SP4

protein-coding

Sp4 transcription factor, the group of Sp transcription factors|Zinc fingers C2H2-type|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene is a transcription factor that can bind to the GC promoter region of a variety of genes, including those of the photoreceptor signal transduction system. The encoded protein binds to the same sites in promoter CpG islands as does the transcription factor SP1, although its expression is much more restricted compared to that of SP1. This gene may be involved in bipolar disorder and schizophrenia. [provided by RefSeq, May 2016]

MANE transcript

NM_003112.5

Inheritance

—

ClinVar variants

U:123B:3

Top phenotype

Cognitive regression

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr7:21,428,043-21,514,822

External References & Databases

Ensembl (ENSG00000105866)

Transcript & Mutation Effects

hg38 • Region Span ~86.8 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 SP4 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 110

not providedTotal: 6

Cognitive regressionTotal: 1

SP4-related disorderTotal: 1

DyslexiaTotal: 1

Attention deficit hyperactivity disorderTotal: 1

SeizureTotal: 1

Monoclonal B-Cell LymphocytosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003112.5. 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			3 clinvar			3
missense			114 clinvar	2 clinvar	1 clinvar	117
nonsense			1 clinvar			1
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	123	2	1	126

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003112.5	RefSeq	NP_003103.2	6	MANE Select
ENST00000222584.8	Ensembl	ENSP00000222584.3	6	MANE Select
NM_001326542.2	RefSeq	NP_001313471.1	5	Standard
NM_001326543.2	RefSeq	NP_001313472.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
positive regulation of nucleic acid-templated transcription

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
transcription coactivator activity
protein binding
sequence-specific DNA binding
metal ion binding

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000222584
Coding exons: 6
Length: 86789
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.395	386	408	0.945	0.0000200	5058
Missense (PolyPhen)		85	137.87	0.61653		1754
Synonymous	-0.738	164	152	1.08	0.00000826	1661
Loss of Function	4.62	4	32.4	0.123	0.00000157	336

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to GT and GC boxes promoters elements. Probable transcriptional activator.;

Recessive Scores

pRec: 0.231

Intolerance Scores

LoFtool: 0.378
RVIS EVS: -0.84
RVIS percentile EVS: 11.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.967

Gene Damage Prediction

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