CCZ1

Summary

CCZ1 (CCZ1 vacuolar protein trafficking and biogenesis associated, HGNC:21691) is a protein-coding gene on chromosome 7p22.1, encoding Vacuolar fusion protein CCZ1 homolog (P86791). Acts in concert with MON1A, as a guanine exchange factor (GEF) for RAB7, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form.

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of Mon1-Ccz1 complex.

Source: NCBI Gene 51622 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 136 total — 2 pathogenic
• MANE Select transcript: NM_015622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21691
Approved symbol	CCZ1
Name	CCZ1 vacuolar protein trafficking and biogenesis associated
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	CGI-43, CCZ1A
Ensembl gene	ENSG00000122674
Ensembl biotype	protein_coding
OMIM	620660
Entrez	51622

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 21 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000325974, ENST00000461592, ENST00000474507, ENST00000478672, ENST00000483394, ENST00000496860, ENST00000628813, ENST00000887568, ENST00000887569, ENST00000887570, ENST00000887571, ENST00000887572, ENST00000887573, ENST00000928073, ENST00000928074, ENST00000928075, ENST00000928076, ENST00000928077, ENST00000928078, ENST00000928079, ENST00000928080, ENST00000928081, ENST00000928082, ENST00000928083, ENST00000971175, ENST00000971176

RefSeq mRNA: 1 — MANE Select: NM_015622 NM_015622

CCDS: CCDS34597

Canonical transcript exons

ENST00000325974 — 15 exons

Exon	Start	End
ENSE00001614698	5900473	5900566
ENSE00001626657	5910035	5910116
ENSE00001639155	5918867	5918900
ENSE00001700559	5911861	5911922
ENSE00001752315	5912843	5912954
ENSE00001789590	5902661	5902744
ENSE00001802981	5919849	5919966
ENSE00001905098	5925632	5926550
ENSE00001942643	5898733	5898919
ENSE00003538155	5901657	5901704
ENSE00003592158	5923387	5923545
ENSE00003615458	5900284	5900381
ENSE00003617807	5923835	5923962
ENSE00003681098	5900855	5900932
ENSE00003682262	5905094	5905269

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5893 / max 66.4794, expressed in 1768 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77128	3.9449	1677
77129	3.6443	1656

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.64	gold quality
right adrenal gland	UBERON:0001233	95.61	gold quality
right adrenal gland cortex	UBERON:0035827	95.44	gold quality
left adrenal gland	UBERON:0001234	95.31	gold quality
lower esophagus mucosa	UBERON:0035834	95.18	gold quality
left adrenal gland cortex	UBERON:0035825	95.13	gold quality
adrenal gland	UBERON:0002369	94.85	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.62	gold quality
Ammon’s horn	UBERON:0001954	94.39	gold quality
adenohypophysis	UBERON:0002196	94.26	gold quality
substantia nigra	UBERON:0002038	94.17	gold quality
stromal cell of endometrium	CL:0002255	94.16	gold quality
amygdala	UBERON:0001876	94.13	gold quality
temporal lobe	UBERON:0001871	94.05	gold quality
hypothalamus	UBERON:0001898	93.89	gold quality
esophagus mucosa	UBERON:0002469	93.86	gold quality
left uterine tube	UBERON:0001303	93.71	gold quality
primary visual cortex	UBERON:0002436	93.61	gold quality
pituitary gland	UBERON:0000007	93.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.45	gold quality
spleen	UBERON:0002106	93.35	gold quality
adrenal tissue	UBERON:0018303	93.28	gold quality
nucleus accumbens	UBERON:0001882	93.16	gold quality
cortical plate	UBERON:0005343	93.16	gold quality
putamen	UBERON:0001874	93.12	gold quality
cerebellar cortex	UBERON:0002129	93.10	gold quality
cerebellar hemisphere	UBERON:0002245	93.10	gold quality
endocervix	UBERON:0000458	93.09	gold quality
esophagus	UBERON:0001043	93.01	gold quality
cerebellum	UBERON:0002037	93.00	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.43
E-MTAB-6142	no	29.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting CCZ1, 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-3692-3P	99.98	70.27	2139
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-6808-3P	94.13	65.24	516

Literature-anchored findings (GeneRIF, showing 3)

• The CCZ1 gene is a member of the class B VPS (vacuolar protein sorting) genes and it is engaged in the last stage of delivery of multiple kinds of cargo to the yeast vacuole. (PMID:20709422)
• Authors identified C18orf8/RMC1 as a new subunit of the CCZ1-MON1 RAB7 guanine exchange factor (GEF) that positively regulates RAB7 recruitment to LE/autophagosomes. (PMID:29038162)
• Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections. (PMID:37880247)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccz1	ENSDARG00000056559
mus_musculus	Ccz1	ENSMUSG00000029617
rattus_norvegicus	Ccz1	ENSRNOG00000001032
drosophila_melanogaster	Ccz1	FBGN0035470
caenorhabditis_elegans		WBGENE00010283

Paralogs (1): CCZ1B (ENSG00000146574)

Protein

Protein identifiers

Vacuolar fusion protein CCZ1 homolog — P86791 (reviewed: P86791)

All UniProt accessions (2): P86791, F8WD66

UniProt curated annotations — full annotation on UniProt →

Function. Acts in concert with MON1A, as a guanine exchange factor (GEF) for RAB7, promotes the exchange of GDP to GTP, converting it from an inactive GDP-bound form into an active GTP-bound form.

Subunit / interactions. Interacts with MON1A. Found in a complex with RMC1, CCZ1, MON1A and MON1B.

Subcellular location. Lysosome membrane.

Similarity. Belongs to the CCZ1 family.

RefSeq proteins (1): NP_056437* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013176	Ccz1	Family
IPR043987	CCZ1/INTU/HSP4_longin_1	Domain
IPR043988	CCZ1/INTU_longin_2	Domain
IPR043989	CCZ1/INTU/HSP4_longin_3	Domain

Pfam: PF19031, PF19032, PF19033

UniProt features (9 total): sequence conflict 4, modified residue 3, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9L0D	ELECTRON MICROSCOPY	3.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P86791-F1	89.12	0.72

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): 2, 76, 266

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking

MSigDB gene sets: 82 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, AAGCAAT_MIR137, TSENG_IRS1_TARGETS_UP, KAAB_FAILED_HEART_ATRIUM_DN, GOCC_VACUOLAR_MEMBRANE, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, chr7p22, BLALOCK_ALZHEIMERS_DISEASE_UP, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, DOUGLAS_BMI1_TARGETS_DN

GO Biological Process (1): vesicle-mediated transport (GO:0016192)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (5): lysosomal membrane (GO:0005765), cytosol (GO:0005829), Mon1-Ccz1 complex (GO:0035658), lysosome (GO:0005764), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Rab regulation of trafficking	1
Vesicle-mediated transport	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
transport	1
cellular process	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
late endosome	1
guanyl-nucleotide exchange factor complex	1
lytic vacuole	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

17 interactions, top by confidence:

A	B	Type	Score
RMC1	CCZ1	psi-mi:“MI:0914”(association)	0.600
RAB7A	CCZ1	psi-mi:“MI:0914”(association)	0.590
MON1A	CCZ1	psi-mi:“MI:0915”(physical association)	0.590
MON1A	CCZ1	psi-mi:“MI:0914”(association)	0.590
CCZ1	RAB7A	psi-mi:“MI:2252”(guanine nucleotide exchange factor reaction)	0.590
RMC1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
RMC1	ARID1A	psi-mi:“MI:0914”(association)	0.350
MON1B	CCZ1	psi-mi:“MI:0914”(association)	0.350
CCZ1	MON1B	psi-mi:“MI:0914”(association)	0.350
CCZ1B	PRPF40A	psi-mi:“MI:0914”(association)	0.350
CCZ1	CCZ1B	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350

BioGRID (109): CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1B (Proximity Label-MS), CCZ1B (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS), CCZ1 (Affinity Capture-MS)

ESM2 similar proteins: A0JMA8, A0JPP5, A1A535, A1A5P5, F1S5L4, O70481, P86790, P86791, P97564, Q008S8, Q0VA04, Q0VD30, Q14D04, Q16K67, Q19317, Q28HU2, Q2KI89, Q3KQ18, Q45GW3, Q4R6I5, Q4S4I5, Q5GJ77, Q5PQS3, Q5R629, Q5R6E9, Q5RD58, Q5SWX8, Q5U245, Q5XIR8, Q5ZKK3, Q5ZLN2, Q61586, Q6NU25, Q6PA97, Q7Z3E5, Q803R2, Q86VS3, Q8C1Y8, Q8CDK3, Q8IWV7

Diamond homologs: A7RJI7, P86790, P86791, Q0VD30, Q28HU2, Q4S4I5, Q54IQ5, Q5ZLN2, Q7T102, Q803R2, Q8C1Y8, Q9VZL5

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CCZ1	“form complex”	“MON1-CCZ1 guanyl-nucleotide exchange factor complex, MON1B variant”	binding
CCZ1	“form complex”	“MON1-CCZ1 guanyl-nucleotide exchange factor complex, MON1A variant”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	94
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2423253	NC_000007.13:g.(?5834270)(6018235_?)del	Pathogenic
3245662	NC_000007.13:g.(?5900029)(6018317_?)del	Pathogenic

SpliceAI

2206 predictions. Top by Δscore:

Variant	Effect	Δscore
7:5898916:ACAGG:A	donor_loss	1.0000
7:5898919:GGT:G	donor_loss	1.0000
7:5898920:G:GC	donor_loss	1.0000
7:5898921:T:G	donor_loss	1.0000
7:5900275:AT:A	acceptor_gain	1.0000
7:5900276:T:G	acceptor_gain	1.0000
7:5900278:TTTCA:T	acceptor_loss	1.0000
7:5900279:TTCA:T	acceptor_loss	1.0000
7:5900280:TCA:T	acceptor_loss	1.0000
7:5900281:CAG:C	acceptor_loss	1.0000
7:5900283:G:T	acceptor_loss	1.0000
7:5900377:ACAAG:A	donor_loss	1.0000
7:5900378:CAAG:C	donor_loss	1.0000
7:5900379:AAGG:A	donor_loss	1.0000
7:5900380:AGGT:A	donor_loss	1.0000
7:5900382:GTAAT:G	donor_loss	1.0000
7:5900383:T:A	donor_loss	1.0000
7:5900582:GT:G	donor_gain	1.0000
7:5900850:TGTAG:T	acceptor_loss	1.0000
7:5900852:TA:T	acceptor_loss	1.0000
7:5900854:GGTT:G	acceptor_gain	1.0000
7:5900926:GTT:G	donor_gain	1.0000
7:5900933:G:GG	donor_gain	1.0000
7:5901654:CAG:C	acceptor_loss	1.0000
7:5901703:AGGTA:A	donor_loss	1.0000
7:5901706:T:A	donor_loss	1.0000
7:5902651:A:AG	acceptor_gain	1.0000
7:5902657:CTAGC:C	acceptor_loss	1.0000
7:5902659:A:AG	acceptor_gain	1.0000
7:5902659:A:C	acceptor_loss	1.0000

AlphaMissense

3254 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000051403 (7:5901100 G>A), RS1000495260 (7:5898832 G>A,C,T), RS1000511075 (7:5907572 T>A), RS1000670916 (7:5915026 A>G), RS1000747338 (7:5907023 A>C,G), RS1000803330 (7:5914499 G>C), RS1001010513 (7:5907350 A>T), RS1001121503 (7:5899378 T>C,G), RS1001360894 (7:5924020 G>A), RS1001454224 (7:5923288 G>T), RS1001673138 (7:5902279 C>A,G,T), RS1002195467 (7:5900780 A>C,G,T), RS1002304821 (7:5909134 A>G), RS1002363246 (7:5918608 T>C,G), RS1002808246 (7:5908671 C>T)

Disease associations

OMIM: gene MIM:620660 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Cocaine	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Crack Cocaine	increases expression	1
Gold Compounds	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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