C2orf68

Summary

C2orf68 (chromosome 2 open reading frame 68, HGNC:34353) is a protein-coding gene on chromosome 2p11.2, encoding UPF0561 protein C2orf68 (Q2NKX9).

At a glance

• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_001013649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34353
Approved symbol	C2orf68
Name	chromosome 2 open reading frame 68
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168887
Ensembl biotype	protein_coding
OMIM	618519
Entrez	388969

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000306336, ENST00000409734, ENST00000420686, ENST00000423181, ENST00000478626, ENST00000855090, ENST00000920274

RefSeq mRNA: 1 — MANE Select: NM_001013649 NM_001013649

CCDS: CCDS42704

Canonical transcript exons

ENST00000306336 — 4 exons

Exon	Start	End
ENSE00001135399	85611668	85611786
ENSE00001154940	85611878	85612066
ENSE00001532313	85605254	85609067
ENSE00003676909	85609435	85609586

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 94.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.3360 / max 1373.9343, expressed in 1819 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29431	21.0077	1812
29430	10.3283	1718

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	94.37	gold quality
gastrocnemius	UBERON:0001388	93.77	gold quality
muscle of leg	UBERON:0001383	93.39	gold quality
ventricular zone	UBERON:0003053	91.30	gold quality
monocyte	CL:0000576	91.28	gold quality
leukocyte	CL:0000738	91.26	gold quality
mononuclear cell	CL:0000842	91.20	gold quality
skeletal muscle organ	UBERON:0014892	91.06	gold quality
muscle organ	UBERON:0001630	91.05	gold quality
blood	UBERON:0000178	90.94	gold quality
ganglionic eminence	UBERON:0004023	90.69	gold quality
granulocyte	CL:0000094	90.51	gold quality
apex of heart	UBERON:0002098	90.47	gold quality
right uterine tube	UBERON:0001302	89.93	gold quality
cortical plate	UBERON:0005343	89.37	gold quality
body of pancreas	UBERON:0001150	89.28	gold quality
right lobe of thyroid gland	UBERON:0001119	89.27	gold quality
trabecular bone tissue	UBERON:0002483	89.15	gold quality
metanephros cortex	UBERON:0010533	89.06	gold quality
left ovary	UBERON:0002119	88.99	gold quality
lower esophagus mucosa	UBERON:0035834	88.96	gold quality
left testis	UBERON:0004533	88.82	gold quality
minor salivary gland	UBERON:0001830	88.75	gold quality
left lobe of thyroid gland	UBERON:0001120	88.71	gold quality
mucosa of transverse colon	UBERON:0004991	88.65	gold quality
right testis	UBERON:0004534	88.63	gold quality
body of stomach	UBERON:0001161	88.44	gold quality
nipple	UBERON:0002030	88.44	gold quality
right ovary	UBERON:0002118	88.16	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.11	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	47.68
E-ANND-3	yes	11.54
E-MTAB-7303	no	351.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

157 targeting C2orf68, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3671	99.90	73.04	3897

Literature-anchored findings (GeneRIF, showing 5)

• The mRNA levels of NM_001013649.3 are significantly down-regulated in colorectal adenocarcinoma tissue, and this down-regulation is most likely correlated with the differentiation status of the cancer. (PMID:21874238)
• Observations of the current study indicate that hcrcn81 may play a role in tumorigenesis by regulating the mTOR signaling pathway. (PMID:23404111)
• c2orf68 expression correlates with the pathogenesis of colorectal cancer through PI3K/Akt/mTOR pathway. (PMID:25023051)
• hcrcn81 might promote carcinogenesis and progression through regulation of the Wnt/beta-catenin signaling pathway and plays an important role in the carcinogenesis of colorectal cancer. (PMID:26607374)
• Study suggested that c2orf68 is a potential carcinogenesis factor in colorectal cancer (CRC). Furthermore, c2orf68 may have a synergistic effect with HuR in the onset and development of CRC. (PMID:30664176)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	C5H2orf68	ENSDARG00000059459
mus_musculus	0610030E20Rik	ENSMUSG00000058706
rattus_norvegicus	C4h2orf68	ENSRNOG00000011713

Protein

Protein identifiers

UPF0561 protein C2orf68 — Q2NKX9 (reviewed: Q2NKX9)

All UniProt accessions (4): Q2NKX9, F6S878, H7C1Q5, L7T9J5

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the UPF0561 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q2NKX9-1	1	yes
Q2NKX9-3	2

RefSeq proteins (1): NP_001013671* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018888	UPF0561	Family

Pfam: PF10573

UniProt features (7 total): compositionally biased region 3, splice variant 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2NKX9-F1	77.79	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 127 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, INGRAM_SHH_TARGETS_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, chr2p11, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, OSMAN_BLADDER_CANCER_DN, SENESE_HDAC3_TARGETS_DN, LIU_PROSTATE_CANCER_DN, GINESTIER_BREAST_CANCER_20Q13_AMPLIFICATION_DN, HOELZEL_NF1_TARGETS_DN, LEE_DIFFERENTIATING_T_LYMPHOCYTE, STK33_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2orf68	C19orf73	Q9NVV2	571
C2orf68	ZNF316	A6NFI3	480
C2orf68	SH2D6	Q7Z4S9	480
C2orf68	F5GXT2	F5GXT2	479
C2orf68	PWWP2B	Q6NUJ5	474
C2orf68	HDDC2	Q7Z4H3	447
C2orf68	TMEM150A	Q86TG1	418
C2orf68	SBSPON	Q8IVN8	393
C2orf68	ELMOD3	Q96FG2	392
C2orf68	SGCZ	Q96LD1	392
C2orf68	REG4	Q9BYZ8	387
C2orf68	NDOR1	Q9UHB4	371
C2orf68	RNF181	Q9P0P0	370
C2orf68	METTL15	A6NJ78	367
C2orf68	LRRC37A	A6NMS7	356

IntAct

47 interactions, top by confidence:

A	B	Type	Score
C2orf68	KANK2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	C2orf68	psi-mi:“MI:0915”(physical association)	0.560
KEAP1	C2orf68	psi-mi:“MI:0915”(physical association)	0.560
SIVA1	C2orf68	psi-mi:“MI:0915”(physical association)	0.560
C2orf68	KRT40	psi-mi:“MI:0915”(physical association)	0.560
ZBTB14	C2orf68	psi-mi:“MI:0915”(physical association)	0.560
C2orf68	AXIN2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	C2orf68	psi-mi:“MI:0915”(physical association)	0.560
C2orf68	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.560
C2orf68	HYPK	psi-mi:“MI:0915”(physical association)	0.560
C2orf68	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
TNNI1	C2orf68	psi-mi:“MI:0915”(physical association)	0.560
C2orf68	PIR	psi-mi:“MI:0914”(association)	0.530
C2orf68	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
C2orf68	KANK2	psi-mi:“MI:0915”(physical association)	0.000
C2orf68	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
C2orf68	KEAP1	psi-mi:“MI:0915”(physical association)	0.000
C2orf68	KRTAP1-3	psi-mi:“MI:0915”(physical association)	0.000
C2orf68	RAB3IL1	psi-mi:“MI:0915”(physical association)	0.000
C2orf68	SIVA1	psi-mi:“MI:0915”(physical association)	0.000
C2orf68	KRT40	psi-mi:“MI:0915”(physical association)	0.000
C2orf68	ZBTB14	psi-mi:“MI:0915”(physical association)	0.000
C2orf68	AXIN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (41): KLHL15 (Affinity Capture-MS), GMNN (Affinity Capture-MS), SMG6 (Affinity Capture-MS), GNE (Affinity Capture-MS), DDHD2 (Affinity Capture-MS), PIR (Affinity Capture-MS), NAGK (Affinity Capture-MS), C2orf68 (Affinity Capture-MS), SMG6 (Affinity Capture-MS), GNE (Affinity Capture-MS), PIR (Affinity Capture-MS), DDHD2 (Affinity Capture-MS), GMNN (Affinity Capture-MS), KLHL15 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HTT5, A1A5R9, A2RSX4, A4IFR8, A5WUY6, A6QPC0, A7YWH3, B0BNE4, E1BNS6, G3X6E2, Q08BC4, Q0P591, Q0VB26, Q14BB9, Q17RG1, Q1XFL1, Q2NKX9, Q2T9Q3, Q2TA11, Q2TBS4, Q3KQ80, Q3SX64, Q3UFT3, Q3ZBR0, Q4QR77, Q4R5Y0, Q4VXA5, Q562E2, Q6J272, Q6ZQR2, Q7T3U0, Q8C8J0, Q8N1D5, Q8N412, Q8N7X2, Q8N801, Q8TCI5, Q8WW14, Q99932, Q9BWG6

Diamond homologs: A3KQ58, A4IFR8, Q149G0, Q2NKX9, Q4V817

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

561 predictions. Top by Δscore:

Variant	Effect	Δscore
2:85609429:GCGTA:G	donor_loss	1.0000
2:85609430:CGTA:C	donor_loss	1.0000
2:85609432:TACCT:T	donor_loss	1.0000
2:85609434:C:CG	donor_loss	1.0000
2:85609584:CAT:C	acceptor_gain	1.0000
2:85609601:CACAG:C	acceptor_gain	1.0000
2:85609066:CC:C	acceptor_gain	0.9900
2:85609067:CC:C	acceptor_gain	0.9900
2:85609587:C:CC	acceptor_gain	0.9900
2:85609587:CTGG:C	acceptor_loss	0.9900
2:85609588:T:C	acceptor_loss	0.9900
2:85609595:A:AC	acceptor_gain	0.9900
2:85609595:A:C	acceptor_gain	0.9900
2:85609604:A:T	acceptor_gain	0.9900
2:85611316:A:AC	donor_gain	0.9900
2:85611317:C:CC	donor_gain	0.9900
2:85611472:A:C	donor_gain	0.9900
2:85609386:C:CT	donor_gain	0.9800
2:85609387:T:TT	donor_gain	0.9800
2:85609582:GACAT:G	acceptor_gain	0.9800
2:85609601:C:T	acceptor_gain	0.9800
2:85609603:CAG:C	acceptor_gain	0.9800
2:85611435:T:TA	donor_gain	0.9800
2:85611662:CCTCA:C	donor_loss	0.9800
2:85611663:CTCA:C	donor_loss	0.9800
2:85611664:TCA:T	donor_loss	0.9800
2:85611665:CACC:C	donor_loss	0.9800
2:85611667:C:T	donor_loss	0.9800
2:85609064:CACC:C	acceptor_gain	0.9700
2:85609065:ACCC:A	acceptor_loss	0.9700

AlphaMissense

1081 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:85611910:G:C	F25L	0.999
2:85611910:G:T	F25L	0.999
2:85611912:A:G	F25L	0.999
2:85611899:A:G	I29T	0.998
2:85611911:A:C	F25C	0.998
2:85611911:A:G	F25S	0.998
2:85611899:A:T	I29N	0.997
2:85611899:A:C	I29S	0.996
2:85609442:A:T	V124D	0.995
2:85611916:G:C	H23Q	0.995
2:85611916:G:T	H23Q	0.995
2:85609484:A:G	L110S	0.994
2:85611886:C:A	Q33H	0.994
2:85611886:C:G	Q33H	0.994
2:85611891:T:C	N32D	0.993
2:85609490:A:G	F108S	0.991
2:85609489:G:C	F108L	0.990
2:85609489:G:T	F108L	0.990
2:85609491:A:G	F108L	0.990
2:85611889:G:C	N32K	0.990
2:85611889:G:T	N32K	0.990
2:85611893:C:G	R31P	0.990
2:85611929:A:T	L19Q	0.990
2:85611878:C:G	R36P	0.989
2:85611887:T:G	Q33P	0.989
2:85611903:G:C	H28D	0.989
2:85611784:T:A	D37V	0.988
2:85611785:C:G	D37H	0.987
2:85611902:T:G	H28P	0.987
2:85611914:C:T	G24D	0.987

dbSNP variants (sampled 300 via entrez): RS1000033559 (2:85605076 A>G), RS1000106784 (2:85605460 T>C), RS1000211109 (2:85612206 C>A,T), RS1000351466 (2:85611292 A>G,T), RS1000410980 (2:85612056 C>T), RS1000954990 (2:85612443 G>T), RS1001007725 (2:85606176 G>A,T), RS1001050491 (2:85606398 A>C), RS1001112481 (2:85606264 G>A), RS1001300566 (2:85612201 G>A), RS1001902235 (2:85613540 G>C), RS1002052434 (2:85607775 T>G), RS1002354663 (2:85613789 T>A), RS1002457894 (2:85612010 G>A,T), RS1003053570 (2:85610684 C>T)

Disease associations

OMIM: gene MIM:618519 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, decreases expression	8
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dimethylarsinous acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Diuron	decreases expression	1
Estradiol	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery