CHMP1A

Summary

CHMP1A (charged multivesicular body protein 1A, HGNC:8740) is a protein-coding gene on chromosome 16q24.3, encoding Charged multivesicular body protein 1a (Q9HD42). 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: 23.3% of cell lines).

This gene encodes a member of the CHMP/Chmp family of proteins which are involved in multivesicular body sorting of proteins to the interiors of lysosomes. The initial prediction of the protein sequence encoded by this gene suggested that the encoded protein was a metallopeptidase. The nomenclature has been updated recently to reflect the correct biological function of this encoded protein. Several transcripts encoding different isoforms have been found for this gene.

Source: NCBI Gene 5119 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pontocerebellar hypoplasia type 8 (Strong, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 274 total — 1 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 51
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 23.3% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_002768

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8740
Approved symbol	CHMP1A
Name	charged multivesicular body protein 1A
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0047, CHMP1, Vps46A
Ensembl gene	ENSG00000131165
Ensembl biotype	protein_coding
OMIM	164010
Entrez	5119

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 10 protein_coding, 7 retained_intron, 7 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000397901, ENST00000535997, ENST00000547614, ENST00000547687, ENST00000548650, ENST00000549139, ENST00000549328, ENST00000550102, ENST00000550872, ENST00000551981, ENST00000674799, ENST00000675016, ENST00000675076, ENST00000675161, ENST00000675309, ENST00000675536, ENST00000675760, ENST00000675778, ENST00000675909, ENST00000675942, ENST00000675952, ENST00000676118, ENST00000676275, ENST00000676342, ENST00000676355, ENST00000676402, ENST00000949331, ENST00000949332

RefSeq mRNA: 2 — MANE Select: NM_002768 NM_001083314, NM_002768

CCDS: CCDS45552

Canonical transcript exons

ENST00000397901 — 7 exons

Exon	Start	End
ENSE00002339458	89657582	89657708
ENSE00002348401	89644435	89646087
ENSE00003467749	89653904	89653923
ENSE00003492546	89651569	89651646
ENSE00003574170	89647203	89647331
ENSE00003637397	89646527	89646714
ENSE00003678280	89649351	89649497

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.2133 / max 252.8718, expressed in 1821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158640	38.3296	1821
158639	0.8838	569

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	97.23	gold quality
lower esophagus mucosa	UBERON:0035834	97.14	gold quality
mucosa of transverse colon	UBERON:0004991	96.81	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.34	gold quality
left testis	UBERON:0004533	96.24	gold quality
right testis	UBERON:0004534	96.19	gold quality
granulocyte	CL:0000094	95.89	gold quality
esophagus mucosa	UBERON:0002469	95.71	gold quality
small intestine	UBERON:0002108	95.53	gold quality
metanephros cortex	UBERON:0010533	95.50	gold quality
right uterine tube	UBERON:0001302	95.40	gold quality
transverse colon	UBERON:0001157	95.32	gold quality
skin of leg	UBERON:0001511	95.32	gold quality
esophagus	UBERON:0001043	95.06	gold quality
skin of abdomen	UBERON:0001416	95.01	gold quality
body of stomach	UBERON:0001161	94.70	gold quality
right frontal lobe	UBERON:0002810	94.63	gold quality
cingulate cortex	UBERON:0003027	94.57	gold quality
lower esophagus	UBERON:0013473	94.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.54	gold quality
stromal cell of endometrium	CL:0002255	94.51	gold quality
anterior cingulate cortex	UBERON:0009835	94.50	gold quality
ectocervix	UBERON:0012249	94.50	gold quality
body of uterus	UBERON:0009853	94.47	gold quality
endocervix	UBERON:0000458	94.44	gold quality
left uterine tube	UBERON:0001303	94.42	gold quality
right lobe of thyroid gland	UBERON:0001119	94.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.38	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.37	gold quality
right coronary artery	UBERON:0001625	94.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting CHMP1A, 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-4713-3P	100.00	65.92	505
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6734-3P	99.15	66.27	1627

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 23.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• UBPY MIT domain and another ubiquitin isopeptidase, AMSH, reveals common interactions with CHMP1A and CHMP1B but a distinct selectivity of AMSH for CHMP3/VPS24, a core subunit of the ESCRT-III complex, and UBPY for CHMP7. (PMID:17711858)
• Chmp1A is a novel tumor suppressor, especially in pancreas and that Chmp1A regulates tumor growth potentially through p53 signaling pathway. (PMID:18787405)
• Both Vps4A and CHMP1A localized in the vicinity of viral cytoplasmic assembly compartments, sites of viral maturation that develop in Cytomegalovirus-infected cells. Thus, ESCRT machinery is involved in the final steps of HCMV replication. (PMID:19640981)
• Chmp1A regulates tumor growth through ATM sugnaling and that neclear locaization of Chmp1A is reqired for the growth inhibition and ATM activation. (PMID:21705858)
• our results demonstrate that Chmp1A functions as a tumor suppressor gene in renal cells (PMID:22261332)
• Our results suggest that CHMP1A serves as a critical link between cytoplasmic signals and BMI1-mediated chromatin modifications that regulate proliferation of central nervous system progenitor cells. (PMID:23023333)
• Study reports the discovery of a chimeric RNA between ZC3HAV1L and CHMP1A in human, located on chromosome 7 and 16, respectively. The fusion occurs at an exon-exon boundary, and was detected both computationally and experimentally from different cells or tissue types. (PMID:23273016)
• we identified Ser(179) and Ser(182) located in the C-terminal region of the CHMP1A as major phosphorylation sites that cause a mobility shift. (PMID:23748770)
• Letter: rs6860 polymorphism of the CHMP1A gene, is associated with fibromyalgia susceptibility in southern Spanish women. (PMID:29247346)
• Findings show CHMP1A loss impairs secretion of SHH on ART-EVs, providing molecular mechanistic insights into the role of ESCRT proteins and EVs in the brain. (PMID:30044992)
• A single genetic locus controls both expression of DPEP1/CHMP1A and kidney disease development via ferroptosis. (PMID:34426578)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chmp1a	ENSDARG00000102643
mus_musculus	Chmp1a	ENSMUSG00000000743
rattus_norvegicus	Chmp1a	ENSRNOG00000016001

Paralogs (4): CHMP2B (ENSG00000083937), CHMP3 (ENSG00000115561), CHMP2A (ENSG00000130724), CHMP1B (ENSG00000255112)

Protein

Protein identifiers

Charged multivesicular body protein 1a — Q9HD42 (reviewed: Q9HD42)

Alternative names: Chromatin-modifying protein 1a, Vacuolar protein sorting-associated protein 46-1

All UniProt accessions (14): A0A6Q8PF26, A0A6Q8PF35, A0A6Q8PFF8, A0A6Q8PFF9, A0A6Q8PFX8, A0A6Q8PG85, A0A6Q8PGI9, A0A6Q8PGM8, A0A6Q8PGV2, A0A6Q8PHU0, Q9HD42, F5H875, F8VUA2, F8VVT7

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 cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing.

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. Self-associates. Interacts with CHMP1B. Interacts with VPS4A. Interacts with VPS4B. Interacts with PHF1. Interacts with IST1. Interacts with MITD1.

Subcellular location. Cytoplasm. Endosome membrane. Nucleus matrix.

Tissue specificity. Expressed in placenta, cultured skin fibroblasts and in osteoblast cell line MG-63.

Disease relevance. Pontocerebellar hypoplasia 8 (PCH8) [MIM:614961] An autosomal recessive neurodevelopmental disorder characterized by severe psychomotor retardation, abnormal movements, hypotonia, spasticity, and variable visual defects. Brain MRI shows pontocerebellar hypoplasia, decreased cerebral white matter, and a thin corpus callosum. The disease is caused by variants affecting the gene represented in this entry.

Induction. By muristerone.

Similarity. Belongs to the SNF7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HD42-1	1	yes
Q9HD42-2	2

RefSeq proteins (2): NP_001076783, NP_002759* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005024	Snf7_fam	Family

Pfam: PF03357

UniProt features (13 total): modified residue 3, mutagenesis site 2, coiled-coil region 2, chain 1, region of interest 1, sequence conflict 1, helix 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4A5X	X-RAY DIFFRACTION	1.91
2YMB	X-RAY DIFFRACTION	3.4
2JQ9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HD42-F1	78.44	0.26

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 (3): 1, 101, 173

Mutagenesis-validated functional residues (2):

Position	Phenotype
194	no effect on interaction with ist1; when associated with l-194.
191	no effect on interaction with ist1; when associated with l-194.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9610379	HCMV Late Events

MSigDB gene sets: 0 (showing top):

GO Biological Process (27): plasma membrane repair (GO:0001778), autophagy (GO:0006914), nucleus organization (GO:0006997), mitotic chromosome condensation (GO:0007076), mitotic metaphase chromosome alignment (GO:0007080), negative regulation of gene expression (GO:0010629), regulation of centrosome duplication (GO:0010824), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), nuclear membrane reassembly (GO:0031468), endosome transport via multivesicular body sorting pathway (GO:0032509), 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), late endosome to vacuole transport (GO:0045324), viral budding from plasma membrane (GO:0046761), cell division (GO:0051301), 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), ESCRT III complex disassembly (GO:1904903), vacuolar transport (GO:0007034)

GO Molecular Function (6): metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), protein domain specific binding (GO:0019904), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (25): autophagosome membrane (GO:0000421), kinetochore (GO:0000776), condensed nuclear chromosome (GO:0000794), ESCRT III complex (GO:0000815), nuclear pore (GO:0005643), lysosomal membrane (GO:0005765), early endosome (GO:0005769), multivesicular body (GO:0005771), microtubule organizing center (GO:0005815), kinetochore microtubule (GO:0005828), cytosol (GO:0005829), plasma membrane (GO:0005886), endomembrane system (GO:0012505), nuclear matrix (GO:0016363), midbody (GO:0030496), multivesicular body membrane (GO:0032585), extracellular exosome (GO:0070062), amphisome membrane (GO:1904930), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endosome (GO:0005768), centrosome (GO:0005813), endosome membrane (GO:0010008), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
HCMV Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
mitotic sister chromatid segregation	2
mitotic cell cycle	2
mitotic cell cycle process	2
transport	2
cellular process	2
multivesicular body sorting pathway	2
viral budding	2
vesicle fusion	2
protein binding	2
nuclear lumen	2
plasma membrane organization	1
wound healing	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
organelle organization	1
chromosome condensation	1
metaphase chromosome alignment	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
regulation of centrosome cycle	1
centrosome duplication	1
intracellular protein localization	1
establishment of protein localization	1
membrane assembly	1
nuclear membrane organization	1
endosomal transport	1
multivesicular body organization	1
organelle assembly	1
ubiquitin-dependent protein catabolic process	1
protein catabolic process in the vacuole	1
vacuolar transport	1
intercellular transport	1
vesicle-mediated transport	1
non-lytic viral release	1
vacuole fusion	1
endosome to lysosome transport via multivesicular body sorting pathway	1
lysosomal membrane organization	1

Protein interactions and networks

STRING

1408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHMP1A	CHMP3	Q9Y3E7	995
CHMP1A	A0A140T963	A0A140T963	995
CHMP1A	IST1	P53990	984
CHMP1A	CHMP6	Q96FZ7	981
CHMP1A	CHMP5	Q9NZZ3	978
CHMP1A	VPS4A	Q9UN37	975
CHMP1A	VPS4B	O75351	968
CHMP1A	CHMP4A	Q9BY43	960
CHMP1A	CHMP2B	Q9UQN3	957
CHMP1A	CHMP4C	Q96CF2	942
CHMP1A	CHMP2A	O43633	940
CHMP1A	VTA1	Q9NP79	904
CHMP1A	VPS25	Q9BRG1	893
CHMP1A	CHMP7	Q8WUX9	866
CHMP1A	MITD1	Q8WV92	797

IntAct

210 interactions, top by confidence:

A	B	Type	Score
CHMP1A	STAMBP	psi-mi:“MI:0915”(physical association)	0.830
STAMBP	CHMP1A	psi-mi:“MI:0915”(physical association)	0.830
STAMBP	PIK3C2A	psi-mi:“MI:0914”(association)	0.730
CHMP1A	VTA1	psi-mi:“MI:0915”(physical association)	0.680
CHMP1A	CHMP1A	psi-mi:“MI:0915”(physical association)	0.670
USP8	CHMP1A	psi-mi:“MI:0915”(physical association)	0.670
CHMP1A	USP8	psi-mi:“MI:0915”(physical association)	0.670
CHMP1A	VPS4A	psi-mi:“MI:0915”(physical association)	0.660
VPS4A	CHMP1A	psi-mi:“MI:0915”(physical association)	0.660
GPX7	GAK	psi-mi:“MI:0914”(association)	0.640
HEY2	ARL10	psi-mi:“MI:0914”(association)	0.640
BROX	TCEA1	psi-mi:“MI:0914”(association)	0.560
YES1	CHMP1A	psi-mi:“MI:0915”(physical association)	0.560
VPS4B	CHMP1A	psi-mi:“MI:0915”(physical association)	0.560
SDCBP	CHMP1A	psi-mi:“MI:0915”(physical association)	0.560
CHMP1A	C14orf119	psi-mi:“MI:0915”(physical association)	0.560
TXN2	CHMP1A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (175): CHMP1A (Affinity Capture-RNA), CHMP1A (Affinity Capture-RNA), CHMP1A (Two-hybrid), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS), CHMP1A (Affinity Capture-MS)

ESM2 similar proteins: A0R5Z0, A4R8N4, A5U697, A9MI67, A9MZC5, B2AWS3, B2J6D9, B4TBY1, B4TPQ7, B7UNM4, C0Q3L2, P03689, P0AF78, P0AF79, P0AFM6, P0AFM7, P0AFM8, P32780, P54617, P9WHP4, P9WHP5, Q01076, Q2H922, Q4V8C8, Q55707, Q5E994, Q5R605, Q5ZKX1, Q5ZLM0, Q6NUD8, Q6P1J9, Q6PHF0, Q7LBR1, Q7T339, Q7ZVB1, Q8GXN6, Q8JZM7, Q91VH2, Q921W0, Q9CQD4

Diamond homologs: O60074, O96552, P69771, Q5E994, Q5R605, Q5ZKX1, Q6DF27, Q6NUD8, Q6PHF0, Q7LBR1, Q7SZB5, Q7ZVB1, Q84VG1, Q8LE58, Q921W0, Q99LU0, Q9CQD4, Q9HD42, Q9SSM4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CHMP1A	“form complex”	ESCRT-III	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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	28.3×	2e-06
Endosomal Sorting Complex Required For Transport (ESCRT)	7	25.5×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
nuclear membrane reassembly	6	42.5×	6e-07
midbody abscission	8	41.9×	3e-09
viral budding via host ESCRT complex	7	40.1×	6e-08
multivesicular body sorting pathway	7	40.1×	6e-08
positive regulation of exosomal secretion	5	40.1×	1e-05
multivesicular body assembly	9	33.9×	2e-09
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	7	27.2×	7e-07
regulation of centrosome duplication	5	26.2×	8e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	89
Likely benign	106
Benign	39

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1393947	NM_002768.5(CHMP1A):c.19del (p.Gln7fs)	Pathogenic
2442121	NM_002768.5(CHMP1A):c.28-2A>G	Likely pathogenic
2501136	NM_002768.5(CHMP1A):c.271C>T (p.Gln91Ter)	Likely pathogenic
3377250	NM_002768.5(CHMP1A):c.34del (p.Ala12fs)	Likely pathogenic

SpliceAI

1344 predictions. Top by Δscore:

Variant	Effect	Δscore
16:89646020:T:TA	donor_gain	1.0000
16:89646522:CCTA:C	donor_loss	1.0000
16:89646523:CTAC:C	donor_loss	1.0000
16:89646524:TA:T	donor_loss	1.0000
16:89646525:ACCT:A	donor_gain	1.0000
16:89646526:CC:C	donor_loss	1.0000
16:89646526:CCT:C	donor_gain	1.0000
16:89646526:CCTC:C	donor_gain	1.0000
16:89646528:T:TA	donor_gain	1.0000
16:89646545:T:TA	donor_gain	1.0000
16:89646714:CCTGG:C	acceptor_loss	1.0000
16:89646715:CT:C	acceptor_loss	1.0000
16:89646716:T:A	acceptor_loss	1.0000
16:89647094:C:CT	acceptor_gain	1.0000
16:89647201:A:AC	donor_gain	1.0000
16:89647201:A:T	donor_loss	1.0000
16:89647202:C:CT	donor_gain	1.0000
16:89647338:C:CT	acceptor_gain	1.0000
16:89647339:A:T	acceptor_gain	1.0000
16:89649345:ACTCA:A	donor_loss	1.0000
16:89649346:CTCAC:C	donor_loss	1.0000
16:89649347:T:TA	donor_loss	1.0000
16:89649348:C:CG	donor_loss	1.0000
16:89649349:AC:A	donor_gain	1.0000
16:89649349:ACC:A	donor_gain	1.0000
16:89649349:ACCC:A	donor_gain	1.0000
16:89649349:ACCCC:A	donor_gain	1.0000
16:89649350:C:CA	donor_loss	1.0000
16:89649350:CC:C	donor_gain	1.0000
16:89649350:CCC:C	donor_gain	1.0000

AlphaMissense

1292 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:89649442:C:G	R54P	0.999
16:89649449:C:G	A52P	0.999
16:89649457:G:T	A49D	0.999
16:89649469:G:T	A45D	0.999
16:89646650:A:G	L149P	0.998
16:89649368:C:G	A79P	0.998
16:89649400:C:G	R68P	0.998
16:89649407:C:G	A66P	0.998
16:89649458:C:G	A49P	0.998
16:89646635:G:T	A154D	0.997
16:89646636:C:G	A154P	0.997
16:89647297:A:G	L96P	0.997
16:89649392:C:G	A71P	0.997
16:89651630:A:G	L15P	0.997
16:89646073:C:A	R195M	0.996
16:89647239:G:C	F115L	0.996
16:89647239:G:T	F115L	0.996
16:89647241:A:G	F115L	0.996
16:89649386:C:G	A73P	0.996
16:89646076:A:G	L194S	0.995
16:89647240:A:G	F115S	0.995
16:89649493:A:G	L37P	0.995
16:89649497:C:G	A36P	0.995
16:89651610:C:G	A22P	0.995
16:89646085:A:G	L191S	0.994
16:89646527:C:A	R190M	0.994
16:89647289:C:G	A99P	0.994
16:89649367:G:T	A79D	0.994
16:89649383:A:G	S74P	0.994
16:89649404:A:G	S67P	0.994

dbSNP variants (sampled 300 via entrez): RS1000100089 (16:89650346 G>T), RS1000172329 (16:89652240 G>C), RS1000284429 (16:89655361 C>T), RS1000335852 (16:89659132 C>G), RS1000388476 (16:89659228 G>A), RS1000506944 (16:89653449 T>C), RS1000651160 (16:89647162 C>G), RS1000820019 (16:89644411 G>A), RS1000871047 (16:89644661 C>A,T), RS1000876604 (16:89656743 G>C), RS1000887887 (16:89656207 G>A), RS1001316421 (16:89645474 A>G), RS1001503523 (16:89648506 A>G), RS1001555571 (16:89654508 C>G,T), RS1001714195 (16:89644007 A>C,G)

Disease associations

OMIM: gene MIM:164010 | disease phenotypes: MIM:614961, MIM:607596

GenCC curated gene-disease

Disease	Classification	Inheritance
pontocerebellar hypoplasia type 8	Strong	Autosomal recessive

Mondo (4): pontocerebellar hypoplasia type 8 (MONDO:0013990), pontocerebellar hypoplasia (MONDO:0020135), pontocerebellar hypoplasia type 1A (MONDO:0011866), intellectual disability (MONDO:0001071)

Orphanet (5): Pontocerebellar hypoplasia type 8 (Orphanet:324569), Non-syndromic pontocerebellar hypoplasia (Orphanet:98523), Pontocerebellar hypoplasia type 1 (Orphanet:2254), Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

51 total (30 of 51 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000463	Anteverted nares
HP:0000483	Astigmatism
HP:0000527	Long eyelashes
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0000574	Thick eyebrow
HP:0000664	Synophrys
HP:0000998	Hypertrichosis
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001290	Generalized hypotonia
HP:0001321	Cerebellar hypoplasia
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001387	Joint stiffness
HP:0001629	Ventricular septal defect
HP:0001655	Patent foramen ovale
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002020	Gastroesophageal reflux

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST005897_48	Low tan response	7.000000e-206
GCST005897_49	Low tan response	1.000000e-129
GCST006986_30	Red vs. brown/black hair color	7.000000e-50
GCST007268_58	Diastolic blood pressure	7.000000e-12
GCST007578_4	Plasma homocysteine levels	4.000000e-08
GCST007928_65	Medication use (diuretics)	5.000000e-10
GCST007929_18	Medication use (calcium channel blockers)	8.000000e-17
GCST007930_33	Medication use (agents acting on the renin-angiotensin system)	2.000000e-15
GCST008058_72	Estimated glomerular filtration rate	3.000000e-24
GCST008059_61	Estimated glomerular filtration rate	2.000000e-24
GCST010083_322	Hemoglobin levels	3.000000e-22
GCST010703_280	Brain morphology (MOSTest)	2.000000e-15
GCST90002396_604	Mean reticulocyte volume	9.000000e-21
GCST90013410_53	Basal cell carcinoma	2.000000e-67

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004279	suntan
EFO:0003924	hair color
EFO:0006336	diastolic blood pressure
EFO:0004578	homocysteine measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004509	hemoglobin measurement
EFO:0004346	neuroimaging measurement
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C580383	Pontocerebellar Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724785 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment	2
sodium arsenite	decreases expression, increases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
selenomethylselenocysteine	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	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
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases response to substance	1
Acetaminophen	increases expression	1
Glyphosate	affects methylation	1
Aspirin	decreases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression, increases abundance	1
Cisplatin	increases expression	1
Dactinomycin	increases secretion, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Gasoline	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697464	Binding	Inhibition of CHMP1A (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 1 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3HI	IPS(IMR90)-4-CHMP1A KO	Induced pluripotent stem cell	Female
CVCL_C3HJ	SVG-A CHMP1A null	Transformed cell line	Male
CVCL_SI98	HAP1 CHMP1A (-) 1	Cancer cell line	Male
CVCL_XM76	HAP1 CHMP1A (-) 2	Cancer cell line	Male
CVCL_XM77	HAP1 CHMP1A (-) 3	Cancer cell line	Male
CVCL_XM78	HAP1 CHMP1A (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders