CHMP5

Summary

CHMP5 (charged multivesicular body protein 5, HGNC:26942) is a protein-coding gene on chromosome 9p13.3, encoding Charged multivesicular body protein 5 (Q9NZZ3). Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. It is a selective cancer dependency (DepMap: 75.2% of cell lines).

CHMP5 belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (MIM 164010), is required for both MVB formation and regulation of cell cycle progression (Tsang et al., 2006 [PubMed 16730941]).

Source: NCBI Gene 51510 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 31 total
• Cancer dependency (DepMap): dependent in 75.2% of screened cell lines
• MANE Select transcript: NM_016410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26942
Approved symbol	CHMP5
Name	charged multivesicular body protein 5
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Spike, Vps60, CGI-34, HSPC177
Ensembl gene	ENSG00000086065
Ensembl biotype	protein_coding
OMIM	610900
Entrez	51510

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000223500, ENST00000419016, ENST00000487080, ENST00000909949, ENST00000909950, ENST00000909951, ENST00000909952, ENST00000909953, ENST00000909954, ENST00000937844, ENST00000937845, ENST00000937846, ENST00000937847, ENST00000948350, ENST00000948351

RefSeq mRNA: 2 — MANE Select: NM_016410 NM_001195536, NM_016410

CCDS: CCDS56569, CCDS6537

Canonical transcript exons

ENST00000223500 — 8 exons

Exon	Start	End
ENSE00000695875	33276456	33276564
ENSE00000695919	33278113	33278225
ENSE00000832793	33280809	33282070
ENSE00000928063	33265049	33265147
ENSE00000928064	33266010	33266114
ENSE00000928065	33267853	33267899
ENSE00000928066	33270623	33270716
ENSE00000928067	33271152	33271223

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.2407 / max 1684.1445, expressed in 1825 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96442	79.0740	1824
96443	1.7805	770
96441	0.3382	138
96440	0.0480	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	99.44	gold quality
epithelium of nasopharynx	UBERON:0001951	99.39	gold quality
nasopharynx	UBERON:0001728	99.37	gold quality
esophagus squamous epithelium	UBERON:0006920	99.35	gold quality
palpebral conjunctiva	UBERON:0001812	99.34	gold quality
amniotic fluid	UBERON:0000173	99.32	gold quality
visceral pleura	UBERON:0002401	98.94	gold quality
sperm	CL:0000019	98.86	gold quality
eye	UBERON:0000970	98.78	gold quality
parietal pleura	UBERON:0002400	98.66	gold quality
pleura	UBERON:0000977	98.65	gold quality
choroid plexus epithelium	UBERON:0003911	98.62	gold quality
gingival epithelium	UBERON:0001949	98.58	gold quality
epithelium of esophagus	UBERON:0001976	98.48	gold quality
squamous epithelium	UBERON:0006914	98.34	gold quality
male germ cell	CL:0000015	98.31	gold quality
bronchial epithelial cell	CL:0002328	98.29	gold quality
gingiva	UBERON:0001828	98.13	gold quality
endothelial cell	CL:0000115	97.95	gold quality
jejunal mucosa	UBERON:0000399	97.90	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.82	gold quality
epithelium of bronchus	UBERON:0002031	97.79	gold quality
bronchus	UBERON:0002185	97.70	gold quality
renal glomerulus	UBERON:0000074	97.66	gold quality
metanephric glomerulus	UBERON:0004736	97.61	gold quality
tibia	UBERON:0000979	97.58	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.54	gold quality
nephron tubule	UBERON:0001231	97.51	gold quality
oral cavity	UBERON:0000167	97.41	gold quality
secondary oocyte	CL:0000655	97.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	14.23
E-ANND-3	yes	12.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting CHMP5, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-29B-2-5P	99.67	68.98	1726

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 75.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• The pnas-2 gene may be closely related with apotosis of arsenic sulfide treated APL cells. (PMID:17708794)
• PNAS-2 was shown to be anti-apoptotic and may participate in leukemogenesis (PMID:17855796)
• pnas-2 is specifically up-regulated in acute leukemia patients. (PMID:18426649)
• after CHMP5 inhibition, both Granzyme B/Perforin apoptotic pathway and apoptosis-inducing factor-mediated necrotic pathway were activated, while autophagic pathway was not activated (PMID:23619569)
• ESCRT-III protein CHMP5 inhibits LIP5-mediated VPS4 activation by inducing a moderate conformational change within LIP5. (PMID:25637630)
• CHMP5 might be involved in the homeostatic regulation of TCR on the cell surface, presumably through TCR recycling or degradation. Thus CHMP5 is implicated in TCR-mediated signaling. (PMID:26821576)
• Our findings show that CHMP5 is a direct target of MIR429 in human colon cancer cell lines and suggest that CHMP5 up-regulation as a result of reduced MIR429 expression in DSS-induced mice colitis tissues and human UC tissues may restrict apoptosis and promote cell proliferation. (PMID:30334065)
• Interactions of ubiquitin and CHMP5 with the V domain of HD-PTP reveals role for regulation of Vps4 ATPase. (PMID:34586919)
• Circ_CHMP5 aggravates oxidized low-density lipoprotein-induced damage to human umbilical vein endothelial cells through miR-516b-5p/TGFbetaR2 axis. (PMID:37212088)
• Vps60 initiates alternative ESCRT-III filaments. (PMID:37768378)
• CHMP5 attenuates osteoarthritis via inhibiting chondrocyte apoptosis and extracellular matrix degradation: involvement of NF-kappaB pathway. (PMID:38664616)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	chmp5a	ENSDARG00000038855
danio_rerio	chmp5b	ENSDARG00000103718
mus_musculus	Chmp5	ENSMUSG00000028419
rattus_norvegicus	Chmp5	ENSRNOG00000008672
drosophila_melanogaster	Vps60	FBGN0036740
caenorhabditis_elegans		WBGENE00018290

Paralogs (5): CHMP4B (ENSG00000101421), CHMP7 (ENSG00000147457), CHMP4C (ENSG00000164695), CHMP4A (ENSG00000254505), CHMP4BP1 (ENSG00000258469)

Protein

Protein identifiers

Charged multivesicular body protein 5 — Q9NZZ3 (reviewed: Q9NZZ3)

Alternative names: Chromatin-modifying protein 5, SNF7 domain-containing protein 2, Vacuolar protein sorting-associated protein 60

All UniProt accessions (1): Q9NZZ3

UniProt curated annotations — full annotation on UniProt →

Function. Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in HIV-1 p6- and p9-dependent virus release.

Subunit / interactions. Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Interacts with VTA1; the interaction involves soluble CHMP5. Interacts with CHMP2A. Interacts with NOD2. Interacts with BROX.

Subcellular location. Cytoplasm. Cytosol. Endosome membrane. Midbody.

Post-translational modifications. (Microbial infection) Stearoylated By S.flexneri N-epsilon-fatty acyltransferase IcsB, promoting S.flexneri evasion of autophagy. ISGylated. Isgylation inhibits its interaction with VTA1.

Induction. Up-regulated by muramyl-dipeptide and lipopolysaccharide.

Similarity. Belongs to the SNF7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NZZ3-1	1	yes
Q9NZZ3-2	2

RefSeq proteins (2): NP_001182465, NP_057494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005024	Snf7_fam	Family

Pfam: PF03357

UniProt features (17 total): sequence conflict 4, region of interest 3, mutagenesis site 2, helix 2, chain 1, coiled-coil region 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4TXR	X-RAY DIFFRACTION	1
3UM2	X-RAY DIFFRACTION	2.59
3ULY	X-RAY DIFFRACTION	2.6
3UM1	X-RAY DIFFRACTION	2.71
3UM0	X-RAY DIFFRACTION	3.1
2LXM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZZ3-F1	80.05	0.46

Functional residue map

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

Post-translational modifications (2): 86, 7

Mutagenesis-validated functional residues (2):

Position	Phenotype
7	decreased stearoylation in response to s.flexneri infection.
7–11	decreased stearoylation in response to s.flexneri infection.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-162588	Budding and maturation of HIV virion
R-HSA-917729	Endosomal Sorting Complex Required For Transport (ESCRT)

MSigDB gene sets: 316 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MITOTIC_CYTOKINESIS, REACTOME_ENDOSOMAL_SORTING_COMPLEX_REQUIRED_FOR_TRANSPORT_ESCRT, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NUCLEAR_MEMBRANE_REASSEMBLY, GOBP_LYSOSOMAL_TRANSPORT, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_ENDOSOME_ORGANIZATION, TGCGCANK_UNKNOWN, GOBP_VACUOLE_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_MEMBRANE_BIOGENESIS, GOCC_VACUOLAR_MEMBRANE

GO Biological Process (30): plasma membrane repair (GO:0001778), regulation of receptor recycling (GO:0001919), vesicle budding from membrane (GO:0006900), autophagy (GO:0006914), nucleus organization (GO:0006997), mitotic metaphase chromosome alignment (GO:0007080), regulation of centrosome duplication (GO:0010824), protein transport (GO:0015031), erythrocyte differentiation (GO:0030218), nuclear membrane reassembly (GO:0031468), late endosome to vacuole transport via multivesicular body sorting pathway (GO:0032511), multivesicular body assembly (GO:0036258), viral budding via host ESCRT complex (GO:0039702), ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162), viral budding (GO:0046755), viral budding from plasma membrane (GO:0046761), vesicle fusion with vacuole (GO:0051469), multivesicular body-lysosome fusion (GO:0061763), midbody abscission (GO:0061952), cellular response to lipopolysaccharide (GO:0071222), cellular response to muramyl dipeptide (GO:0071225), multivesicular body sorting pathway (GO:0071985), membrane fission (GO:0090148), autophagosome maturation (GO:0097352), regulation of mitotic spindle assembly (GO:1901673), late endosome to lysosome transport (GO:1902774), ESCRT III complex disassembly (GO:1904903), vacuolar transport (GO:0007034), lysosome organization (GO:0007040), endosome to lysosome transport (GO:0008333)

GO Molecular Function (2): cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (18): autophagosome membrane (GO:0000421), kinetochore (GO:0000776), ESCRT III complex (GO:0000815), nuclear pore (GO:0005643), lysosomal membrane (GO:0005765), multivesicular body (GO:0005771), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), plasma membrane (GO:0005886), midbody (GO:0030496), multivesicular body membrane (GO:0032585), extracellular exosome (GO:0070062), amphisome membrane (GO:1904930), nucleus (GO:0005634), cytoplasm (GO:0005737), endosome (GO:0005768), endosome membrane (GO:0010008), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Late Phase of HIV Life Cycle	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane organization	2
viral budding	2
vesicle fusion	2
plasma membrane organization	1
wound healing	1
receptor recycling	1
regulation of signaling	1
regulation of macromolecule metabolic process	1
vesicle organization	1
vesicle-mediated transport	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
organelle organization	1
mitotic sister chromatid segregation	1
mitotic cell cycle	1
metaphase chromosome alignment	1
mitotic cell cycle process	1
regulation of centrosome cycle	1
centrosome duplication	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
myeloid cell differentiation	1
erythrocyte homeostasis	1
membrane assembly	1
nuclear membrane organization	1
endosome transport via multivesicular body sorting pathway	1
late endosome to vacuole transport	1
multivesicular body organization	1
organelle assembly	1
ubiquitin-dependent protein catabolic process	1
protein catabolic process in the vacuole	1
multivesicular body sorting pathway	1
viral process	1
virion assembly	1
non-lytic viral release	1
vacuole fusion	1
endosome to lysosome transport via multivesicular body sorting pathway	1

Protein interactions and networks

STRING

1263 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHMP5	VTA1	Q9NP79	998
CHMP5	CHMP6	Q96FZ7	995
CHMP5	CHMP3	Q9Y3E7	989
CHMP5	A0A140T963	A0A140T963	988
CHMP5	CHMP1A	Q9HD42	978
CHMP5	IST1	P53990	974
CHMP5	VPS4A	Q9UN37	970
CHMP5	VPS4B	O75351	968
CHMP5	CHMP2A	O43633	954
CHMP5	CHMP4C	Q96CF2	919
CHMP5	CHMP1B	Q7LBR1	914
CHMP5	VPS25	Q9BRG1	895
CHMP5	CHMP7	Q8WUX9	883
CHMP5	VPS28	Q9UK41	843
CHMP5	TSG101	Q99816	779

IntAct

103 interactions, top by confidence:

A	B	Type	Score
CHMP5	VPS4B	psi-mi:“MI:0915”(physical association)	0.720
VPS4B	CHMP5	psi-mi:“MI:0915”(physical association)	0.720
VTA1	CHMP5	psi-mi:“MI:0915”(physical association)	0.660
CHMP5	STAMBP	psi-mi:“MI:0915”(physical association)	0.570
STAMBP	CHMP5	psi-mi:“MI:0915”(physical association)	0.570
MITD1	CHMP5	psi-mi:“MI:0915”(physical association)	0.560
CHMP5	MITD1	psi-mi:“MI:0915”(physical association)	0.560
CHMP5	CHMP4B	psi-mi:“MI:0915”(physical association)	0.550
CHMP4B	CHMP5	psi-mi:“MI:0915”(physical association)	0.550
NOD2	CHMP5	psi-mi:“MI:0915”(physical association)	0.550
CHMP5	NOD2	psi-mi:“MI:0915”(physical association)	0.550
VPS4A	CHMP2A	psi-mi:“MI:0914”(association)	0.550
CHMP5	NOD2	psi-mi:“MI:2364”(proximity)	0.550
CHMP2A	DECR1	psi-mi:“MI:0914”(association)	0.530
CHMP5	TCP10L	psi-mi:“MI:0914”(association)	0.530
CLTB	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
CHMP5	SH3KBP1	psi-mi:“MI:0914”(association)	0.530
CHMP5	USP8	psi-mi:“MI:0407”(direct interaction)	0.440
USP54	CHMP5	psi-mi:“MI:0407”(direct interaction)	0.440
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
CHMP5	CHMP1B	psi-mi:“MI:0915”(physical association)	0.370
CHMP5	CHMP4A	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (141): CHMP5 (Two-hybrid), MITD1 (Two-hybrid), CHMP5 (Two-hybrid), CHMP5 (Affinity Capture-RNA), CHMP4A (Co-fractionation), CHMP4B (Co-fractionation), CHMP5 (Co-fractionation), HABP4 (Co-fractionation), PSMA4 (Co-fractionation), SNRPD2 (Co-fractionation), UBA2 (Co-fractionation), CHMP5 (Proximity Label-MS), CHMP5 (Proximity Label-MS), CHMP5 (Affinity Capture-MS), CHMP5 (Affinity Capture-MS)

ESM2 similar proteins: A0JN61, B5FZ63, O14737, O43242, O82197, P02643, P13412, P27768, P48788, P49205, P50502, P50503, P56812, Q06364, Q08AG7, Q15691, Q2HJH9, Q3ZBD9, Q3ZBJ0, Q4QQV8, Q5R7Z5, Q5RBR3, Q5RBT0, Q5RF31, Q5SRX1, Q5XGW6, Q5XGY9, Q5ZHP5, Q5ZLF0, Q61166, Q66HR2, Q6DD52, Q6GL11, Q6IQ73, Q6PBL0, Q6ZVM7, Q7ZVC4, Q8K396, Q8NFI4, Q99L47

Diamond homologs: O74422, Q03390, Q4QQV8, Q54JK4, Q5FW29, Q5RBR3, Q5XGW6, Q6DD52, Q6GL11, Q6IQ73, Q753W3, Q7T339, Q8IL52, Q9D7S9, Q9FMC5, Q9LPN5, Q9NZZ3, Q9VVI9, P39929, Q9SZE4, O82197, Q5ABD0, Q5ZHP5, Q6BSH2, Q7ZVC4, Q8T0Q4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CHMP5	“form complex”	ESCRT-III	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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
Budding and maturation of HIV virion	7	43.9×	9e-08
Endosomal Sorting Complex Required For Transport (ESCRT)	7	39.7×	1e-07
Sealing of the nuclear envelope (NE) by ESCRT-III	5	26.6×	2e-04
Transcriptional and post-translational regulation of MITF-M expression and activity	5	13.7×	3e-03
HCMV Late Events	6	9.1×	3e-03
Dengue Virus-Host Interactions	8	5.6×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
nuclear membrane reassembly	6	72.5×	1e-08
midbody abscission	8	71.5×	4e-11
viral budding via host ESCRT complex	7	68.5×	9e-10
multivesicular body sorting pathway	7	68.5×	9e-10
multivesicular body assembly	9	57.8×	2e-11
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	7	46.4×	1e-08
regulation of mitotic spindle assembly	5	44.7×	5e-06
plasma membrane repair	6	42.5×	4e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1313 predictions. Top by Δscore:

Variant	Effect	Δscore
9:33264216:ACACT:A	donor_loss	1.0000
9:33264217:CACT:C	donor_loss	1.0000
9:33264218:ACTC:A	donor_loss	1.0000
9:33264219:CTCA:C	donor_loss	1.0000
9:33264220:TCA:T	donor_loss	1.0000
9:33264221:CACTG:C	donor_loss	1.0000
9:33264222:A:AC	donor_gain	1.0000
9:33264222:AC:A	donor_loss	1.0000
9:33264223:C:CA	donor_loss	1.0000
9:33264223:C:CC	donor_gain	1.0000
9:33264266:C:CA	donor_gain	1.0000
9:33264277:T:TA	donor_gain	1.0000
9:33265097:A:T	donor_gain	1.0000
9:33265164:GCA:G	donor_gain	1.0000
9:33266006:TAAG:T	acceptor_loss	1.0000
9:33266007:AAGGT:A	acceptor_gain	1.0000
9:33266008:A:G	acceptor_gain	1.0000
9:33266009:G:GT	acceptor_loss	1.0000
9:33266112:AAG:A	donor_loss	1.0000
9:33266114:GG:G	donor_loss	1.0000
9:33266115:GT:G	donor_loss	1.0000
9:33266116:T:A	donor_loss	1.0000
9:33267170:ACT:A	acceptor_gain	1.0000
9:33267172:T:A	acceptor_gain	1.0000
9:33267896:GGAT:G	donor_gain	1.0000
9:33267897:GAT:G	donor_gain	1.0000
9:33267897:GATG:G	donor_gain	1.0000
9:33267900:G:GG	donor_gain	1.0000
9:33271148:TTAGG:T	acceptor_loss	1.0000
9:33271149:TAG:T	acceptor_loss	1.0000

AlphaMissense

1455 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:33270646:T:C	L82P	1.000
9:33270675:G:C	A92P	1.000
9:33271158:G:C	A108P	1.000
9:33266065:T:C	L42P	0.999
9:33267871:G:C	A65P	0.999
9:33267872:C:A	A65D	0.999
9:33270637:G:C	R79P	0.999
9:33270673:A:C	Q91P	0.999
9:33276472:T:C	L135P	0.999
9:33276492:G:C	A142P	0.999
9:33267894:G:C	K72N	0.998
9:33267894:G:T	K72N	0.998
9:33270657:T:C	S86P	0.998
9:33270676:C:A	A92D	0.998
9:33270693:T:C	S98P	0.998
9:33271153:T:A	V106D	0.998
9:33276514:T:C	L149P	0.998
9:33278116:T:C	L167S	0.998
9:33265095:G:A	G6E	0.997
9:33266103:G:C	G55R	0.997
9:33267860:T:A	V61D	0.997
9:33267878:G:C	R67P	0.997
9:33267884:T:C	L69S	0.997
9:33270634:A:C	Q78P	0.997
9:33270655:A:C	Q85P	0.997
9:33270667:T:G	M89R	0.997
9:33271159:C:A	A108D	0.997
9:33271170:G:A	G112R	0.997
9:33271170:G:C	G112R	0.997
9:33276510:G:C	A148P	0.997

dbSNP variants (sampled 300 via entrez): RS1000011527 (9:33269702 C>T), RS1000127245 (9:33280399 C>G), RS1000234535 (9:33263396 C>A,G), RS1000289708 (9:33276647 G>A,T), RS1000510498 (9:33269429 A>G,T), RS1000666029 (9:33281070 T>C,G), RS1000773231 (9:33270915 C>A,T), RS1000839816 (9:33274464 C>G), RS1000888666 (9:33269675 T>A), RS1000939596 (9:33281400 T>C), RS1000982073 (9:33264981 G>A), RS1001164147 (9:33274894 G>A), RS1001285661 (9:33274901 C>T), RS1001287597 (9:33264657 C>A,G,T), RS1001347764 (9:33275196 A>T)

Disease associations

OMIM: gene MIM:610900 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000824_16	Erectile dysfunction and prostate cancer treatment	1.000000e-06
GCST010796_5113	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
bisphenol A	increases expression	2
arsenic trisulfide	affects expression, decreases expression	2
Valproic Acid	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
arsenite	affects binding, increases reaction	1
zinc chromate	increases abundance, increases expression	1
ciglitazone	affects binding, increases expression	1
arsenic disulfide	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
chloropicrin	increases expression	1
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Diuron	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	decreases expression	1
Formaldehyde	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Mustard Gas	increases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Thimerosal	increases expression	1

Clinical trials (associated diseases)

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