

Previous symbols:

NRD1

MANE transcript

NM_001101662.2

Inheritance

ClinVar variants

U:31B:3

Top phenotype

Developmental disorder

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr1:51,789,191-51,878,805

External References & Databases

Ensembl (ENSG00000078618)

Transcript & Mutation Effects

hg38 • Region Span ~89.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NRDC variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 7

not providedTotal: 4

Developmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001101662.2. 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			5 clinvar	1 clinvar	1 clinvar	7
missense			15 clinvar		1 clinvar	16
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	31	1	2	34

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 96 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001101662.2	RefSeq	NP_001095132.1	31	MANE Select
ENST00000352171.12	Ensembl	ENSP00000262679.8	31	MANE Select
NM_001242361.2	RefSeq	NP_001229290.1	32	Standard
NM_002525.3	RefSeq	NP_002516.2	33	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
neuromuscular junction development
cell population proliferation
cell migration
positive regulation of membrane protein ectodomain proteolysis

Molecular Function

metalloendopeptidase activity
protein binding
metal ion binding
epidermal growth factor binding

Cellular Component

mitochondrion
cytosol
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354831
Coding exons: 33
Length: 89615
Individuals with no LoFs: 125698
Homozygous LoFs: 0
Heterozygous LoFs: 50
Defined: 125748
p: 0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.56	450	631	0.713	0.0000306	8052
Missense (PolyPhen)		82	186.94	0.43864		2436
Synonymous	0.826	218	234	0.931	0.0000120	2228
Loss of Function	5.75	17	68.3	0.249	0.00000304	878

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00086	0.00076	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0.00035	0.00033	rare
Other	0.00052	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cleaves peptide substrates on the N-terminus of arginine residues in dibasic pairs.;

Recessive Scores

pRec: 0.103

Intolerance Scores

RVIS EVS: -1.04
RVIS percentile EVS: 7.84

Essentials

Essential (gene trap): N