C8orf76

Summary

C8orf76 (chromosome 8 open reading frame 76, HGNC:25924) is a protein-coding gene on chromosome 8q24.13, encoding Uncharacterized protein C8orf76 (Q96K31).

At a glance

• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_032847

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25924
Approved symbol	C8orf76
Name	chromosome 8 open reading frame 76
Location	8q24.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14825
Ensembl gene	ENSG00000189376
Ensembl biotype	protein_coding
Entrez	84933

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000276704, ENST00000517760, ENST00000518996, ENST00000519791, ENST00000521310, ENST00000522477, ENST00000523726, ENST00000915509, ENST00000915510, ENST00000915511, ENST00000915512, ENST00000915513

RefSeq mRNA: 1 — MANE Select: NM_032847 NM_032847

CCDS: CCDS6341

Canonical transcript exons

ENST00000276704 — 6 exons

Exon	Start	End
ENSE00000981412	123219967	123220297
ENSE00002108162	123241230	123241377
ENSE00003519106	123231300	123231757
ENSE00003582527	123239049	123239144
ENSE00003647816	123237798	123237941
ENSE00003670008	123226500	123226632

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 92.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7927 / max 80.8415, expressed in 1790 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94709	10.7927	1790

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.96	gold quality
lower esophagus mucosa	UBERON:0035834	91.00	gold quality
islet of Langerhans	UBERON:0000006	90.33	gold quality
mucosa of transverse colon	UBERON:0004991	89.68	gold quality
pituitary gland	UBERON:0000007	89.47	gold quality
adenohypophysis	UBERON:0002196	89.28	gold quality
ganglionic eminence	UBERON:0004023	88.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.49	gold quality
monocyte	CL:0000576	88.07	gold quality
endometrium	UBERON:0001295	88.04	gold quality
leukocyte	CL:0000738	87.97	gold quality
right adrenal gland cortex	UBERON:0035827	87.92	gold quality
right adrenal gland	UBERON:0001233	87.81	gold quality
adrenal tissue	UBERON:0018303	87.80	gold quality
esophagus mucosa	UBERON:0002469	87.79	gold quality
granulocyte	CL:0000094	87.78	gold quality
gastrocnemius	UBERON:0001388	87.33	gold quality
placenta	UBERON:0001987	87.20	gold quality
left adrenal gland	UBERON:0001234	87.17	gold quality
pancreas	UBERON:0001264	87.04	gold quality
right lobe of liver	UBERON:0001114	87.02	gold quality
muscle of leg	UBERON:0001383	86.98	gold quality
left adrenal gland cortex	UBERON:0035825	86.96	gold quality
tonsil	UBERON:0002372	86.83	gold quality
lymph node	UBERON:0000029	86.62	gold quality
adrenal gland	UBERON:0002369	86.56	gold quality
ventricular zone	UBERON:0003053	86.54	gold quality
stromal cell of endometrium	CL:0002255	86.50	gold quality
body of pancreas	UBERON:0001150	86.39	gold quality
heart left ventricle	UBERON:0002084	86.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA

miRNA regulators (miRDB)

18 targeting C8orf76, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-4421	97.99	64.89	701
HSA-MIR-5699-3P	97.81	65.00	861

Literature-anchored findings (GeneRIF, showing 2)

• C8orf76 amplication or overexpression plays a pivotal oncogenic role in gastric carcinogenesis and is an independent prognostic factor for gastric cancer patients. (PMID:30733230)
• High Expression of C8orf76 Is an Independent Predictive Factor of Poor Prognosis in Patients with Breast Cancer. (PMID:35482249)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:101716	ENSDARG00000010738
mus_musculus	9130401M01Rik	ENSMUSG00000101892
rattus_norvegicus	C7h8orf76	ENSRNOG00000006370

Protein

Protein identifiers

Uncharacterized protein C8orf76 — Q96K31 (reviewed: Q96K31)

All UniProt accessions (1): Q96K31

Isoforms (2)

UniProt ID	Names	Canonical?
Q96K31-1	3	yes
Q96EF9-1	2, ZHX1-C8orf76

RefSeq proteins (1): NP_116236* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR041404	DUF5588	Family

Pfam: PF17826

UniProt features (2 total): chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96K31-F1	76.93	0.47

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 67 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, TCCCRNNRTGC_UNKNOWN, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, HEIDENBLAD_AMPLICON_8Q24_UP, JOHNSTONE_PARVB_TARGETS_3_DN, chr8q24, CSR_EARLY_UP.V1_UP, ALKBH3_TARGET_GENES, CBX7_TARGET_GENES, PAX3_TARGET_GENES, PAX7_TARGET_GENES, ZNF618_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

294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C8orf76	ZNF623	O75123	474
C8orf76	SACK1H	Q6ZRV2	459
C8orf76	POP1	Q99575	448
C8orf76	TIGD5	Q53EQ6	445
C8orf76	C8orf33	Q9H7E9	418
C8orf76	UBR5	O95071	402
C8orf76	BOP1	Q14137	389
C8orf76	ZNF16	P17020	370
C8orf76	ZNF250	P15622	369
C8orf76	PUSL1	Q8N0Z8	367
C8orf76	YDJC	A8MPS7	366
C8orf76	NUDCD1	Q96RS6	348
C8orf76	LRRC14	Q15048	348
C8orf76	COMMD5	Q9GZQ3	348
C8orf76	PLEKHO1	Q53GL0	326

IntAct

3 interactions, top by confidence:

A	B	Type	Score
C8orf76	FECH	psi-mi:“MI:0914”(association)	0.350
C8orf76	PLCB3	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): C8orf76 (Reconstituted Complex), C8orf76 (Affinity Capture-RNA), IQGAP2 (Affinity Capture-MS), DISC1 (Affinity Capture-MS), TPRKB (Affinity Capture-MS), FECH (Affinity Capture-MS), CTDSP1 (Affinity Capture-MS), SLK (Affinity Capture-MS), PLCB3 (Affinity Capture-MS), EPS8L2 (Affinity Capture-MS), TRIP10 (Affinity Capture-MS), C8orf76 (Negative Genetic)

ESM2 similar proteins: A1L1K3, A5A6J9, A6H6E9, B0BF33, D3ZSP7, O14879, O88196, P09913, P09914, P97357, Q14AT2, Q14D04, Q15573, Q32NR4, Q3B7U2, Q4R6I5, Q4R6M4, Q4R7V1, Q4V7F0, Q5H9U9, Q5PQQ9, Q5PQS3, Q5U2X2, Q5XIR8, Q5ZKK3, Q5ZLS8, Q60462, Q64112, Q64282, Q64345, Q6AYP3, Q6IQY5, Q7Z3E5, Q80VM3, Q86VD1, Q8C6S9, Q8CHY7, Q8IYW2, Q8K2A7, Q8NA56

Diamond homologs: Q5BK24, Q96EF9, Q96K31, Q9D2X8

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	2
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

979 predictions. Top by Δscore:

Variant	Effect	Δscore
8:123239142:CCACT:C	acceptor_gain	1.0000
8:123239143:CACT:C	acceptor_gain	1.0000
8:123239146:T:TC	acceptor_gain	1.0000
8:123241224:TCTCA:T	donor_loss	1.0000
8:123241225:CTCAC:C	donor_loss	1.0000
8:123241228:A:AC	donor_gain	1.0000
8:123241229:C:CC	donor_gain	1.0000
8:123241229:C:CG	donor_loss	1.0000
8:123241229:CCTG:C	donor_gain	1.0000
8:123220294:TAACC:T	acceptor_loss	0.9900
8:123220295:AACC:A	acceptor_loss	0.9900
8:123220296:ACCTA:A	acceptor_loss	0.9900
8:123220297:CCTAT:C	acceptor_loss	0.9900
8:123220298:C:CG	acceptor_loss	0.9900
8:123220299:T:A	acceptor_loss	0.9900
8:123226495:CTCA:C	donor_loss	0.9900
8:123226496:TCA:T	donor_loss	0.9900
8:123226497:CA:C	donor_loss	0.9900
8:123226498:A:C	donor_loss	0.9900
8:123226499:C:CT	donor_loss	0.9900
8:123226499:CCT:C	donor_gain	0.9900
8:123231294:GCTTA:G	donor_loss	0.9900
8:123231295:CTTA:C	donor_loss	0.9900
8:123231296:TTA:T	donor_loss	0.9900
8:123231297:T:TG	donor_loss	0.9900
8:123231297:TACCT:T	donor_loss	0.9900
8:123231298:A:AG	donor_loss	0.9900
8:123231298:ACCTG:A	donor_loss	0.9900
8:123231299:C:T	donor_loss	0.9900
8:123231753:TTTTC:T	acceptor_gain	0.9900

AlphaMissense

2515 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:123237851:A:G	C70R	0.986
8:123237857:C:G	A68P	0.986
8:123231616:A:G	W135R	0.984
8:123231616:A:T	W135R	0.984
8:123220177:A:G	W357R	0.983
8:123220177:A:T	W357R	0.983
8:123239081:C:G	G29R	0.983
8:123239081:C:T	G29R	0.983
8:123237926:A:G	Y45H	0.981
8:123231306:C:G	R238P	0.980
8:123239080:C:T	G29E	0.980
8:123237849:A:C	C70W	0.978
8:123237847:A:G	L71P	0.977
8:123231648:A:G	L124P	0.976
8:123220187:A:C	F353L	0.975
8:123220187:A:T	F353L	0.975
8:123220189:A:G	F353L	0.975
8:123237853:C:G	R69P	0.975
8:123226624:A:G	L243P	0.974
8:123239085:G:C	F27L	0.974
8:123239085:G:T	F27L	0.974
8:123239087:A:G	F27L	0.974
8:123231657:A:G	L121P	0.973
8:123237925:T:G	Y45S	0.970
8:123220172:G:C	F358L	0.969
8:123220172:G:T	F358L	0.969
8:123220174:A:G	F358L	0.969
8:123226593:A:C	F253L	0.969
8:123226593:A:T	F253L	0.969
8:123226595:A:G	F253L	0.969

dbSNP variants (sampled 300 via entrez): RS1000117185 (8:123234140 A>G), RS1000151804 (8:123241124 C>A), RS1000187769 (8:123232800 T>C,G), RS1000288390 (8:123231325 C>G,T), RS1000411422 (8:123237966 A>T), RS1000463750 (8:123222610 C>T), RS1000552279 (8:123232998 C>A), RS1000565715 (8:123225322 G>C), RS1000624360 (8:123232731 G>C,T), RS1000752274 (8:123223914 G>A), RS1000781499 (8:123240150 G>C), RS1000824727 (8:123237515 A>G), RS1000952280 (8:123221426 T>C), RS1001058776 (8:123220971 C>T), RS1001173982 (8:123235784 A>C,G)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	increases methylation, increases expression	3
entinostat	decreases expression, affects cotreatment	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Benzene	increases expression	1
Hydrogen Peroxide	affects expression	1
Ozone	affects expression, increases abundance	1
Phenylmercuric Acetate	decreases expression, affects cotreatment	1
Phthalic Acids	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	increases expression	1
Gold Compounds	decreases expression	1
tert-Butylhydroperoxide	affects expression	1
Vitamin K 3	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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