NDN

protein-coding

necdin, MAGE family member, the group of MAGE family

Gene summary

This intronless gene is located in the Prader-Willi syndrome deletion region. It is an imprinted gene and is expressed exclusively from the paternal allele. Studies in mouse suggest that the protein encoded by this gene may suppress growth in postmitotic neurons. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002487.3

Inheritance

ClinVar variants

U:49B:15

Top phenotype

Prader-Willi syndrome

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr15:23,685,400-23,687,305

External References & Databases

Ensembl (ENSG00000182636)

Transcript & Mutation Effects

hg38 • Region Span ~1.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Prader-Willi syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008300

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NDN variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 16

Prader-Willi syndromeTotal: 4

NDN-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002487.3. 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				8 clinvar	3 clinvar	11
missense			48 clinvar	3 clinvar	1 clinvar	52
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	49	11	4	64

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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_002487.3	RefSeq	NP_002478.1	1	MANE Select
ENST00000649030.2	Ensembl	ENSP00000497916.1	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Adipogenesis
Prader-Willi and Angelman Syndrome
Interleukin-4 and 13 signaling
p75(NTR)-mediated signaling

Biological Process

neuron migration
respiratory system process
nervous system development
axonal fasciculation
central nervous system development

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific
gamma-tubulin binding

Cellular Component

nucleoplasm
centrosome
cytosol
cell projection
perikaryon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331837
Coding exons: 1
Length: 1886
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	0.707	167	195	0.857	0.0000119	2053
Missense (PolyPhen)		64	94.544	0.67693		956
Synonymous	-1.06	104	91.1	1.14	0.00000631	660
Loss of Function	2.28	1	7.95	0.126	3.42e-7	84

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: Growth suppressor that facilitates the entry of the cell into cell cycle arrest. Functionally similar to the retinoblastoma protein it binds to and represses the activity of cell-cycle- promoting proteins such as SV40 large T antigen, adenovirus E1A, and the transcription factor E2F. Necdin also interacts with p53 and works in an additive manner to inhibit cell growth. Functions also as transcription factor and binds directly to specific guanosine-rich DNA sequences (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.205

Intolerance Scores

LoFtool: 0.230
RVIS EVS: 0.22
RVIS percentile EVS: 68.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.974

Gene Damage Prediction

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