SPICE1

Chr 3

spindle and centriole associated protein 1

Also known as: CCDC52, SPICE

NCBI Gene: 152185 ENSG00000163611 UniProt: Q8N0Z3 OMIM: 613447

The protein regulates centriole duplication and is required for proper bipolar spindle formation and chromosome congression during mitosis. Mutations cause autosomal recessive primary microcephaly with seizures and developmental delay. This gene is extremely intolerant to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

Involved in metaphase chromosome alignment; mitotic spindle assembly; and regulation of centriole replication. Located in intracellular membrane-bounded organelle; microtubule cytoskeleton; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.89

Clinical Summary— SPICE1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

131 VUS of 159 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.89LOEUF

pLI 0.000

Z-score 2.15

OE 0.66 (0.49–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.35Z-score

OE missense 0.95 (0.88–1.03)

439 obs / 460.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.49–0.89)

0≤0.351.4

Missense OE?0.95 (0.88–1.03)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 30 / 45.7Missense obs/exp: 439 / 460.0Syn Z: 0.60

This gene — mechanism propensity

0.6454th %ile

GOF

0.5856th %ile

LOF

0.4233th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

159 submitted variants in ClinVar

ClinVar

Classification Summary

VUS131

Likely Benign13

131

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	131	0	131
Likely Benign	11	2	13
Benign	0	0	0
Total	142	2	144

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

30 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap SPICE1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →