VMA22

Summary

VMA22 (vacuolar ATPase assembly factor VMA22, HGNC:28178) is a protein-coding gene on chromosome 2q21.1, encoding Vacuolar ATPase assembly protein VMA22 (Q96NT0). Accessory component of the proton-transporting vacuolar (V)-ATPase protein pump involved in intracellular iron homeostasis. It is a selective cancer dependency (DepMap: 85.0% of cell lines).

The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) vesicles in some human cells. The encoded protein shares some homology with the yeast V-ATPase assembly factor Vma22p, and the orthologous protein in mouse promotes cell proliferation and suppresses cell death. Defects in this gene are a cause of congenital disorder of glycosylation, type IIo in humans.

Source: NCBI Gene 84317 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CCDC115-CDG (Definitive, GenCC)
• Clinical variants (ClinVar): 86 total — 8 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 25
• Cancer dependency (DepMap): dependent in 85.0% of screened cell lines
• MANE Select transcript: NM_032357

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28178
Approved symbol	VMA22
Name	vacuolar ATPase assembly factor VMA22
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC12981, FLJ30131, ccp1
Ensembl gene	ENSG00000136710
Ensembl biotype	protein_coding
OMIM	613734
Entrez	84317

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000259229, ENST00000409127, ENST00000442217, ENST00000465315, ENST00000651709, ENST00000902734, ENST00000902735, ENST00000902736, ENST00000912734

RefSeq mRNA: 3 — MANE Select: NM_032357 NM_001321118, NM_001321119, NM_032357

CCDS: CCDS2159, CCDS82512

Canonical transcript exons

ENST00000259229 — 5 exons

Exon	Start	End
ENSE00000925896	130341667	130341749
ENSE00000925897	130340908	130341039
ENSE00000964161	130341841	130341944
ENSE00003849339	130342015	130342164
ENSE00003851165	130337933	130339232

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 96.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.7460 / max 331.1897, expressed in 1817 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30620	18.8855	1816
30622	1.6988	756
30623	0.8675	530
30621	0.2943	132

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	96.11	gold quality
ileal mucosa	UBERON:0000331	95.29	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.99	silver quality
left ventricle myocardium	UBERON:0006566	94.20	silver quality
upper arm skin	UBERON:0004263	94.00	gold quality
palpebral conjunctiva	UBERON:0001812	93.92	gold quality
prefrontal cortex	UBERON:0000451	93.85	gold quality
cortical plate	UBERON:0005343	93.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.97	gold quality
popliteal artery	UBERON:0002250	92.81	gold quality
tibial artery	UBERON:0007610	92.80	gold quality
decidua	UBERON:0002450	92.53	gold quality
granulocyte	CL:0000094	92.37	gold quality
right coronary artery	UBERON:0001625	92.36	gold quality
urethra	UBERON:0000057	92.26	gold quality
anterior cingulate cortex	UBERON:0009835	92.13	gold quality
aorta	UBERON:0000947	92.12	gold quality
leukocyte	CL:0000738	92.05	gold quality
descending thoracic aorta	UBERON:0002345	92.03	gold quality
monocyte	CL:0000576	91.94	gold quality
pons	UBERON:0000988	91.93	gold quality
skin of leg	UBERON:0001511	91.87	gold quality
endocervix	UBERON:0000458	91.77	gold quality
frontal cortex	UBERON:0001870	91.76	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.76	gold quality
frontal lobe	UBERON:0016525	91.76	gold quality
ectocervix	UBERON:0012249	91.64	gold quality
neocortex	UBERON:0001950	91.59	gold quality
esophagus squamous epithelium	UBERON:0006920	91.59	gold quality
skin of abdomen	UBERON:0001416	91.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	51.85
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

56 targeting VMA22, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 85.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• Our study reveals CCDC115 deficiency as a disorder of Golgi homeostasis that can be readily identified via screening for abnormal glycosylation in plasma. (PMID:26833332)
• Vacuolar H+ ATPase (V-ATPase), the key proton pump for endo-lysosomal acidification, and two previously uncharacterised V-ATPase assembly factors, TMEM199 and CCDC115, stabilise HIF1alpha in aerobic conditions. (PMID:28296633)
• CCDC115 mutation is associated with Congenital disorders of glycosylation causing liver disease. (PMID:29759592)
• CCDC115 is associated with less aggressive prostate cancer in humans. (PMID:29890952)
• Genetics of Wilson disease and Wilson-like phenotype in a clinical series from eastern Spain. (PMID:32043565)
• Genetic screens reveal CCDC115 as a modulator of erythroid iron and heme trafficking. (PMID:32510613)
• Defective Lipid Droplet-Lysosome Interaction Causes Fatty Liver Disease as Evidenced by Human Mutations in TMEM199 and CCDC115. (PMID:34626841)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccdc115	ENSDARG00000033533
mus_musculus	Ccdc115	ENSMUSG00000042111
rattus_norvegicus	Ccdc115	ENSRNOG00000013234

Protein

Protein identifiers

Vacuolar ATPase assembly protein VMA22 — Q96NT0 (reviewed: Q96NT0)

Alternative names: Coiled-coil domain-containing protein 115

All UniProt accessions (3): B8ZZ99, F8WCZ3, Q96NT0

UniProt curated annotations — full annotation on UniProt →

Function. Accessory component of the proton-transporting vacuolar (V)-ATPase protein pump involved in intracellular iron homeostasis. In aerobic conditions, required for intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation. Necessary for endolysosomal acidification and lysosomal degradation. May be involved in Golgi homeostasis.

Subunit / interactions. Accessory component of the multisubunit proton-transporting vacuolar (V)-ATPase protein pump.

Subcellular location. Endosome. Lysosome. Endoplasmic reticulum-Golgi intermediate compartment. Cytoplasmic vesicle. COPI-coated vesicle. Endoplasmic reticulum.

Tissue specificity. Expressed throughout the brain.

Disease relevance. Congenital disorder of glycosylation 2O (CDG2O) [MIM:616828] A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2O is characterized by hepatosplenomegaly, liver failure, hypotonia, and psychomotor disability. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96NT0-1	1	yes
Q96NT0-2	2

RefSeq proteins (3): NP_001308047, NP_001308048, NP_115733* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040357	Vma22/CCDC115	Family

Pfam: PF21730

UniProt features (9 total): coiled-coil region 2, splice variant 2, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NT0-F1	83.32	0.65

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 211 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_VACUOLE_ORGANIZATION, GOCC_VACUOLAR_MEMBRANE, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_INCREASED_OXYGEN_LEVELS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS, GOBP_RESPONSE_TO_OXYGEN_LEVELS, GOCC_COATED_VESICLE, GOBP_VACUOLAR_ACIDIFICATION, GOCC_GOLGI_ASSOCIATED_VESICLE, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, STONER_ESOPHAGEAL_CARCINOGENESIS_UP, GOBP_REGULATION_OF_PH

GO Biological Process (5): intracellular iron ion homeostasis (GO:0006879), lysosomal lumen acidification (GO:0007042), cellular response to increased oxygen levels (GO:0036295), vacuolar proton-transporting V-type ATPase complex assembly (GO:0070072), lysosomal protein catabolic process (GO:1905146)

GO Molecular Function (2): obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515)

GO Cellular Component (9): lysosome (GO:0005764), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), membrane (GO:0016020), vacuolar proton-transporting V-type ATPase complex (GO:0016471), COPI-coated vesicle (GO:0030137), vacuole (GO:0005773), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
intracellular membrane-bounded organelle	3
endomembrane system	2
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
vacuolar acidification	1
response to increased oxygen levels	1
cellular response to oxygen levels	1
proton-transporting V-type ATPase complex assembly	1
lysosome	1
protein catabolic process in the vacuole	1
binding	1
lytic vacuole	1
cytoplasmic vesicle	1
cellular anatomical structure	1
vacuolar membrane	1
proton-transporting V-type ATPase complex	1
Golgi-associated vesicle	1
coated vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VMA22	VMA12	Q8N511	883
VMA22	ATP6AP1	Q15904	765
VMA22	WDR7	Q9Y4E6	738
VMA22	ATP6V1H	Q9UI12	688
VMA22	ATP6V1C1	P21283	682
VMA22	ATP6V1E1	P36543	615
VMA22	FGF13	Q92913	547
VMA22	ATP6AP2	O75787	525
VMA22	CMTR1	Q8N1G2	522
VMA22	SUSD1	Q6UWL2	518
VMA22	ALG2	Q9H553	513
VMA22	SERGEF	Q9UGK8	513
VMA22	DCTN6	O00399	496
VMA22	FGF2	P09038	495
VMA22	ATP6V1A	P38606	489

IntAct

113 interactions, top by confidence:

A	B	Type	Score
ATP6AP2	ATP6V0C	psi-mi:“MI:0914”(association)	0.730
RARS1	VMA22	psi-mi:“MI:0915”(physical association)	0.670
VMA12	ATP6AP2	psi-mi:“MI:0914”(association)	0.640
BZW2	ENDOD1	psi-mi:“MI:0914”(association)	0.640
TCIRG1	ATP6AP2	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
ALOX15B	VMA22	psi-mi:“MI:0915”(physical association)	0.560
MIS18A	VMA22	psi-mi:“MI:0915”(physical association)	0.560
VMA22	ABI2	psi-mi:“MI:0915”(physical association)	0.560
VMA22	MIS18A	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	VMA22	psi-mi:“MI:0915”(physical association)	0.560
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PLXDC2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ATP6V0A2	B4GALT3	psi-mi:“MI:0914”(association)	0.530
ATP6AP2	ATP6V1C1	psi-mi:“MI:0914”(association)	0.530
atp6v0d_human	ATP6AP2	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
TCIRG1	AP3D1	psi-mi:“MI:0914”(association)	0.530
ATP6AP2	CLGN	psi-mi:“MI:0914”(association)	0.530

BioGRID (142): CCDC115 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), CCDC115 (Proximity Label-MS), CCDC115 (Proximity Label-MS), CCDC115 (Proximity Label-MS), CCDC115 (Proximity Label-MS), CCDC115 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), CCDC115 (Affinity Capture-MS), CCDC115 (Proximity Label-MS)

ESM2 similar proteins: A0JN53, A1L3T7, A4IFI1, A7E3N7, D2I4M3, D3Z5T1, G3HQ82, O60826, O94812, P86182, P97680, Q17Q97, Q17RC7, Q1RMI8, Q3KNJ2, Q3SZB5, Q3T1I9, Q3UK37, Q569K6, Q571B6, Q58CQ5, Q58EX7, Q5SPX1, Q66H85, Q6AYI4, Q6IUP3, Q6PJG6, Q7Z412, Q80TE0, Q80TT2, Q80UU1, Q8BGI5, Q8C3R1, Q8CJ00, Q8N9W5, Q8TE82, Q8TF30, Q8VE99, Q921Q7, Q95K25

Diamond homologs: Q3SZB5, Q5EAR6, Q8VE99, Q96NT0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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
Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	8	71.7×	7e-12
Insulin receptor recycling	13	66.0×	7e-19
Transferrin endocytosis and recycling	11	54.0×	8e-15
ROS and RNS production in phagocytes	11	49.3×	2e-14
Amino acids regulate mTORC1	8	21.4×	2e-07
Ion channel transport	12	15.3×	1e-09
Constitutive Signaling by Aberrant PI3K in Cancer	6	10.2×	2e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	9.0×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle lumen acidification	8	78.0×	1e-11
vacuolar acidification	10	76.3×	2e-14
lysosomal lumen acidification	7	49.1×	1e-08
proton transmembrane transport	10	32.5×	1e-10
regulation of macroautophagy	8	24.6×	1e-07
positive regulation of MAPK cascade	8	6.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	36
Likely benign	19
Benign	12

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1074572	NC_000002.11:g.(?131098481)(131104041_?)del	Pathogenic
1460303	NC_000002.11:g.(?131096693)(131099698_?)del	Pathogenic
1953265	NM_032357.4(VMA22):c.243del (p.Phe81fs)	Pathogenic
218963	NM_032357.4(CCDC115):c.31G>T (p.Asp11Tyr)	Pathogenic
218967	NM_032357.4(VMA22):c.92T>C (p.Leu31Ser)	Pathogenic
2579260	GRCh38/hg38 2q21.1(chr2:130099219-130374931)x1	Pathogenic
3247572	NC_000002.11:g.(?131098461)(131099698_?)del	Pathogenic
3772685	NM_032357.4(VMA22):c.227del (p.Glu76fs)	Pathogenic
4782326	NM_032357.4(VMA22):c.298+1G>A	Likely pathogenic

SpliceAI

590 predictions. Top by Δscore:

Variant	Effect	Δscore
2:130339230:GGC:G	acceptor_gain	1.0000
2:130339233:C:CC	acceptor_gain	1.0000
2:130340903:CTCA:C	donor_loss	1.0000
2:130340904:TCACC:T	donor_loss	1.0000
2:130340905:CA:C	donor_loss	1.0000
2:130340906:A:AC	donor_gain	1.0000
2:130340906:ACCAT:A	donor_gain	1.0000
2:130340907:C:CC	donor_gain	1.0000
2:130340907:C:CT	donor_loss	1.0000
2:130340907:CCAT:C	donor_gain	1.0000
2:130340907:CCATC:C	donor_gain	1.0000
2:130341038:ACC:A	acceptor_loss	1.0000
2:130341040:C:CC	acceptor_gain	1.0000
2:130341040:CT:C	acceptor_loss	1.0000
2:130341041:T:C	acceptor_loss	1.0000
2:130341746:CTCG:C	acceptor_gain	1.0000
2:130341747:TCG:T	acceptor_gain	1.0000
2:130341748:CG:C	acceptor_gain	1.0000
2:130341748:CGC:C	acceptor_gain	1.0000
2:130341750:C:CC	acceptor_gain	1.0000
2:130341838:CAC:C	donor_loss	1.0000
2:130341839:A:AC	donor_gain	1.0000
2:130341840:C:CC	donor_gain	1.0000
2:130341840:CCTGG:C	donor_gain	1.0000
2:130341940:CAGCC:C	acceptor_gain	1.0000
2:130341941:AGCC:A	acceptor_gain	1.0000
2:130341942:GCC:G	acceptor_gain	1.0000
2:130341943:CC:C	acceptor_gain	1.0000
2:130341943:CCC:C	acceptor_gain	1.0000
2:130341944:CC:C	acceptor_gain	1.0000

AlphaMissense

1140 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:130340960:A:C	F126L	0.996
2:130340960:A:T	F126L	0.996
2:130340962:A:G	F126L	0.996
2:130340915:G:C	F141L	0.988
2:130340915:G:T	F141L	0.988
2:130340917:A:G	F141L	0.988
2:130341944:C:G	G38R	0.985
2:130340916:A:G	F141S	0.984
2:130340949:A:T	V130D	0.983
2:130341923:C:G	A45P	0.981
2:130340929:C:G	A137P	0.980
2:130340958:C:T	G127E	0.980
2:130340961:A:G	F126S	0.976
2:130340955:A:G	I128T	0.975
2:130340962:A:T	F126I	0.974
2:130341943:C:T	G38D	0.972
2:130340935:G:T	R135S	0.970
2:130341922:G:T	A45D	0.970
2:130341941:A:G	W39R	0.969
2:130341941:A:T	W39R	0.969
2:130340928:G:T	A137D	0.967
2:130340961:A:C	F126C	0.966
2:130341928:G:T	A43D	0.966
2:130340958:C:A	G127V	0.965
2:130339208:G:T	A152D	0.963
2:130340962:A:C	F126V	0.963
2:130340908:C:G	G144R	0.958
2:130341881:A:C	Y59D	0.958
2:130341919:C:G	R46P	0.957
2:130340916:A:C	F141C	0.956

dbSNP variants (sampled 300 via entrez): RS1000095126 (2:130341416 C>T), RS1000327396 (2:130344162 A>T), RS1000490505 (2:130342695 A>C,G), RS1000878086 (2:130340242 G>A), RS1001264700 (2:130340556 G>A), RS1001628280 (2:130340225 C>T), RS1001702748 (2:130339320 C>T), RS1001823779 (2:130339871 T>A), RS1002322825 (2:130341306 G>C), RS1003066533 (2:130342516 G>T), RS1003265265 (2:130343879 G>T), RS1003386114 (2:130344150 A>G), RS1003677034 (2:130341995 T>A,C), RS1003901446 (2:130338415 C>A,T), RS1003938501 (2:130344485 C>A,T)

Disease associations

OMIM: gene MIM:613734 | disease phenotypes: MIM:616828, MIM:618622, MIM:618752

GenCC curated gene-disease

Disease	Classification	Inheritance
CCDC115-CDG	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
CCDC115-CDG	Moderate	AR

Mondo (4): CCDC115-CDG (MONDO:0014789), primary ovarian failure (MONDO:0005387), neurodevelopmental disorder with microcephaly, arthrogryposis, and structural brain anomalies (MONDO:0032838), neutropenia, severe congenital, 8, autosomal dominant (MONDO:0032899)

Orphanet (4): CCDC115-CDG (Orphanet:468684), Congenital arthrogryposis-microcephaly-facial dysmorphism-severe neurodevelopmental delay syndrome (Orphanet:664923), Severe congenital neutropenia-developmental delay syndrome due to SRP54 deficiency (Orphanet:675767), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

25 total (25 of 25 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000276	Long face
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001394	Cirrhosis
HP:0001399	Hepatic failure
HP:0001433	Hepatosplenomegaly
HP:0001744	Splenomegaly
HP:0001999	Abnormal facial shape
HP:0002240	Hepatomegaly
HP:0002611	Cholestatic liver disease
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003124	Hypercholesterolemia
HP:0003141	Increased LDL cholesterol concentration
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003593	Infantile onset
HP:0006579	Prolonged neonatal jaundice
HP:0010639	Elevated alkaline phosphatase of bone origin
HP:0010837	Decreased circulating ceruloplasmin concentration
HP:0012345	Abnormal glycosylation
HP:0025321	Copper accumulation in liver

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
dicrotophos	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
Grape Seed Proanthocyanidins	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Catechin	decreases expression, affects cotreatment	1
Cisplatin	affects cotreatment, increases expression	1
Estradiol	affects expression	1
Formaldehyde	increases expression	1
Cyclosporine	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9ZJ	Ubigene HeLa CCDC115 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists