C12orf60

Summary

C12orf60 (chromosome 12 open reading frame 60, HGNC:28726) is a protein-coding gene on chromosome 12p12.3, encoding Uncharacterized protein C12orf60 (Q5U649).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 49 total — 2 pathogenic
• MANE Select transcript: NM_175874

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28726
Approved symbol	C12orf60
Name	chromosome 12 open reading frame 60
Location	12p12.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC47869
Ensembl gene	ENSG00000182993
Ensembl biotype	protein_coding
Entrez	144608

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000330828, ENST00000527783, ENST00000533472, ENST00000543822, ENST00000648334, ENST00000857839, ENST00000857840, ENST00000857841, ENST00000857842, ENST00000934407

RefSeq mRNA: 1 — MANE Select: NM_175874 NM_175874

CCDS: CCDS8667

Canonical transcript exons

ENST00000330828 — 2 exons

Exon	Start	End
ENSE00001311633	14822912	14824415
ENSE00001318471	14803670	14803751

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 88.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6304 / max 117.1167, expressed in 1253 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124461	3.2113	1166
124462	0.4190	213

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	88.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.39	gold quality
left testis	UBERON:0004533	84.82	gold quality
right testis	UBERON:0004534	84.35	gold quality
testis	UBERON:0000473	83.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.02	gold quality
right lobe of liver	UBERON:0001114	76.99	gold quality
left ventricle myocardium	UBERON:0006566	76.46	silver quality
adult organism	UBERON:0007023	76.32	gold quality
islet of Langerhans	UBERON:0000006	76.18	gold quality
right adrenal gland cortex	UBERON:0035827	75.97	gold quality
right atrium auricular region	UBERON:0006631	75.76	gold quality
cardiac atrium	UBERON:0002081	75.40	gold quality
right adrenal gland	UBERON:0001233	75.32	gold quality
sural nerve	UBERON:0015488	74.94	gold quality
heart left ventricle	UBERON:0002084	74.92	gold quality
myocardium	UBERON:0002349	74.82	silver quality
cardiac ventricle	UBERON:0002082	74.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.48	gold quality
left adrenal gland cortex	UBERON:0035825	74.45	gold quality
heart	UBERON:0000948	74.22	gold quality
adrenal cortex	UBERON:0001235	74.02	gold quality
left adrenal gland	UBERON:0001234	73.97	gold quality
adrenal gland	UBERON:0002369	73.72	gold quality
ascending aorta	UBERON:0001496	72.89	gold quality
thoracic aorta	UBERON:0001515	72.83	gold quality
right coronary artery	UBERON:0001625	72.66	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.52	gold quality
descending thoracic aorta	UBERON:0002345	72.29	gold quality
secondary oocyte	CL:0000655	72.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting C12orf60, 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-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-548D-3P	99.87	70.67	4362
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-5010-3P	99.83	70.60	2357
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-606	98.72	67.34	960
HSA-MIR-6730-3P	97.03	67.54	889
HSA-MIR-3156-5P	96.93	67.36	800
HSA-MIR-7161-3P	96.79	68.79	798

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	BC049715	ENSMUSG00000047515
rattus_norvegicus	C4h12orf60	ENSRNOG00000027979

Protein

Protein identifiers

Uncharacterized protein C12orf60 — Q5U649 (reviewed: Q5U649)

All UniProt accessions (1): Q5U649

RefSeq proteins (1): NP_787070* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027895	DUF4533	Family

Pfam: PF15047

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5U649-F1	81.24	0.46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): KONDO_PROSTATE_CANCER_HCP_WITH_H3K27ME3, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MARSON_BOUND_BY_E2F4_UNSTIMULATED, chr12p12, SENGUPTA_EBNA1_ANTICORRELATED, BARX1_TARGET_GENES, CEBPZ_TARGET_GENES, CREB3L4_TARGET_GENES, ID1_TARGET_GENES, NKX2_2_TARGET_GENES, NKX2_3_TARGET_GENES, NR1I2_TARGET_GENES, PAX3_TARGET_GENES, PAX7_TARGET_GENES

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

116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C12orf60	SMCO3	A2RU48	609
C12orf60	CFAP20DC	Q6ZVT6	447
C12orf60	ZNF678	Q5SXM1	446
C12orf60	FAM234B	A2RU67	435
C12orf60	DYM	Q7RTS9	417
C12orf60	BRSK1	Q8TDC3	398
C12orf60	PXDC1	Q5TGL8	395
C12orf60	LRRN4	Q8WUT4	359
C12orf60	L3MBTL4	Q8NA19	349
C12orf60	ERP27	Q96DN0	348
C12orf60	H2AJ	Q9BTM1	315
C12orf60	AKNA	Q7Z591	300
C12orf60	RBBP6	Q7Z6E9	300
C12orf60	SLC39A8	Q9C0K1	300
C12orf60	NUDT3	O95989	297

IntAct

5 interactions, top by confidence:

A	B	Type	Score
C12orf60	ERP27	psi-mi:“MI:0915”(physical association)	0.560
C12orf60	BMP4	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1): C12orf60 (Two-hybrid)

ESM2 similar proteins: A0A1S4F550, A4GCK2, A4K148, A4U7B1, C0HMB7, F4J1G1, F5HCM1, O36392, O57571, P01580, P03872, P11619, P17773, P23705, P28333, P33493, P34289, P35259, P42161, P52473, P52546, P69259, P69260, P69266, P69267, P79154, Q01048, Q01640, Q03039, Q04685, Q04686, Q0G825, Q13352, Q197A6, Q1K9P8, Q1PD52, Q1PDC9, Q25BC0, Q5U649, Q5UR54

Diamond homologs: Q4KLZ4, Q5U649, Q810N5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
161159	NM_004963.4(GUCY2C):c.2782T>C (p.Cys928Arg)	Pathogenic
31605	NM_004963.4(GUCY2C):c.2270dup (p.Asn757fs)	Pathogenic

SpliceAI

1459 predictions. Top by Δscore:

Variant	Effect	Δscore
12:14803345:CA:C	donor_gain	1.0000
12:14803349:CA:C	donor_loss	1.0000
12:14803350:A:AC	donor_gain	1.0000
12:14803351:C:CC	donor_gain	1.0000
12:14803351:CA:C	donor_gain	1.0000
12:14803351:CACT:C	donor_gain	1.0000
12:14803351:CACTT:C	donor_gain	1.0000
12:14840567:T:TA	donor_gain	1.0000
12:14882279:TC:T	acceptor_gain	1.0000
12:14882280:CC:C	acceptor_gain	1.0000
12:14882281:C:CC	acceptor_gain	1.0000
12:14882288:G:C	acceptor_gain	1.0000
12:14882288:G:GC	acceptor_gain	1.0000
12:14883049:T:C	acceptor_gain	1.0000
12:14884211:A:AC	donor_gain	1.0000
12:14884212:C:CC	donor_gain	1.0000
12:14884212:CT:C	donor_gain	1.0000
12:14884212:CTA:C	donor_gain	1.0000
12:14884212:CTAA:C	donor_gain	1.0000
12:14884212:CTAAG:C	donor_gain	1.0000
12:14884244:TT:T	acceptor_gain	1.0000
12:14884244:TTC:T	acceptor_loss	1.0000
12:14884245:TC:T	acceptor_loss	1.0000
12:14884246:C:A	acceptor_loss	1.0000
12:14884246:C:CC	acceptor_gain	1.0000
12:14884247:T:A	acceptor_loss	1.0000
12:14884252:T:C	acceptor_gain	1.0000
12:14884252:T:TC	acceptor_gain	1.0000
12:14803399:C:CA	donor_gain	0.9900
12:14806694:TCG:T	acceptor_gain	0.9900

AlphaMissense

1657 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:14822981:G:C	A16P	0.862
12:14822978:G:C	A15P	0.849
12:14823387:T:C	L151P	0.847
12:14822970:T:C	L12P	0.835
12:14823557:G:C	A208P	0.834
12:14823012:T:C	L26P	0.811
12:14823507:T:C	L191P	0.803
12:14823567:T:C	L211S	0.802
12:14822993:T:C	F20L	0.783
12:14822995:C:A	F20L	0.783
12:14822995:C:G	F20L	0.783
12:14822982:C:A	A16D	0.777
12:14823354:T:C	L140P	0.777
12:14823033:T:C	L33P	0.767
12:14823402:T:C	F156S	0.767
12:14823044:T:C	F37L	0.761
12:14823046:T:A	F37L	0.761
12:14823046:T:G	F37L	0.761
12:14823342:T:C	L136P	0.740
12:14823609:T:C	L225P	0.737
12:14822990:T:C	F19L	0.736
12:14822992:C:A	F19L	0.736
12:14822992:C:G	F19L	0.736
12:14823393:T:C	L153S	0.726
12:14822968:A:C	R11S	0.712
12:14822968:A:T	R11S	0.712
12:14823617:G:C	A228P	0.709
12:14823382:G:A	M149I	0.699
12:14823382:G:C	M149I	0.699
12:14823382:G:T	M149I	0.699

dbSNP variants (sampled 300 via entrez): RS1000020920 (12:14751430 C>A), RS1000032688 (12:14789796 G>A), RS1000059617 (12:14632907 C>A,T), RS1000069841 (12:14652495 T>C), RS1000100853 (12:14681220 A>G), RS1000177640 (12:14666761 A>C), RS1000187686 (12:14791547 G>A), RS1000222940 (12:14809439 G>T), RS1000225158 (12:14816787 C>G,T), RS1000232852 (12:14719310 T>G), RS1000246096 (12:14718812 G>A,T), RS1000247578 (12:14765074 G>A), RS1000254290 (12:14809151 A>G), RS1000268395 (12:14627654 A>G), RS1000282550 (12:14763721 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): meconium ileus (MONDO:0054868)

Orphanet (1): Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency (Orphanet:314376)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001875_5	Pubertal anthropometrics	8.000000e-07
GCST90007526_8	Low hand grip strength (60 years and older) (EWGSOP)	3.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006941	grip strength measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000074270	Meconium Ileus	C06.405.469.531.788

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
2-palmitoylglycerol	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
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Vorinostat	increases expression	1
Benzo(a)pyrene	increases methylation	1
Hydrogen Peroxide	affects expression	1
Quercetin	increases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01515696	PHASE4	COMPLETED	Impact of Oral Application of Gastrografin on the Meconium Evacuation in Very Low Birth Weight Infants
NCT02140710	PHASE4	COMPLETED	Impact of Visceral Osteopathic Treatment on Meconium Evacuation in Preterm Infants
NCT02710383	Not specified	TERMINATED	Biomarker for Cystic Fibrosis
NCT03593252	Not specified	UNKNOWN	Bowel Preparation in Elective Pediatric Colorectal Surgery
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04713579	Not specified	COMPLETED	Timing of Stoma Closure in Neonates
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems