MYO18B

Summary

MYO18B (myosin XVIIIB, HGNC:18150) is a protein-coding gene on chromosome 22q12.1, encoding Unconventional myosin-XVIIIb (Q8IUG5). May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes.

The protein encoded by this gene may regulate muscle-specific genes when in the nucleus and may influence intracellular trafficking when in the cytoplasm. The encoded protein functions as a homodimer and may interact with F actin. Mutations in this gene are associated with lung cancer.

Source: NCBI Gene 84700 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (Definitive, ClinGen)
• GWAS associations: 41
• Clinical variants (ClinVar): 2,523 total — 100 pathogenic, 35 likely-pathogenic
• Phenotypes (HPO): 25
• MANE Select transcript: NM_032608

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18150
Approved symbol	MYO18B
Name	myosin XVIIIB
Location	22q12.1
Locus type	gene with protein product
Status	Approved
Aliases	BK125H2.1
Ensembl gene	ENSG00000133454
Ensembl biotype	protein_coding
OMIM	607295
Entrez	84700

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000335473, ENST00000407587, ENST00000418374, ENST00000534908, ENST00000536101, ENST00000536204, ENST00000539302, ENST00000539544, ENST00000540454, ENST00000543971

RefSeq mRNA: 2 — MANE Select: NM_032608 NM_001318245, NM_032608

CCDS: CCDS54507, CCDS82703

Canonical transcript exons

ENST00000335473 — 44 exons

Exon	Start	End
ENSE00001151060	25770110	25770176
ENSE00001151068	25768115	25769428
ENSE00001151100	25763231	25763389
ENSE00001258415	26030443	26031045
ENSE00001364972	25760984	25761131
ENSE00001542549	25742188	25742293
ENSE00003467091	25902613	25902736
ENSE00003491141	25992363	25992493
ENSE00003493688	25921257	25921409
ENSE00003499688	25851470	25851579
ENSE00003506773	25770872	25770984
ENSE00003507311	25891304	25891412
ENSE00003509410	25781734	25781834
ENSE00003519591	25895156	25895280
ENSE00003549770	25947712	25947828
ENSE00003562975	25910946	25911050
ENSE00003563513	25952286	25952423
ENSE00003565202	25785428	25785491
ENSE00003568317	25780056	25780198
ENSE00003568621	25890756	25890875
ENSE00003571997	25877959	25878048
ENSE00003572159	25797953	25798097
ENSE00003574575	25874286	25874414
ENSE00003583071	25777583	25777781
ENSE00003584278	25846100	25846283
ENSE00003587405	25832917	25832997
ENSE00003587609	25908322	25908432
ENSE00003588286	25876189	25876332
ENSE00003597400	26003265	26003309
ENSE00003602675	25826409	25826499
ENSE00003618835	26004718	26004855
ENSE00003623513	25898307	25898461
ENSE00003625143	25903631	25903831
ENSE00003636381	25946137	25946250
ENSE00003636905	26026445	26027690
ENSE00003647177	25955179	25955364
ENSE00003648590	25950367	25950450
ENSE00003648754	25843735	25843894
ENSE00003651569	25847430	25847652
ENSE00003665597	25823505	25823678
ENSE00003678521	25772334	25772510
ENSE00003678683	25828776	25828968
ENSE00003686736	25868320	25868385
ENSE00003687380	25835296	25835443

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 98.74.

FANTOM5 (CAGE): breadth broad, TPM avg 4.5834 / max 532.7105, expressed in 301 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191482	4.5834	301

Top tissues by expression

236 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.74	gold quality
gastrocnemius	UBERON:0001388	98.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.16	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.99	gold quality
heart left ventricle	UBERON:0002084	96.74	gold quality
cardiac ventricle	UBERON:0002082	96.53	gold quality
muscle of leg	UBERON:0001383	96.22	gold quality
skeletal muscle tissue	UBERON:0001134	96.06	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.86	gold quality
biceps brachii	UBERON:0001507	95.16	gold quality
right atrium auricular region	UBERON:0006631	95.03	gold quality
cardiac atrium	UBERON:0002081	94.80	gold quality
heart	UBERON:0000948	93.57	gold quality
quadriceps femoris	UBERON:0001377	92.48	gold quality
vastus lateralis	UBERON:0001379	92.39	gold quality
heart right ventricle	UBERON:0002080	91.14	gold quality
myocardium	UBERON:0002349	90.13	gold quality
muscle tissue	UBERON:0002385	89.74	gold quality
deltoid	UBERON:0001476	89.53	gold quality
left testis	UBERON:0004533	85.91	gold quality
right testis	UBERON:0004534	85.80	gold quality
right coronary artery	UBERON:0001625	85.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.71	gold quality
thoracic aorta	UBERON:0001515	84.44	gold quality
ascending aorta	UBERON:0001496	84.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.00	gold quality
descending thoracic aorta	UBERON:0002345	84.00	gold quality
testis	UBERON:0000473	82.55	gold quality
body of tongue	UBERON:0011876	80.39	gold quality
left coronary artery	UBERON:0001626	79.33	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.14
E-MTAB-11268	no	1639.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting MYO18B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-8065	99.19	70.38	1289
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748

Literature-anchored findings (GeneRIF, showing 14)

• candidate tumor suppressor gene at chromosome 22q12.1, deleted, mutated, and methylated in human lung cancer (PMID:12209013)
• Human MYO18B, a novel unconventional myosin heavy chain expressed in striated muscles moves into the myonuclei upon differentiation (PMID:12547197)
• MYO18B alterations, including both epigenetic and genetic alterations, play an important role in ovarian carcinogenesis (PMID:15305387)
• Proteasome dysfunction by a proteasome inhibitor or siRNA-mediated knock-down of Sug1 caused the up-regulation of MYO18B protein and MYO18B was polyubiquitinated in vivo. (PMID:16499872)
• The restored expression of MYO18B may be a useful therapeutic strategy for the treatment of locally advanced Malignant pleural mesothelioma(MPM)in humans. (PMID:17294804)
• A common MYO18B variant is associated with mathematical disability in children with dyslexia and with intraparietal sulcus variability in neurotypical adults. (PMID:23423138)
• Deficiency of MYO18B is linked to a novel developmental disorder which combines KFA with myopathy. (PMID:25748484)
• No associations were found between rs133885 in myosin-18B and mathematical abilities among individuals with dyslexia or in the general population. (PMID:25778778)
• Full loss of myo18b function results in a complete lack of sarcomeric structure, revealing a highly surprising and essential role for myo18b in sarcomere assembly. Importantly, scattered thin and thick filaments assemble throughout the sarcoplasm. These observations suggest a novel model of sarcomere assembly where Myo18b coordinates the integration of preformed thick and thin filaments into the sarcomere (PMID:28104788)
• MYO18B promoted hepatocellular carcinoma growth and migration via the activation of PI3K/AKT/mTOR signaling pathway. (PMID:30390677)
• The results reveal a critical role for myosin-18B in myosin II stack assembly and provide evidence that myosin II stacks are important for a variety of vital processes in cells. (PMID:30581023)
• Myosin-18B Regulates Higher-Order Organization of the Cardiac Sarcomere through Thin Filament Cross-Linking and Thick Filament Dynamics. (PMID:32877672)
• Further delineation of MYO18B-related autosomal recessive Klippel-Feil syndrome with myopathy and facial dysmorphism. (PMID:33179433)
• Myosin18B predicts favorable prognosis of cutaneous squamous-cell carcinoma. (PMID:33555505)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Myo18b	ENSMUSG00000072720
rattus_norvegicus	Myo18b	ENSRNOG00000048430

Paralogs (44): MYH13 (ENSG00000006788), MYO16 (ENSG00000041515), MYO9A (ENSG00000066933), MYO3B (ENSG00000071909), MYH7B (ENSG00000078814), MYO15A (ENSG00000091536), MYH7 (ENSG00000092054), MYO3A (ENSG00000095777), MYO9B (ENSG00000099331), MYH9 (ENSG00000100345), MYH14 (ENSG00000105357), MYH1 (ENSG00000109061), MYH3 (ENSG00000109063), MYH2 (ENSG00000125414), MYO1B (ENSG00000128641), MYO5C (ENSG00000128833), CGNL1 (ENSG00000128849), MYH8 (ENSG00000133020), MYH10 (ENSG00000133026), MYH11 (ENSG00000133392), CCDC102A (ENSG00000135736), MYO1G (ENSG00000136286), MYO7A (ENSG00000137474), MYO1F (ENSG00000142347), CGN (ENSG00000143375), TMF1 (ENSG00000144747), MYH15 (ENSG00000144821), MYO10 (ENSG00000145555), CCDC102B (ENSG00000150636), MYO1E (ENSG00000157483), CCDC158 (ENSG00000163749), MYO1A (ENSG00000166866), MYO5B (ENSG00000167306), MYO7B (ENSG00000169994), MYO1H (ENSG00000174527), MYO1D (ENSG00000176658), MYO18A (ENSG00000196535), MYO6 (ENSG00000196586), MYO5A (ENSG00000197535), MYH6 (ENSG00000197616)

Protein

Protein identifiers

Unconventional myosin-XVIIIb — Q8IUG5 (reviewed: Q8IUG5)

All UniProt accessions (4): A0A2Q2TCQ6, Q8IUG5, F5H6I8, H0YGQ4

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in intracellular trafficking of the muscle cell when in the cytoplasm, whereas entering the nucleus, may be involved in the regulation of muscle specific genes. May play a role in the control of tumor development and progression; restored MYO18B expression in lung cancer cells suppresses anchorage-independent growth.

Subunit / interactions. Homodimer. May interact with F actin through the GPA motif (Gly/Pro/Ala-rich).

Subcellular location. Cytoplasm. Nucleus. Myofibril. Sarcomere.

Tissue specificity. Selectively expressed in cardiac and skeletal muscles. Weakly expressed in testis, pancreas, placenta, prostate, lung and thymus.

Disease relevance. Klippel-Feil syndrome 4, autosomal recessive, with nemaline myopathy and facial dysmorphism (KFS4) [MIM:616549] A form of Klippel-Feil syndrome, a skeletal disorder characterized by congenital fusion of cervical vertebrae. It is due to a failure in the normal segmentation of vertebrae during the early weeks of fetal development. The clinical triad consists of short neck, low posterior hairline, and limited neck movement. KFS4 features additionally include myopathy, mild short stature, microcephaly, and distinctive facies. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Frequently deleted, mutated, and hypermethylated in lung cancers.

Similarity. Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IUG5-1	1	yes
Q8IUG5-2	2
Q8IUG5-3	3

RefSeq proteins (2): NP_001305174, NP_115997* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001609	Myosin_head_motor_dom-like	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036064	MYSc_Myo18	Domain
IPR036961	Kinesin_motor_dom_sf	Homologous_superfamily

Pfam: PF00063

UniProt features (83 total): sequence variant 31, compositionally biased region 20, region of interest 9, sequence conflict 7, modified residue 6, coiled-coil region 3, splice variant 3, domain 2, chain 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUG5-F1	60.66	0.12

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 660–667

Post-translational modifications (6): 1216, 1829, 2193, 2296, 2309, 2377

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 164 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER, SRF_C, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, ROZANOV_MMP14_TARGETS_UP, GOBP_CARDIAC_MUSCLE_CELL_DIFFERENTIATION, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOCC_CENTROSOME, GOBP_ACTOMYOSIN_STRUCTURE_ORGANIZATION, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_VASCULOGENESIS

GO Biological Process (3): vasculogenesis (GO:0001570), in utero embryonic development (GO:0001701), cardiac muscle cell development (GO:0055013)

GO Molecular Function (5): cytoskeletal motor activity (GO:0003774), ATP binding (GO:0005524), actin filament binding (GO:0051015), nucleotide binding (GO:0000166), actin binding (GO:0003779)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), myosin II complex (GO:0016460), unconventional myosin complex (GO:0016461), Z disc (GO:0030018), filamentous actin (GO:0031941), myosin filament (GO:0032982), cytoskeleton (GO:0005856), myosin complex (GO:0016459), sarcomere (GO:0030017)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
myosin complex	3
protein-containing complex	2
cell differentiation	1
blood vessel morphogenesis	1
chordate embryonic development	1
striated muscle cell development	1
cardiac cell development	1
cardiac muscle cell differentiation	1
molecular_function	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
actin binding	1
protein-containing complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cytoskeletal protein binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
I band	1
actin filament	1
supramolecular fiber	1
intracellular membraneless organelle	1
actin cytoskeleton	1
myofibril	1

Protein interactions and networks

STRING

1738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYO18B	SEZ6L	Q9BYH1	924
MYO18B	GRK3	P35626	819
MYO18B	MYO18A	O95411	650
MYO18B	KBTBD13	C9JR72	598
MYO18B	KLHL40	Q2TBA0	588
MYO18B	LMOD3	Q0VAK6	585
MYO18B	GOLPH3	Q9H4A6	578
MYO18B	KLHL41	O60662	572
MYO18B	OR4K17	Q8NGC6	542
MYO18B	OR3A3	P47888	500
MYO18B	MYPN	Q86TC9	498
MYO18B	PSMC5	P47210	495
MYO18B	C10orf71	Q711Q0	473
MYO18B	TPM2	P06468	464
MYO18B	TNNT1	P13805	464

IntAct

19 interactions, top by confidence:

A	B	Type	Score
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
LURAP1	TRIM24	psi-mi:“MI:0914”(association)	0.530
NDEL1	OFD1	psi-mi:“MI:0914”(association)	0.530
SGF29	MATN2	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
TNKS2	MYO18B	psi-mi:“MI:0407”(direct interaction)	0.440
MYO18B	CRK	psi-mi:“MI:0915”(physical association)	0.400
MYO18B	PLEC	psi-mi:“MI:0915”(physical association)	0.400
MAP3K10	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
MEAF6	WDR46	psi-mi:“MI:0914”(association)	0.350
MYL12B	MYL1	psi-mi:“MI:0914”(association)	0.350
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
ZRANB2	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
TULP3	MYO18B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): MYO18B (Biochemical Activity), MYO18B (Affinity Capture-MS), MYO18B (Affinity Capture-MS), MYO18B (Proximity Label-MS), MYO18B (Two-hybrid), MYO18B (Affinity Capture-MS), MYO18B (Co-fractionation), MYO18B (Affinity Capture-MS), MYO18B (Cross-Linking-MS (XL-MS)), SCN8A (Cross-Linking-MS (XL-MS)), MYO18B (Cross-Linking-MS (XL-MS)), DBI (Cross-Linking-MS (XL-MS)), MYO18B (Cross-Linking-MS (XL-MS)), RBM26 (Cross-Linking-MS (XL-MS)), MYO18B (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZM56, A0JNJ4, A2AJI0, A5D7L8, A7E321, O15446, O75683, O75807, P17564, P49919, P70279, Q0P5N2, Q0VCY3, Q14684, Q149B8, Q2TBX7, Q32LQ1, Q5R7E7, Q5RB69, Q5SV97, Q5SXM2, Q5TM66, Q5XIB5, Q60465, Q62187, Q66H19, Q68DK7, Q6IN02, Q6NYC8, Q767M0, Q8BQ30, Q8BSI6, Q8BZW2, Q8IUG5, Q8IY92, Q8K124, Q8N1P7, Q8NC74, Q8TD55, Q8VD63

Diamond homologs: D3ZFD0, O08638, O14745, P10587, P14105, P35579, P35580, P35748, P35749, P39922, P70441, P81271, Q258K2, Q27991, Q28619, Q3SZK8, Q4R6G4, Q5ZM14, Q61879, Q62812, Q63862, Q7Z406, Q8IUG5, Q8VDD5, Q92614, Q9JJ19, Q9JLT0, Q9JMH9, A2AQP0, A7E2Y1, G3UW82, P02562, P02563, P02564, P02565, P02566, P02567, P04460, P04461, P06198

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of apoptotic process	5	14.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2523 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	100
Likely pathogenic	35
Uncertain significance	1130
Likely benign	948
Benign	220

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1323314	NM_032608.7(MYO18B):c.1195del (p.Gln399fs)	Pathogenic
1367348	NM_032608.7(MYO18B):c.7594C>T (p.Arg2532Ter)	Pathogenic
1374582	NM_032608.7(MYO18B):c.6752C>A (p.Ser2251Ter)	Pathogenic
1380883	NM_032608.7(MYO18B):c.2080C>T (p.Arg694Ter)	Pathogenic
1381618	NM_032608.7(MYO18B):c.4802del (p.Glu1601fs)	Pathogenic
1383440	NM_032608.7(MYO18B):c.2859del (p.His954fs)	Pathogenic
1384301	NM_032608.7(MYO18B):c.1551G>A (p.Trp517Ter)	Pathogenic
1405809	NM_032608.7(MYO18B):c.5869C>T (p.Gln1957Ter)	Pathogenic
1407417	NM_032608.7(MYO18B):c.6436C>T (p.Gln2146Ter)	Pathogenic
1411912	NM_032608.7(MYO18B):c.6926C>G (p.Ser2309Ter)	Pathogenic
1422911	NM_032608.7(MYO18B):c.4634C>A (p.Ser1545Ter)	Pathogenic
1436766	NC_000022.10:g.(?26157060)(26157118_?)del	Pathogenic
1441547	NC_000022.10:g.(?26388309)(26388479_?)del	Pathogenic
1479326	NM_032608.7(MYO18B):c.3329C>A (p.Ser1110Ter)	Pathogenic
1483109	NM_032608.7(MYO18B):c.3463C>T (p.Gln1155Ter)	Pathogenic
1504711	NM_032608.7(MYO18B):c.2583C>A (p.Cys861Ter)	Pathogenic
1512501	NM_032608.7(MYO18B):c.3241del (p.Leu1081fs)	Pathogenic
1517223	NM_032608.7(MYO18B):c.6640C>T (p.Gln2214Ter)	Pathogenic
1897111	NM_032608.7(MYO18B):c.7405C>T (p.Gln2469Ter)	Pathogenic
1904386	NM_032608.7(MYO18B):c.6895_6896dup (p.Asn2300fs)	Pathogenic
1947764	NM_032608.7(MYO18B):c.6940G>T (p.Glu2314Ter)	Pathogenic
1954656	NM_032608.7(MYO18B):c.3122del (p.Glu1041fs)	Pathogenic
1960957	NM_032608.7(MYO18B):c.534C>A (p.Cys178Ter)	Pathogenic
1962756	NM_032608.7(MYO18B):c.6567del (p.Asp2189fs)	Pathogenic
1965493	NM_032608.7(MYO18B):c.1935G>A (p.Trp645Ter)	Pathogenic
1974970	NM_032608.7(MYO18B):c.424_425del (p.Val142fs)	Pathogenic
1981423	NM_032608.7(MYO18B):c.3958dup (p.Leu1320fs)	Pathogenic
1994675	NM_032608.7(MYO18B):c.5295T>G (p.Tyr1765Ter)	Pathogenic
2022086	NM_032608.7(MYO18B):c.4717C>T (p.Gln1573Ter)	Pathogenic
2032479	NM_032608.7(MYO18B):c.7354C>T (p.Gln2452Ter)	Pathogenic

SpliceAI

6908 predictions. Top by Δscore:

Variant	Effect	Δscore
22:25763385:GAGAG:G	donor_gain	1.0000
22:25763387:GAG:G	donor_gain	1.0000
22:25763388:AGG:A	donor_loss	1.0000
22:25763390:G:C	donor_loss	1.0000
22:25763391:T:G	donor_loss	1.0000
22:25770856:T:A	acceptor_gain	1.0000
22:25770857:G:A	acceptor_gain	1.0000
22:25770871:GCT:G	acceptor_gain	1.0000
22:25772331:CA:C	acceptor_loss	1.0000
22:25772332:A:AG	acceptor_gain	1.0000
22:25772332:AGGCC:A	acceptor_loss	1.0000
22:25772333:G:GG	acceptor_gain	1.0000
22:25772333:GGCC:G	acceptor_gain	1.0000
22:25772507:G:T	donor_gain	1.0000
22:25777579:GCAG:G	acceptor_loss	1.0000
22:25777580:CAGG:C	acceptor_loss	1.0000
22:25780197:AGG:A	donor_loss	1.0000
22:25780199:G:GG	donor_gain	1.0000
22:25781729:T:TA	acceptor_gain	1.0000
22:25781729:TGCA:T	acceptor_loss	1.0000
22:25781730:GCA:G	acceptor_loss	1.0000
22:25781731:CA:C	acceptor_loss	1.0000
22:25781732:A:AC	acceptor_loss	1.0000
22:25781732:A:AG	acceptor_gain	1.0000
22:25781733:G:GC	acceptor_gain	1.0000
22:25781733:GA:G	acceptor_gain	1.0000
22:25781733:GAC:G	acceptor_gain	1.0000
22:25781733:GACA:G	acceptor_gain	1.0000
22:25781733:GACAA:G	acceptor_gain	1.0000
22:25781780:A:T	donor_gain	1.0000

AlphaMissense

16768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:25921303:T:C	L1804P	0.997
22:25921291:T:C	L1800P	0.995
22:25955195:T:C	L1996P	0.995
22:25955198:G:C	R1997P	0.994
22:25992433:G:C	R2076P	0.994
22:25992445:T:C	L2080P	0.994
22:25921321:T:C	L1810P	0.993
22:25761122:G:C	W10C	0.992
22:25761122:G:T	W10C	0.992
22:25921294:G:C	R1801P	0.992
22:25947818:T:C	L1913P	0.992
22:25946167:G:C	A1850P	0.991
22:25921317:G:C	A1809P	0.990
22:25946201:T:C	L1861P	0.990
22:25952361:G:C	A1970P	0.990
22:25992415:T:C	L2070P	0.990
22:25823594:T:C	F871L	0.989
22:25823596:C:A	F871L	0.989
22:25823596:C:G	F871L	0.989
22:25761120:T:A	W10R	0.988
22:25761120:T:C	W10R	0.988
22:25823520:T:C	F846S	0.988
22:25921288:G:C	R1799P	0.988
22:25947797:T:C	L1906P	0.988
22:25823519:T:C	F846L	0.987
22:25823521:C:A	F846L	0.987
22:25823521:C:G	F846L	0.987
22:25947788:T:C	L1903P	0.987
22:25952377:T:C	L1975P	0.987
22:25992403:T:C	L2066P	0.987

dbSNP variants (sampled 300 via entrez): RS1000015228 (22:25754664 T>G), RS1000034510 (22:25997067 A>G), RS1000035610 (22:25769687 A>C), RS1000051126 (22:25928116 G>T), RS1000060165 (22:25947656 T>G), RS1000061278 (22:25744094 C>T), RS1000070962 (22:25915577 T>C), RS1000076191 (22:25816839 A>C,T), RS1000077812 (22:26007910 A>T), RS1000081719 (22:25793249 G>A), RS1000095141 (22:25955617 A>G), RS1000097759 (22:25949165 G>C), RS1000099138 (22:26047309 G>A), RS1000121686 (22:25816258 G>A), RS1000123350 (22:25774359 G>A,C)

Disease associations

OMIM: gene MIM:607295 | disease phenotypes: MIM:616549, MIM:256030, MIM:118100, MIM:617667

GenCC curated gene-disease

Disease	Classification	Inheritance
Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome	Definitive	AR

Mondo (6): limb-girdle muscular dystrophy (MONDO:0016971), Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (MONDO:0014689), cardiomyopathy (MONDO:0004994), nemaline myopathy (MONDO:0018958), Klippel-Feil syndrome (MONDO:0001029), Fraser syndrome 3 (MONDO:0054739)

Orphanet (5): Limb-girdle muscular dystrophy (Orphanet:263), Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome (Orphanet:447974), Rare cardiomyopathy (Orphanet:167848), Nemaline myopathy (Orphanet:607), Isolated Klippel-Feil syndrome (Orphanet:2345)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000414	Bulbous nose
HP:0000430	Underdeveloped nasal alae
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000508	Ptosis
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001371	Flexion contracture
HP:0001638	Cardiomyopathy
HP:0002162	Low posterior hairline
HP:0002944	Thoracolumbar scoliosis
HP:0003198	Myopathy
HP:0003798	Nemaline bodies
HP:0004322	Short stature
HP:0004602	Cervical C2/C3 vertebral fusion
HP:0008807	Acetabular dysplasia

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST000774_5	Schizophrenia, bipolar disorder and depression (combined)	2.000000e-06
GCST001866_1	Mathematical ability in children with dyslexia	8.000000e-10
GCST002337_143	Amyotrophic lateral sclerosis (sporadic)	2.000000e-10
GCST002830_18	Urate levels in lean individuals	4.000000e-06
GCST002830_35	Urate levels in lean individuals	6.000000e-06
GCST002938_28	Copper levels	5.000000e-06
GCST003854_32	Gut microbiota (functional units)	4.000000e-09
GCST006061_131	Atrial fibrillation	1.000000e-07
GCST006414_42	Atrial fibrillation	9.000000e-10
GCST009676_14	Urinary calcium excretion	2.000000e-06
GCST010796_3347	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-36
GCST010796_3348	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-10
GCST010796_3349	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-17
GCST010796_3350	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-26
GCST010796_4726	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-33
GCST010796_4727	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-34
GCST010796_4728	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-26
GCST010796_4729	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-18
GCST010796_4730	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-11
GCST010796_4731	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4732	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4733	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_4734	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4735	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-09
GCST010796_4736	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_4737	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-09
GCST010796_4738	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_4739	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09
GCST010796_4740	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4741	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004875	mathematical ability
EFO:0004531	urate measurement
EFO:0007874	gut microbiome measurement
EFO:0004838	calcium measurement
EFO:0004327	electrocardiography
EFO:0010556	Left ventricular mass to end-diastolic volume ratio
EFO:0008205	left ventricular structural measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D007714	Klippel-Feil Syndrome	C05.116.099.370.535; C05.660.551; C16.131.621.551
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
D017696	Myopathies, Nemaline	C05.651.575.290; C10.668.491.550.290

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Resveratrol	decreases expression, affects cotreatment	1
Arsenic	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Copper	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Niclosamide	increases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT03783923	PHASE3	TERMINATED	A Study of Deflazacort (Emflaza®) in Participants With Limb-Girdle Muscular Dystrophy 2I (LGMD2I)
NCT06246513	PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Learn More About an Experimental Gene Therapy Called Bidridistrogene Xeboparvovec (SRP-9003) as a Possible Treatment for Limb Girdle Muscular Dystrophy 2E/R4
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	PHASE3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT04054375	PHASE2	COMPLETED	Weekly Steroids in Muscular Dystrophy