SNRPN

Chr 15

small nuclear ribonucleoprotein polypeptide N

Also known as: HCERN3, PWCR, RT-LI, SM-D, SMN, SNRNP-N, SNURF-SNRPN, sm-N

NCBI Gene: 6638 ENSG00000128739 UniProt: P63162 OMIM: 182279

The protein functions as a component of the small nuclear ribonucleoprotein complex involved in pre-mRNA processing and may contribute to tissue-specific alternative splicing. Mutations or alterations in this paternally-expressed, imprinted gene located in the Prader-Willi syndrome critical region on chromosome 15 are associated with Prader-Willi syndrome and Angelman syndrome. The gene shows low constraint against loss-of-function variants (pLI 0.04, LOEUF 0.83), and these disorders typically present in infancy with distinct neurodevelopmental phenotypes depending on the parent of origin of the genetic alteration.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

This gene is located within the Prader-Willi Syndrome critical region on chromosome 15 and is imprinted and expressed from the paternal allele. It encodes a component of the small nuclear ribonucleoprotein complex, which functions in pre-mRNA processing and may contribute to tissue-specific alternative splicing. Alternative promoter use and alternative splicing result in a multitude of transcript variants encoding the same protein. Transcript variants that initiate at the CpG island-associated imprinting center may be bicistronic and also encode the SNRPN upstream reading frame protein (SNURF) from an upstream open reading frame. In addition, long spliced transcripts for small nucleolar RNA host gene 14 (SNHG14) may originate from the promoters at this locus and share exons with this gene. Alterations in this region are associated with parental imprint switch failure, which may cause Angelman syndrome or Prader-Willi syndrome. [provided by RefSeq, Mar 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.83

Clinical Summary— SNRPN

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Population Constraint (gnomAD)

Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 58 VUS of 82 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 →

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GeneReview available — SNRPN

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.043

Z-score 1.95

OE 0.36 (0.18–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.43Z-score

OE missense 0.44 (0.36–0.54)

66 obs / 149.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.36 (0.18–0.83)

0≤0.351.4

Missense OE?0.44 (0.36–0.54)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 11.0Missense obs/exp: 66 / 149.6Syn Z: -0.25

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSNRPN-related Prader-Willi syndromeLOFAD

This gene — mechanism propensity

0.74top 25%

GOF

0.4875th %ile

LOF

0.50top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

82 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS58

Likely Benign18

Benign5

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	3	52	3	0	58
Likely Benign	0	0	8	10	18
Benign	0	0	1	4	5
Total	4	52	12	14	82

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

View in ClinVar →

316 pathogenic / likely-pathogenic (of 344) ClinVar copy-number / structural variants overlap SNRPN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →