NUMA1

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

Basic information

Region (hg38): 11:72002863-72080693

Links

ENSG00000137497 ∙ NCBI:4926 ∙ OMIM:164009 ∙ HGNC:8059 ∙ Uniprot:Q14980 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NUMA1 gene.

• Inborn genetic diseases (88 variants)
• not provided (27 variants)
• Autosomal recessive nonsyndromic hearing loss 63 (8 variants)
• Acute promyelocytic leukemia (2 variants)
• NUMA1-related condition (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	3	8
missense			88	8	10	106
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			6	1		7
Total	0	0	94	14	13

Variants in NUMA1

This is a list of pathogenic ClinVar variants found in the NUMA1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-72003944-G-A		NUMA1-related disorder	Likely benign (Apr 04, 2019)
11-72003967-G-A		not specified	Uncertain significance (Mar 14, 2023)
11-72003981-C-T		not specified	Uncertain significance (May 18, 2023)
11-72004029-C-T		not specified	Uncertain significance (Sep 27, 2022)
11-72004092-C-T		not specified	Uncertain significance (Jul 14, 2021)
11-72004093-G-A		not specified	Uncertain significance (Jan 10, 2023)
11-72004647-G-A		not specified	Uncertain significance (Oct 06, 2021)
11-72004680-C-T		not specified	Uncertain significance (May 01, 2022)
11-72004687-G-A			Likely benign (Aug 28, 2018)
11-72004706-G-T		NUMA1-related disorder	Likely benign (Mar 26, 2019)
11-72004715-C-G		not specified	Uncertain significance (Jul 06, 2021)
11-72004750-G-A		not specified	Uncertain significance (Jun 30, 2022)
11-72005249-T-C		not specified	Uncertain significance (Apr 07, 2022)
11-72005307-G-A		not specified	Uncertain significance (Mar 28, 2023)
11-72005334-C-T		not specified	Uncertain significance (Dec 21, 2022)
11-72006045-C-T			Likely benign (May 22, 2018)
11-72006063-C-G		not specified	Uncertain significance (Oct 25, 2022)
11-72006074-G-A		not specified	Uncertain significance (Nov 10, 2022)
11-72006137-C-T		not specified	Uncertain significance (Aug 11, 2021)
11-72006217-C-G		not specified	Uncertain significance (Mar 29, 2023)
11-72006221-A-G			Likely benign (Apr 01, 2023)
11-72006247-T-A		not specified	Uncertain significance (Nov 03, 2023)
11-72006254-C-T		NUMA1-related disorder	Benign (Jul 30, 2019)
11-72006255-A-T		not specified	Uncertain significance (Oct 12, 2021)
11-72007223-C-T		not specified	Uncertain significance (Jun 22, 2023)

GnomAD

Source: gnomAD

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: 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}.
• 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