SP3

protein-coding

Sp3 transcription factor, the group of Zinc fingers C2H2-type|Sp transcription factors

Gene summary

This gene belongs to a family of Sp1 related genes that encode transcription factors that regulate transcription by binding to consensus GC- and GT-box regulatory elements in target genes. This protein contains a zinc finger DNA-binding domain and several transactivation domains, and has been reported to function as a bifunctional transcription factor that either stimulates or represses the transcription of numerous genes. Transcript variants encoding different isoforms have been described for this gene, and one has been reported to initiate translation from a non-AUG (AUA) start codon. Additional isoforms, resulting from the use of alternate downstream translation initiation sites, have also been noted. A related pseudogene has been identified on chromosome 13. [provided by RefSeq, Feb 2010]

MANE transcript

NM_003111.5

Inheritance

—

ClinVar variants

U:104B:4

Top phenotype

See cases

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr2:173,880,850-173,965,373

External References & Databases

Ensembl (ENSG00000172845)

Transcript & Mutation Effects

hg38 • Region Span ~84.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SP3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 96

not providedTotal: 3

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003111.5. 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			1 clinvar		3 clinvar	4
missense			99 clinvar	1 clinvar		100
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	104	1	3	108

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003111.5	RefSeq	NP_003102.1	7	MANE Select
ENST00000310015.12	Ensembl	ENSP00000310301.6	7	MANE Select
NM_001017371.5	RefSeq	NP_001017371.3	5	Standard
NM_001172712.1	RefSeq	NP_001166183.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Selenium Metabolism and Selenoproteins
MECP2 and Associated Rett Syndrome
Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways
overview of telomerase rna component gene hterc transcriptional regulation
effects of calcineurin in keratinocyte differentiation

Biological Process

negative regulation of transcription by RNA polymerase II
ossification
natural killer cell differentiation
trophectodermal cell differentiation
liver development

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
proximal promoter sequence-specific DNA binding
DNA-binding transcription repressor activity, RNA polymerase II-specific

Cellular Component

nucleus
nucleoplasm
PML body
transcriptional repressor complex
protein-DNA complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310015
Coding exons: 7
Length: 59244
Individuals with no LoFs: 125729
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125731
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.63	309	401	0.771	0.0000199	5033
Missense (PolyPhen)		80	145.7	0.54906		1900
Synonymous	-2.82	192	148	1.29	0.00000781	1618
Loss of Function	5.11	1	32.4	0.0308	0.00000164	351

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	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000096	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional factor that can act as an activator or repressor depending on isoform and/or post-translational modifications. Binds to GT and GC boxes promoter elements. Competes with SP1 for the GC-box promoters. Weak activator of transcription but can activate a number of genes involved in different processes such as cell-cycle regulation, hormone- induction and house-keeping. {ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11812829, ECO:0000269|PubMed:12419227, ECO:0000269|PubMed:12837748, ECO:0000269|PubMed:15247228, ECO:0000269|PubMed:15494207, ECO:0000269|PubMed:15554904, ECO:0000269|PubMed:16781829, ECO:0000269|PubMed:17548428, ECO:0000269|PubMed:18187045, ECO:0000269|PubMed:18617891, ECO:0000269|PubMed:9278495}.;

Recessive Scores

pRec: 0.191

Intolerance Scores

LoFtool: 0.122
RVIS EVS: -0.07
RVIS percentile EVS: 48.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: N
Indispensability score: 0.339

Gene Damage Prediction

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