SPIRE2

protein-coding

spire type actin nucleation factor 2

Gene summary

Predicted to enable microtubule binding activity. Involved in establishment of meiotic spindle localization; formin-nucleated actin cable assembly; and positive regulation of double-strand break repair. Predicted to be located in cleavage furrow. Predicted to be active in cell cortex and cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_032451.2

Inheritance

—

ClinVar variants

U:184B:6

Top phenotype

Fanconi anemia

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr16:89,818,179-89,871,319

External References & Databases

Ensembl (ENSG00000204991)

Transcript & Mutation Effects

hg38 • Region Span ~53.1 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 SPIRE2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 177

not providedTotal: 1

Fanconi anemiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032451.2. 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				1 clinvar		1
missense			174 clinvar	5 clinvar		179
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	184	6	0	190

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032451.2	RefSeq	NP_115827.1	15	MANE Select
ENST00000378247.8	Ensembl	ENSP00000367494.3	15	MANE Select
ENST00000393062.6	Ensembl	ENSP00000376782.2	13	Standard
ENST00000393062.7	Ensembl	ENSP00000376782.2	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein transport
vesicle-mediated transport
actin cytoskeleton organization
cleavage furrow formation
polar body extrusion after meiotic divisions

Molecular Function

actin binding

Cellular Component

cytosol
cytoskeleton
cell cortex
cytoplasmic vesicle membrane
cleavage furrow

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000378247
Coding exons: 15
Length: 53141
Individuals with no LoFs: 125646
Homozygous LoFs: 0
Heterozygous LoFs: 102
Defined: 125748
p: 0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.259	448	433	1.03	0.0000302	4514
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00099	0.00082	rare
Finnish	0.00063	0.00042	rare
European (Non-Finnish)	0.00046	0.00045	rare
South Asian	0.00030	0.00029	rare
Other	0.00084	0.00081	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.684

Gene Damage Prediction

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