SF1

protein-coding

splicing factor 1, the group of Zinc fingers CCHC-type|Spliceosomal A complex|Spliceosomal E complex

Gene summary

This gene encodes a nuclear pre-mRNA splicing factor. The encoded protein specifically recognizes the intron branch point sequence at the 3' splice site, together with the large subunit of U2 auxiliary factor (U2AF), and is required for the early stages of spliceosome assembly. It also plays a role in nuclear pre-mRNA retention and transcriptional repression. The encoded protein contains an N-terminal U2AF ligand motif, a central hnRNP K homology motif and quaking 2 region which bind a key branch-site adenosine within the branch point sequence, a zinc knuckles domain, and a C-terminal proline-rich domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

Previous symbols:

ZNF162

MANE transcript

NM_004630.4

Inheritance

ClinVar variants

P:2U:62B:7

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr11:64,764,606-64,778,786

External References & Databases

Ensembl (ENSG00000168066)

Transcript & Mutation Effects

hg38 • Region Span ~14.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SF1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 89

not providedTotal: 13

Neurodevelopmental disorderTotal: 2

SF1-associated neurodevelopmental disorderTotal: 1

SF1-related neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004630.4. 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			1 clinvar	7 clinvar		8
missense			50 clinvar			50
nonsense			2 clinvar			2
start loss						0
frameshift		2 clinvar	3 clinvar			5
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	2	62	7	0	71

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004630.4	RefSeq	NP_004621.2	13	MANE Select
ENST00000377390.8	Ensembl	ENSP00000366607.3	13	MANE Select
NM_001178030.2	RefSeq	NP_001171501.1	13	Standard
NM_001178031.3	RefSeq	NP_001171502.1	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sf1	Danio rerio	Structure: anatomical system Quality: quality abnormal

Gene / Model

Organism

Observed Phenotype

sf1

Danio rerio

Structure: anatomical system

Quality: quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of RNA
mRNA Splicing - Major Pathway
AndrogenReceptor
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

spliceosomal complex assembly
mRNA 3'-splice site recognition
mRNA splicing, via spliceosome
male sex determination
nuclear body organization

Molecular Function

transcription corepressor activity
RNA binding
protein binding
zinc ion binding
identical protein binding

Cellular Component

nucleus
nucleoplasm
spliceosomal complex
ribosome
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377387
Coding exons: 13
Length: 14181
Individuals with no LoFs: 120659
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 120660
p: 0.00000414

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.62	151	338	0.446	0.0000202	4316
Missense (PolyPhen)		16	108.73	0.14716		1186
Synonymous	-2.27	152	120	1.26	0.00000716	1456
Loss of Function	4.54	1	25.9	0.0386	0.00000133	323

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000048	0.000048	rare
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Necessary for the ATP-dependent first step of spliceosome assembly. Binds to the intron branch point sequence (BPS) 5'-UACUAAC-3' of the pre-mRNA. May act as transcription repressor. {ECO:0000269|PubMed:10449420, ECO:0000269|PubMed:8752089, ECO:0000269|PubMed:9660765}.;

Recessive Scores

pRec: 0.0867

Intolerance Scores

LoFtool: 0.0225
RVIS EVS: -0.87
RVIS percentile EVS: 10.65

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

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