SNRPA

protein-coding

small nuclear ribonucleoprotein polypeptide A, the group of U1 small nuclear ribonucleoprotein|RNA binding motif containing

Gene summary

The protein encoded by this gene associates with stem loop II of the U1 small nuclear ribonucleoprotein, which binds the 5' splice site of precursor mRNAs and is required for splicing. The encoded protein autoregulates itself by polyadenylation inhibition of its own pre-mRNA via dimerization and has been implicated in the coupling of splicing and polyadenylation. [provided by RefSeq, Oct 2010]

MANE transcript

NM_004596.5

Inheritance

ClinVar variants

P:2U:33B:5

Top phenotype

SNRPA-related disorder

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr19:40,750,637-40,765,389

External References & Databases

Ensembl (ENSG00000077312)

Transcript & Mutation Effects

hg38 • Region Span ~14.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SNRPA variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 30

SNRPA-related disorderTotal: 5

SpliceosomepathyTotal: 3

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004596.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar	1 clinvar	6
missense		2 clinvar	30 clinvar	1 clinvar		33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	2	33	4	1	40

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004596.5	RefSeq	NP_004587.1	6	MANE Select
ENST00000243563.8	Ensembl	ENSP00000243563.2	6	MANE Select
ENST00000597353.5	Ensembl	ENSP00000472449.1	4	Standard
ENST00000599362.5	Ensembl	ENSP00000472258.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
mRNA Processing
spliceosomal assembly
Metabolism of RNA
mRNA Splicing - Major Pathway

Biological Process

mRNA splicing, via spliceosome
regulation of mRNA polyadenylation

Molecular Function

RNA binding
protein binding
U1 snRNA binding
snRNA stem-loop binding
identical protein binding

Cellular Component

nucleoplasm
spliceosomal complex
U1 snRNP

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000243563
Coding exons: 6
Length: 14753
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125747
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.75	116	183	0.635	0.0000112	1865
Missense (PolyPhen)		25	54.835	0.45591		585
Synonymous	-0.601	77	70.6	1.09	0.00000457	547
Loss of Function	0.681	8	10.4	0.772	4.39e-7	129

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000080	0.000079	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. U1 snRNP is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP. SNRPA binds stem loop II of U1 snRNA. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. May bind preferentially to the 5'-UGCAC-3' motif on RNAs. {ECO:0000269|PubMed:9848648}.;

Recessive Scores

pRec: 0.290

Intolerance Scores

LoFtool: 0.485
RVIS EVS: -0.54
RVIS percentile EVS: 20.26

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.997

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium