NUMB

NUMB endocytic adaptor protein

Basic information

Region (hg38): 14:73275106-73458617

Previous symbols: [ "C14orf41" ]

Links

ENSG00000133961 ∙ NCBI:8650 ∙ OMIM:603728 ∙ HGNC:8060 ∙ Uniprot:P49757 ∙ 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 NUMB gene.

• Inborn genetic diseases (16 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NUMB 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				1	3	4
missense			16			16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	1	3

Variants in NUMB

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

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

Position	Type	Phenotype	Significance	ClinVar
14-73276596-C-T			Likely benign (Jul 01, 2022)
14-73276646-G-A		not specified	Uncertain significance (Apr 25, 2023)
14-73276659-A-G			Benign (Feb 25, 2018)
14-73276696-A-C		not specified	Uncertain significance (Feb 15, 2023)
14-73276897-T-C		not specified	Uncertain significance (Jan 04, 2022)
14-73276922-C-T		not specified	Uncertain significance (Jan 10, 2023)
14-73277007-C-G		not specified	Uncertain significance (Jun 21, 2021)
14-73277093-G-A		not specified	Uncertain significance (Nov 10, 2022)
14-73277135-G-A		not specified	Uncertain significance (Sep 27, 2021)
14-73277156-C-G		not specified	Uncertain significance (Nov 09, 2021)
14-73277195-C-T		not specified	Uncertain significance (May 24, 2023)
14-73277282-C-A		not specified	Uncertain significance (Feb 05, 2024)
14-73277288-C-T		not specified	Uncertain significance (Aug 11, 2023)
14-73279391-G-A		not specified	Uncertain significance (Mar 01, 2023)
14-73279391-G-T		not specified	Uncertain significance (Feb 15, 2023)
14-73282366-G-A			Benign (Feb 25, 2018)
14-73284141-G-A		not specified	Uncertain significance (Feb 02, 2024)
14-73284155-C-T		not specified	Uncertain significance (Oct 12, 2022)
14-73284156-G-A		not specified	Uncertain significance (Dec 21, 2022)
14-73284360-T-C		not specified	Uncertain significance (Feb 28, 2023)
14-73287140-T-C		not specified	Uncertain significance (Sep 01, 2021)
14-73287154-G-A		not specified	Uncertain significance (Dec 15, 2023)
14-73287208-C-T		not specified	Uncertain significance (Dec 14, 2023)
14-73287238-C-T		not specified	Uncertain significance (Mar 20, 2023)
14-73292839-A-G			Benign (May 30, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NUMB	protein_coding	protein_coding	ENST00000355058	10	188534

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00400	0.996	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.37	303	378	0.802	0.0000206	4245
Missense in Polyphen		89	133.38	0.66725		1425
Synonymous	-0.228	136	133	1.03	0.00000695	1341
Loss of Function	3.15	9	26.5	0.340	0.00000126	311

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000306	0.000239
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000974	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000992	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. May also mediate local repair of brain ventricular wall damage.
• Pathway: Notch signaling pathway - Homo sapiens (human);NOTCH-Ncore;Notch Signaling Pathway;Notch Signaling Pathway;Notch Signaling Pathway;Developmental Biology;Notch;Signal Transduction;Recycling pathway of L1;Notch;Signaling by NOTCH1;Signaling by NOTCH;Degradation of GLI1 by the proteasome;Hedgehog ,off, state;Hedgehog ,on, state;Signaling by Hedgehog;L1CAM interactions;Notch signaling pathway;Axon guidance;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Activated NOTCH1 Transmits Signal to the Nucleus (Consensus)

Recessive Scores

• pRec: 0.264

Intolerance Scores

• loftool: 0.806
• rvis_EVS: -0.33
• rvis_percentile_EVS: 30.7

Haploinsufficiency Scores

• pHI: 0.759
• hipred: Y
• hipred_score: 0.731
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Numb
• Phenotype: normal 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); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: numb
• Affected structure: erythroid lineage cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: axonogenesis;lateral ventricle development;neuroblast division in subventricular zone;positive regulation of cell migration;adherens junction organization;positive regulation of neurogenesis;regulation of postsynaptic neurotransmitter receptor internalization;negative regulation of protein localization to plasma membrane
• Cellular component: nucleus;early endosome;plasma membrane;focal adhesion;basolateral plasma membrane;extrinsic component of plasma membrane;clathrin-coated vesicle;apical part of cell;glutamatergic synapse
• Molecular function: protein binding;beta-catenin binding;alpha-catenin binding;cadherin binding