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

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]

417

ClinVar variants

312

Pathogenic / LP

0.04

pLI score

Active trials

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

312 Pathogenic / Likely Pathogenic· 76 VUS of 417 total submissions

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Clinical Trials

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.83LOEUF

pLI 0.043

Z-score 1.95

OE 0.36 (0.18–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.36 (0.18–0.83)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.36–0.54)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05

0≤1.21.6

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