SP6

protein-coding

Sp6 transcription factor, the group of Sp transcription factors|Zinc fingers C2H2-type

Gene summary

SP6 belongs to a family of transcription factors that contain 3 classical zinc finger DNA-binding domains consisting of a zinc atom tetrahedrally coordinated by 2 cysteines and 2 histidines (C2H2 motif). These transcription factors bind to GC-rich sequences and related GT and CACCC boxes (Scohy et al., 2000 [PubMed 11087666]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_001258248.2

Inheritance

ClinVar variants

P:2U:53B:1

Top phenotype

Amelogenesis imperfecta, type IK

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr17:47,844,908-47,855,874

External References & Databases

Ensembl (ENSG00000189120)

Transcript & Mutation Effects

hg38 • Region Span ~11.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

amelogenesis imperfecta, IIa 1KSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0031084

Submitter: Labcorp Genetics (formerly Invitae)

amelogenesis imperfecta, IIa 1KSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0031084

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Amelogenesis imperfecta, type IKAD

Manifestation: Dental

Intervention: General

Rationale: 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

Refs: 32167558; 33652941

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SP6 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 52

Amelogenesis imperfecta, IIa 1KTotal: 2

not providedTotal: 1

SP6-related conditionTotal: 1

Amelogenesis imperfectaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001258248.2. 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						0
missense	2 clinvar		53 clinvar		1 clinvar	56
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	2	0	53	0	1	56

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001258248.2	RefSeq	NP_001245177.1	1	MANE Select
ENST00000536300.2	Ensembl	ENSP00000438209.1	1	MANE Select
NM_199262.3	RefSeq	NP_954871.1	1	Standard
ENST00000342234.3	Ensembl	ENSP00000340799.2	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
regulation of odontogenesis

Molecular Function

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

Cellular Component

nucleus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000536300
Coding exons: 1
Length: 10962
Individuals with no LoFs: 125557
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125565
p: 0.0000319

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.34	169	226	0.748	0.0000127	2364
Missense (PolyPhen)		45	69.89	0.64387		685
Synonymous	0.827	98	109	0.899	0.00000675	801
Loss of Function	2.09	3	10.2	0.295	4.78e-7	105

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Promotes cell proliferation. {ECO:0000250}.;

Recessive Scores

pRec: 0.110

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.210

Gene Damage Prediction

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