GeneBe

NUMA1

protein-coding

nuclear mitotic apparatus protein 1, the group of MicroRNA protein coding host genes

Gene summary

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]

MANE transcript

NM_006185.4

Inheritance

—

ClinVar variants

P:1U:314B:60

Top phenotype

NUMA1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr11:72,002,864-72,080,693

External References & Databases

Ensembl (ENSG00000137497)NCBI Gene (4926)OMIM (164009)HGNC:8059GenCCUniProt (Q14980)AlphaFoldClinVar (NUMA1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~77.8 kb
Loading mutation effect viewer...

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 NUMA1 variants in ClinVar

6 Conditions Cataloged
not specifiedTotal: 295
not providedTotal: 42
NUMA1-related disorderTotal: 23
Autosomal recessive nonsyndromic hearing loss 63Total: 4
Acute promyelocytic leukemiaTotal: 2
Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006185.4. 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.

EffectPLPVUSLBBSum
synonymous
5
clinvar
18
clinvar
3
clinvar
 26
missense
1
clinvar
288
clinvar
29
clinvar
10
clinvar
 328
nonsense
3
clinvar
 3
start loss
0
frameshift
4
clinvar
 4
splice donor/acceptor (+/-2bp)
14
clinvar
 14
Total103144713375
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 121 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006185.4RefSeqNP_006176.225MANE Select
ENST00000393695.8EnsemblENSP00000377298.425MANE Select
NM_001286561.2RefSeqNP_001273490.124Standard
ENST00000351960.10EnsemblENSP00000260051.823Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
numa1Danio rerio

Structure: establishment of spindle orientation

Quality: process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • establishment of mitotic spindle orientation
  • microtubule bundle formation
  • nucleus organization
  • chromosome segregation
  • positive regulation of BMP signaling pathway

Molecular Function

  • structural molecule activity
  • protein binding
  • microtubule binding
  • protein C-terminus binding
  • tubulin binding

Cellular Component

  • Golgi membrane
  • spindle pole
  • nucleus
  • nucleoplasm
  • chromosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000393695
Coding exons
25
Length
77830
Individuals with no LoFs
125716
Homozygous LoFs
0
Heterozygous LoFs
32
Defined
125748
p
0.000127
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.88111191.21e+30.9290.000078513647
Missense (PolyPhen)396457.560.865465283
Synonymous0.1414814850.9920.00002674279
Loss of Function8.21151060.1410.000005711142

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000260.00026rare
Ashkenazi Jewish00.0absent
East Asian0.000220.00022rare
Finnish0.000140.00014rare
European (Non-Finnish)0.000110.00011rare
South Asian0.0000650.000065rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

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}.;

Recessive Scores

pRec
0.254

Intolerance Scores

LoFtool
0.402
RVIS EVS
-0.55
RVIS percentile EVS
19.97

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
E
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.667

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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