C2orf78

Summary

C2orf78 (chromosome 2 open reading frame 78, HGNC:34349) is a protein-coding gene on chromosome 2p13.1, encoding Uncharacterized protein C2orf78 (A6NCI8).

At a glance

• Clinical variants (ClinVar): 7 total — 1 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001080474

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34349
Approved symbol	C2orf78
Name	chromosome 2 open reading frame 78
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ43987, hCG1989538, COG5373
Ensembl gene	ENSG00000187833
Ensembl biotype	protein_coding
Entrez	388960

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000409561

RefSeq mRNA: 2 — MANE Select: NM_001080474 NM_001080474, NM_001353344

CCDS: CCDS46338

Canonical transcript exons

ENST00000409561 — 3 exons

Exon	Start	End
ENSE00001391464	73813477	73814226
ENSE00003978182	73815071	73817148
ENSE00003978183	73784183	73784406

Expression profiles

Bgee: expression breadth tissue_specific, 7 present calls, max score 82.58.

Top tissues by expression

130 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	82.58	gold quality
left testis	UBERON:0004533	77.94	gold quality
right testis	UBERON:0004534	77.77	gold quality
testis	UBERON:0000473	77.59	gold quality
sural nerve	UBERON:0015488	42.70	gold quality
bone marrow cell	CL:0002092	40.24	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.69	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
bone marrow	UBERON:0002371	34.93	gold quality
skeletal muscle tissue	UBERON:0001134	34.77	gold quality
granulocyte	CL:0000094	34.30	gold quality
monocyte	CL:0000576	33.74	gold quality
leukocyte	CL:0000738	33.66	gold quality
muscle tissue	UBERON:0002385	33.18	gold quality
duodenum	UBERON:0002114	32.45	gold quality
prefrontal cortex	UBERON:0000451	30.41	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
muscle of leg	UBERON:0001383	29.43	gold quality
lymph node	UBERON:0000029	28.82	gold quality
tonsil	UBERON:0002372	28.66	gold quality
gastrocnemius	UBERON:0001388	28.57	gold quality
right uterine tube	UBERON:0001302	28.50	gold quality
blood	UBERON:0000178	28.45	gold quality
gall bladder	UBERON:0002110	28.42	gold quality
islet of Langerhans	UBERON:0000006	28.24	gold quality
kidney	UBERON:0002113	27.91	gold quality
urinary bladder	UBERON:0001255	27.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting C2orf78, 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-4307	99.82	70.45	3374
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-3074-3P	97.83	67.26	922
HSA-MIR-4491	96.53	66.20	935
HSA-MIR-4657	96.53	66.57	895

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gm4884	ENSMUSG00000048312
mus_musculus	Gm5114	ENSMUSG00000053742
mus_musculus	Gm5591	ENSMUSG00000060565
mus_musculus	Gm5592	ENSMUSG00000072259
mus_musculus	4930433I11Rik	ENSMUSG00000091692
rattus_norvegicus	C1h2orf78	ENSRNOG00000027102
rattus_norvegicus	4930433I11Rikl	ENSRNOG00000027112
rattus_norvegicus	C1h2orf78l1	ENSRNOG00000027370

Protein

Protein identifiers

Uncharacterized protein C2orf78 — A6NCI8 (reviewed: A6NCI8)

All UniProt accessions (1): A6NCI8

RefSeq proteins (2): NP_001073943, NP_001340273 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027898	DUF4629	Domain
IPR040292	C2orf78-like	Family

Pfam: PF15442

UniProt features (13 total): compositionally biased region 6, region of interest 5, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NCI8-F1	42.92	0.02

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 6 (showing top): chr2p13, MIR4307, MIR2115_3P, MIR361_5P, MIR3074_3P, DNMT3A_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

122 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2orf78	GIMAP2	Q9UG22	573
C2orf78	NBPF14	Q5TI25	447
C2orf78	CDKL4	Q5MAI5	445
C2orf78	MELTF	P08582	415
C2orf78	LCE1F	Q5T754	398
C2orf78	C22orf31	O95567	377
C2orf78	OR8G1	Q15617	348
C2orf78	MRPL40	Q9NQ50	323
C2orf78	NOTCH2NLB	P0DPK3	311
C2orf78	DUSP11	O75319	307
C2orf78	ZNF574	Q6ZN55	296
C2orf78	HOXD13	P35453	284
C2orf78	TBCEL	Q5QJ74	259
C2orf78	COX11	Q9Y6N1	256
C2orf78	TIMD4	Q96H15	253

IntAct

4 interactions, top by confidence:

A	B	Type	Score
C2orf78	PHB1	psi-mi:“MI:0915”(physical association)	0.400
C2orf78	HNRNPCL2	psi-mi:“MI:0915”(physical association)	0.400
C2orf78	KRT8	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (7): C2orf78 (Synthetic Lethality), KRT8 (Proximity Label-MS), PHB (Proximity Label-MS), HNRNPCL2 (Proximity Label-MS), HNRNPA3 (Cross-Linking-MS (XL-MS)), HNRNPA2B1 (Cross-Linking-MS (XL-MS)), HNRNPA1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A096MK47, A0JNH1, A6H5Y1, A6NCI8, A6NFA0, A6NGG8, B2RQL2, D3Z1D3, D3ZMK9, E9Q286, E9Q309, M0RD54, O14513, P51816, Q01613, Q03172, Q05860, Q2M2Z5, Q32LN6, Q3MHH3, Q3UXL4, Q3V0A6, Q569L8, Q571I4, Q5DTX6, Q5FW52, Q5HYW2, Q5R9I1, Q5VT06, Q5VWP3, Q60988, Q66HG9, Q68DA7, Q6P1W5, Q6P9P0, Q6PAC4, Q6PG16, Q711Q0, Q7TP36, Q7TSA6

Diamond homologs: A6NCI8, Q3V0A6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2424629	NC_000002.11:g.(?71004499)(74779761_?)del	Pathogenic

SpliceAI

641 predictions. Top by Δscore:

Variant	Effect	Δscore
2:73813564:G:GT	donor_gain	0.9900
2:73815069:A:AG	acceptor_gain	0.9900
2:73815070:G:GG	acceptor_gain	0.9900
2:73813660:G:T	donor_gain	0.9800
2:73784403:TCAG:T	donor_loss	0.9700
2:73784404:CAG:C	donor_loss	0.9700
2:73784407:GTAAA:G	donor_loss	0.9700
2:73784408:T:C	donor_loss	0.9700
2:73813607:C:G	donor_gain	0.9700
2:73813660:G:GT	donor_gain	0.9600
2:73815069:AGT:A	acceptor_gain	0.9600
2:73815070:GT:G	acceptor_gain	0.9600
2:73815070:GTG:G	acceptor_gain	0.9600
2:73813475:A:AG	acceptor_gain	0.9500
2:73813476:G:GG	acceptor_gain	0.9500
2:73813476:GA:G	acceptor_gain	0.9500
2:73813476:GAAT:G	acceptor_gain	0.9100
2:73815070:GTGAT:G	acceptor_gain	0.9100
2:73813471:CTACA:C	acceptor_loss	0.8900
2:73813472:TACAG:T	acceptor_loss	0.8900
2:73813473:ACAG:A	acceptor_loss	0.8900
2:73813474:CA:C	acceptor_loss	0.8900
2:73813475:A:AT	acceptor_loss	0.8900
2:73813465:T:A	acceptor_loss	0.8800
2:73784212:T:TA	donor_gain	0.8500
2:73784213:A:AA	donor_gain	0.8500
2:73813662:A:AG	donor_gain	0.8500
2:73813663:G:GG	donor_gain	0.8500
2:73784433:TTTTC:T	donor_gain	0.8300
2:73803021:T:G	donor_gain	0.8300

AlphaMissense

6004 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:73816872:G:C	K883N	0.958
2:73816872:G:T	K883N	0.958
2:73816132:T:C	F637L	0.954
2:73816134:C:A	F637L	0.954
2:73816134:C:G	F637L	0.954
2:73816859:G:C	R879P	0.934
2:73816879:G:C	A886P	0.927
2:73816947:G:C	R908S	0.927
2:73816947:G:T	R908S	0.927
2:73816900:G:C	A893P	0.926
2:73816851:G:C	R876S	0.924
2:73816851:G:T	R876S	0.924
2:73816858:C:A	R879S	0.923
2:73816892:G:C	R890P	0.918
2:73816933:T:C	F904L	0.915
2:73816935:T:A	F904L	0.915
2:73816935:T:G	F904L	0.915
2:73816771:T:C	F850L	0.911
2:73816773:C:A	F850L	0.911
2:73816773:C:G	F850L	0.911
2:73816871:A:C	K883T	0.906
2:73816903:G:C	A894P	0.903
2:73816835:T:G	I871S	0.901
2:73816891:C:A	R890S	0.901
2:73816864:G:C	A881P	0.895
2:73816835:T:A	I871N	0.888
2:73816835:T:C	I871T	0.887
2:73816966:G:C	A915P	0.885
2:73816883:A:C	Q887P	0.877
2:73816792:T:A	W857R	0.874

dbSNP variants (sampled 300 via entrez): RS1000001547 (2:73810711 T>C), RS1000231716 (2:73782696 G>C), RS1000233665 (2:73812408 C>T), RS1000317575 (2:73812737 A>G), RS1000328894 (2:73813055 C>G,T), RS1000358302 (2:73807066 A>C,G), RS1000389622 (2:73786492 C>T), RS1000595490 (2:73783320 G>C), RS1000667243 (2:73782533 G>C), RS1000694749 (2:73808381 T>C), RS1000726885 (2:73808128 C>G), RS1000967901 (2:73783458 A>C), RS1001371893 (2:73811295 G>C,T), RS1001782014 (2:73811649 A>G), RS1001795640 (2:73807985 G>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:251120

GenCC curated gene-disease

Mondo (2): dystonic disorder (MONDO:0003441), methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (MONDO:0009615)

Orphanet (1): Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (Orphanet:308425)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001332	Dystonia

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020821	Dystonic Disorders	C10.228.662.300
C565386	Methylmalonyl-CoA Epimerase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
abrine	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00142259	PHASE4	UNKNOWN	Efficacy and Safety of DBS of the GPi in Patients With Primary Generalized and Segmental Dystonia
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02263417	PHASE4	COMPLETED	A Randomized Controlled Trail Comparing Subthalamic and Pallidal Deep Brain Stimulation for Dystonia
NCT00169403	PHASE3	UNKNOWN	Pallidal Stimulation in Patients With Idiopathic Generalised Dystonia
NCT03232320	PHASE3	COMPLETED	Meditoxin® Treatment in Patients With Cervical Dystonia
NCT00001784	PHASE2	COMPLETED	Mexiletine for the Treatment of Focal Dystonia
NCT00105430	PHASE2	COMPLETED	Deep Brain Stimulation for Cervical Dystonia
NCT00106782	PHASE2	COMPLETED	Transcranial Electrical Polarization to Treat Focal Hand Dystonia
NCT00122044	PHASE2	COMPLETED	Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects
NCT00169338	PHASE2	COMPLETED	Pallidal Stimulation in Patients With Post-anoxic and Idiopathic Dystonia
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT02107261	PHASE2	COMPLETED	Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician’s Hand
NCT02470325	PHASE2	UNKNOWN	The Effects of Cannabis on Dystonia and Spasticity on Pediatric Patients
NCT05027997	PHASE2	COMPLETED	Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm
NCT06412653	PHASE2	COMPLETED	Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders
NCT07304089	PHASE2	RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of VIM0423 in Individuals With Isolated Dystonia
NCT01433757	PHASE1	COMPLETED	Ampicillin for DYT-1 Dystonia Motor Symptoms
NCT01698450	PHASE1	COMPLETED	Magnetic Resonance (MR) Guided Functional Ultrasound-Neurosurgery for Movement Disorders
NCT02982304	PHASE1	UNKNOWN	Multi-Target Pallidal and Thalamic Deep Brain Stimulation for Hemi-Dystonia
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT06554288	PHASE1	RECRUITING	Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy
NCT00004421	PHASE2/PHASE3	COMPLETED	Deep Brain Stimulation in Treating Patients With Dystonia
NCT00272246	PHASE2/PHASE3	UNKNOWN	Bilateral Internal Pallidum Stimulation in Primary Generalized Dystonia
NCT00608231	PHASE2/PHASE3	WITHDRAWN	Dexmedetomidine Effects on Microelectrode Recording in Deep Brain Stimulation
NCT04277247	PHASE2/PHASE3	UNKNOWN	Botulinum Toxin Type A for Foot Dystonia-associated Pain in Parkinson’s Disease
NCT02015039	PHASE1/PHASE2	COMPLETED	Pilot Trial of Botulinum Toxin and Occupational Therapy for Writer’s Cramp
NCT02911103	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Deep Brain Stimulation Surgery for Focal Hand Dystonia
NCT04727177	EARLY_PHASE1	UNKNOWN	Precision-targeted Transcranial Magnetic Stimulation in the Treatment of Primary Dystonia
NCT00006336	Not specified	COMPLETED	Sensory Training to Treat Focal Dystonia
NCT00017875	Not specified	COMPLETED	Transcranial Magnetic Stimulation (TMS) Studies of Dystonia
NCT00029601	Not specified	COMPLETED	Surround Inhibition in Patients With Dystonia
NCT00031369	Not specified	TERMINATED	Brain Anatomy in Dystonia
NCT00047957	Not specified	COMPLETED	Brain Inhibition of Muscle Movement in Normal Volunteers
NCT00050024	Not specified	COMPLETED	Transcranial Magnetic Stimulation and Electrical Stimulation of Nerves to Study Focal Dystonia
NCT00072956	Not specified	COMPLETED	The Physiology of Tricks
NCT00082615	Not specified	COMPLETED	Neurophysiological Markers in Patients With Craniofacial Dystonia and Their Relatives
NCT00102999	Not specified	COMPLETED	Brain Function in Focal Dystonia
NCT00285870	Not specified	COMPLETED	Quantification of Upper Extremity Hypertonia
NCT00355927	Not specified	UNKNOWN	Sedation During Microelectrode Recordings Before Deep Brain Stimulation for Movement Disorders.