CCZ1B

Summary

CCZ1B (CCZ1B vacuolar protein trafficking and biogenesis associated, HGNC:21717) is a protein-coding gene on chromosome 7p22.1, encoding Vacuolar fusion protein CCZ1 homolog B (P86790).

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 221960 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 87 total
• MANE Select transcript: NM_198097

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21717
Approved symbol	CCZ1B
Name	CCZ1B vacuolar protein trafficking and biogenesis associated
Location	7p22.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP586I1023, H_NH0577018.2, MGC19819
Ensembl gene	ENSG00000146574
Ensembl biotype	protein_coding
Entrez	221960

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 11 protein_coding, 8 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000316731, ENST00000411858, ENST00000429267, ENST00000462378, ENST00000464543, ENST00000467004, ENST00000468078, ENST00000472464, ENST00000481830, ENST00000485620, ENST00000486840, ENST00000490178, ENST00000496187, ENST00000597208, ENST00000626257, ENST00000861916, ENST00000861917, ENST00000861918, ENST00000861919, ENST00000861920, ENST00000861921, ENST00000966866, ENST00000966867, ENST00000966868

RefSeq mRNA: 1 — MANE Select: NM_198097 NM_198097

CCDS: CCDS5354

Canonical transcript exons

ENST00000316731 — 15 exons

Exon	Start	End
ENSE00001693552	6811952	6812063
ENSE00001782432	6812976	6813037
ENSE00001790542	6804938	6805055
ENSE00001842849	6798937	6799279
ENSE00003466750	6822281	6822364
ENSE00003475011	6801365	6801523
ENSE00003487895	6824455	6824548
ENSE00003566938	6814764	6814845
ENSE00003575512	6823313	6823360
ENSE00003650385	6806004	6806037
ENSE00003664489	6824089	6824166
ENSE00003668846	6800948	6801075
ENSE00003669086	6824640	6824737
ENSE00003673900	6819766	6819941
ENSE00003907032	6826078	6826275

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 98.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1070 / max 18.7415, expressed in 35 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82667	0.1070	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.19	gold quality
left adrenal gland	UBERON:0001234	97.67	gold quality
left adrenal gland cortex	UBERON:0035825	97.67	gold quality
right adrenal gland cortex	UBERON:0035827	97.64	gold quality
right adrenal gland	UBERON:0001233	97.53	gold quality
right uterine tube	UBERON:0001302	97.45	gold quality
adrenal gland	UBERON:0002369	97.45	gold quality
cortical plate	UBERON:0005343	97.29	gold quality
granulocyte	CL:0000094	97.27	gold quality
corpus callosum	UBERON:0002336	97.15	gold quality
ganglionic eminence	UBERON:0004023	96.97	gold quality
adenohypophysis	UBERON:0002196	96.86	gold quality
primary visual cortex	UBERON:0002436	96.86	gold quality
endometrium	UBERON:0001295	96.83	gold quality
lower esophagus mucosa	UBERON:0035834	96.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.78	gold quality
pituitary gland	UBERON:0000007	96.67	gold quality
mucosa of transverse colon	UBERON:0004991	96.57	gold quality
stromal cell of endometrium	CL:0002255	96.51	gold quality
spleen	UBERON:0002106	96.51	gold quality
cerebellar hemisphere	UBERON:0002245	96.51	gold quality
cerebellar cortex	UBERON:0002129	96.49	gold quality
esophagus mucosa	UBERON:0002469	96.48	gold quality
mucosa of stomach	UBERON:0001199	96.43	gold quality
Ammon’s horn	UBERON:0001954	96.42	gold quality
cerebellum	UBERON:0002037	96.41	gold quality
myometrium	UBERON:0001296	96.39	gold quality
right coronary artery	UBERON:0001625	96.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.36	gold quality
spinal cord	UBERON:0002240	96.35	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting CCZ1B, 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-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
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-552-5P	99.93	68.56	1583
HSA-MIR-3671	99.90	73.04	3897
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-3180-5P	99.82	69.12	2422
HSA-MIR-545-5P	99.66	70.18	2308
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-4712-5P	97.24	67.79	775
HSA-MIR-770-5P	97.24	68.10	758
HSA-MIR-6808-3P	94.13	65.24	516

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): CCZ1 (ENSG00000122674)

Protein

Protein identifiers

Vacuolar fusion protein CCZ1 homolog B — P86790 (reviewed: P86790)

Alternative names: Vacuolar fusion protein CCZ1 homolog-like

All UniProt accessions (2): P86790, F8WD66

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. The MON1A-CCZ1B complex interacts with RIMOC1. The MON1A-CCZ1B complex interacts with RAB7A and this interaction is enhanced in the presence of RIMOC1.

Subcellular location. Lysosome membrane.

Similarity. Belongs to the CCZ1 family.

RefSeq proteins (1): NP_932765* (*=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 (5 total): modified residue 3, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9LOL	ELECTRON MICROSCOPY	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P86790-F1	88.86	0.70

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: 75 (showing top): AAGCAAT_MIR137, GOCC_VACUOLAR_MEMBRANE, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, chr7p22, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOBP_INTRACELLULAR_TRANSPORT, GOCC_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_COMPLEX

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

GO Molecular Function (0):

GO Cellular Component (4): lysosomal membrane (GO:0005765), 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
transport	1
cellular process	1
lysosome	1
lytic vacuole membrane	1
late endosome	1
guanyl-nucleotide exchange factor complex	1
lytic vacuole	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1150 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCZ1B	MON1A	Q86VX9	999
CCZ1B	MON1B	Q7L1V2	932
CCZ1B	RAB5A	P20339	918
CCZ1B	RABIF	P47224	835
CCZ1B	RABGEF1	Q9UJ41	791
CCZ1B	RMC1	Q96DM3	742
CCZ1B	VPS39	Q96JC1	742
CCZ1B	GAPVD1	Q14C86	730
CCZ1B	VPS8	Q8N3P4	714
CCZ1B	VPS16	Q9H269	706
CCZ1B	EEA1	Q15075	692
CCZ1B	RABEP1	Q15276	672
CCZ1B	VPS11	Q9H270	665
CCZ1B	VPS18	Q9P253	663
CCZ1B	F5GZY7	F5GZY7	645

IntAct

87 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
ETFRF1	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
CACNB1	CACNB3	psi-mi:“MI:0914”(association)	0.640
RPS14	CCZ1B	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
RPS14	MAGEB2	psi-mi:“MI:0914”(association)	0.560
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
KLHDC2	PFDN1	psi-mi:“MI:0914”(association)	0.530
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
KBTBD4	KPNA5	psi-mi:“MI:0914”(association)	0.530
SP6	CCZ1B	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
PRKAG3	PFDN6	psi-mi:“MI:0914”(association)	0.530
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.530
PLEKHN1	ELP1	psi-mi:“MI:0914”(association)	0.530
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
UPP2	CCZ1B	psi-mi:“MI:0915”(physical association)	0.400
LMO2	APBB1	psi-mi:“MI:0914”(association)	0.350
THBS3	APBB1	psi-mi:“MI:0914”(association)	0.350
RPS14	RRP8	psi-mi:“MI:0914”(association)	0.350
KIF16B	SPAG9	psi-mi:“MI:0914”(association)	0.350
SP6	GNB2	psi-mi:“MI:0914”(association)	0.350
RHOG	COPE	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
CCZ1B	PRPF40A	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
CCZ1B	“form complex”	“MON1-CCZ1B guanyl-nucleotide exchange factor complex, MON1A variant”	binding
CCZ1B	“form complex”	“MON1-CCZ1B guanyl-nucleotide exchange factor complex, MON1B variant”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2629 predictions. Top by Δscore:

Variant	Effect	Δscore
7:6798359:TTAG:T	acceptor_loss	1.0000
7:6798361:A:AC	acceptor_loss	1.0000
7:6798361:A:AG	acceptor_gain	1.0000
7:6798361:AG:A	acceptor_gain	1.0000
7:6798361:AGGCT:A	acceptor_gain	1.0000
7:6798362:G:GA	acceptor_gain	1.0000
7:6798362:GG:G	acceptor_gain	1.0000
7:6798362:GGC:G	acceptor_gain	1.0000
7:6798362:GGCT:G	acceptor_gain	1.0000
7:6798362:GGCTG:G	acceptor_gain	1.0000
7:6799275:CTCTT:C	acceptor_gain	1.0000
7:6799277:CTT:C	acceptor_gain	1.0000
7:6799277:CTTCT:C	acceptor_loss	1.0000
7:6799278:TT:T	acceptor_gain	1.0000
7:6799279:TCTGC:T	acceptor_loss	1.0000
7:6799280:C:CC	acceptor_gain	1.0000
7:6799281:T:C	acceptor_loss	1.0000
7:6799286:C:CT	acceptor_gain	1.0000
7:6799295:A:T	acceptor_gain	1.0000
7:6799298:A:T	acceptor_gain	1.0000
7:6800943:CTT:C	donor_loss	1.0000
7:6800944:TTA:T	donor_loss	1.0000
7:6800945:T:TG	donor_loss	1.0000
7:6800946:A:AC	donor_gain	1.0000
7:6800946:A:C	donor_loss	1.0000
7:6800946:AC:A	donor_gain	1.0000
7:6800947:C:CA	donor_loss	1.0000
7:6800947:C:CC	donor_gain	1.0000
7:6800947:CC:C	donor_gain	1.0000
7:6800947:CCA:C	donor_gain	1.0000

AlphaMissense

3254 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:6800989:A:T	V451D	1.000
7:6800995:A:G	L449P	1.000
7:6801001:C:G	R447P	1.000
7:6801019:C:T	G441E	1.000
7:6801025:A:T	V439D	1.000
7:6801027:C:A	W438C	1.000
7:6801027:C:G	W438C	1.000
7:6801029:A:G	W438R	1.000
7:6801029:A:T	W438R	1.000
7:6801470:G:T	A387D	1.000
7:6801475:A:C	N385K	1.000
7:6801475:A:T	N385K	1.000
7:6801484:G:C	N382K	1.000
7:6801484:G:T	N382K	1.000
7:6801492:A:C	Y380D	1.000
7:6804995:A:G	L350P	1.000
7:6806019:A:G	C325R	1.000
7:6811957:A:C	Y317D	1.000
7:6811959:A:T	V316D	1.000
7:6812979:C:T	G280E	1.000
7:6814801:A:G	L248P	1.000
7:6824542:A:C	F75L	1.000
7:6824542:A:T	F75L	1.000
7:6824544:A:G	F75L	1.000
7:6824645:A:C	F71L	1.000
7:6824645:A:T	F71L	1.000
7:6824647:A:G	F71L	1.000
7:6824659:C:G	A67P	1.000
7:6799264:A:G	L470P	0.999
7:6800962:A:G	L460P	0.999

dbSNP variants (sampled 300 via entrez): RS1000403446 (7:6821241 A>C), RS1000405111 (7:6805540 A>AG,AGG), RS1000859159 (7:6806273 G>A), RS1001540212 (7:6824819 C>T), RS1001681430 (7:6827898 T>C), RS1001969054 (7:6819783 A>G), RS1002129660 (7:6810397 T>C), RS1002215658 (7:6828250 T>C,G), RS1002482200 (7:6810038 G>A), RS1002509441 (7:6823525 T>G), RS1002755344 (7:6815024 C>G), RS1003055042 (7:6824225 C>T), RS1003308211 (7:6798762 C>T), RS1003641824 (7:6821954 C>G), RS1003746842 (7:6812658 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003380_4	Bone mineral density (spine)	8.000000e-08
GCST005951_155	Body mass index	1.000000e-08
GCST006291_105	Spherical equivalent or myopia (age of diagnosis)	1.000000e-18
GCST007511_15	Alzheimer’s disease (late onset)	2.000000e-06
GCST011878_12	Mitochondrial heteroplasmy measurement	2.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007701	spine bone mineral density
EFO:0004340	body mass index
EFO:0004847	age at onset
EFO:1001870	late-onset Alzheimers disease
EFO:0600008	mitochondrial heteroplasmy measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
methylmercuric chloride	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
sodium arsenite	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Doxorubicin	affects expression	1
Hydralazine	affects cotreatment, increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Thimerosal	increases expression	1
Okadaic Acid	increases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	1

Clinical trials (associated diseases)

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