VMA21

Summary

VMA21 (vacuolar ATPase assembly factor VMA21, HGNC:22082) is a protein-coding gene on chromosome Xq28, encoding Vacuolar ATPase assembly integral membrane protein VMA21 (Q3ZAQ7). Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum. It is a selective cancer dependency (DepMap: 27.6% of cell lines).

This gene encodes a chaperone for assembly of lysosomal vacuolar ATPase.

Source: NCBI Gene 203547 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked myopathy with excessive autophagy (Strong, GenCC)
• Clinical variants (ClinVar): 118 total — 7 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 23
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 27.6% of screened cell lines
• MANE Select transcript: NM_001017980

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22082
Approved symbol	VMA21
Name	vacuolar ATPase assembly factor VMA21
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	XMEA
Ensembl gene	ENSG00000160131
Ensembl biotype	protein_coding
OMIM	300913
Entrez	203547

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000330374, ENST00000370361, ENST00000477649, ENST00000932111

RefSeq mRNA: 2 — MANE Select: NM_001017980 NM_001017980, NM_001363810

CCDS: CCDS35430, CCDS87789

Canonical transcript exons

ENST00000330374 — 3 exons

Exon	Start	End
ENSE00001294550	151397206	151397361
ENSE00001809985	151404916	151409364
ENSE00003661486	151403631	151403740

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 97.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 80.4670 / max 443.8248, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197990	52.7189	1823
197991	26.7441	1813
197989	0.9161	419
197988	0.0879	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.01	gold quality
kidney epithelium	UBERON:0004819	95.70	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.74	gold quality
tibialis anterior	UBERON:0001385	94.64	gold quality
upper leg skin	UBERON:0004262	94.33	gold quality
upper arm skin	UBERON:0004263	94.31	gold quality
skin of hip	UBERON:0001554	93.96	gold quality
adrenal tissue	UBERON:0018303	93.56	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.27	silver quality
adult organism	UBERON:0007023	93.23	gold quality
superficial temporal artery	UBERON:0001614	92.32	gold quality
left ventricle myocardium	UBERON:0006566	92.10	gold quality
cartilage tissue	UBERON:0002418	91.67	gold quality
decidua	UBERON:0002450	91.59	gold quality
caput epididymis	UBERON:0004358	91.59	gold quality
corpus epididymis	UBERON:0004359	91.53	gold quality
endothelial cell	CL:0000115	91.41	gold quality
substantia nigra pars compacta	UBERON:0001965	91.41	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.41	gold quality
mammary duct	UBERON:0001765	90.99	gold quality
epithelium of mammary gland	UBERON:0003244	90.95	gold quality
mammalian vulva	UBERON:0000997	90.80	gold quality
pigmented layer of retina	UBERON:0001782	90.79	gold quality
Brodmann (1909) area 46	UBERON:0006483	90.69	gold quality
germinal epithelium of ovary	UBERON:0001304	90.60	gold quality
postcentral gyrus	UBERON:0002581	90.42	gold quality
myocardium	UBERON:0002349	90.33	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.23	gold quality
bronchial epithelial cell	CL:0002328	90.23	gold quality
cortical plate	UBERON:0005343	90.15	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	6.99
E-ANND-3	yes	6.68
E-GEOD-109979	no	636.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

142 targeting VMA21, 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-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 27.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• This study showed that LOC203547 is the human ortholog of Vma21p, and that hypomorphic mutations of the VMA21 gene disrupt autophagy and cause -linked Myopathy with Excessive Autophagy. (PMID:23315026)
• A Japanese family afflicted by X-linked myopathy with excessive autophagy displayed high urinary beta2 microglobulin without renal dysfunction. Decreased urine acidification in the distal convoluted tubules might be caused by the VMA21 gene mutation. (PMID:23850239)
• lncRNA ZFPM2-AS1 promotes proliferation via miR-18b-5p/VMA21 axis in lung adenocarcinoma. (PMID:31297866)
• Mutations in the V-ATPase Assembly Factor VMA21 Cause a Congenital Disorder of Glycosylation With Autophagic Liver Disease. (PMID:32145091)
• Clinical, imaging, morphologic, and molecular features of X-linked VMA21-related myopathy in two unrelated Brazilian families. (PMID:32535249)
• circ_VMA21 protects WI-38 cells against LPS-induced apoptotic and inflammatory injury by acting on the miR-409-3p/KLF4 axis. (PMID:34350833)
• Hsa_circ_0001361 facilitates the progress of lung adenocarcinoma cells via targeting miR-525-5p/VMA21 axis. (PMID:34507559)
• Follicular lymphoma-associated mutations in the V-ATPase chaperone VMA21 activate autophagy creating a targetable dependency. (PMID:35287545)
• Identification of a muscle-specific isoform of VMA21 as a potent actor in X-linked myopathy with excessive autophagy pathogenesis. (PMID:37756622)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	vma21	ENSDARG00000093945
mus_musculus	Vma21	ENSMUSG00000073131
rattus_norvegicus	Vma21	ENSRNOG00000048606
drosophila_melanogaster	CG5969	FBGN0036998
drosophila_melanogaster	CG42359	FBGN0259705
caenorhabditis_elegans		WBGENE00011115
caenorhabditis_elegans		WBGENE00303105

Protein

Protein identifiers

Vacuolar ATPase assembly integral membrane protein VMA21 — Q3ZAQ7 (reviewed: Q3ZAQ7)

Alternative names: Myopathy with excessive autophagy protein

All UniProt accessions (1): Q3ZAQ7

UniProt curated annotations — full annotation on UniProt →

Function. Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum.

Subunit / interactions. Associates with the V0 complex of the vacuolar ATPase (V-ATPase). Interacts with ATP6AP2.

Subcellular location. Endoplasmic reticulum membrane. Endoplasmic reticulum-Golgi intermediate compartment membrane. Cytoplasmic vesicle. COPII-coated vesicle membrane.

Disease relevance. Myopathy, X-linked, with excessive autophagy (MEAX) [MIM:310440] A muscle disorder characterized by childhood early onset of a slowly progressive proximal limb muscle weakness (especially in legs) and elevation of serum creatine kinase, without evidence of cardiac, respiratory or central nervous system involvement. Histopathological analysis reveals diseased muscle fibers that are not necrotic, but show abnormal autophagic vacuolation as a manifestation of excessive autophagic activity in skeletal muscle cells. The disease is caused by variants affecting the gene represented in this entry. VMA21 deficiency results in an increase of lysosomal pH from 4.7 to 5.2, which reduces lysosomal degradative ability and blocks autophagy. This reduces cellular free amino acids, which up-regulates the mTOR pathway and mTOR-dependent macroautophagy, resulting in proliferation of large and ineffective autolysosomes that engulf sections of cytoplasm, merge together, and vacuolate the cell.

Similarity. Belongs to the VMA21 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q3ZAQ7-1	1	yes
Q3ZAQ7-2	2

RefSeq proteins (2): NP_001017980, NP_001350739 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019013	Vma21	Family

Pfam: PF09446

UniProt features (7 total): topological domain 3, transmembrane region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3ZAQ7-F1	70.41	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GCACCTT_MIR18A_MIR18B, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_VACUOLE_ORGANIZATION, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, WEI_MYCN_TARGETS_WITH_E_BOX, GOCC_COATED_VESICLE, GOBP_VACUOLAR_ACIDIFICATION, GOBP_REGULATION_OF_PH, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_LYTIC_VACUOLE_ORGANIZATION, CUI_TCF21_TARGETS_2_DN, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, NUYTTEN_EZH2_TARGETS_DN

GO Biological Process (2): lysosomal lumen acidification (GO:0007042), vacuolar proton-transporting V-type ATPase complex assembly (GO:0070072)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): lysosome (GO:0005764), endoplasmic reticulum membrane (GO:0005789), ER to Golgi transport vesicle membrane (GO:0012507), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
vacuolar acidification	1
proton-transporting V-type ATPase complex assembly	1
binding	1
lytic vacuole	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1
coated vesicle membrane	1
endoplasmic reticulum-Golgi intermediate compartment	1
bounding membrane of organelle	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VMA21	EMD	P50402	762
VMA21	LAMP2	P13473	584
VMA21	ATP6V0C	P27449	416
VMA21	EPG5	Q9HCE0	405
VMA21	WDR47	O94967	369
VMA21	ATP6V1F	Q16864	350
VMA21	ATP6V0B	Q99437	350
VMA21	SNX14	Q9Y5W7	348
VMA21	TSPAN4	O14817	311
VMA21	WDR45	Q9Y484	308
VMA21	CLPTM1	O96005	287
VMA21	FAT2	Q9NYQ8	285
VMA21	SEMA4B	Q9NPR2	280
VMA21	CHCHD3	Q9NX63	276
VMA21	FOXRED1	Q96CU9	274
VMA21	RPL10	P27635	274

IntAct

175 interactions, top by confidence:

A	B	Type	Score
ATP6V0C	ATP6AP2	psi-mi:“MI:0914”(association)	0.730
ATP6AP2	ATP6V0C	psi-mi:“MI:0914”(association)	0.730
ATP6V0A2	ATP6AP2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
VMA12	ATP6AP2	psi-mi:“MI:0914”(association)	0.640
VAMP2	VMA21	psi-mi:“MI:0915”(physical association)	0.560
CLEC12B	VMA21	psi-mi:“MI:0915”(physical association)	0.560
VMA21	DAGLA	psi-mi:“MI:0915”(physical association)	0.560
	VMA21	psi-mi:“MI:0915”(physical association)	0.560
AQP6	VMA21	psi-mi:“MI:0915”(physical association)	0.560
VMA21	ORMDL1	psi-mi:“MI:0915”(physical association)	0.560
VMA21	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
VMA21	PLLP	psi-mi:“MI:0915”(physical association)	0.560
VMA21	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	VMA21	psi-mi:“MI:0915”(physical association)	0.560
CDIPT	VMA21	psi-mi:“MI:0915”(physical association)	0.560
VMA21	SLC35E4	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	VMA21	psi-mi:“MI:0915”(physical association)	0.560
VMA21	THSD7A	psi-mi:“MI:0915”(physical association)	0.560
VMA21	INSIG2	psi-mi:“MI:0915”(physical association)	0.560
VMA21	NIPAL3	psi-mi:“MI:0915”(physical association)	0.560
VMA21	ATP13A1	psi-mi:“MI:0915”(physical association)	0.560
VMA21	ATP6V0B	psi-mi:“MI:0915”(physical association)	0.560
VMA21	NINJ2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (148): VMA21 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), VMA21 (Proximity Label-MS), VMA21 (Proximity Label-MS), VMA21 (Proximity Label-MS), VMA21 (Proximity Label-MS), VMA21 (Proximity Label-MS), VMA21 (Proximity Label-MS), VMA21 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), VMA21 (Affinity Capture-MS), VMA21 (Affinity Capture-MS)

ESM2 similar proteins: A2VDK9, A4R0J5, A9JRA0, B0FWK4, B8JLV7, D3ZEH5, E1BD52, P83362, Q0VCK9, Q15005, Q28250, Q28GR4, Q2TBU2, Q3SYY9, Q3T134, Q3ZAQ7, Q4R512, Q4R5B4, Q4R5E3, Q4V7U1, Q58DA4, Q5BJI9, Q5BJW3, Q5F3F5, Q5F409, Q5M8Y1, Q5RAY6, Q5RDV3, Q5RF53, Q5RFE0, Q5XIK2, Q5ZI05, Q5ZKG8, Q5ZLL0, Q62302, Q6AZ61, Q6NYF1, Q6UWH6, Q78T54, Q7ZUA6

Diamond homologs: A1CJW1, A1D7K7, A2VDK9, A3LU53, A4R0J5, A5DGY3, A6R3V7, A6ZV87, A7F5K4, A7TSA7, B0XYF0, B2WDD8, B3LIC1, B4UN04, C6Y4C8, P0CS24, P0CS25, P41806, Q0CXF5, Q0UV26, Q1DPX9, Q2HDV5, Q3ZAQ7, Q4WX68, Q5B905, Q5RDV3, Q6BXM0, Q6CDK3, Q6CQP9, Q75EI3, Q78T54, Q7S158, A5JYQ9, B3M9A8, B3NIN0, B4IAB8, B4PET6, B4QJ33, B8JLV7, Q28GR4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 130 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	8	56.6×	5e-11
Insulin receptor recycling	12	48.1×	2e-15
Transferrin endocytosis and recycling	11	42.7×	1e-13
ROS and RNS production in phagocytes	11	38.9×	3e-13
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	5	20.7×	3e-04
Amino acids regulate mTORC1	8	16.9×	2e-06
Ion channel transport	14	14.1×	8e-11

GO biological processes:

GO term	Partners	Fold	FDR
vacuolar acidification	11	66.1×	2e-15
synaptic vesicle lumen acidification	7	53.7×	7e-09
lysosomal lumen acidification	7	38.7×	7e-08
proton transmembrane transport	13	33.2×	3e-14
regulation of macroautophagy	8	19.4×	9e-07
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	7	19.3×	6e-06
ERAD pathway	6	8.9×	4e-03
transmembrane transport	6	8.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	47
Likely benign	33
Benign	13

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
208720	NM_001017980.4(VMA21):c.163+4A>G	Pathogenic
208798	NM_001017980.4(VMA21):c.54-27A>C	Pathogenic
208799	NM_001017980.4(VMA21):c.54-27A>T	Pathogenic
208801	NM_001017980.4(VMA21):c.164-7T>G	Pathogenic
208804	NM_001017980.4(VMA21):c.164-6T>G	Pathogenic
208805	NM_001017980.4(VMA21):c.*13_*104del	Pathogenic
208806	NM_001017980.4(VMA21):c.54-16_54-8del	Pathogenic
208802	NM_001017980.4(VMA21):c.272G>C (p.Gly91Ala)	Likely pathogenic

SpliceAI

467 predictions. Top by Δscore:

Variant	Effect	Δscore
X:151397357:TTC:T	donor_gain	1.0000
X:151397425:G:T	donor_gain	1.0000
X:151405053:G:GT	donor_gain	1.0000
X:151405060:G:GG	donor_gain	1.0000
X:151397321:GA:G	donor_gain	0.9900
X:151397322:A:G	donor_gain	0.9900
X:151397357:TTCAG:T	donor_loss	0.9900
X:151397358:TCAG:T	donor_loss	0.9900
X:151397361:GGTAG:G	donor_loss	0.9900
X:151397362:G:GA	donor_loss	0.9900
X:151397363:T:G	donor_loss	0.9900
X:151397416:GGCT:G	donor_gain	0.9900
X:151403709:A:AG	donor_gain	0.9900
X:151405046:C:T	donor_gain	0.9900
X:151397357:T:G	donor_gain	0.9800
X:151397352:C:CG	donor_gain	0.9700
X:151397425:G:GT	donor_gain	0.9700
X:151403629:A:AG	acceptor_gain	0.9700
X:151403630:G:GG	acceptor_gain	0.9700
X:151403630:GA:G	acceptor_gain	0.9700
X:151403630:GAA:G	acceptor_gain	0.9700
X:151403630:GAAAT:G	acceptor_gain	0.9700
X:151405183:G:GG	donor_gain	0.9600
X:151397352:C:G	donor_gain	0.9500
X:151403625:TTCCA:T	acceptor_loss	0.9300
X:151403626:TCCA:T	acceptor_loss	0.9300
X:151403627:CCAGA:C	acceptor_loss	0.9300
X:151403628:CA:C	acceptor_loss	0.9300
X:151403629:A:AT	acceptor_loss	0.9300
X:151403630:G:GA	acceptor_loss	0.9300

AlphaMissense

646 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:151403699:C:A	P41H	1.000
X:151403678:C:A	T34K	0.999
X:151403687:T:A	M37K	0.999
X:151403687:T:G	M37R	0.999
X:151403699:C:G	P41R	0.999
X:151404955:C:A	A68D	0.999
X:151404958:C:A	A69D	0.999
X:151404991:T:A	L80Q	0.999
X:151404994:C:A	A81D	0.999
X:151404999:T:C	F83L	0.999
X:151405001:T:A	F83L	0.999
X:151405001:T:G	F83L	0.999
X:151405012:C:A	A87D	0.999
X:151403666:T:A	L30H	0.998
X:151403666:T:C	L30P	0.998
X:151403678:C:G	T34R	0.998
X:151403698:C:T	P41S	0.998
X:151403704:G:A	G43R	0.998
X:151403704:G:C	G43R	0.998
X:151403705:G:A	G43E	0.998
X:151403713:T:C	F46L	0.998
X:151403715:C:A	F46L	0.998
X:151403715:C:G	F46L	0.998
X:151404967:C:A	A72E	0.998
X:151404979:T:A	V76D	0.998
X:151404981:C:G	H77D	0.998
X:151404982:A:G	H77R	0.998
X:151404991:T:C	L80P	0.998
X:151403674:T:C	F33L	0.997
X:151403676:C:A	F33L	0.997

dbSNP variants (sampled 300 via entrez): RS1000238164 (X:151396613 T>C), RS1000296290 (X:151396327 G>A), RS1000458857 (X:151404665 C>A,T), RS1001633132 (X:151405823 C>T), RS1001696795 (X:151397210 C>G,T), RS1001763505 (X:151406287 A>G), RS1001905369 (X:151395588 G>T), RS1002146023 (X:151399952 C>T), RS1002480266 (X:151394833 C>T), RS1002497087 (X:151400489 A>G), RS1002899245 (X:151408039 G>A,C), RS1003226200 (X:151399149 T>A), RS1003761813 (X:151403102 C>A), RS1004031301 (X:151395488 TG>T), RS1004103129 (X:151395781 T>C)

Disease associations

OMIM: gene MIM:300913 | disease phenotypes: MIM:310440

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked myopathy with excessive autophagy	Strong	X-linked

Mondo (1): X-linked myopathy with excessive autophagy (MONDO:0010684)

Orphanet (1): X-linked myopathy with excessive autophagy (Orphanet:25980)

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0001249	Intellectual disability
HP:0001270	Motor delay
HP:0001319	Neonatal hypotonia
HP:0001371	Flexion contracture
HP:0001419	X-linked recessive inheritance
HP:0001626	Abnormality of the cardiovascular system
HP:0002093	Respiratory insufficiency
HP:0002486	Myotonia
HP:0002650	Scoliosis
HP:0003198	Myopathy
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003391	Gowers sign
HP:0003551	Difficulty climbing stairs
HP:0003677	Slowly progressive
HP:0003713	Muscle fiber necrosis
HP:0003829	Typified by incomplete penetrance
HP:0007941	Limited extraocular movements
HP:0008956	Proximal lower limb amyotrophy
HP:0008994	Proximal lower limb muscle weakness
HP:0009046	Difficulty running
HP:0011463	Childhood onset
HP:0025717	Skeletal muscle autophagosome accumulation

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536522	Vacuolar myopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067119 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.56	Kd	2770	nM	CHEMBL5653589
5.56	ED50	2770	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149767: Binding affinity to human VMA21 incubated for 45 mins by Kinobead based pull down assay	kd	2.7702	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression, affects expression	3
Ozone	affects expression, affects cotreatment, increases expression, increases abundance	2
Smoke	decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
sodium arsenite	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Ethanol	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Cadmium	increases abundance, increases expression	1
Estradiol	increases expression	1
Ivermectin	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1
Volatile Organic Compounds	increases expression, affects cotreatment	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652809	Binding	Binding affinity to human VMA21 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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