NUMBL

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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			77 clinvar	3 clinvar		80
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	82	3	0	85

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004756.5	RefSeq	NP_004747.1	10	MANE Select
ENST00000252891.8	Ensembl	ENSP00000252891.3	10	MANE Select
NM_001289979.2	RefSeq	NP_001276908.1	8	Standard
NM_001289980.2	RefSeq	NP_001276909.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
numbl	Danio rerio	Structure: erythroid lineage cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

numbl

Danio rerio

Structure: erythroid lineage cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Notch signaling pathway - Homo sapiens (human)
NOTCH-Ncore
Notch Signaling Pathway
Notch Signaling Pathway
Notch Signaling Pathway

Biological Process

nervous system development
axonogenesis
cytokine-mediated signaling pathway
protein metabolic process
lateral ventricle development

Molecular Function

protein binding

Cellular Component

cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252891
Coding exons: 10
Length: 24282
Individuals with no LoFs: 125690
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125727
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.03	217	384	0.565	0.0000258	3811
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0019	0.0019	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.187

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.939

Gene Damage Prediction

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