IST1

Summary

IST1 (IST1 factor associated with ESCRT-III, HGNC:28977) is a protein-coding gene on chromosome 16q22.2, encoding IST1 homolog (P53990). ESCRT-III-like protein involved in cytokinesis, nuclear envelope reassembly and endosomal tubulation.

This gene encodes a protein with MIT-interacting motifs that interacts with components of endosomal sorting complexes required for transport (ESCRT). ESCRT functions in vesicle budding, such as that which occurs during membrane abscission in cytokinesis. There is a pseudogene for this gene on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 9798 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 75 total
• MANE Select transcript: NM_001270975

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28977
Approved symbol	IST1
Name	IST1 factor associated with ESCRT-III
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Aliases	CHMP8
Ensembl gene	ENSG00000182149
Ensembl biotype	protein_coding
OMIM	616434
Entrez	9798

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 38 protein_coding, 6 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000329908, ENST00000378798, ENST00000378799, ENST00000424485, ENST00000439924, ENST00000456820, ENST00000534994, ENST00000535424, ENST00000536027, ENST00000537571, ENST00000537613, ENST00000538104, ENST00000538565, ENST00000538709, ENST00000538850, ENST00000539186, ENST00000540296, ENST00000541180, ENST00000541571, ENST00000541918, ENST00000544564, ENST00000545388, ENST00000545518, ENST00000566536, ENST00000568581, ENST00000606369, ENST00000880113, ENST00000880114, ENST00000880115, ENST00000880116, ENST00000880117, ENST00000880118, ENST00000880119, ENST00000880120, ENST00000916862, ENST00000916863, ENST00000916864, ENST00000916865, ENST00000916866, ENST00000916867, ENST00000916868, ENST00000916869, ENST00000916870, ENST00000916871, ENST00000916872, ENST00000916873, ENST00000916874

RefSeq mRNA: 6 — MANE Select: NM_001270975 NM_001270975, NM_001270976, NM_001270977, NM_001270978, NM_001270979, NM_014761

CCDS: CCDS10905, CCDS59271, CCDS59272, CCDS59273, CCDS59274

Canonical transcript exons

ENST00000378799 — 10 exons

Exon	Start	End
ENSE00002317756	71895531	71895589
ENSE00003480546	71924769	71924817
ENSE00003539054	71923288	71923380
ENSE00003543488	71920739	71920822
ENSE00003565480	71917047	71917134
ENSE00003572981	71921343	71921453
ENSE00003660256	71927614	71931199
ENSE00003708236	71916462	71916642
ENSE00003710128	71915626	71915728
ENSE00003785909	71922474	71922680

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0629 / max 237.9970, expressed in 1780 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154935	64.7855	1823
154933	11.0629	1780

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	98.96	gold quality
mucosa of stomach	UBERON:0001199	98.93	gold quality
rectum	UBERON:0001052	98.92	gold quality
right ovary	UBERON:0002118	98.90	gold quality
right uterine tube	UBERON:0001302	98.88	gold quality
skin of leg	UBERON:0001511	98.87	gold quality
skin of abdomen	UBERON:0001416	98.86	gold quality
body of uterus	UBERON:0009853	98.86	gold quality
endocervix	UBERON:0000458	98.84	gold quality
gall bladder	UBERON:0002110	98.83	gold quality
adenohypophysis	UBERON:0002196	98.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.80	gold quality
pituitary gland	UBERON:0000007	98.78	gold quality
ectocervix	UBERON:0012249	98.78	gold quality
right lobe of thyroid gland	UBERON:0001119	98.76	gold quality
right lung	UBERON:0002167	98.76	gold quality
left lobe of thyroid gland	UBERON:0001120	98.73	gold quality
tibial nerve	UBERON:0001323	98.72	gold quality
upper lobe of left lung	UBERON:0008952	98.66	gold quality
metanephros cortex	UBERON:0010533	98.66	gold quality
left uterine tube	UBERON:0001303	98.65	gold quality
transverse colon	UBERON:0001157	98.60	gold quality
calcaneal tendon	UBERON:0003701	98.60	gold quality
minor salivary gland	UBERON:0001830	98.58	gold quality
descending thoracic aorta	UBERON:0002345	98.51	gold quality
granulocyte	CL:0000094	98.49	gold quality
body of stomach	UBERON:0001161	98.49	gold quality
thyroid gland	UBERON:0002046	98.49	gold quality
right testis	UBERON:0004534	98.49	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

112 targeting IST1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6124	99.87	69.78	3551
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-765	99.84	68.24	2442

Literature-anchored findings (GeneRIF, showing 22)

• OLC1 (KIAA0174) is a candidate oncogene in lung cancer whose expression may be regulated by exposure to cigarette smoke. (PMID:19001599)
• IST1 and CHMP1 act together to recruit and modulate specific VPS4 activities required during the final stages of cell division. (PMID:19129479)
• hIST1 is essential for cytokinesis in mammalian cells. (PMID:19129480)
• Data show that the N-terminal core domains of increased sodium tolerance-1 (IST1) and charged multivesicular body protein-3 (CHMP3) form equivalent four-helix bundles, revealing that IST1 is a previously unrecognized ESCRT-III family member. (PMID:19525971)
• These data suggest that Ist1 interaction is important for spartin recruitment to the midbody and that spartin participates in cytokinesis. (PMID:20719964)
• Results demonstrate that human calpain 7 is proteolytically active, and imply that calpain 7 is activated by ESCRT-III-related protein IST1. (PMID:20849418)
• These results demonstrate that cigarette smoke regulates OLC1 expression in lung cancer cells by compromising its ubiquitination and subsequent degradation through the ubiquitin E3 ligase APC. (PMID:21439932)
• The interaction between CL7MIT and CHMP1B and between CL7MIT and IST1 became stronger when IST1 or CHMP1B was additionally coexpressed, suggesting formation of ternary complex of calpain-7, IST1 and CHMP1B. (PMID:21616915)
• OLC1 over-expression is an important factor in epithelial ovarian carcinoma prognosis and can be a potential biomarker for ovarian carcinoma. (PMID:23609236)
• the binding of ALG-2 to IST1 is Ca(2+)-dependent (PMID:23649269)
• The results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. (PMID:23897888)
• Over-expression of the OCL1 is associated with colorectal cancer. (PMID:24403489)
• Overexpression of OLC1 promotes tumorigenesis of human esophageal squamous cell carcinoma. (PMID:24608342)
• Findings indicate that a high expression level of overexpressed in lung cancer 1 (OLC1) serves as a biomarker for poor prognosis for breast cancer, suggesting that OLC1 may be a potential target of antiangiogenic therapy for breast cancer. (PMID:24880589)
• Crystal structures of three molecular complexes reveal that IST1 binds to the MIT domains of VPS4 and LIP5. (PMID:25657007)
• Structural and biochemical studies reveal an unusually tight interaction between ULK3 and IST1, an ESCRT-III subunit required for cytokinetic abscission. (PMID:26011858)
• Nuclear overexpression of OLC1 was associated with clinicopathological parameters and could predict a poor overall survival in gastric adenocarcinoma. (PMID:28038462)
• The expression of OLC1 in the tumor tissues of lung adenocarcinoma is higher than that in squamous cell carcinoma. (PMID:28532543)
• Visualization of IST1 structures in cells lacking the microtubule-severing enzyme spastin and in cells depleted of specific ESCRT-III components or the ATPase VPS4 demonstrated the contribution of these components to the organization and function of ESCRTs in cells. (PMID:30110633)
• To learn how certain ESCRT-IIIs shape positively curved membranes, we determined structures of human membrane-bound CHMP1B-only, membrane-bound CHMP1B + IST1, and IST1-only filaments by cryo-EM (PMID:32251413)
• Friction-driven membrane scission by the human ESCRT-III proteins CHMP1B and IST1. (PMID:35858336)
• Cigarette smoking-related OLC1 overexpression associated with poor prognosis in bladder urothelial carcinoma. (PMID:38880167)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ist1	ENSDARG00000051888
mus_musculus	Ist1	ENSMUSG00000031729
rattus_norvegicus	Ist1	ENSRNOG00000015144
drosophila_melanogaster	Ist1	FBGN0035715
caenorhabditis_elegans		WBGENE00010736

Protein

Protein identifiers

IST1 homolog — P53990 (reviewed: P53990)

Alternative names: Charged multivesicular body protein 8, Putative MAPK-activating protein PM28

All UniProt accessions (11): P53990, E9PF00, F5GXM3, H3BMU1, H3BPP6, H3BQ38, H3BQF7, H3BRE2, H3BUI0, J3KR23, J3QQP8

UniProt curated annotations — full annotation on UniProt →

Function. ESCRT-III-like protein involved in cytokinesis, nuclear envelope reassembly and endosomal tubulation. Is required for efficient abscission during cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. During late anaphase, involved in nuclear envelope reassembly and mitotic spindle disassembly together with the ESCRT-III complex: IST1 acts by mediating the recruitment of SPAST to the nuclear membrane, leading to microtubule severing. Recruited to the reforming nuclear envelope (NE) during anaphase by LEMD2. Regulates early endosomal tubulation together with the ESCRT-III complex by mediating the recruitment of SPAST.

Subunit / interactions. Interacts with CHMP1A, CHMP1B, VPS4A and VTA1. Interacts with SPAST, STAMBP, and USP8. May interact with VPS37B. May associate with the ESCRT-I complex. Interacts with MITD1, in competition with VSP4. Interacts with SPART (via MIT domain); leading to the recruitment of SPART to midbodies. Interacts with SPAST.

Subcellular location. Cytoplasmic vesicle. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Midbody. Nucleus envelope.

Similarity. Belongs to the IST1 family.

Isoforms (6)

UniProt ID	Names	Canonical?
P53990-1	1	yes
P53990-2	2
P53990-5	5
P53990-4	4
P53990-3	3
P53990-6	6

RefSeq proteins (6): NP_001257904, NP_001257905, NP_001257906, NP_001257907, NP_001257908, NP_055576 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005061	Ist1	Family
IPR042277	IST1-like	Homologous_superfamily

Pfam: PF03398

UniProt features (35 total): helix 11, splice variant 6, region of interest 5, mutagenesis site 5, modified residue 2, turn 2, short sequence motif 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
7S7J	X-RAY DIFFRACTION	1.15
4WZX	X-RAY DIFFRACTION	1.39
4U7E	X-RAY DIFFRACTION	1.6
4U7I	X-RAY DIFFRACTION	1.79
3FRR	X-RAY DIFFRACTION	1.8
4U7Y	X-RAY DIFFRACTION	2.5
3FRS	X-RAY DIFFRACTION	2.61
8UC6	X-RAY DIFFRACTION	2.7
8V2S	ELECTRON MICROSCOPY	2.72
6E8G	ELECTRON MICROSCOPY	2.9
8V2Q	ELECTRON MICROSCOPY	2.95
8V2R	ELECTRON MICROSCOPY	3.01
6TZ5	ELECTRON MICROSCOPY	3.1
6TZ4	ELECTRON MICROSCOPY	3.2
3JC1	ELECTRON MICROSCOPY	4
6TZA	ELECTRON MICROSCOPY	7.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P53990-F1	73.90	0.50

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): 43, 4

Mutagenesis-validated functional residues (5):

Position	Phenotype
323	diminishes interaction with vps4a. greatly diminishes interaction with vps4a; when associated with a-353.
326	diminishes interaction with vps4a. greatly diminishes interaction with vps4a and abolishes interaction with vta1; when a
353	diminishes interaction with vps4a. greatly diminishes interaction with vps4a and abolishes interaction with vta1; when a
360–361	abolishes interaction with vta1, mitd1 and usp8; diminishes interaction with vps4a.
360	diminishes interaction with vps4a. greatly diminishes interaction with vps4a; when associated with d-326.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9668328	Sealing of the nuclear envelope (NE) by ESCRT-III
R-HSA-1640170	Cell Cycle
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-2555396	Mitotic Metaphase and Anaphase
R-HSA-2995410	Nuclear Envelope (NE) Reassembly
R-HSA-68882	Mitotic Anaphase
R-HSA-68886	M Phase
R-HSA-69278	Cell Cycle, Mitotic

MSigDB gene sets: 267 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_MITOTIC_CYTOKINESIS, GOBP_REGULATION_OF_COLLATERAL_SPROUTING, REACTOME_INNATE_IMMUNE_SYSTEM, MORF_MBD4, chr16q22, GOBP_ENDOSOME_ORGANIZATION, MORF_RAB5A, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_VESICLE_ORGANIZATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, GOBP_GROWTH

GO Biological Process (11): intracellular protein localization (GO:0008104), protein transport (GO:0015031), multivesicular body assembly (GO:0036258), establishment of protein localization (GO:0045184), positive regulation of proteolysis (GO:0045862), collateral sprouting (GO:0048668), positive regulation of collateral sprouting (GO:0048672), cell division (GO:0051301), cytoskeleton-dependent cytokinesis (GO:0061640), midbody abscission (GO:0061952), ESCRT III complex disassembly (GO:1904903)

GO Molecular Function (6): protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), cadherin binding (GO:0045296), MIT domain binding (GO:0090541), protein binding (GO:0005515)

GO Cellular Component (14): chromatin (GO:0000785), extracellular region (GO:0005576), nuclear envelope (GO:0005635), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), centrosome (GO:0005813), cytosol (GO:0005829), midbody (GO:0030496), azurophil granule lumen (GO:0035578), extracellular exosome (GO:0070062), Flemming body (GO:0090543), nucleus (GO:0005634), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Innate Immune System	1
Nuclear Envelope (NE) Reassembly	1
Immune System	1
M Phase	1
Mitotic Anaphase	1
Mitotic Metaphase and Anaphase	1
Cell Cycle, Mitotic	1
Cell Cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	3
protein binding	2
binding	2
intracellular membrane-bounded organelle	2
macromolecule localization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
multivesicular body organization	1
organelle assembly	1
establishment of localization	1
proteolysis	1
regulation of proteolysis	1
positive regulation of protein metabolic process	1
axonogenesis	1
developmental cell growth	1
developmental growth involved in morphogenesis	1
positive regulation of cell growth	1
positive regulation of developmental growth	1
collateral sprouting	1
regulation of collateral sprouting	1
positive regulation of axonogenesis	1
cellular process	1
cytokinesis	1
membrane organization	1
mitotic cytokinetic process	1
ESCRT complex disassembly	1
cell adhesion molecule binding	1
protein domain specific binding	1
chromosome	1
nucleus	1
endomembrane system	1
organelle envelope	1
centriole	1
microtubule organizing center	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

1110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IST1	CHMP1B	Q7LBR1	996
IST1	SPAST	Q9UBP0	987
IST1	CHMP6	Q96FZ7	984
IST1	CHMP1A	Q9HD42	984
IST1	CHMP5	Q9NZZ3	974
IST1	CHMP3	Q9Y3E7	970
IST1	A0A140T963	A0A140T963	967
IST1	CHMP2A	O43633	949
IST1	CHMP7	Q8WUX9	892
IST1	VTA1	Q9NP79	878
IST1	CHMP4A	Q9BY43	860
IST1	VPS4B	O75351	811
IST1	VPS4A	Q9UN37	803
IST1	CHMP4C	Q96CF2	803
IST1	CHMP2B	Q9UQN3	746

IntAct

144 interactions, top by confidence:

A	B	Type	Score
IST1	APEH	psi-mi:“MI:0915”(physical association)	0.750
APEH	IST1	psi-mi:“MI:0915”(physical association)	0.750
PDCD6	SEC31A	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CAPN7	IST1	psi-mi:“MI:0915”(physical association)	0.680
IST1	CAPN7	psi-mi:“MI:0407”(direct interaction)	0.680
IST1	CAPN7	psi-mi:“MI:0915”(physical association)	0.680
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
CAPN7	IST1	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	IST1	psi-mi:“MI:0915”(physical association)	0.560
IST1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
VPS9D1	IST1	psi-mi:“MI:0915”(physical association)	0.560
VPS4A	CHMP2A	psi-mi:“MI:0914”(association)	0.550
CLTB	PIK3C2A	psi-mi:“MI:0914”(association)	0.530
CHMP1B	IST1	psi-mi:“MI:0914”(association)	0.530
VTA1	CHMP2A	psi-mi:“MI:0914”(association)	0.530
VPS4A	IST1	psi-mi:“MI:0914”(association)	0.530
ATXN1	IST1	psi-mi:“MI:0915”(physical association)	0.510
USP8	IST1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (151): IST1 (Two-hybrid), CAPN7 (Two-hybrid), UBQLN1 (Two-hybrid), IST1 (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), IST1 (Two-hybrid), AP1G2 (Co-fractionation), IST1 (Co-fractionation), IST1 (Co-fractionation), MIB2 (Co-fractionation), VPS4A (Co-fractionation), VPS4B (Co-fractionation), IST1 (Affinity Capture-MS), IST1 (Affinity Capture-MS), IST1 (Affinity Capture-MS)

ESM2 similar proteins: A1L2S8, A2RRV3, A4IG66, A6H8J1, B5DF93, D4A2Y9, F1NVK6, O08719, O94876, O95071, P53990, P62447, P70429, P80667, Q08B53, Q0P5B1, Q0VFM0, Q19951, Q1KKR9, Q1KKT4, Q28HF6, Q2T9I5, Q3TC46, Q3ZBV1, Q503U3, Q5F3I0, Q5R6G8, Q5R891, Q5R8Q4, Q5XI29, Q5XJA3, Q62671, Q66IE4, Q69ZZ6, Q6DFJ8, Q6P870, Q6PFM4, Q80TP3, Q86TB9, Q8BHR2

Diamond homologs: O74490, P53843, P53990, Q3ZBV1, Q54I39, Q568Z6, Q5R6G8, Q9CX00

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IST1	“up-regulates activity”	SPAST	relocalization
ULK3	“down-regulates activity”	IST1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Endosomal Sorting Complex Required For Transport (ESCRT)	8	34.7×	3e-08
Budding and maturation of HIV virion	7	33.6×	3e-07
Late endosomal microautophagy	5	19.2×	1e-03
Clathrin-mediated endocytosis	7	7.0×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
nuclear membrane reassembly	7	58.8×	3e-09
viral budding via host ESCRT complex	8	54.4×	3e-10
multivesicular body sorting pathway	7	47.6×	1e-08
multivesicular body assembly	10	44.6×	1e-11
late endosome to lysosome transport	5	42.0×	6e-06
midbody abscission	6	37.3×	9e-07
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	8	36.9×	6e-09
membrane fission	10	34.8×	1e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3955 predictions. Top by Δscore:

Variant	Effect	Δscore
16:71846100:GGCTG:G	donor_gain	1.0000
16:71846101:GCTGG:G	donor_gain	1.0000
16:71847909:G:GT	donor_gain	1.0000
16:71848004:TTCTA:T	acceptor_loss	1.0000
16:71848005:TCTA:T	acceptor_loss	1.0000
16:71848008:A:AG	acceptor_gain	1.0000
16:71848008:AGG:A	acceptor_loss	1.0000
16:71848009:G:GA	acceptor_loss	1.0000
16:71848009:G:GG	acceptor_gain	1.0000
16:71860668:TCTCA:T	acceptor_gain	1.0000
16:71860669:CTCA:C	acceptor_gain	1.0000
16:71860669:CTCAC:C	acceptor_gain	1.0000
16:71860670:TCA:T	acceptor_gain	1.0000
16:71860670:TCACT:T	acceptor_gain	1.0000
16:71860671:CA:C	acceptor_gain	1.0000
16:71860671:CAC:C	acceptor_gain	1.0000
16:71860672:ACTG:A	acceptor_loss	1.0000
16:71860673:C:CC	acceptor_gain	1.0000
16:71860673:C:CG	acceptor_loss	1.0000
16:71864985:T:TA	donor_gain	1.0000
16:71879899:ATACT:A	donor_loss	1.0000
16:71879901:ACT:A	donor_loss	1.0000
16:71879902:CTC:C	donor_loss	1.0000
16:71879904:CA:C	donor_loss	1.0000
16:71879905:A:AC	donor_gain	1.0000
16:71879905:ACA:A	donor_loss	1.0000
16:71879906:C:CG	donor_gain	1.0000
16:71879906:CA:C	donor_gain	1.0000
16:71879906:CAGTG:C	donor_gain	1.0000
16:71880019:CTAAC:C	acceptor_gain	1.0000

AlphaMissense

2365 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000025639 (16:71899094 A>T), RS1000108891 (16:71923567 C>G), RS1000192989 (16:71916899 C>A,T), RS1000214207 (16:71903001 C>A), RS1000224223 (16:71917212 T>A,C), RS1000287692 (16:71895226 G>A), RS1000288306 (16:71900504 A>G), RS1000338976 (16:71900757 A>G), RS1000344998 (16:71929744 A>C,G), RS1000385612 (16:71921857 G>A), RS1000508698 (16:71919861 T>C), RS1000516599 (16:71903774 G>A), RS1000634420 (16:71905602 A>G,T), RS1000687062 (16:71922545 C>T), RS1000756549 (16:71921613 G>A,T)

Disease associations

OMIM: gene MIM:616434 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000253_4	Attention deficit hyperactivity disorder and conduct disorder	7.000000e-06
GCST003329_10	Response to anti-TNF therapy in rheumatoid arthritis	9.000000e-06
GCST005316_210	Intelligence (MTAG)	4.000000e-08
GCST010243_41	Apolipoprotein B levels	1.000000e-17
GCST90002385_82	High light scatter reticulocyte count	4.000000e-17
GCST90002386_288	High light scatter reticulocyte percentage of red cells	4.000000e-15
GCST90002405_312	Reticulocyte count	5.000000e-19
GCST90002406_437	Reticulocyte fraction of red cells	1.000000e-16

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0004337	intelligence
EFO:0004615	apolipoprotein B measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Acrolein	increases oxidation, increases abundance, affects cotreatment, increases expression	2
Nickel	decreases expression	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
bisphenol F	decreases expression, affects cotreatment	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression, increases oxidation	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
methylparaben	increases expression	1
tetrabromobisphenol A	decreases expression	1
mercuric bromide	affects cotreatment, decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2A5	HAP1 IST1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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