NUMA1

Chr 11

nuclear mitotic apparatus protein 1

Also known as: NMP-22, NUMA

NCBI Gene: 4926ENSG00000137497UniProt: Q14980

This gene encodes a large protein that forms a structural component of the nuclear matrix. The encoded protein interacts with microtubules and plays a role in the formation and organization of the mitotic spindle during cell division. Chromosomal translocation of this gene with the RARA (retinoic acid receptor, alpha) gene on chromosome 17 have been detected in patients with acute promyelocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

400
ClinVar variants
9
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— NUMA1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 291 VUS of 400 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.22LOEUF
pLI 1.000
Z-score 8.21
OE 0.14 (0.09–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.88Z-score
OE missense 0.93 (0.88–0.98)
1119 obs / 1205.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.14 (0.09–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.88–0.98)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 15 / 106.4Missense obs/exp: 1119 / 1205.1Syn Z: 0.14

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
VUS291
Likely Benign46
Benign13
Conflicting3
9
Pathogenic
291
VUS
46
Likely Benign
13
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
8
0
9
Likely Pathogenic
0
0
0
0
0
VUS
0
279
12
0
291
Likely Benign
0
25
3
18
46
Benign
0
10
0
3
13
Conflicting
—3
Total03152321362

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

View in ClinVar →

Protein Context — Lollipop Plot

NUMA1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Anti-NuMA1 and anti-NuMA2 (anti-HsEg5) antibodies: Clinical and immunological features: A propos of 40 new cases and review of the literature.
Szalat R et al.·Autoimmun Rev
2010Review
Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations.
Klubíčková N et al.·J Pathol
2024
Recurrence in Patients With Lymph Node-Negative Pancreatic Neuroendocrine Tumors.
Ventin M et al.·JAMA Surg
2026Cohort
A genome-wide enrichment screen identifies NUMA1-loss as a resistance mechanism against mitotic cell-death induced by BMI1 inhibition.
Gisler S et al.·PLoS One
2020Functional
Calcium-channel blockers: Clinical outcome associations with reported pharmacogenetics variants in 32 000 patients.
Türkmen D et al.·Br J Clin Pharmacol
2023Cohort
Anti-NuMA antibodies: clinical associations and significance in patients with primary Sjögren's syndrome or systemic lupus erythematosus.
Arcani R et al.·Rheumatology (Oxford)
2021Cohort
Potential-resolved electrochemiluminescence for simultaneous determination of multiplex bladder cancer markers.
Wang J et al.·Chem Commun (Camb)
2024
A common coding variant in CASP8 is associated with breast cancer risk.
Cox A et al.·Nat Genet
2007
Two major autoantigen-antibody systems of the mitotic spindle apparatus.
Andrade LE et al.·Arthritis Rheum
1996
Targeted next-generation sequencing for molecular diagnosis of endometriosis-associated ovarian cancer.
Er TK et al.·J Mol Med (Berl)
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools