SP7

Sp7 transcription factor, the group of Zinc fingers C2H2-type|Sp transcription factors

Basic information

Region (hg38): 12:53326575-53345315

Links

ENSG00000170374 ∙ NCBI:121340 ∙ OMIM:606633 ∙ HGNC:17321 ∙ Uniprot:Q8TDD2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta type 12 (Strong), mode of inheritance: AR
• osteogenesis imperfecta type 4 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 12 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type XII	AR	General	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	Dental; Musculoskeletal	20579626

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SP7 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SP7 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	40	5	47
missense			62	3		65
nonsense			3			3
start loss			1			1
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding			2	4	5	11
Total	0	0	72	47	10

Variants in SP7

This is a list of pathogenic ClinVar variants found in the SP7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-53327732-TAAG-T		Osteogenesis Imperfecta, Recessive	Uncertain significance (Jun 14, 2016)
12-53328087-T-A			Likely benign (Jul 31, 2018)
12-53328138-C-CA		not specified	Uncertain significance (May 09, 2024)
12-53328142-C-T		not specified	Benign (Nov 25, 2015)
12-53328143-G-A		not specified	Uncertain significance (Jul 18, 2024)
12-53328170-C-T		Osteogenesis imperfecta type 12	Conflicting classifications of pathogenicity (Jan 18, 2024)
12-53328189-G-A		not specified	Uncertain significance (Feb 14, 2023)
12-53328221-T-C			Likely benign (Nov 28, 2023)
12-53328222-C-T			Uncertain significance (Nov 20, 2021)
12-53328228-G-A			Uncertain significance (Aug 19, 2022)
12-53328251-C-T			Likely benign (Jul 19, 2022)
12-53328258-C-T		Osteogenesis imperfecta	Conflicting classifications of pathogenicity (Nov 12, 2023)
12-53328259-G-A		not specified	Uncertain significance (Jul 21, 2022)
12-53328265-C-T		not specified	Uncertain significance (Jun 22, 2023)
12-53328272-C-A		not specified	Uncertain significance (Oct 03, 2022)
12-53328276-T-C			Uncertain significance (Nov 11, 2022)
12-53328294-G-A		not specified	Uncertain significance (Aug 10, 2023)
12-53328296-A-G			Likely benign (Jun 29, 2023)
12-53328300-G-A			Uncertain significance (Aug 28, 2021)
12-53328303-C-G			Uncertain significance (Jun 22, 2022)
12-53328313-C-T			Uncertain significance (Jun 29, 2022)
12-53328314-A-G		not specified • Osteogenesis imperfecta type 12	Benign (Jan 31, 2024)
12-53328322-G-A			Uncertain significance (Nov 01, 2022)
12-53328338-G-T			Uncertain significance (Oct 27, 2021)
12-53328341-G-A			Likely benign (Dec 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SP7	protein_coding	protein_coding	ENST00000536324	2	18738

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.583	0.415	125225	0	34	125259	0.000136

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.501	231	253	0.911	0.0000142	2739
Missense in Polyphen		59	76.361	0.77264		796
Synonymous	0.352	97	102	0.956	0.00000551	952
Loss of Function	2.56	2	11.3	0.177	5.34e-7	133

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000584	0.0000584
Ashkenazi Jewish	0.000795	0.000795
East Asian	0.0000559	0.0000551
Finnish	0.0000471	0.0000464
European (Non-Finnish)	0.000188	0.000185
Middle Eastern	0.0000559	0.0000551
South Asian	0.00	0.00
Other	0.000165	0.000164

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator essential for osteoblast differentiation (PubMed:23457570). Binds to SP1 and EKLF consensus sequences and to other G/C-rich sequences (By similarity). {ECO:0000250|UniProtKB:Q8VI67, ECO:0000269|PubMed:23457570}.
• Disease: DISEASE: Osteogenesis imperfecta 12 (OI12) [MIM:613849]: A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI12 is an autosomal recessive form characterized by recurrent fractures, mild bone deformations, generalized osteoporosis, delayed teeth eruption, no dentinogenesis imperfecta, normal hearing, and white sclerae. {ECO:0000269|PubMed:20579626}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Role of Osx and miRNAs in tooth development;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription (Consensus)

Recessive Scores

• pRec: 0.310

Intolerance Scores

• loftool: 0.433
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.24

Haploinsufficiency Scores

• pHI: 0.320
• hipred: Y
• hipred_score: 0.685
• ghis: 0.465

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.235

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sp7
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; respiratory system phenotype; skeleton phenotype; limbs/digits/tail phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype

Zebrafish Information Network

• Gene name: sp7
• Affected structure: osteoblast
• Phenotype tag: abnormal
• Phenotype quality: composition

Gene ontology

• Biological process: osteoblast differentiation;regulation of transcription by RNA polymerase II;positive regulation of transcription by RNA polymerase II;hematopoietic stem cell differentiation;positive regulation of stem cell differentiation
• Cellular component: nucleus;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DEAD/H-box RNA helicase binding;metal ion binding