NUMA1
nuclear mitotic apparatus protein 1, the group of MicroRNA protein coding host genes
Basic information
Region (hg38): 11:72002864-72080693
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (261 variants)
- not_provided (35 variants)
- NUMA1-related_disorder (22 variants)
- Autosomal_recessive_nonsyndromic_hearing_loss_63 (4 variants)
- Acute_promyelocytic_leukemia (2 variants)
- Myoepithelial_tumor (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NUMA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006185.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 18 | 21 | ||||
| missense | 250 | 24 | 10 | 285 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 1 | 0 | 250 | 42 | 13 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NUMA1 | protein_coding | protein_coding | ENST00000393695 | 25 | 77830 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 5.25e-7 | 125716 | 0 | 32 | 125748 | 0.000127 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.881 | 1119 | 1.21e+3 | 0.929 | 0.0000785 | 13647 |
| Missense in Polyphen | 396 | 457.56 | 0.86546 | 5283 | ||
| Synonymous | 0.141 | 481 | 485 | 0.992 | 0.0000267 | 4279 |
| Loss of Function | 8.21 | 15 | 106 | 0.141 | 0.00000571 | 1142 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000262 | 0.000262 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000218 | 0.000217 |
| Finnish | 0.000140 | 0.000139 |
| European (Non-Finnish) | 0.000115 | 0.000114 |
| Middle Eastern | 0.000218 | 0.000217 |
| South Asian | 0.0000654 | 0.0000653 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Microtubule (MT)-binding protein that plays a role in the formation and maintenance of the spindle poles and the alignement and the segregation of chromosomes during mitotic cell division (PubMed:7769006, PubMed:17172455, PubMed:19255246, PubMed:24996901, PubMed:26195665, PubMed:27462074). Functions to tether the minus ends of MTs at the spindle poles, which is critical for the establishment and maintenance of the spindle poles (PubMed:12445386, PubMed:11956313). Plays a role in the establishment of the mitotic spindle orientation during metaphase and elongation during anaphase in a dynein-dynactin-dependent manner (PubMed:23870127, PubMed:24109598, PubMed:24996901, PubMed:26765568). In metaphase, part of a ternary complex composed of GPSM2 and G(i) alpha proteins, that regulates the recruitment and anchorage of the dynein-dynactin complex in the mitotic cell cortex regions situated above the two spindle poles, and hence regulates the correct oritentation of the mitotic spindle (PubMed:23027904, PubMed:22327364, PubMed:23921553). During anaphase, mediates the recruitment and accumulation of the dynein- dynactin complex at the cell membrane of the polar cortical region through direct association with phosphatidylinositol 4,5- bisphosphate (PI(4,5)P2), and hence participates in the regulation of the spindle elongation and chromosome segregation (PubMed:22327364, PubMed:23921553, PubMed:24996901, PubMed:24371089). Binds also to other polyanionic phosphoinositides, such as phosphatidylinositol 3-phosphate (PIP), lysophosphatidic acid (LPA) and phosphatidylinositol triphosphate (PIP3), in vitro (PubMed:24996901, PubMed:24371089). Also required for proper orientation of the mitotic spindle during asymmetric cell divisions (PubMed:21816348). Plays a role in mitotic MT aster assembly (PubMed:11163243, PubMed:11229403, PubMed:12445386). Involved in anastral spindle assembly (PubMed:25657325). Positively regulates TNKS protein localization to spindle poles in mitosis (PubMed:16076287). Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume (PubMed:10075938). Required for epidermal differentiation and hair follicle morphogenesis (By similarity). {ECO:0000250|UniProtKB:E9Q7G0, ECO:0000269|PubMed:11163243, ECO:0000269|PubMed:11229403, ECO:0000269|PubMed:11956313, ECO:0000269|PubMed:12445386, ECO:0000269|PubMed:16076287, ECO:0000269|PubMed:17172455, ECO:0000269|PubMed:19255246, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:23027904, ECO:0000269|PubMed:23870127, ECO:0000269|PubMed:23921553, ECO:0000269|PubMed:24109598, ECO:0000269|PubMed:24371089, ECO:0000269|PubMed:24996901, ECO:0000269|PubMed:25657325, ECO:0000269|PubMed:26195665, ECO:0000269|PubMed:26765568, ECO:0000269|PubMed:27462074, ECO:0000269|PubMed:7769006, ECO:0000305|PubMed:10075938, ECO:0000305|PubMed:21816348}.;
- Pathway
- Ectoderm Differentiation;role of ran in mitotic spindle regulation;hiv-1 nef: negative effector of fas and tnf;Mitotic Prophase;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Caspase Cascade in Apoptosis
(Consensus)
Recessive Scores
- pRec
- 0.254
Intolerance Scores
- loftool
- 0.402
- rvis_EVS
- -0.55
- rvis_percentile_EVS
- 19.97
Haploinsufficiency Scores
- pHI
- 0.0873
- hipred
- Y
- hipred_score
- 0.520
- ghis
- 0.573
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.667
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Numa1
- Phenotype
- cellular 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);
Zebrafish Information Network
- Gene name
- numa1
- Affected structure
- establishment of spindle orientation
- Phenotype tag
- abnormal
- Phenotype quality
- process quality
Gene ontology
- Biological process
- establishment of mitotic spindle orientation;microtubule bundle formation;nucleus organization;chromosome segregation;positive regulation of BMP signaling pathway;astral microtubule organization;positive regulation of microtubule polymerization;positive regulation of intracellular transport;positive regulation of keratinocyte differentiation;cell division;meiotic cell cycle;positive regulation of hair follicle development;positive regulation of chromosome segregation;anastral spindle assembly;regulation of mitotic spindle organization;regulation of metaphase plate congression;positive regulation of protein localization to spindle pole body;positive regulation of mitotic spindle elongation;positive regulation of protein localization to cell cortex;positive regulation of chromosome separation;positive regulation of spindle assembly
- Cellular component
- Golgi membrane;spindle pole;nucleus;nucleoplasm;chromosome;cytoplasm;centrosome;spindle;cytosol;spindle microtubule;cell cortex;lateral plasma membrane;nuclear matrix;extrinsic component of plasma membrane;dendrite;spindle pole centrosome;protein-containing complex;microtubule plus-end;microtubule minus-end;neuronal cell body;cortical microtubule;mitotic spindle astral microtubule;extracellular exosome;mitotic spindle;microtubule bundle;mitotic spindle pole;lateral cell cortex;cell cortex region;cytoplasmic microtubule bundle;mitotic spindle midzone
- Molecular function
- structural molecule activity;protein binding;microtubule binding;protein C-terminus binding;tubulin binding;protein domain specific binding;phosphatidylinositol binding;protein-containing complex binding;microtubule plus-end binding;microtubule minus-end binding;dynein complex binding;disordered domain specific binding