SNAPC4

protein-coding

small nuclear RNA activating complex polypeptide 4, the group of Myb/SANT domain containing|SNAP complex

Gene summary

This gene encodes the largest subunit of the small nuclear RNA-activating protein (SNAP) complex. The encoded protein contains a Myb DNA-binding domain, and is essential for RNA polymerase II and III polymerase transcription from small nuclear RNA promoters. A mutation in this gene is associated with ankylosing spondylitis. [provided by RefSeq, Jul 2016]

MANE transcript

NM_003086.4

Inheritance

ClinVar variants

P:11U:351B:60

Top phenotype

Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr9:136,375,567-136,400,176

External References & Databases

Ensembl (ENSG00000165684)

Transcript & Mutation Effects

hg38 • Region Span ~24.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunctionSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957791

Submitter: PanelApp Australia

neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunctionMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957791

Submitter: G2P

neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunctionMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957791

Submitter: Baylor College of Medicine Research Center

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunctionAR

Manifestation: Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 36965478

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SNAPC4 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 343

not providedTotal: 60

Neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunctionTotal: 15

SNAPC4 related conditionTotal: 4

not specifiedTotal: 3

Long QT syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003086.4. 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			3 clinvar	21 clinvar		24
missense	3 clinvar		336 clinvar	37 clinvar	2 clinvar	378
nonsense	1 clinvar	2 clinvar	3 clinvar			6
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)	1 clinvar	4 clinvar	7 clinvar			12
Total	5	6	351	58	2	422

Highest pathogenic variant AF is 0.00008551839

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003086.4	RefSeq	NP_003077.2	22	MANE Select
ENST00000684778.1	Ensembl	ENSP00000510559.1	22	MANE Select
NM_001394201.1	RefSeq	NP_001381130.1	22	Standard
NM_001394202.1	RefSeq	NP_001381131.1	22	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
snapc4	Danio rerio	Structure: intrahepatic bile duct Quality: hypoplastic abnormal

Gene / Model

Organism

Observed Phenotype

snapc4

Danio rerio

Structure: intrahepatic bile duct

Quality: hypoplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
RNA polymerase II transcribes snRNA genes
RNA Polymerase II Transcription
RNA Polymerase III Abortive And Retractive Initiation
RNA Polymerase III Transcription Initiation From Type 3 Promoter

Biological Process

regulation of transcription by RNA polymerase II
transcription by RNA polymerase II
transcription by RNA polymerase III
snRNA transcription
snRNA transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
DNA-binding transcription factor activity

Cellular Component

nucleus
nucleoplasm
snRNA-activating protein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298532
Coding exons: 22
Length: 23221
Individuals with no LoFs: 125536
Homozygous LoFs: 0
Heterozygous LoFs: 211
Defined: 125747
p: 0.000839

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.08	957	868	1.10	0.0000553	9282
Missense (PolyPhen)		215	234.03	0.9187		2746
Synonymous	-4.51	496	384	1.29	0.0000257	3158
Loss of Function	1.71	53	68.3	0.776	0.00000383	706

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0011	notable
Latino/Admixed American	0.0011	0.0011	notable
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.0016	0.0015	notable
Finnish	0.00014	0.000092	rare
European (Non-Finnish)	0.00076	0.00072	rare
South Asian	0.0012	0.0012	notable
Other	0.00072	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box. {ECO:0000269|PubMed:12621023, ECO:0000269|PubMed:9418884}.;

Recessive Scores

pRec: 0.0850

Intolerance Scores

LoFtool: 0.896
RVIS EVS: 0.32
RVIS percentile EVS: 72.76

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.853

Gene Damage Prediction

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