NGB

protein-coding

neuroglobin

Gene summary

This gene encodes an oxygen-binding protein that is distantly related to members of the globin gene family. It is highly conserved among other vertebrates. It is expressed in the central and peripheral nervous system where it may be involved in increasing oxygen availability and providing protection under hypoxic/ischemic conditions. [provided by RefSeq, Jul 2008]

MANE transcript

NM_021257.4

Inheritance

—

ClinVar variants

U:21

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr14:77,265,483-77,271,206

External References & Databases

Ensembl (ENSG00000165553)

Transcript & Mutation Effects

hg38 • Region Span ~5.7 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 NGB variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 20

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021257.4. 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			20 clinvar			20
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	21	0	0	21

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021257.4	RefSeq	NP_067080.1	4	MANE Select
ENST00000298352.5	Ensembl	ENSP00000298352.4	4	MANE Select
ENST00001130510.1	Ensembl	ENSP00000800315.1	3	Standard
ENST00001137185.1	Ensembl	ENSP00000805268.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transport of small molecules
Intracellular oxygen transport

Biological Process

apoptotic process
oxygen transport

Molecular Function

oxygen carrier activity
protein binding
oxygen binding
heme binding
metal ion binding

Cellular Component

mitochondrion
cytosol
perikaryon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298352
Coding exons: 4
Length: 5830
Individuals with no LoFs: 125687
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125689
p: 0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.314	76	84.1	0.904	0.00000451	952
Missense (PolyPhen)		19	24.779	0.76678		308
Synonymous	0.680	31	36.2	0.856	0.00000195	307
Loss of Function	0.676	4	5.75	0.696	2.45e-7	69

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in oxygen transport in the brain. Hexacoordinate globin, displaying competitive binding of oxygen or the distal His residue to the iron atom. Not capable of penetrating cell membranes. The deoxygenated form exhibits nitrite reductase activity inhibiting cellular respiration via NO-binding to cytochrome c oxidase. Involved in neuroprotection during oxidative stress. May exert its anti-apoptotic activity by acting to reset the trigger level of mitochondrial cytochrome c release necessary to commit the cells to apoptosis. {ECO:0000269|PubMed:11029004, ECO:0000269|PubMed:11473128, ECO:0000269|PubMed:18416560, ECO:0000269|PubMed:21190290, ECO:0000269|PubMed:21296891}.;

Recessive Scores

pRec: 0.384

Intolerance Scores

LoFtool: 0.418
RVIS EVS: 0.17
RVIS percentile EVS: 65.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.903

Gene Damage Prediction

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