MYO9B

protein-coding

myosin IXB, the group of Myosin heavy chains, class IX

Gene summary

This gene encodes a member of the myosin family of actin-based molecular motor heavy chain proteins. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). The protein has four IQ motifs located in the neck domain that bind calmodulin, which serves as a light chain. The protein complex has a single-headed structure and exhibits processive movement on actin filaments toward the minus-end. The protein also has rho-GTPase activity. Polymorphisms in this gene are associated with celiac disease and ulcerative colitis susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

Previous symbols:

CELIAC4

MANE transcript

NM_004145.4

Inheritance

ClinVar variants

P:1U:339B:67

Top phenotype

MYO9B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr19:17,075,777-17,214,537

External References & Databases

Ensembl (ENSG00000099331)

Transcript & Mutation Effects

hg38 • Region Span ~138.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Charcot-Marie-Tooth disease type 2MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0018993

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYO9B variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 323

MYO9B-related disorderTotal: 41

not providedTotal: 24

Celiac disease, susceptibility to, 4Total: 2

Sensorimotor neuropathyTotal: 1

Muscle weaknessTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004145.4. 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			10 clinvar	32 clinvar	5 clinvar	47
missense		1 clinvar	315 clinvar	25 clinvar	5 clinvar	346
nonsense			4 clinvar			4
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	1	339	57	10	407

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004145.4	RefSeq	NP_004136.2	39	MANE Select
ENST00000682292.1	Ensembl	ENSP00000507803.1	39	MANE Select
NM_001130065.2	RefSeq	NP_001123537.1	38	Standard
ENST00000397274.6	Ensembl	ENSP00000380444.2	38	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vitamin D Receptor Pathway
Developmental Biology
Signal Transduction
SLIT2:ROBO1 increases RHOA activity
Rho GTPase cycle

Biological Process

Rho protein signal transduction
actin filament-based movement
ARF protein signal transduction
regulation of Rho protein signal transduction
Roundabout signaling pathway

Molecular Function

microfilament motor activity
actin binding
GTPase activator activity
protein binding
calmodulin binding

Cellular Component

cytoplasm
cytosol
actin filament
cell cortex
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000595618
Coding exons: 38
Length: 138756
Individuals with no LoFs: 124632
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 124652
p: 0.0000802

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.97	843	1.24e+3	0.682	0.0000847	13078
Missense (PolyPhen)		303	557.89	0.54312		6082
Synonymous	0.262	538	546	0.986	0.0000412	3923
Loss of Function	8.14	10	96.1	0.104	0.00000466	1152

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000081	0.000071	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Binds actin with high affinity both in the absence and presence of ATP and its mechanochemical activity is inhibited by calcium ions (PubMed:9490638). Also acts as a GTPase activator for RHOA (PubMed:9490638, PubMed:26529257). Plays a role in the regulation of cell migration via its role as RHOA GTPase activator. This is regulated by its interaction with the SLIT2 receptor ROBO1; interaction with ROBO1 impairs interaction with RHOA and subsequent activation of RHOA GTPase activity, and thereby leads to increased levels of active, GTP-bound RHOA (PubMed:26529257). {ECO:0000269|PubMed:26529257, ECO:0000269|PubMed:9490638}.;

Recessive Scores

pRec: 0.364

Intolerance Scores

LoFtool: 0.0526
RVIS EVS: -0.86
RVIS percentile EVS: 10.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.899

Gene Damage Prediction

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