C2orf66

Summary

C2orf66 (chromosome 2 open reading frame 66, HGNC:33809) is a protein-coding gene on chromosome 2q33.1, encoding Uncharacterized protein C2orf66 (Q6UXQ4).

Predicted to be located in extracellular region.

Source: NCBI Gene 401027 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_213608

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33809
Approved symbol	C2orf66
Name	chromosome 2 open reading frame 66
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	UNQ6411
Ensembl gene	ENSG00000187944
Ensembl biotype	protein_coding
Entrez	401027

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000342506

RefSeq mRNA: 1 — MANE Select: NM_213608 NM_213608

CCDS: CCDS2317

Canonical transcript exons

ENST00000342506 — 3 exons

Exon	Start	End
ENSE00001366204	196804417	196805408
ENSE00001368967	196807424	196807622
ENSE00003902316	196809214	196809355

Expression profiles

Bgee: expression breadth ubiquitous, 123 present calls, max score 94.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0443 / max 25.0367, expressed in 11 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33046	0.0443	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.30	gold quality
pituitary gland	UBERON:0000007	76.74	gold quality
adenohypophysis	UBERON:0002196	75.57	gold quality
hypothalamus	UBERON:0001898	72.86	gold quality
lower esophagus mucosa	UBERON:0035834	64.54	gold quality
left adrenal gland cortex	UBERON:0035825	63.78	gold quality
substantia nigra	UBERON:0002038	63.32	gold quality
mucosa of transverse colon	UBERON:0004991	63.03	gold quality
left adrenal gland	UBERON:0001234	62.72	gold quality
right adrenal gland cortex	UBERON:0035827	62.67	gold quality
amygdala	UBERON:0001876	61.93	gold quality
left testis	UBERON:0004533	61.90	gold quality
temporal lobe	UBERON:0001871	61.43	gold quality
nucleus accumbens	UBERON:0001882	61.21	gold quality
right uterine tube	UBERON:0001302	61.17	gold quality
right testis	UBERON:0004534	61.16	gold quality
Ammon’s horn	UBERON:0001954	61.05	gold quality
testis	UBERON:0000473	60.60	gold quality
right adrenal gland	UBERON:0001233	60.52	gold quality
anterior cingulate cortex	UBERON:0009835	59.49	gold quality
stromal cell of endometrium	CL:0002255	59.10	gold quality
right atrium auricular region	UBERON:0006631	58.94	gold quality
adrenal gland	UBERON:0002369	58.81	gold quality
islet of Langerhans	UBERON:0000006	58.67	gold quality
omental fat pad	UBERON:0010414	57.36	gold quality
brain	UBERON:0000955	57.32	gold quality
skin of leg	UBERON:0001511	56.98	gold quality
skin of abdomen	UBERON:0001416	56.97	gold quality
caudate nucleus	UBERON:0001873	56.88	gold quality
zone of skin	UBERON:0000014	56.82	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting C2orf66, 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-8068	99.98	73.85	2376
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4666A-3P	99.96	71.71	3434
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-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-7-5P	99.67	70.53	1809

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pgap1	ENSDARG00000062465
mus_musculus	Gm34066	ENSMUSG00000109809
rattus_norvegicus	C9h2orf66	ENSRNOG00000067303
drosophila_melanogaster	PGAP1	FBGN0029789
caenorhabditis_elegans		WBGENE00011835

Paralogs (1): PGAP1 (ENSG00000197121)

Protein

Protein identifiers

Uncharacterized protein C2orf66 — Q6UXQ4 (reviewed: Q6UXQ4)

All UniProt accessions (1): A0A5K1VW65

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

RefSeq proteins (1): NP_998773* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031699	DUF4720	Family

Pfam: PF15846

UniProt features (2 total): signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXQ4-F1	72.23	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): FREAC3_01, RFX1_02, MIR4666A_3P, MIR338_5P, MIR3978, MIR29B_2_5P, MIR4760_5P, MIR4735_5P, MIR8061, MIR5583_3P, MIR20B_3P, BLANCO_MELO_COVID19_SARS_COV_2_LOW_MOI_INFECTION_A594_ACE2_EXPRESSING_CELLS_UP, BLANCO_MELO_BRONCHIAL_EPITHELIAL_CELLS_INFLUENZA_A_DEL_NS1_INFECTION_UP, OSMAN_BLOOD_CHAD63_KH_AGE_18_50YO_HIGH_DOSE_SUBJECTS_24HR_UP, SMAD3_Q6

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2orf66	CCDC190	Q86UF4	515
C2orf66	TMEM217B	A0A494BZU4	480
C2orf66	TMEM217	Q8N7C4	479
C2orf66	Q8NG57	Q8NG57	447
C2orf66	C2CD4B	A6NLJ0	366
C2orf66	RPF2	Q9H7B2	360
C2orf66	SLC41A2	Q96JW4	350
C2orf66	PIGT	Q969N2	348
C2orf66	PGAP3	Q96FM1	348
C2orf66	PIGK	Q92643	348
C2orf66	GPAA1	O43292	347
C2orf66	CSNK1G1	Q9HCP0	338
C2orf66	PIGS	Q96S52	320
C2orf66	MPZL2	O60487	307
C2orf66	PLA2G4C	Q9UP65	305

IntAct

2 interactions, top by confidence:

A	B	Type	Score
C2orf66	EFCAB2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): C2orf66 (Positive Genetic), EFCAB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTC6, A0A2U3Y4D7, A0A2Y9HRM2, G5BQH4, G5BWH8, G8F204, P01257, P01261, P02652, P02656, P06759, P0CE37, P0CE39, P0CF78, P0DJD2, P0DJG2, P0DKV2, P0DKV3, P0DKV4, P0DM95, P0DM96, P0DMP9, P0DMR2, P0DMT9, P0DN36, P0DP50, P0DP84, P0DP85, P0DP86, P0DP87, P0DTQ3, P0DTQ5, P0DTR6, P0DTS5, P18656, P18659, P33622, P40148, P41547, P70160

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

194 predictions. Top by Δscore:

Variant	Effect	Δscore
2:196807623:C:CC	acceptor_gain	1.0000
2:196809208:TCTTA:T	donor_loss	1.0000
2:196809209:CTTA:C	donor_loss	1.0000
2:196809210:TTAC:T	donor_loss	1.0000
2:196809211:TA:T	donor_loss	1.0000
2:196809212:ACC:A	donor_loss	1.0000
2:196809213:C:CA	donor_loss	1.0000
2:196807019:TTCA:T	donor_gain	0.9900
2:196807621:AA:A	acceptor_gain	0.9900
2:196809212:A:AC	donor_gain	0.9900
2:196809213:C:CC	donor_gain	0.9900
2:196805409:CTGA:C	acceptor_loss	0.9800
2:196805410:T:G	acceptor_loss	0.9800
2:196807418:TTTTA:T	donor_loss	0.9800
2:196807419:TTTA:T	donor_loss	0.9800
2:196807420:TTAC:T	donor_loss	0.9800
2:196807421:TAC:T	donor_loss	0.9800
2:196807422:A:T	donor_loss	0.9800
2:196807423:CCTG:C	donor_loss	0.9800
2:196807620:AAA:A	acceptor_gain	0.9800
2:196807622:ACTA:A	acceptor_loss	0.9700
2:196807624:T:C	acceptor_loss	0.9700
2:196809213:CCAG:C	donor_gain	0.9700
2:196805406:CAC:C	acceptor_gain	0.9600
2:196807622:ACT:A	acceptor_gain	0.9600
2:196807623:CTA:C	acceptor_gain	0.9600
2:196807624:T:A	acceptor_gain	0.9600
2:196807618:AAAAA:A	acceptor_gain	0.9500
2:196807620:AAACT:A	acceptor_gain	0.9500
2:196807621:AACTA:A	acceptor_gain	0.9500

AlphaMissense

646 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:196809247:C:A	W47C	0.883
2:196809247:C:G	W47C	0.883
2:196809249:A:G	W47R	0.878
2:196809249:A:T	W47R	0.878
2:196807617:G:C	F60L	0.874
2:196807617:G:T	F60L	0.874
2:196807619:A:G	F60L	0.874
2:196807620:A:C	F59L	0.832
2:196807620:A:T	F59L	0.832
2:196807622:A:G	F59L	0.832
2:196809223:G:C	N55K	0.737
2:196809223:G:T	N55K	0.737
2:196809244:C:A	K48N	0.732
2:196809244:C:G	K48N	0.732
2:196807609:A:T	L63H	0.712
2:196809220:T:A	R56S	0.710
2:196809220:T:G	R56S	0.710
2:196809239:A:T	L50H	0.704
2:196807597:A:G	F67S	0.693
2:196807618:A:C	F60C	0.685
2:196809248:C:A	W47L	0.679
2:196807609:A:G	L63P	0.677
2:196807587:T:A	R70S	0.673
2:196807587:T:G	R70S	0.673
2:196807566:A:C	F77L	0.666
2:196807566:A:T	F77L	0.666
2:196807568:A:G	F77L	0.666
2:196807604:C:G	A65P	0.664
2:196807621:A:G	F59S	0.661
2:196807618:A:G	F60S	0.657

dbSNP variants (sampled 300 via entrez): RS1000089402 (2:196829813 T>C), RS1000090416 (2:196806575 G>T), RS1000141937 (2:196823365 G>A), RS1000142798 (2:196806329 C>G), RS1000173692 (2:196832004 G>A), RS1000191013 (2:196810463 T>C), RS1000335206 (2:196824236 T>C), RS1000356019 (2:196826834 C>G,T), RS1000368279 (2:196819869 G>C,T), RS1000475518 (2:196806614 G>T), RS1000763016 (2:196806963 G>A), RS1000778598 (2:196819424 T>A), RS1000881019 (2:196825860 G>T), RS1001091435 (2:196825432 T>C), RS1001209384 (2:196829702 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

1 associations (top):

Study	Trait	p-value
GCST010396_207	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

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
aristolochic acid I	increases expression	1
1-hydroxypyrene	decreases expression	1
3,4,5,4’-tetramethoxystilbene	affects expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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