SPIRE2

spire type actin nucleation factor 2

Basic information

Region (hg38): 16:89818178-89871319

Links

ENSG00000204991 ∙ NCBI:84501 ∙ OMIM:609217 ∙ HGNC:30623 ∙ Uniprot:Q8WWL2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPIRE2 gene.

• Inborn genetic diseases (55 variants)
• Fanconi anemia (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPIRE2 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				1		1
missense			52	3		55
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	53	4	0

Variants in SPIRE2

This is a list of pathogenic ClinVar variants found in the SPIRE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-89828570-G-C		not specified	Uncertain significance (Dec 17, 2023)
16-89828591-C-A		not specified	Uncertain significance (May 03, 2023)
16-89828618-C-G		not specified	Uncertain significance (Dec 06, 2021)
16-89828642-A-T		not specified	Uncertain significance (May 17, 2023)
16-89828663-A-G		not specified	Uncertain significance (May 03, 2023)
16-89828677-G-A		not specified	Uncertain significance (Aug 02, 2022)
16-89828737-G-T		not specified	Uncertain significance (Jul 11, 2022)
16-89839795-C-G		Fanconi anemia	Uncertain significance (-)
16-89845325-C-T		not specified	Uncertain significance (Oct 03, 2022)
16-89845339-G-A		not specified	Uncertain significance (Nov 10, 2022)
16-89850325-G-A		not specified	Uncertain significance (Nov 22, 2022)
16-89850366-G-C		not specified	Uncertain significance (May 17, 2023)
16-89850382-C-T		not specified	Uncertain significance (Jan 31, 2024)
16-89850383-C-T		not specified	Uncertain significance (Sep 22, 2023)
16-89850417-C-A		not specified	Uncertain significance (Jun 09, 2022)
16-89850428-A-G		not specified	Uncertain significance (Nov 14, 2023)
16-89850451-G-A		not specified	Uncertain significance (Oct 12, 2021)
16-89850461-A-G		not specified	Uncertain significance (Mar 29, 2023)
16-89850463-G-C		not specified	Uncertain significance (Sep 06, 2022)
16-89850475-G-A		not specified	Uncertain significance (Jun 11, 2021)
16-89850487-G-A		not specified	Uncertain significance (Dec 06, 2022)
16-89850500-C-A		not specified	Uncertain significance (Jul 19, 2023)
16-89850626-G-A		not specified	Uncertain significance (Aug 12, 2021)
16-89850640-A-G		not specified	Uncertain significance (May 18, 2023)
16-89850646-C-T		not specified	Uncertain significance (Nov 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPIRE2	protein_coding	protein_coding	ENST00000378247	15	53141

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.44e-9	0.973	125646	0	102	125748	0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.259	448	433	1.03	0.0000302	4514
Missense in Polyphen		197	199.73	0.98635		2003
Synonymous	-1.58	215	187	1.15	0.0000136	1476
Loss of Function	2.18	19	32.4	0.587	0.00000169	374

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000491	0.000486
Ashkenazi Jewish	0.000201	0.000198
East Asian	0.000989	0.000816
Finnish	0.000634	0.000416
European (Non-Finnish)	0.000458	0.000448
Middle Eastern	0.000989	0.000816
South Asian	0.000296	0.000294
Other	0.000845	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as an actin nucleation factor, remains associated with the slow-growing pointed end of the new filament (PubMed:21620703). Involved in intracellular vesicle transport along actin fibers, providing a novel link between actin cytoskeleton dynamics and intracellular transport (By similarity). Required for asymmetric spindle positioning and asymmetric cell division during meiosis (PubMed:21620703). Required for normal formation of the cleavage furrow and for polar body extrusion during female germ cell meiosis (PubMed:21620703). Also acts in the nucleus: together with SPIRE1 and SPIRE2, promotes assembly of nuclear actin filaments in response to DNA damage in order to facilitate movement of chromatin and repair factors after DNA damage (PubMed:26287480). {ECO:0000250|UniProtKB:Q8K1S6, ECO:0000269|PubMed:21620703, ECO:0000269|PubMed:26287480}.

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.735
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.78

Haploinsufficiency Scores

• pHI: 0.143
• hipred: N
• hipred_score: 0.197
• ghis: 0.570

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.684

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spire2

Gene ontology

• Biological process: protein transport;vesicle-mediated transport;actin cytoskeleton organization;cleavage furrow formation;polar body extrusion after meiotic divisions;actin nucleation;intracellular transport;establishment of meiotic spindle localization;formin-nucleated actin cable assembly;positive regulation of double-strand break repair
• Cellular component: cytosol;cytoskeleton;cell cortex;cytoplasmic vesicle membrane;cleavage furrow
• Molecular function: actin binding