SNRPN

Chr 15

small nuclear ribonucleoprotein polypeptide N

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.83
Clinical SummarySNRPN
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
315 unique Pathogenic / Likely Pathogenic· 77 VUS of 423 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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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

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.043
Z-score 1.95
OE 0.36 (0.180.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.43Z-score
OE missense 0.44 (0.360.54)
66 obs / 149.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.36 (0.180.83)
00.351.4
Missense OE0.44 (0.360.54)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 4 / 11.0Missense obs/exp: 66 / 149.6Syn Z: -0.25
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSNRPN-related Prader-Willi syndromeLOFAD
DN
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

423 submitted variants in ClinVar

Classification Summary

Pathogenic303
Likely Pathogenic12
VUS77
Likely Benign22
Benign9
303
Pathogenic
12
Likely Pathogenic
77
VUS
22
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
302
0
303
Likely Pathogenic
0
0
12
0
12
VUS
3
52
22
0
77
Likely Benign
0
0
12
10
22
Benign
0
0
5
4
9
Total45235314423

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

View in ClinVar →

Protein Context — Lollipop Plot

SNRPN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗