NDN

Chr 15

necdin, MAGE family member

Also known as: HsT16328, PWCR

NCBI Gene: 4692 ENSG00000182636 UniProt: Q99608 OMIM: 602117

Necdin functions as a growth suppressor that facilitates cell cycle arrest in postmitotic neurons and acts as a transcription factor that binds to guanosine-rich DNA sequences. Mutations cause Prader-Willi syndrome, a complex neurodevelopmental disorder with neonatal hypotonia, feeding difficulties, hyperphagia, intellectual disability, and behavioral problems. The gene shows paternal-only expression due to genomic imprinting, so disease occurs through paternal deletions or maternal uniparental disomy of the 15q11-q13 region.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.60

Clinical Summary— NDN

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.67) — some intolerance to loss-of-function variants.

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ClinVar Variants

50 VUS of 66 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.60LOEUF

pLI 0.675

Z-score 2.28

OE 0.13 (0.04–0.60)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.71Z-score

OE missense 0.86 (0.76–0.97)

167 obs / 194.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.13 (0.04–0.60)

0≤0.351.4

Missense OE?0.86 (0.76–0.97)

0≤0.61.4

Synonymous OE?1.14

0≤1.21.6

LoF obs/exp: 1 / 7.9Missense obs/exp: 167 / 194.8Syn Z: -1.06

ClinVar Variant Classifications

66 submitted variants in ClinVar

ClinVar

Classification Summary

VUS50

Likely Benign11

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	48	1	0	50
Likely Benign	0	3	0	8	11
Benign	0	1	0	4	5
Total	1	52	1	12	66

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

308 pathogenic / likely-pathogenic (of 313) ClinVar copy-number / structural variants overlap NDN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →