SNUPN

Chr 15AR

snurportin 1

Also known as: KPNBL, LGMDR29, RNUT1, Snurportin1

NCBI Gene: 10073 ENSG00000169371 UniProt: O95149 OMIM: 607902

The protein functions as a nuclear import receptor that specifically recognizes the trimethylguanosine cap structure of spliceosomal U snRNPs and facilitates their transport into the nucleus. Mutations cause limb-girdle muscular dystrophy type 29, which follows autosomal recessive inheritance. The gene shows extreme intolerance to loss-of-function variants (pLI ~1.0), indicating that biallelic variants are required for disease manifestation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The nuclear import of the spliceosomal snRNPs U1, U2, U4 and U5, is dependent on the presence of a complex nuclear localization signal. The latter is composed of the 5'-2,2,7-terminal trimethylguanosine (m3G) cap structure of the U snRNA and the Sm core domain. The protein encoded by this gene interacts specifically with m3G-cap and functions as an snRNP-specific nuclear import receptor. Alternatively spliced transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.491 OMIM phenotype

Clinical Summary— SNUPN

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Gene-Disease Validity (ClinGen)

SNUPN-related muscular dystrophy with or without multi-system involvement · ARStrong

Strong evidence — appropriate for clinical testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 46 VUS of 63 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.49LOEUF

pLI 0.000

Z-score -0.16

OE 1.04 (0.73–1.49)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.61Z-score

OE missense 0.88 (0.78–1.00)

175 obs / 199.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.04 (0.73–1.49)

0≤0.351.4

Missense OE?0.88 (0.78–1.00)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 21 / 20.2Missense obs/exp: 175 / 199.2Syn Z: 1.09

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic2

VUS46

Likely Benign3

Conflicting1

Likely Pathogenic

VUS

Likely Benign

Conflicting

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	2	0	0	0	2
VUS	0	46	0	0	46
Likely Benign	0	3	0	0	3
Benign	0	0	0	0	0
Conflicting	—				1
Total	2	49	0	0	52

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap SNUPN — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →