NBL1

protein-coding

NBL1, DAN family BMP antagonist, the group of DAN family

Gene summary

This gene product is the founding member of the evolutionarily conserved CAN (Cerberus and DAN) family of proteins, which contain a domain resembling the CTCK (C-terminal cystine knot-like) motif found in a number of signaling molecules. These proteins are secreted, and act as BMP (bone morphogenetic protein) antagonists by binding to BMPs and preventing them from interacting with their receptors. They may thus play an important role during growth and development. Alternatively spliced transcript variants have been identified for this gene. Read-through transcripts between this locus and the upstream mitochondrial inner membrane organizing system 1 gene (GeneID 440574) have been observed. [provided by RefSeq, May 2013]

MANE transcript

NM_005380.8

Inheritance

—

ClinVar variants

U:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr1:19,596,979-19,658,456

External References & Databases

Ensembl (ENSG00000158747)

Transcript & Mutation Effects

hg38 • Region Span ~61.5 kb

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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 NBL1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005380.8. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			12 clinvar			12
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	12	0	0	12

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005380.8	RefSeq	NP_005371.2	3	MANE Select
ENST00000375136.8	Ensembl	ENSP00000364278.4	3	MANE Select
NM_001204084.3	RefSeq	NP_001191013.1	3	Standard
NM_001204085.2	RefSeq	NP_001191014.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
nbl1	Danio rerio	Structure: pars superior ear Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

nbl1

Danio rerio

Structure: pars superior ear

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TGF-beta signaling pathway - Homo sapiens (human)

Biological Process

nervous system development
regulation of signaling receptor activity
negative regulation of BMP signaling pathway
sequestering of BMP in extracellular matrix
sequestering of BMP from receptor via BMP binding

Molecular Function

protein binding
morphogen activity
BMP binding
protein homodimerization activity

Cellular Component

extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000289749
Coding exons: 4
Length: 17898
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125709
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.52	78	126	0.619	0.00000689	1407
Missense (PolyPhen)		17	45.248	0.37571		510
Synonymous	0.678	48	54.4	0.883	0.00000366	424
Loss of Function	1.54	3	7.57	0.396	3.22e-7	86

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Possible candidate as a tumor suppressor gene of neuroblastoma. May play an important role in preventing cells from entering the final stage (G1/S) of the transformation process.;

Recessive Scores

pRec: 0.232

Intolerance Scores

RVIS EVS: 0.01
RVIS percentile EVS: 54.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.749

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low