CHMP4B

Summary

CHMP4B (charged multivesicular body protein 4B, HGNC:16171) is a protein-coding gene on chromosome 20q11.22, encoding Charged multivesicular body protein 4b (Q9H444). Probable core 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: 86.4% of cell lines).

This gene encodes a member of the chromatin-modifying protein/charged multivesicular body protein (CHMP) protein family. The protein is part of the endosomal sorting complex required for transport (ESCRT) complex III (ESCRT-III), which functions in the sorting of endocytosed cell-surface receptors into multivesicular endosomes. The ESCRT machinery also functions in the final abscisson stage of cytokinesis and in the budding of enveloped viruses such as HIV-1. The three proteins of the CHMP4 subfamily interact with programmed cell death 6 interacting protein (PDCD6IP, also known as ALIX), which also functions in the ESCRT pathway. The CHMP4 proteins assemble into membrane-attached 5-nm filaments that form circular scaffolds and promote or stabilize outward budding. These polymers are proposed to help generate the luminal vesicles of multivesicular bodies. Mutations in this gene result in autosomal dominant posterior polar cataracts.

Source: NCBI Gene 128866 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 31 multiple types (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 53 total — 2 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 20 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 4
• Cancer dependency (DepMap): dependent in 86.4% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.21 (highly constrained)
• MANE Select transcript: NM_176812
• Interaction hub: 1,901 STRING partners (top 8% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16171
Approved symbol	CHMP4B
Name	charged multivesicular body protein 4B
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	dJ553F4.4, Shax1, SNF7-2, VPS32B
Ensembl gene	ENSG00000101421
Ensembl biotype	protein_coding
OMIM	610897
Entrez	128866

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

MANE Select: ENST00000217402

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000217402, ENST00000873319, ENST00001108515, ENST00001133998

RefSeq mRNA: 1 — MANE Select: NM_176812 NM_176812

CCDS: CCDS13228

Canonical transcript exons

ENST00000217402 — 5 exons

Exon	Start	End
ENSE00000661352	33811348	33811658
ENSE00000661353	33848467	33848644
ENSE00000661354	33850952	33851066
ENSE00000860068	33852077	33852203
ENSE00001288764	33853496	33854366

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 89.2518 / max 1472.6062, expressed in 1824 samples.

Highest expression (Bgee): ileal mucosa, upper arm skin, tibialis anterior, nasal cavity epithelium, mucosa of transverse colon.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CHMP4B is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	1.1e-34	-0.21	20:33821336:G:A
Muscle Skeletal	eqtl	1.0e-09	-0.13	20:33811394:C:G
Testis	eqtl	1.7e-08	-0.17	20:33830966:G:T
Esophagus Muscularis	eqtl	7.1e-08	-0.12	20:33859889:A:G
Artery Tibial	eqtl	3.0e-05	-0.10	20:33811394:C:G
Colon Sigmoid	eqtl	4.7e-05	-0.12	20:33878248:C:T
Brain Putamen basal ganglia	eqtl	1.5e-04	-0.21	20:33832268:A:G
Brain Substantia nigra	eqtl	1.5e-04	-0.25	20:33810284:A:G
Cells EBV-transformed lymphocytes	eqtl	2.7e-04	+0.17	20:33778742:T:C
Esophagus Mucosa	eqtl	5.1e-04	+0.12	20:33799296:C:T
Brain Caudate basal ganglia	eqtl	8.7e-04	-0.15	20:33832268:A:G
Heart Atrial Appendage	eqtl	8.9e-04	-0.09	20:33810489:A:C
Adipose Subcutaneous	eqtl	1.4e-03	-0.09	20:33859889:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.7e-03	-0.11	20:33865770:C:T
Adipose Visceral Omentum	eqtl	1.8e-03	-0.09	20:33817411:A:G
Breast Mammary Tissue	eqtl	3.3e-03	-0.10	20:33844581:G:A
Artery Aorta	eqtl	1.3e-02	-0.10	20:33883667:TA:T
Brain Nucleus accumbens basal ganglia	eqtl	3.1e-02	-0.12	20:33870882:G:A
Heart Left Ventricle	eqtl	3.2e-02	-0.06	20:33859889:A:G
Esophagus Gastroesophageal Junction	eqtl	4.8e-02	-0.09	20:33859889:A:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
184178	77.9988	1823
184180	6.0553	1716
184181	1.6813	1162
184179	1.5677	1012
184177	1.1812	636
184182	0.7675	404

Top tissues by expression

showing 100 of 260 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	99.50	gold quality
upper arm skin	UBERON:0004263	99.15	gold quality
tibialis anterior	UBERON:0001385	99.09	gold quality
nasal cavity epithelium	UBERON:0005384	99.00	gold quality
mucosa of transverse colon	UBERON:0004991	98.83	gold quality
kidney epithelium	UBERON:0004819	98.75	gold quality
cartilage tissue	UBERON:0002418	98.74	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.45	gold quality
mucosa of stomach	UBERON:0001199	98.44	gold quality
popliteal artery	UBERON:0002250	98.40	gold quality
tibial artery	UBERON:0007610	98.40	gold quality
left ventricle myocardium	UBERON:0006566	98.39	gold quality
transverse colon	UBERON:0001157	98.37	gold quality
prefrontal cortex	UBERON:0000451	98.35	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.35	gold quality
monocyte	CL:0000576	98.32	gold quality
colonic mucosa	UBERON:0000317	98.31	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.31	gold quality
leukocyte	CL:0000738	98.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.26	gold quality
aorta	UBERON:0000947	98.25	gold quality
right coronary artery	UBERON:0001625	98.25	gold quality
gastrocnemius	UBERON:0001388	98.23	gold quality
colon	UBERON:0001155	98.16	gold quality
anterior cingulate cortex	UBERON:0009835	98.16	gold quality
large intestine	UBERON:0000059	98.14	gold quality
frontal cortex	UBERON:0001870	98.14	gold quality
myocardium	UBERON:0002349	98.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.08	gold quality
amygdala	UBERON:0001876	98.07	gold quality
descending thoracic aorta	UBERON:0002345	98.07	gold quality
ascending aorta	UBERON:0001496	98.06	gold quality
thoracic aorta	UBERON:0001515	98.06	gold quality
postcentral gyrus	UBERON:0002581	98.04	gold quality
putamen	UBERON:0001874	98.02	gold quality
right frontal lobe	UBERON:0002810	98.02	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.02	gold quality
hypothalamus	UBERON:0001898	98.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.99	gold quality
neocortex	UBERON:0001950	97.98	gold quality
lower esophagus	UBERON:0013473	97.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.98	gold quality
ventricular zone	UBERON:0003053	97.96	gold quality
ectocervix	UBERON:0012249	97.96	gold quality
esophagus mucosa	UBERON:0002469	97.93	gold quality
esophagus	UBERON:0001043	97.92	gold quality
muscle of leg	UBERON:0001383	97.92	gold quality
nucleus accumbens	UBERON:0001882	97.92	gold quality
parietal lobe	UBERON:0001872	97.91	gold quality
pons	UBERON:0000988	97.90	gold quality
substantia nigra	UBERON:0002038	97.89	gold quality
superior frontal gyrus	UBERON:0002661	97.88	gold quality
endocervix	UBERON:0000458	97.87	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.85	gold quality
skin of leg	UBERON:0001511	97.84	gold quality
cerebral cortex	UBERON:0000956	97.80	gold quality
caudate nucleus	UBERON:0001873	97.80	gold quality
midbrain	UBERON:0001891	97.79	gold quality
heart left ventricle	UBERON:0002084	97.78	gold quality
minor salivary gland	UBERON:0001830	97.77	gold quality
intestine	UBERON:0000160	97.76	gold quality
left coronary artery	UBERON:0001626	97.76	gold quality
granulocyte	CL:0000094	97.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.75	gold quality
adult organism	UBERON:0007023	97.74	gold quality
cardiac ventricle	UBERON:0002082	97.73	gold quality
nasal cavity mucosa	UBERON:0001826	97.72	gold quality
urinary bladder	UBERON:0001255	97.71	gold quality
skin of abdomen	UBERON:0001416	97.68	gold quality
decidua	UBERON:0002450	97.68	gold quality
coronary artery	UBERON:0001621	97.67	gold quality
left adrenal gland	UBERON:0001234	97.63	gold quality
forebrain	UBERON:0001890	97.60	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.60	gold quality
zone of skin	UBERON:0000014	97.59	gold quality
rectum	UBERON:0001052	97.57	gold quality
tendon of biceps brachii	UBERON:0008188	97.54	gold quality
urethra	UBERON:0000057	97.53	gold quality
quadriceps femoris	UBERON:0001377	97.52	gold quality
left adrenal gland cortex	UBERON:0035825	97.51	gold quality
Ammon’s horn	UBERON:0001954	97.50	gold quality
gall bladder	UBERON:0002110	97.50	gold quality
spinal cord	UBERON:0002240	97.50	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.50	gold quality
right adrenal gland	UBERON:0001233	97.49	gold quality
deltoid	UBERON:0001476	97.47	gold quality
biceps brachii	UBERON:0001507	97.47	gold quality
small intestine	UBERON:0002108	97.46	gold quality
lateral globus pallidus	UBERON:0002476	97.44	gold quality
right adrenal gland cortex	UBERON:0035827	97.44	gold quality
cardiac atrium	UBERON:0002081	97.43	gold quality
body of uterus	UBERON:0009853	97.43	gold quality
right lung	UBERON:0002167	97.42	gold quality
right atrium auricular region	UBERON:0006631	97.41	gold quality
brain	UBERON:0000955	97.40	gold quality
superior vestibular nucleus	UBERON:0007227	97.36	gold quality
body of stomach	UBERON:0001161	97.35	gold quality
muscle tissue	UBERON:0002385	97.35	gold quality
trabecular bone tissue	UBERON:0002483	97.34	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	591.95
E-HCAD-4	yes	32.73
E-ANND-3	yes	7.73
E-GEOD-110499	no	267.28
E-GEOD-125970	no	14.68

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	201.7	low
Frontal cortex	tissue	180.3
Caudate putamen	tissue	176.0
Skeletal muscle	tissue	170.0	low
Colon	tissue	125.5	medium
Tongue	tissue	123.8
Pons	tissue	114.4
Urinary bladder	tissue	113.0	low
Thalamus	tissue	113.0
Small intestine	tissue	113.0	high
Cerebral cortex	tissue	112.5	medium
Somatosensory cortex	tissue	112.5
Motor cortex	tissue	109.1
Putamen	tissue	108.2
Midbrain	tissue	108.1
Postcentral gyrus	tissue	108.1
Prefrontal cortex	tissue	107.6
Superior colliculi	tissue	106.8
Vagina	tissue	105.4	low
Spinal cord	tissue	102.3
Occipital cortex	tissue	102.1
Medulla oblongata	tissue	101.5
Hippocampal formation	tissue	97.8
Duodenum	tissue	96.9	high
Entorhinal cortex	tissue	96.9
Substantia nigra	tissue	96.1
Hypothalamus	tissue	94.8
Retrosplenial and cingulate cortex	tissue	94.4
Heart muscle	tissue	93.6	medium
Temporal cortex	tissue	93.3
Rectum	tissue	92.7	medium
Ventral forebrain	tissue	92.3
Basal ganglia	tissue	91.7	medium
Septum	tissue	91.3
Stomach 1	tissue	90.5	medium
Retrosplenial cortex	tissue	89.7
Esophagus	tissue	89.6	medium
Periaqueductal gray	tissue	89.4
Locus coeruleus	tissue	84.4
Insular cortex	tissue	83.4
Corpus callosum	tissue	80.4
Salivary gland	tissue	78.6	not detected
Seminal vesicle	tissue	77.7	low
Thymus	tissue	77.1
Ovary	tissue	76.6	low
Gallbladder	tissue	75.6	medium
Nucleus accumbens	tissue	75.0
Cerebellum	tissue	74.2	high
Adrenal gland	tissue	73.8	medium
Pancreas	tissue	73.7	medium
Amygdala	tissue	73.4
Pituitary gland	tissue	73.1
Hippocampus	tissue	72.4	medium
Appendix	tissue	71.5	high
Smooth muscle	tissue	71.3	low
Skin 1	tissue	70.5	medium
Parathyroid gland	tissue	70.2	low
Placenta	tissue	70.2	medium
Prostate	tissue	68.6	medium
Lung	tissue	67.3	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (174.6), Ventral spinal cord (102.3), Area parastriata, superior (98.6), Dorsal hippocampus (97.8), Orbitofrontal gyrus, anterior (96.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NRG1

miRNA regulators (miRDB)

Targeting CHMP4B by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 65 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-135A-5P	99.36	71.85	1601

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.208, missense Z 2.9 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000217402 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
20:33,811,469–33,811,536	28 / 30.5	0.92	no
20:33,811,537–33,852,147	82 / 208.3	0.39	no
20:33,852,148–33,853,557	41 / 50.9	0.81	no
DepMap (CRISPR cell-line fitness): dependent in 86.4% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): SK-N-FI (-3.298), RPMI-7951 (-3.116), EWS502 (-2.932), DK-MG (-2.785), NCI-H226 (-2.775), SK-N-DZ (-2.738), SF-295 (-2.694), G-292, clone A141B1 (-2.62), MFE-280 (-2.619), AM-38 (-2.56), KP-N-YN (-2.527), IMR-32 (-2.478), JHOS-2 (-2.461), SK-N-AS (-2.422), MHH-ES-1 (-2.411).

Literature-anchored findings (GeneRIF, showing 21)

• CHMP4b and Alix participate in formation of multivesicular bodies by cooperating with SKD1 (PMID:12860994)
• ALIX can have a dramatic effect on HIV-1 release by binding at the CHMP4B site; the ability to use ALIX may allow HIV-1 to replicate in cells that express only low levels of Tsg101 (PMID:17428861)
• These data provide the first evidence that CHMP4B plays a vital role the maintenance of lens transparency. (PMID:17701905)
• Results suggest that efficient interaction between CHMP4s and Brox requires Brox farnesylation. (PMID:18190528)
• Study demonstrates that CHMP4A and CHMP4B proteins form novel membrane-attached filaments that can promote or stabilize negative curvature and outward budding. (PMID:18209100)
• The Bro1 domain of ALIX binds specifically to C-terminal residues of the human CHMP4B. (PMID:18511562)
• The CHMP4b- and Src-docking sites in the Bro1 domain are autoinhibited in the native state of Alix. (PMID:19016654)
• hSnf7-1 and hSnf7-2 are preferentially associated with CHMP2A and CHMP2B, respectively, and regulate the turnover of distinct transmembrane cargos such as neurotransmitter receptors in human neurons. (PMID:21975012)
• CC2D1A interaction with CHMP4B/4A blocks HIV-1 budding. (PMID:22258254)
• CHMP4B interacts directly with CC2D1A and CC2D1B with nanomolar affinity by forming a 1:1 complex. (PMID:22406677)
• CHMP4B, through its association with chromatin, may participate in the autophagolysosomal degradation of micronuclei and other extranuclear chromatin. (PMID:24741567)
• our results implied that CHMP4B could be a promising prognostic biomarker as well as a potential therapeutic target of HCC. (PMID:25874485)
• homologous domain of human Bro1 domain-containing proteins, Alix and Brox, binds CHMP4B but not STAM2, despite their high structural similarity (PMID:26866605)
• The ESCRT-III subunit CHMP4B is a key effector in abscission, whereas its paralogue, CHMP4C, is a component in the abscission checkpoint that delays abscission until chromatin is cleared from the intercellular bridge. (PMID:26929449)
• Data (including data from studies using transgenic mice) suggest that the process leading to microparticle release from cardiac myocytes involves recruitment of CHMP4B protein to the forming microparticle membrane which also contains cBIN1; plasma cBIN1 is reduced in patients with heart failure as compared to control subjects. (CHMP4B = charged multivesicular body protein 4B; cBIN1 = cardiac bridging integrator 1) (PMID:28806752)
• CHMP4B was localized to primary cilia in mammalian cells. Knockdown of CHMP4B interfered with cilium assembly and also caused fragmentation of preexisting cilia. (PMID:31914703)
• Up-regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury. (PMID:32585748)
• ESCRT-III controls nuclear envelope deformation induced by progerin. (PMID:33139753)
• The ESCRT-III protein VPS4, but not CHMP4B or CHMP2B, is pathologically increased in familial and sporadic ALS neuronal nuclei. (PMID:34281622)
• HSP90beta prevents aging-related cataract formation through regulation of the charged multivesicular body protein (CHMP4B) and p53. (PMID:37487085)
• CHMP4B and VSP4A reverse GSDMD-mediated pyroptosis by cell membrane remodeling in endometrial carcinoma. (PMID:37931722)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	chmp4bb	ENSDARG00000007323
danio_rerio	chmp4ba	ENSDARG00000016255
mus_musculus	Chmp4b	ENSMUSG00000038467
rattus_norvegicus	Chmp4bl1	ENSRNOG00000034071
rattus_norvegicus	Chmp4b	ENSRNOG00000046585
drosophila_melanogaster	shrb	FBGN0086656
caenorhabditis_elegans		WBGENE00016961

Paralogs (5): CHMP5 (ENSG00000086065), CHMP7 (ENSG00000147457), CHMP4C (ENSG00000164695), CHMP4A (ENSG00000254505), CHMP4BP1 (ENSG00000258469)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1922858) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
embryonic lethality between implantation and somite formation, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cryptococcus deneoformans JEC21	P0CR54	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CR55	100.0%	Diamond
Xenopus laevis	Q5XGW6	99.1%	Diamond
Xenopus tropicalis	Q6GL11	99.1%	Diamond
Bos taurus	A2VDY3	91.4%	Diamond
Gallus gallus	Q5ZHP5	90.6%	Diamond
Arabidopsis thaliana	Q9FY89	80.1%	Diamond
Candida albicans SC5314	Q5ABD0	69.9%	Diamond
Debaryomyces hansenii CBS767	Q6BSH2	69.9%	Diamond
Pyricularia oryzae 70-15	P0C149	68.7%	Diamond
Neurospora crassa OR74A	Q871Y8	68.7%	Diamond
Nakaseomyces glabratus CBS 138	Q6FW96	64.4%	Diamond
Saccharomyces cerevisiae S288C	P39929	61.8%	Diamond
Eremothecium gossypii ATCC 10895	Q753W3	61.8%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CJL0	60.2%	Diamond
Aspergillus nidulans FGSC A4	Q5B5E0	59.3%	Diamond
Yarrowia lipolytica CLIB122	Q6CBS3	55.2%	Diamond
Schizosaccharomyces pombe 972h-	Q9P7F7	47.6%	Diamond
Dictyostelium discoideum	Q86H98	43.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR4755	ncRNA	100616434
RALY-AS1	ncRNA	101926888
RALY	protein-coding	22913
ZNF341	protein-coding	84905
ZNF341-AS1	ncRNA	101929746
PXMP4	protein-coding	11264

Protein

Protein identifiers

Charged multivesicular body protein 4b — Q9H444 (reviewed: Q9H444)

Alternative names: Chromatin-modifying protein 4b, SNF7 homolog associated with Alix 1, SNF7-2, Vacuolar protein sorting-associated protein 32-2

All UniProt accessions (1): Q9H444

UniProt curated annotations — full annotation on UniProt →

Function. Probable core 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. Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan. Majority of the protein exists in a folded closed conformation. (Microbial infection) The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Via its interaction with PDCD6IP involved in HIV-1 p6- and p9-dependent virus release.

Subunit / interactions. Probable core 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 CHMP6 and CHMP4C. Interacts with PDCD6IP; the interaction is direct. Interacts with VPS4A; the interaction is direct. Interacts with VPS4B; the interaction is direct. Interacts with CHMP7. Interacts with CFTR; the interaction requires misfolded CFTR. Interacts with PTPN23. Interacts with CC2D1B.

Subcellular location. Cytoplasm. Cytosol. Late endosome membrane. Midbody. Nucleus envelope.

Tissue specificity. Widely expressed. Expressed at higher level in heart and skeletal muscle. Also expressed in brain, colon, thymus, spleen, kidney, liver, small intestine, placenta, lung and peripheral blood lymphocytes.

Post-translational modifications. ISGylated. Isgylation weakens its interaction with VPS4A.

Disease relevance. Cataract 31, multiple types (CTRCT31) [MIM:605387] An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT31 includes posterior polar, progressive posterior subcapsular, nuclear, and anterior subcapsular cataracts. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The acidic C-terminus and the basic N-termminus are thought to render the protein in a closed, soluble and inactive conformation through an autoinhibitory intramolecular interaction. The open and active conformation, which enables membrane binding and oligomerization, is achieved by interaction with other cellular binding partners, probably including other ESCRT components.

Miscellaneous. Its overexpression strongly inhibits HIV-1 release.

Similarity. Belongs to the SNF7 family.

RefSeq proteins (1): NP_789782* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005024	Snf7-like	Family

Pfam: PF03357

UniProt features (19 total): modified residue 5, helix 4, sequence variant 2, mutagenesis site 2, region of interest 2, initiator methionine 1, chain 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
5MK2	Crystal structure of the His Domain Protein Tyrosine Phosphatase (HD-PTP/PTPN23) Bro1 …	X-RAY DIFFRACTION	1.7
4ABM	Crystal Structure of CHMP4B hairpin	X-RAY DIFFRACTION	1.8
3C3Q	ALIX Bro1-domain:CHMIP4B co-crystal structure	X-RAY DIFFRACTION	2.1
3UM3	Crystal structure of the Brox Bro1 domain in complex with the C-terminal tail of CHMP4B	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H444-F1	79.98	0.45

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Eye disease, Essential proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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 (5)

Type	Positions
Phosphoserine	223, 184
N-acetylserine	2
N6-acetyllysine	6, 114

Mutagenesis-validated functional residues (2)

Position	Phenotype
54	no loss of interaction with cc2d1b and forms a disulfide bond locking the protein in its folded closed conformation when exposed to …
180	no loss of interaction with cc2d1b and forms a disulfide bond locking the protein in its folded closed conformation when exposed to …

Function

Pathways and Gene Ontology

Reactome pathways

7 curated (TAS) of 31; 15 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

31 pathways:

ID	Pathway	Evidence
R-HSA-162588	Budding and maturation of HIV virion ⚕	curated
R-HSA-9610379	HCMV Late Events ⚕	curated
R-HSA-9679504	Translation of Replicase and Assembly of the Replication Transcription Complex ⚕	curated
R-HSA-917729	Endosomal Sorting Complex Required For Transport (ESCRT)	curated
R-HSA-1632852	Macroautophagy	curated
R-HSA-5620971	Pyroptosis	curated
R-HSA-9668328	Sealing of the nuclear envelope (NE) by ESCRT-III	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-9772572	Early SARS-CoV-2 Infection Events ⚕	—
R-HSA-9609646	HCMV Infection ⚕	—
R-HSA-162906	HIV Infection ⚕	—
R-HSA-162587	HIV Life Cycle ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-162599	Late Phase of HIV Life Cycle ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9678108	SARS-CoV-1 Infection ⚕	—
R-HSA-9694516	SARS-CoV-2 Infection ⚕	—
R-HSA-9694676	Translation of Replicase and Assembly of the Replication Transcription Complex ⚕	electronic
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-9612973	Autophagy	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-9615710	Late endosomal microautophagy	electronic
R-HSA-68886	M Phase	—
R-HSA-199991	Membrane Trafficking	—
R-HSA-68882	Mitotic Anaphase	—
R-HSA-2555396	Mitotic Metaphase and Anaphase	—
R-HSA-2995410	Nuclear Envelope (NE) Reassembly	—
R-HSA-5357801	Programmed Cell Death	—
R-HSA-5218859	Regulated Necrosis	—
R-HSA-5653656	Vesicle-mediated transport	—

MSigDB gene sets: 371 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_MITOTIC_CYTOKINESIS, REACTOME_ENDOSOMAL_SORTING_COMPLEX_REQUIRED_FOR_TRANSPORT_ESCRT, GOBP_CHROMOSOME_ORGANIZATION, GOBP_NUCLEAR_MEMBRANE_REASSEMBLY, GOBP_LYSOSOMAL_TRANSPORT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_ENDOSOME_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOBP_MEMBRANE_BIOGENESIS, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_CHROMOSOME_LOCALIZATION, AAGCCAT_MIR135A_MIR135B

GO Biological Process (30): mitotic cytokinesis (GO:0000281), plasma membrane repair (GO:0001778), post-translational protein targeting to endoplasmic reticulum membrane (GO:0006620), vesicle budding from membrane (GO:0006900), autophagy (GO:0006914), nucleus organization (GO:0006997), mitotic metaphase chromosome alignment (GO:0007080), exit from mitosis (GO:0010458), regulation of centrosome duplication (GO:0010824), protein transport (GO:0015031), macroautophagy (GO:0016236), nuclear membrane reassembly (GO:0031468), late endosome to vacuole transport via multivesicular body sorting pathway (GO:0032511), multivesicular body assembly (GO:0036258), maintenance of lens transparency (GO:0036438), 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), nervous system process (GO:0050877), protein polymerization (GO:0051258), vesicle fusion with vacuole (GO:0051469), multivesicular body-lysosome fusion (GO:0061763), midbody abscission (GO:0061952), 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), vacuolar transport (GO:0007034)

GO Molecular Function (4): identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (21): autophagosome membrane (GO:0000421), kinetochore (GO:0000776), ESCRT III complex (GO:0000815), nucleus (GO:0005634), nuclear envelope (GO:0005635), nuclear pore (GO:0005643), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), endosome (GO:0005768), multivesicular body (GO:0005771), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), membrane coat (GO:0030117), midbody (GO:0030496), vesicle (GO:0031982), multivesicular body membrane (GO:0032585), extracellular exosome (GO:0070062), amphisome membrane (GO:1904930), late endosome membrane (GO:0031902)

Reactome top-level categories

15 top-level categories:

Category	Pathways
Autophagy	2
Late Phase of HIV Life Cycle	1
Regulated Necrosis	1
Membrane Trafficking	1
HCMV Infection	1
Nuclear Envelope (NE) Reassembly	1
SARS-CoV-1 Infection	1
Early SARS-CoV-2 Infection Events	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Vesicle-mediated transport	1
M Phase	1
Mitotic Anaphase	1
Programmed Cell Death	1

GO top-level categories

showing 60 of 78 GO namespaces:

Category	Terms
cellular anatomical structure	3
mitotic cell cycle	2
mitotic cell cycle process	2
viral budding	2
membrane protein complex	2
endomembrane system	2
cytoplasm	2
cytoskeleton-dependent cytokinesis	1
plasma membrane organization	1
wound healing	1
protein targeting to membrane	1
protein targeting to ER	1
vesicle organization	1
vesicle-mediated transport	1
membrane organization	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
organelle organization	1
mitotic sister chromatid segregation	1
metaphase chromosome alignment	1
mitotic cell cycle phase transition	1
mitotic nuclear division	1
regulation of centrosome cycle	1
centrosome duplication	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
autophagosome assembly	1
autophagy	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
tissue homeostasis	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
system process	1
protein binding	1
identical protein binding	1
protein dimerization activity	1
cell adhesion molecule binding	1
binding	1
vacuolar membrane	1
autophagosome	1
condensed chromosome, centromeric region	1
intracellular membraneless organelle	1
supramolecular complex	1
endosome membrane	1
ESCRT complex	1
intracellular membrane-bounded organelle	1
nucleus	1
organelle envelope	1
nuclear envelope	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 42 of 56 annotations. The rest are phylogenetic / computational / electronic (IEA).

42 experimentally-supported GO terms:

GO term	NS	Evidence
autophagosome maturation	BP	mutant phenotype
autophagy	BP	mutant phenotype
exit from mitosis	BP	mutant phenotype
late endosome to lysosome transport	BP	mutant phenotype
maintenance of lens transparency	BP	mutant phenotype
membrane fission	BP	mutant phenotype
midbody abscission	BP	mutant phenotype
mitotic cytokinesis	BP	mutant phenotype
mitotic metaphase chromosome alignment	BP	mutant phenotype
multivesicular body sorting pathway	BP	direct assay
nervous system process	BP	mutant phenotype
nuclear membrane reassembly	BP	mutant phenotype
nucleus organization	BP	mutant phenotype
plasma membrane repair	BP	direct assay
post-translational protein targeting to endoplasmic reticulum membrane	BP	mutant phenotype
protein polymerization	BP	direct assay
regulation of centrosome duplication	BP	mutant phenotype
regulation of mitotic spindle assembly	BP	mutant phenotype
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	BP	direct assay
viral budding	BP	mutant phenotype
viral budding from plasma membrane	BP	direct assay
viral budding via host ESCRT complex	BP	direct assay
ESCRT III complex	CC	direct assay
amphisome membrane	CC	direct assay
autophagosome membrane	CC	direct assay
cytoplasm	CC	direct assay
cytoplasmic side of plasma membrane	CC	direct assay
endosome	CC	direct assay
extracellular exosome	CC	high-throughput assay
kinetochore	CC	direct assay
kinetochore microtubule	CC	direct assay
lysosomal membrane	CC	direct assay
membrane coat	CC	direct assay
midbody	CC	direct assay
multivesicular body membrane	CC	direct assay
nuclear envelope	CC	direct assay
nucleus	CC	direct assay
plasma membrane	CC	direct assay
vesicle	CC	direct assay
cadherin binding	MF	high-throughput assay
identical protein binding	MF	physical interaction
protein homodimerization activity	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,901 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHMP4B	TMEM114	B3SHH9	675
CHMP4B	VPS4A	Q9UN37	598
CHMP4B	CRYBB2	P43320	597
CHMP4B	CRYGD	P07320	575
CHMP4B	HSF4	Q9ULV5	570
CHMP4B	GJA8	P48165	567
CHMP4B	CRYBB1	P53674	566
CHMP4B	CRYBA4	P53673	558
CHMP4B	TSG101	Q99816	558
CHMP4B	CRYGS	P22914	557
CHMP4B	BFSP2	Q13515	556
CHMP4B	LIM2	P55344	555
CHMP4B	GJA3	Q9Y6H8	546
CHMP4B	CHMP2A	O43633	537
CHMP4B	MIP	P30301	537

IntAct

Human interaction partners of CHMP4B in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

28 partners by confidence:

Partner	Interaction type	MIscore	Records
PDCD6IP	direct interaction	0.860	5
CHMP3	direct interaction	0.690	3
HTT	physical association	0.670	7
PTPN23	direct interaction	0.660	4
CC2D1A	physical association	0.660	1
BROX	direct interaction	0.610	5
CHMP2A	direct interaction	0.590	1
CHMP2B	direct interaction	0.590	1
CHMP4A	physical association	0.560	7
UBE2I	physical association	0.560	6
PLIN3	physical association	0.560	3
STAMBP	physical association	0.550	3
CHMP5	physical association	0.550	2
CHMP1B	physical association	0.550	1
CHMP4C	physical association	0.550	1
CHMP6	physical association	0.550	1
CHMP7	physical association	0.540	3
USP54	direct interaction	0.440	1
USP8	direct interaction	0.440	1
EXOSC9	physical association	0.370	2
HIPK2	physical association	0.370	2
PIAS2	physical association	0.370	2
VPS4A	physical association	0.370	2
CHD3	physical association	0.370	1
NOD2	physical association	0.370	1
CC2D1B	association	0.350	1
ELOC	association	0.350	1
PRKAR1A	physical association	0.000	1

BioGRID (845 interactions; top human partners by supporting records in a sample of 600 records): PDCD6IP (Affinity Capture-MS; 3 records), BIN1 (Affinity Capture-Western; 2 records), BST2 (Affinity Capture-MS; 2 records), CAPZA2 (Affinity Capture-MS; 2 records), CC2D1A (Affinity Capture-MS; 2 records), CC2D1B (Affinity Capture-MS; 2 records), CHMP1B (Co-fractionation; 2 records), CHMP2A (Co-localization; 2 records), CHMP2B (Co-fractionation; 2 records), CHMP3 (Co-fractionation; 2 records), CHMP5 (Co-fractionation; 2 records), CLTC (Affinity Capture-MS; 2 records), DBN1 (Affinity Capture-MS; 2 records), EIF6 (Co-fractionation; 2 records), FLNA (Affinity Capture-MS; 2 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
TTC19	“up-regulates activity”	CHMP4B	binding
CHMP4B	“form complex”	ESCRT-III	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
ESCRT-III complex	10	CHMP6, CHMP2B, CHMP3, CHMP4A, CHMP5, CHMP1A, CHMP1B, CHMP2A, CHMP4B, CHMP4C

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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	10	169.9×	4e-19
Endosomal Sorting Complex Required For Transport (ESCRT)	9	138.2×	2e-16
Sealing of the nuclear envelope (NE) by ESCRT-III	9	129.8×	3e-16
Pyroptosis	7	123.4×	1e-12
Late endosomal microautophagy	8	108.8×	7e-14
Macroautophagy	7	33.6×	2e-08
HCMV Late Events	8	32.8×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
nuclear membrane reassembly	10	354.0×	4e-23
late endosome to lysosome transport	9	318.6×	2e-20
viral budding via host ESCRT complex	11	315.3×	1e-24
midbody abscission	11	287.8×	4e-24
multivesicular body sorting pathway	10	286.6×	3e-22
vesicle budding from membrane	6	240.7×	9e-13
regulation of mitotic spindle assembly	9	235.5×	4e-19
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	11	213.6×	1e-22

Disease & clinical

Genetic variants

Variant evidence for CHMP4B: 53 ClinVar records (3 pathogenic / likely pathogenic); 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	18
Likely benign	12
Benign	11

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2841293	NM_176812.5(CHMP4B):c.200A>G (p.Gln67Arg)	Likely pathogenic	criteria provided, single submitter	1
1085	NM_176812.5(CHMP4B):c.386A>T (p.Asp129Val)	Pathogenic	no assertion criteria provided	1
1086	NM_176812.5(CHMP4B):c.481G>A (p.Glu161Lys)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CHMP4B’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 390):

Position(s)	Effect	Δscore	Sites
20:33848462	acceptor_gain	1.0000
20:33848465–33848466	acceptor_loss	1.0000	6
20:33848645–33848646	donor_loss	1.0000	4
20:33851067–33851068	donor_loss	1.0000	5
20:33852073	acceptor_gain	1.0000
20:33852075–33852076	acceptor_loss	1.0000	4
20:33852204–33852205	donor_loss	1.0000	5
20:33853493	acceptor_gain	1.0000
20:33811659–33811660	donor_loss	0.9900	5
20:33828037	donor_gain	0.9900

AlphaMissense

841 missense substitutions predicted likely pathogenic (of 1,480 scored), across 184 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M109	9	0.932	0.997
M132	9	0.882	0.987
D83	8	0.988	0.997
H120	8	0.941	0.994
N61	8	0.932	0.991
N102	8	0.928	0.999
F8	8	0.925	0.962
D160	8	0.918	0.974
D177	8	0.859	0.974
D129	8	0.829	0.984
Q92	7	0.985	1.000
E97	7	0.976	0.996
F91	7	0.973	0.991
F42	7	0.966	0.996
E167	7	0.961	0.991
W220	7	0.957	0.996
R74	7	0.951	0.991
E90	7	0.950	0.995
I145	7	0.950	0.999
E33	7	0.947	0.992

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000234

Disease associations

OMIM: gene MIM:610897 | disease phenotypes: MIM:605387

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
cataract 31 multiple types	Strong	Autosomal dominant	3
early-onset posterior subcapsular cataract	Supportive	Autosomal dominant
early-onset posterior polar cataract	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Bilateral congenital or childhood onset cataracts	green

Mondo (3): cataract 31 multiple types (MONDO:0011547), early-onset posterior subcapsular cataract (MONDO:0018610), early-onset posterior polar cataract (MONDO:0020378)

Orphanet (1): Early onset non-syndromic cataract (Orphanet:91492)

HPO phenotypes

4 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0007787	Posterior subcapsular cataract
HP:0010923	Anterior subcapsular cataract
HP:0100018	Nuclear cataract

GWAS associations

5 associations:

Study	Trait	p-value
GCST010002_340	Refractive error	5e-19
GCST008363_12	Offspring birth weight	3e-9
GCST006948_28	Feeling nervous	2e-8
GCST001840_2	Stearic acid (18:0) levels	3e-7
GCST003771_22	Loneliness	3e-7

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007865	loneliness measurement
EFO:0009597	feeling nervous measurement
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C535343	Cataract, posterior polar, 3 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066344 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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
5.58	Kd	2613	nM	CHEMBL5653589
5.48	ED50	3285	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	2148070: Binding affinity to human CHMP4B incubated for 45 mins by Kinobead based pull down assay	kd	2.6131	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Arsenic	decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dexamethasone	affects cotreatment, decreases expression	1
Furaldehyde	affects cotreatment, affects localization, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Sodium Chloride	increases expression, affects cotreatment, affects localization, decreases expression	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	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
CHEMBL5651112	Binding	Binding affinity to human CHMP4B 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CHMP4B across ~30M SureChEMBL compounds — explore on Sugi Predict.