C9orf78

Summary

C9orf78 (chromosome 9 open reading frame 78, HGNC:24932) is a protein-coding gene on chromosome 9q34.11, encoding Splicing factor C9orf78 (Q9NZ63). Plays a role in pre-mRNA splicing by promoting usage of the upstream 3’-splice site at alternative NAGNAG splice sites; these are sites featuring alternative acceptor motifs separated by only a few nucleotides. It is a selective cancer dependency (DepMap: 57.0% of cell lines).

Enables U5 snRNA binding activity. Involved in mRNA cis splicing, via spliceosome and regulation of homologous chromosome segregation. Located in chromosome, centromeric region; cytosol; and nucleoplasm.

Source: NCBI Gene 51759 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• Cancer dependency (DepMap): dependent in 57.0% of screened cell lines
• MANE Select transcript: NM_016520

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24932
Approved symbol	C9orf78
Name	chromosome 9 open reading frame 78
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	HSPC220, HCA59, CSU2
Ensembl gene	ENSG00000136819
Ensembl biotype	protein_coding
OMIM	619569
Entrez	51759

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000372447, ENST00000461349, ENST00000461539, ENST00000461762, ENST00000480023, ENST00000492991, ENST00000495934, ENST00000875653, ENST00000875654, ENST00000875655, ENST00000912502, ENST00000912503, ENST00000912504, ENST00000912505, ENST00000912506, ENST00000912507, ENST00000912508, ENST00000912509, ENST00000950227, ENST00000950228, ENST00000950229

RefSeq mRNA: 1 — MANE Select: NM_016520 NM_016520

CCDS: CCDS6931

Canonical transcript exons

ENST00000372447 — 9 exons

Exon	Start	End
ENSE00001688070	129834707	129834766
ENSE00001692714	129827290	129828252
ENSE00001932884	129835139	129835275
ENSE00003538793	129833658	129833709
ENSE00003564405	129829405	129829541
ENSE00003582250	129831896	129831973
ENSE00003586818	129829205	129829303
ENSE00003598913	129833447	129833517
ENSE00003686675	129830871	129831068

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.8932 / max 1228.0360, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102767	55.7826	1825
102766	9.1106	1744

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.12	gold quality
calcaneal tendon	UBERON:0003701	97.94	gold quality
mononuclear cell	CL:0000842	97.81	gold quality
leukocyte	CL:0000738	97.67	gold quality
cortical plate	UBERON:0005343	96.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.90	gold quality
gastrocnemius	UBERON:0001388	95.68	gold quality
tendon	UBERON:0000043	95.62	gold quality
muscle of leg	UBERON:0001383	95.47	gold quality
anterior cingulate cortex	UBERON:0009835	95.43	gold quality
cingulate cortex	UBERON:0003027	95.34	gold quality
popliteal artery	UBERON:0002250	95.29	gold quality
tibial artery	UBERON:0007610	95.29	gold quality
descending thoracic aorta	UBERON:0002345	95.17	gold quality
aorta	UBERON:0000947	95.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.07	gold quality
stromal cell of endometrium	CL:0002255	95.04	gold quality
thoracic aorta	UBERON:0001515	95.04	gold quality
mucosa of stomach	UBERON:0001199	95.03	gold quality
blood	UBERON:0000178	94.96	gold quality
granulocyte	CL:0000094	94.95	gold quality
ascending aorta	UBERON:0001496	94.95	gold quality
nucleus accumbens	UBERON:0001882	94.92	gold quality
rectum	UBERON:0001052	94.85	gold quality
islet of Langerhans	UBERON:0000006	94.84	gold quality
right coronary artery	UBERON:0001625	94.83	gold quality
caudate nucleus	UBERON:0001873	94.82	gold quality
gall bladder	UBERON:0002110	94.71	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.67	gold quality
amygdala	UBERON:0001876	94.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	20.45
E-HCAD-9	yes	6.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting C9orf78, 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-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-153-5P	99.89	73.86	6317
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-4728-5P	99.85	69.39	4718
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4473	98.89	69.10	652

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 57.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• C9ORF78 partially localizes to centromeres and plays a role in chromosome segregation. (PMID:35167828)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	C5H9orf78	ENSDARG00000002220
mus_musculus	BC005624	ENSMUSG00000026851
rattus_norvegicus	C3h9orf78	ENSRNOG00000007532
drosophila_melanogaster	CG7974	FBGN0035254
caenorhabditis_elegans	T23G11.4	WBGENE00011969

Protein

Protein identifiers

Splicing factor C9orf78 — Q9NZ63 (reviewed: Q9NZ63)

Alternative names: Hepatocellular carcinoma-associated antigen 59

All UniProt accessions (1): Q9NZ63

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in pre-mRNA splicing by promoting usage of the upstream 3’-splice site at alternative NAGNAG splice sites; these are sites featuring alternative acceptor motifs separated by only a few nucleotides. May also modulate exon inclusion events. Plays a role in spliceosomal remodeling by displacing WBP4 from SNRNP200 and may act to inhibit SNRNP200 helicase activity. Binds U5 snRNA. Required for proper chromosome segregation. Not required for splicing of shelterin components.

Subunit / interactions. Component of the spliceosome. Interacts with SNRNP200; the interaction is direct. Interacts with PRPF8.

Subcellular location. Nucleus. Chromosome. Centromere.

Similarity. Belongs to the TLS1 family.

RefSeq proteins (1): NP_057604* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010756	Tls1-like	Family

Pfam: PF07052

UniProt features (20 total): modified residue 5, region of interest 3, helix 3, mutagenesis site 2, sequence conflict 2, compositionally biased region 2, chain 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7OS2	ELECTRON MICROSCOPY	2.76
8C6J	ELECTRON MICROSCOPY	2.8
9FMD	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZ63-F1	68.64	0.07

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 261, 15, 17, 147, 253

Mutagenesis-validated functional residues (2):

Position	Phenotype
8	decreases binding to snrnp200.
41	abolishes binding to snrnp200.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway

MSigDB gene sets: 127 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_ORGANELLE_FISSION, GOBP_REGULATION_OF_CHROMOSOME_SEGREGATION, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_RNA_SPLICING, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, REACTOME_MRNA_SPLICING, GOBP_HOMOLOGOUS_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS

GO Biological Process (6): mRNA splicing, via spliceosome (GO:0000398), chromosome segregation (GO:0007059), mRNA cis splicing, via spliceosome (GO:0045292), regulation of homologous chromosome segregation (GO:0060629), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (3): U5 snRNA binding (GO:0030623), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (6): chromosome, centromeric region (GO:0000775), nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytosol (GO:0005829), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
cellular anatomical structure	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
cell cycle process	1
mRNA splicing, via spliceosome	1
homologous chromosome segregation	1
regulation of chromosome segregation	1
regulation of reproductive process	1
mRNA metabolic process	1
snRNA binding	1
nucleic acid binding	1
binding	1
chromosomal region	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
cytoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2133 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C9orf78	FNBP1	Q96RU3	491
C9orf78	NOSIP	Q9Y314	455
C9orf78	RAI1	Q7Z5J4	424
C9orf78	SYK	P43405	424
C9orf78	FSAF1	Q8NDD1	420
C9orf78	MED22	Q15528	405
C9orf78	TOR1B	O14657	396
C9orf78	SEC63	Q9UGP8	393
C9orf78	USP20	Q9Y2K6	392
C9orf78	HPDL	Q96IR7	392
C9orf78	CWC27	Q6UX04	392
C9orf78	CHP2	O43745	390
C9orf78	DISP3	Q9P2K9	388
C9orf78	TOR1A	O14656	382
C9orf78	DHX34	Q14147	375

IntAct

43 interactions, top by confidence:

A	B	Type	Score
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
C9orf78	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
Prpf8		psi-mi:“MI:0915”(physical association)	0.400
C9orf78	TNNC2	psi-mi:“MI:0915”(physical association)	0.400
TAB1	C9orf78	psi-mi:“MI:0915”(physical association)	0.370
C9orf78	MAPK11	psi-mi:“MI:0915”(physical association)	0.370
Klc3	ZC3HAV1	psi-mi:“MI:0914”(association)	0.350
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
SERPINB13	TTC4	psi-mi:“MI:0914”(association)	0.350
NKAPD1	CASC3	psi-mi:“MI:0914”(association)	0.350
NAB2	GRN	psi-mi:“MI:0914”(association)	0.350
C9orf78	CEP120	psi-mi:“MI:0914”(association)	0.350
ARHGEF19	NUP42	psi-mi:“MI:0914”(association)	0.350
CCP110	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCP110	KIF2A	psi-mi:“MI:0914”(association)	0.350
C9orf78	SNRNP200	psi-mi:“MI:0914”(association)	0.350
CD2BP2	PRPF4	psi-mi:“MI:0914”(association)	0.350
FAM50A	SNRNP200	psi-mi:“MI:0914”(association)	0.350
JPH3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
H2AJ	WDR46	psi-mi:“MI:0914”(association)	0.350
SERF2	WDR46	psi-mi:“MI:0914”(association)	0.350
ZC3H11A	DDX3Y	psi-mi:“MI:0914”(association)	0.350
IFI27L1	KIF1C	psi-mi:“MI:0914”(association)	0.350
SF3B1	RBM10	psi-mi:“MI:0914”(association)	0.350
SF3B1	FAM83G	psi-mi:“MI:0914”(association)	0.350
LMNA	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (662): OCRL (Affinity Capture-MS), CEP120 (Affinity Capture-MS), BTBD1 (Affinity Capture-MS), BTBD2 (Affinity Capture-MS), C9orf78 (Co-fractionation), C9orf78 (Co-fractionation), HARS (Co-fractionation), HNRNPH1 (Co-fractionation), C9orf78 (Proximity Label-MS), C9orf78 (Proximity Label-MS), C9orf78 (Affinity Capture-MS), C9orf78 (Biochemical Activity), C9orf78 (Affinity Capture-MS), EFTUD2 (Affinity Capture-MS), SNRNP200 (Affinity Capture-MS)

ESM2 similar proteins: A4IGY3, A7SD85, A8WMM4, E1C760, F4ICK8, O08837, O15541, O48713, P19351, P92948, Q0JHZ2, Q0VFP5, Q12000, Q16543, Q1RMM1, Q28Y69, Q2KJC1, Q2KJD3, Q3TIV5, Q3TQI7, Q54DA5, Q568A0, Q5BH88, Q5BJP2, Q5EAC6, Q5H7N8, Q5PQS7, Q5RC87, Q5RE65, Q67ER4, Q6A068, Q6DD06, Q6DKE6, Q6NUB2, Q6U6G5, Q7JWR9, Q803J8, Q8GX84, Q8WU90, Q93618

Diamond homologs: F4HVZ5, Q3TQI7, Q5RC87, Q9NZ63

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SMURF1	unknown	C9orf78	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
mRNA Splicing - Minor Pathway	5	26.7×	8e-05
Transport of Mature mRNA derived from an Intron-Containing Transcript	5	18.1×	4e-04
mRNA Splicing - Major Pathway	12	15.6×	2e-09
Processing of Capped Intron-Containing Pre-mRNA	7	13.7×	6e-05
mRNA Splicing	5	13.1×	1e-03
CHD1 and CHD2 subfamily	5	12.9×	1e-03
mRNA Polyadenylation	6	12.6×	4e-04
Dengue Virus-Host Interactions	11	12.0×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	9	15.6×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

21 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

1174 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129828251:CC:C	acceptor_gain	1.0000
9:129828252:CC:C	acceptor_gain	1.0000
9:129828252:CCTGA:C	acceptor_loss	1.0000
9:129828253:C:CG	acceptor_loss	1.0000
9:129828254:T:A	acceptor_loss	1.0000
9:129829203:A:AC	donor_gain	1.0000
9:129829204:C:CC	donor_gain	1.0000
9:129829204:CG:C	donor_gain	1.0000
9:129829204:CGCT:C	donor_gain	1.0000
9:129829235:CT:C	donor_gain	1.0000
9:129829299:ATAAA:A	acceptor_gain	1.0000
9:129829300:TAAA:T	acceptor_gain	1.0000
9:129829301:AAA:A	acceptor_gain	1.0000
9:129829301:AAAC:A	acceptor_loss	1.0000
9:129829302:AA:A	acceptor_gain	1.0000
9:129829302:AAC:A	acceptor_loss	1.0000
9:129829303:ACT:A	acceptor_loss	1.0000
9:129829304:C:CC	acceptor_gain	1.0000
9:129829305:T:C	acceptor_loss	1.0000
9:129829311:C:CT	acceptor_gain	1.0000
9:129829311:C:T	acceptor_gain	1.0000
9:129829312:A:T	acceptor_gain	1.0000
9:129829320:C:CT	acceptor_gain	1.0000
9:129829399:GCTTA:G	donor_loss	1.0000
9:129829400:CTTAC:C	donor_loss	1.0000
9:129829401:TTA:T	donor_loss	1.0000
9:129829402:TACA:T	donor_loss	1.0000
9:129829403:A:AC	donor_gain	1.0000
9:129829403:A:AG	donor_loss	1.0000
9:129829403:ACAT:A	donor_gain	1.0000

AlphaMissense

1925 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:129828182:C:A	K283N	1.000
9:129828182:C:G	K283N	1.000
9:129828185:G:C	F282L	1.000
9:129828185:G:T	F282L	1.000
9:129828186:A:C	F282C	1.000
9:129828186:A:G	F282S	1.000
9:129828187:A:G	F282L	1.000
9:129828199:G:C	H278D	1.000
9:129828206:A:C	D275E	1.000
9:129828206:A:T	D275E	1.000
9:129828207:T:A	D275V	1.000
9:129828207:T:C	D275G	1.000
9:129828207:T:G	D275A	1.000
9:129828208:C:A	D275Y	1.000
9:129828208:C:G	D275H	1.000
9:129828210:G:A	T274I	1.000
9:129829302:A:C	F227L	1.000
9:129829302:A:T	F227L	1.000
9:129829405:A:G	F227L	1.000
9:129829407:C:G	R226T	1.000
9:129829424:A:C	N220K	1.000
9:129829424:A:T	N220K	1.000
9:129829431:G:T	A218D	1.000
9:129829436:G:C	N216K	1.000
9:129829436:G:T	N216K	1.000
9:129829494:A:G	L197P	1.000
9:129829502:C:A	K194N	1.000
9:129829502:C:G	K194N	1.000
9:129829507:C:G	A193P	1.000
9:129829524:A:C	I187S	1.000

dbSNP variants (sampled 300 via entrez): RS1000364254 (9:129835001 G>A,C), RS1000696501 (9:129836376 A>T), RS1000742270 (9:129834042 C>T), RS1000775996 (9:129835221 T>C,G), RS1000798366 (9:129827525 A>G), RS1001088343 (9:129832924 G>C), RS1001420260 (9:129834211 T>G), RS1001643209 (9:129834941 C>A,G,T), RS1002143290 (9:129833856 C>CTACA), RS1002856017 (9:129833223 C>A), RS1002871772 (9:129826879 G>A), RS1002970951 (9:129827211 T>G), RS1002993122 (9:129828805 A>G), RS1003242306 (9:129832288 A>G), RS1003474669 (9:129827437 G>C)

Disease associations

OMIM: gene MIM:619569 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
sodium arsenite	increases expression, increases abundance	1
manganese chloride	increases abundance, increases expression	1
abrine	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1
Quercetin	decreases phosphorylation	1
Smoke	decreases expression	1
Urethane	increases expression	1
Zinc	decreases expression	1
Cyclosporine	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1LW	Abcam HeLa C9orf78 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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