NUMBL

NUMB like endocytic adaptor protein

Basic information

Region (hg38): 19:40665905-40690972

Links

ENSG00000105245 ∙ NCBI:9253 ∙ OMIM:604018 ∙ HGNC:8061 ∙ Uniprot:Q9Y6R0 ∙ 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 NUMBL gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NUMBL 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						0
missense			41	2		43
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	41	2	0

Variants in NUMBL

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

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

Position	Type	Phenotype	Significance	ClinVar
19-40667479-T-C		not specified	Uncertain significance (Oct 28, 2024)
19-40667500-C-T		not specified	Uncertain significance (Dec 07, 2024)
19-40667521-G-A		not specified	Uncertain significance (Dec 13, 2023)
19-40667617-G-T		not specified	Uncertain significance (Mar 21, 2023)
19-40667631-C-T		not specified	Uncertain significance (Sep 03, 2024)
19-40667637-C-A		not specified	Uncertain significance (Jul 10, 2024)
19-40667670-G-C		not specified	Uncertain significance (Sep 02, 2024)
19-40667676-G-A		not specified	Uncertain significance (May 29, 2024)
19-40667677-G-T		not specified	Uncertain significance (Aug 02, 2021)
19-40667679-A-G		not specified	Uncertain significance (Aug 02, 2021)
19-40667685-C-T		not specified	Uncertain significance (Nov 13, 2024)
19-40667686-C-T		not specified	Uncertain significance (Sep 27, 2022)
19-40667706-G-A		not specified	Uncertain significance (Dec 25, 2024)
19-40667779-C-T		not specified	Uncertain significance (Oct 03, 2022)
19-40667788-G-A		not specified	Uncertain significance (Feb 22, 2025)
19-40667814-G-A		not specified	Uncertain significance (Nov 09, 2021)
19-40667821-C-T		not specified	Likely benign (Nov 30, 2022)
19-40667835-G-A		not specified	Uncertain significance (Apr 07, 2022)
19-40667881-C-T		not specified	Uncertain significance (Dec 12, 2024)
19-40667905-C-T		not specified	Uncertain significance (Sep 26, 2024)
19-40667913-G-T		not specified	Uncertain significance (Oct 05, 2023)
19-40668105-G-T		not specified	Uncertain significance (Mar 23, 2022)
19-40668109-G-A		not specified	Uncertain significance (Sep 10, 2024)
19-40668112-C-T		not specified	Uncertain significance (Feb 10, 2022)
19-40668124-C-A		not specified	Uncertain significance (Dec 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NUMBL	protein_coding	protein_coding	ENST00000252891	10	24282

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000980	125690	0	37	125727	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.03	217	384	0.565	0.0000258	3811
Missense in Polyphen		78	146.06	0.53404		1412
Synonymous	0.749	152	164	0.926	0.0000115	1317
Loss of Function	4.64	2	28.9	0.0692	0.00000186	267

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00190	0.00190
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00190	0.00190
South Asian	0.00	0.00
Other	0.000163	0.000163

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 embryonic neurogenesis. Also required postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. Negative regulator of NF-kappa-B signaling pathway. The inhibition of NF- kappa-B activation is mediated at least in part, by preventing MAP3K7IP2 to interact with polyubiquitin chains of TRAF6 and RIPK1 and by stimulating the 'Lys-48'-linked polyubiquitination and degradation of TRAF6 in cortical neurons. {ECO:0000269|PubMed:18299187, ECO:0000269|PubMed:20079715}.
• Pathway: Notch signaling pathway - Homo sapiens (human);NOTCH-Ncore;Notch Signaling Pathway;Notch Signaling Pathway;Notch Signaling Pathway (Consensus)

Recessive Scores

• pRec: 0.187

Haploinsufficiency Scores

• pHI: 0.298
• hipred: Y
• hipred_score: 0.785
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.939

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Numbl
• 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); hearing/vestibular/ear phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system 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); cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

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

Gene ontology

• Biological process: nervous system development;axonogenesis;cytokine-mediated signaling pathway;protein metabolic process;lateral ventricle development;neuroblast division in subventricular zone;adherens junction organization;positive regulation of neurogenesis
• Cellular component: cytoplasm
• Molecular function: protein binding