SPOP

speckle type BTB/POZ protein, the group of BTB domain containing

Basic information

Region (hg38): 17:49598883-49678163

Links

ENSG00000121067 ∙ NCBI:8405 ∙ OMIM:602650 ∙ HGNC:11254 ∙ Uniprot:O43791 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with microcephaly and dysmorphic facies (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with microcephaly and dysmorphic facies (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with microcephaly and dysmorphic facies (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nabais Sa-de Vries syndrome type 2 (Neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies)	AD	Cardiovascular; Endocrine	The condition can include structural cardiovascular anomalies, and awareness may allow early detection and management; Endocrine abnormalities, including hypothyroidism, have been described, and awareness may allow early detection and management	Cardiovascular; Craniofacial; Endocrine; Neurologic; Ophthalmologic	32109420

ClinVar

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

• not provided (18 variants)
• Neurodevelopmental disorder with microcephaly and dysmorphic facies (7 variants)
• Neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies (6 variants)
• Malignant tumor of prostate (3 variants)
• Inborn genetic diseases (3 variants)
• SPOP-related condition (2 variants)
• not specified (1 variants)
• Nabais Sa-de Vries syndrome (1 variants)
• SPOP-related neurodevelopmental condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPOP 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		2
missense	2	11	7	1		21
nonsense			3	1		4
start loss						0
frameshift		1	1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding					1	1
Total	2	12	13	4	1

Variants in SPOP

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

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

Position	Type	Phenotype	Significance	ClinVar
17-49600402-T-G			Likely benign (Apr 01, 2024)
17-49600402-TG-T		Neurodevelopmental disorder with microcephaly and dysmorphic facies	Uncertain significance (Apr 12, 2024)
17-49600408-TC-T		Neurodevelopmental disorder with microcephaly and dysmorphic facies	Uncertain significance (Aug 12, 2022)
17-49600482-T-C		Neurodevelopmental disorder with microcephaly and dysmorphic facies	Uncertain significance (Mar 07, 2021)
17-49600488-T-A		Neurodevelopmental disorder with microcephaly and dysmorphic facies	Likely benign (Jan 18, 2022)
17-49600503-C-A			Uncertain significance (Dec 28, 2022)
17-49601899-G-A			Uncertain significance (May 15, 2023)
17-49601942-G-A			Likely benign (Feb 01, 2023)
17-49601950-C-T		Inborn genetic diseases	Likely benign (Oct 25, 2022)
17-49601958-T-A			Uncertain significance (Jun 01, 2014)
17-49607303-TCCC-T		SPOP-related disorder	Uncertain significance (Sep 23, 2022)
17-49607308-G-A		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
17-49611316-C-T			Likely pathogenic (Jul 25, 2023)
17-49611356-C-A			Uncertain significance (Dec 29, 2022)
17-49611373-C-A		not specified	Uncertain significance (Mar 28, 2022)
17-49611390-T-G			Uncertain significance (Jun 16, 2021)
17-49617910-C-A		Malignant tumor of prostate	Uncertain significance (-)
17-49617916-T-C		Malignant tumor of prostate	Uncertain significance (-)
17-49617922-T-C		Malignant tumor of prostate	Uncertain significance (-)
17-49618930-A-C		Malignant tumor of prostate	Uncertain significance (-)
17-49618942-T-A		Malignant tumor of prostate	Uncertain significance (-)
17-49618943-C-T		Malignant tumor of prostate	Uncertain significance (-)
17-49618953-C-G		Malignant tumor of prostate	Uncertain significance (-)
17-49618964-A-C		Malignant tumor of prostate	Uncertain significance (-)
17-49618976-C-A		Malignant tumor of prostate	Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPOP	protein_coding	protein_coding	ENST00000393331	9	79351

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000783	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.14	46	218	0.211	0.0000124	2474
Missense in Polyphen		7	80.132	0.087356		967
Synonymous	-0.770	89	80.2	1.11	0.00000458	695
Loss of Function	4.21	0	20.7	0.00	0.00000102	248

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation. In complex with CUL3, involved in ubiquitination and proteasomal degradation of BRMS1, DAXX, PDX1/IPF1, GLI2 and GLI3. In complex with CUL3, involved in ubiquitination of H2AFY and BMI1; this does not lead to their proteasomal degradation. Inhibits transcriptional activation of PDX1/IPF1 targets, such as insulin, by promoting PDX1/IPF1 degradation. The cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOP has higher ubiquitin ligase activity than the complex that contains the heterodimer formed by SPOP and SPOPL. {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:19818708, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22632832}.
• Pathway: Hedgehog signaling pathway - Homo sapiens (human);HH-Ncore;mRNA Processing;Hedgehog Signaling Pathway;Signal Transduction;Hedgehog ,on, state;Signaling by Hedgehog;Hedgehog signaling events mediated by Gli proteins (Consensus)

Recessive Scores

• pRec: 0.186

Intolerance Scores

• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.68

Haploinsufficiency Scores

• pHI: 0.219
• hipred: Y
• hipred_score: 0.682
• ghis: 0.628

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spop
• Phenotype: limbs/digits/tail phenotype; skeleton phenotype; immune system phenotype; embryo 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: spop
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: ubiquitin-dependent protein catabolic process;protein ubiquitination;regulation of proteolysis;proteasome-mediated ubiquitin-dependent protein catabolic process
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear speck;Cul3-RING ubiquitin ligase complex
• Molecular function: protein binding;ubiquitin protein ligase binding