SP8

protein-coding

Sp8 transcription factor, the group of Zinc fingers C2H2-type|Sp transcription factors

Gene summary

The protein encoded by this gene is an SP family transcription factor that in mouse has been shown to be essential for proper limb development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

MANE transcript

NM_182700.6

Inheritance

—

ClinVar variants

U:71B:29

Top phenotype

SP8-related disorder

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr7:20,782,279-20,786,886

External References & Databases

Ensembl (ENSG00000164651)

Transcript & Mutation Effects

hg38 • Region Span ~4.6 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 SP8 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 66

SP8-related disorderTotal: 33

not providedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182700.6. 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				23 clinvar	4 clinvar	27
missense			69 clinvar	1 clinvar	1 clinvar	71
nonsense						0
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	0	0	71	24	5	100

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182700.6	RefSeq	NP_874359.2	2	MANE Select
ENST00000418710.3	Ensembl	ENSP00000408792.2	2	MANE Select
NM_198956.4	RefSeq	NP_945194.1	1	Standard
ENST00000361443.4	Ensembl	ENSP00000354482.4	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
dorsal/ventral pattern formation
proximal/distal pattern formation
embryonic limb morphogenesis

Molecular Function

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

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000418710
Coding exons: 2
Length: 2600
Individuals with no LoFs: 124744
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124747
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.69	171	245	0.697	0.0000115	3180
Missense (PolyPhen)		31	81.46	0.38056		971
Synonymous	-1.47	130	110	1.18	0.00000565	1124
Loss of Function	3.00	0	10.5	0.00	4.52e-7	124

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	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor which plays a key role in limb development. Positively regulates FGF8 expression in the apical ectodermal ridge (AER) and contributes to limb outgrowth in embryos (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.155

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.822

Gene Damage Prediction

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