MB

protein-coding

myoglobin

Gene summary

This gene encodes a member of the globin superfamily and is predominantly expressed in skeletal and cardiac muscles. The encoded protein forms a monomeric globular haemoprotein that is primarily responsible for the storage and facilitated transfer of oxygen from the cell membrane to the mitochondria. This protein also plays a role in regulating physiological levels of nitric oxide. Multiple transcript variants encoding distinct isoforms exist for this gene. [provided by RefSeq, May 2020]

MANE transcript

NM_005368.3

Inheritance

ClinVar variants

P:1U:20B:1

Top phenotype

Myopathy, sarcoplasmic body

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr22:35,606,764-35,637,951

External References & Databases

Ensembl (ENSG00000198125)

Transcript & Mutation Effects

hg38 • Region Span ~31.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

myopathy, sarcoplasmic bodySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859530

Submitter: PanelApp Australia

myopathy, sarcoplasmic bodySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859530

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Myopathy, sarcoplasmic bodyAD

Manifestation: Cardiovascular; Musculoskeletal

Intervention: Cardiovascular

Rationale: The condition may involve heart failure, and awareness may enable early diagnosis and management of cardiac sequelae

Refs: 30918256; 35527200

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MB variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 20

not providedTotal: 2

Colorectal carcinomaTotal: 1

Myopathy, sarcoplasmic bodyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005368.3. 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				1 clinvar		1
missense		1 clinvar	20 clinvar			21
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	1	20	1	0	22

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005368.3	RefSeq	NP_005359.1	3	MANE Select
ENST00000397326.7	Ensembl	ENSP00000380489.2	3	MANE Select
NM_001362846.2	RefSeq	NP_001349775.1	3	Standard
NM_001382809.1	RefSeq	NP_001369738.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
mb	Danio rerio	Structure: dorsal longitudinal anastomotic vessel Quality: aplastic abnormal

Gene / Model

Organism

Observed Phenotype

Danio rerio

Structure: dorsal longitudinal anastomotic vessel

Quality: aplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Effects of Nitric Oxide
Transport of small molecules
Intracellular oxygen transport

Biological Process

response to hypoxia
heart development
response to hormone
oxygen transport
slow-twitch skeletal muscle fiber contraction

Molecular Function

oxygen carrier activity
oxygen binding
heme binding
metal ion binding

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397326
Coding exons: 3
Length: 31188
Individuals with no LoFs: 125740
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125747
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.510	77	90.7	0.849	0.00000490	1022
Missense (PolyPhen)		24	30.933	0.77587		344
Synonymous	-0.635	44	39.0	1.13	0.00000239	287
Loss of Function	1.13	3	5.98	0.502	2.52e-7	74

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)	0.000035	0.000035	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles.;

Recessive Scores

pRec: 0.612

Intolerance Scores

LoFtool: 0.206
RVIS EVS: -0.27
RVIS percentile EVS: 33.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.837

Gene Damage Prediction

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