C6orf120

Summary

C6orf120 (chromosome 6 open reading frame 120, HGNC:21247) is a protein-coding gene on chromosome 6q27, encoding UPF0669 protein C6orf120 (Q7Z4R8). May be involved in induction of apoptosis in CD4(+) T-cells, but not CD8(+) T-cells or hepatocytes.

This gene encodes a conserved, N-glycosylated protein that likely functions in the cellular response to endoplasmic reticulum stress. This protein is able to induce apoptosis in vitro in CD4+ T-cells. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 387263 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total — 11 pathogenic, 2 likely-pathogenic
• MANE Select transcript: NM_001029863

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21247
Approved symbol	C6orf120
Name	chromosome 6 open reading frame 120
Location	6q27
Locus type	gene with protein product
Status	Approved
Aliases	bA160E12.4
Ensembl gene	ENSG00000185127
Ensembl biotype	protein_coding
OMIM	616987
Entrez	387263

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000332290

RefSeq mRNA: 2 — MANE Select: NM_001029863 NM_001029863, NM_001317342

CCDS: CCDS34575

Canonical transcript exons

ENST00000332290 — 1 exons

Exon	Start	End
ENSE00003978184	169702126	169706360

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 94.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0382 / max 71.6368, expressed in 1809 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71265	13.7800	1799
71266	2.2582	1258

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	94.11	gold quality
sperm	CL:0000019	94.06	gold quality
pigmented layer of retina	UBERON:0001782	93.48	gold quality
cartilage tissue	UBERON:0002418	92.11	gold quality
male germ cell	CL:0000015	92.09	gold quality
jejunal mucosa	UBERON:0000399	91.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.50	gold quality
colonic mucosa	UBERON:0000317	91.28	gold quality
germinal epithelium of ovary	UBERON:0001304	90.72	gold quality
tibia	UBERON:0000979	90.49	gold quality
renal glomerulus	UBERON:0000074	90.33	gold quality
placenta	UBERON:0001987	90.20	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.13	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.99	gold quality
metanephric glomerulus	UBERON:0004736	89.77	gold quality
parietal pleura	UBERON:0002400	89.62	gold quality
biceps brachii	UBERON:0001507	89.54	gold quality
adrenal tissue	UBERON:0018303	89.48	gold quality
pancreatic ductal cell	CL:0002079	89.33	gold quality
hair follicle	UBERON:0002073	89.22	gold quality
nephron tubule	UBERON:0001231	89.16	gold quality
superficial temporal artery	UBERON:0001614	88.96	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.86	gold quality
parotid gland	UBERON:0001831	88.39	gold quality
mammary duct	UBERON:0001765	88.31	gold quality
kidney epithelium	UBERON:0004819	88.25	gold quality
oral cavity	UBERON:0000167	87.98	gold quality
jejunum	UBERON:0002115	87.92	gold quality
esophagus squamous epithelium	UBERON:0006920	87.92	gold quality
pleura	UBERON:0000977	87.75	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.14
E-MTAB-4850	no	166.87
E-MTAB-6524	no	56.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

229 targeting C6orf120, 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-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197

Literature-anchored findings (GeneRIF, showing 2)

• Results suggested that C6ORF120 could induce apoptosis of CD4(+) T cells, at least in part, mediated with endoplasmic reticulum stress. (PMID:22340178)
• Novel protein C6ORF120 promotes liver fibrosis by activating hepatic stellate cells through the PI3K/Akt/mTOR pathway. (PMID:38523410)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	C11H6orf120	ENSDARG00000017337
mus_musculus	1600012H06Rik	ENSMUSG00000050088
rattus_norvegicus	C1h6orf120	ENSRNOG00000070184

Protein

Protein identifiers

UPF0669 protein C6orf120 — Q7Z4R8 (reviewed: Q7Z4R8)

All UniProt accessions (1): Q7Z4R8

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in induction of apoptosis in CD4(+) T-cells, but not CD8(+) T-cells or hepatocytes.

Subcellular location. Secreted.

Tissue specificity. Mainly expressed in hepatocytes and some weak expression in germinal center cells of lymph nodes.

Similarity. Belongs to the UPF0669 family.

RefSeq proteins (2): NP_001025034, NP_001304271 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031420	UPF0669	Family

Pfam: PF17065

UniProt features (3 total): signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z4R8-F1	81.00	0.60

Functional residue map

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

Glycosylation sites (1): 53

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 157 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, AAGCCAT_MIR135A_MIR135B, IIZUKA_LIVER_CANCER_PROGRESSION_L1_G1_UP, CTATGCA_MIR153, TATCTGG_MIR488, SCHLOSSER_SERUM_RESPONSE_DN, ATAACCT_MIR154, CUI_TCF21_TARGETS_2_DN, GTATGAT_MIR154_MIR487, chr6q27, GOCC_SECRETORY_VESICLE, GOCC_VESICLE_LUMEN, GOCC_VACUOLAR_LUMEN

GO Biological Process (1): apoptotic process (GO:0006915)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), azurophil granule lumen (GO:0035578)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
binding	1
cellular anatomical structure	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1

Protein interactions and networks

STRING

428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C6orf120	WDR27	A2RRH5	607
C6orf120	DYNLT2	Q8IZS6	571
C6orf120	PGAP3	Q96FM1	515
C6orf120	TMEM259	Q4ZIN3	504
C6orf120	TMUB2	Q71RG4	495
C6orf120	TMUB1	Q9BVT8	495
C6orf120	RNF170	Q96K19	487
C6orf120	TMCO1	Q9UM00	450
C6orf120	PHF10	Q8WUB8	447
C6orf120	C6orf118	Q5T5N4	446
C6orf120	ERLIN1	O75477	439
C6orf120	TMBIM6	P55061	420
C6orf120	PTRHD1	Q6GMV3	419
C6orf120	OR11H4	Q8NGC9	418
C6orf120	B9ZVM9	B9ZVM9	418

IntAct

55 interactions, top by confidence:

A	B	Type	Score
RELL2	OXSR1	psi-mi:“MI:0914”(association)	0.830
ERLIN1	ERLIN2	psi-mi:“MI:0914”(association)	0.740
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
ERLIN1	C6orf120	psi-mi:“MI:0915”(physical association)	0.620
SCGB1D4	EGFR	psi-mi:“MI:0914”(association)	0.530
ERLIN1	DUSP3	psi-mi:“MI:0914”(association)	0.530
DUSP3	ERLIN1	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
NTRK3	FAM171A2	psi-mi:“MI:0914”(association)	0.480
RAB7A		psi-mi:“MI:0914”(association)	0.350
Tmed10	TARS3	psi-mi:“MI:0914”(association)	0.350
Tmed2		psi-mi:“MI:0914”(association)	0.350
GOLT1B		psi-mi:“MI:0914”(association)	0.350
ST3GAL1	ITGAV	psi-mi:“MI:0914”(association)	0.350
TMPRSS11B		psi-mi:“MI:0914”(association)	0.350
NTRK3	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SRPRB	GOSR1	psi-mi:“MI:0914”(association)	0.350
ADAM2	ADAMTS2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
RIPK2	CNOT1	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS), C6orf120 (Affinity Capture-MS)

ESM2 similar proteins: A2ARP1, A2VDZ5, A7SAZ1, B4K4M0, B4LZT9, D3Z7H8, O00562, O08721, O08722, O14976, O35954, O75460, P0C644, P52802, Q2TA35, Q3SZL5, Q3V1T4, Q4KLM6, Q5RCC0, Q5U2N3, Q5XI31, Q5XIL0, Q5ZLK8, Q68J42, Q6AY64, Q6DIW0, Q6JHU7, Q6NZZ3, Q6PD26, Q6ZN44, Q7T2Z5, Q7Z4R8, Q8BH02, Q8CG71, Q8IUL8, Q8IVL5, Q8IZJ1, Q8K1S3, Q8K1S4, Q8N159

Diamond homologs: A2VDZ5, A7SAZ1, Q5ZLK8, Q6AY64, Q6DIW0, Q6NZZ3, Q7Z4R8, Q9BGQ6, Q9DAY5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	2
Uncertain significance	24
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1330195	GRCh37/hg19 6q27(chr6:169830713-171022896)x1	Pathogenic
1340986	GRCh37/hg19 6q27(chr6:168939661-170919482)x1	Pathogenic
147670	GRCh38/hg38 6q27(chr6:169688809-170583214)x1	Pathogenic
148678	GRCh38/hg38 6q27(chr6:168881467-170602152)x1	Pathogenic
151758	GRCh38/hg38 6q27(chr6:168581259-170610394)x1	Pathogenic
1703662	GRCh37/hg19 6q27(chr6:168643852-170919482)	Pathogenic
1711095	GRCh37/hg19 6q27(chr6:168552894-170919482)x1	Pathogenic
57021	GRCh38/hg38 6q27(chr6:169441378-170612001)x1	Pathogenic
57303	GRCh38/hg38 6q27(chr6:168524169-170612001)x1	Pathogenic
57508	GRCh38/hg38 6q27(chr6:169641704-170612001)x1	Pathogenic
58487	GRCh38/hg38 6q27(chr6:169021176-170602152)x1	Pathogenic
148570	GRCh38/hg38 6q27(chr6:168802993-170714507)x1	Likely pathogenic
4796079	GRCh38/hg38 6q25.2-27(chr6:153483970-170605209)x3	Likely pathogenic

SpliceAI

302 predictions. Top by Δscore:

Variant	Effect	Δscore
6:169705725:C:CC	acceptor_gain	0.9900
6:169705720:TTTGG:T	acceptor_gain	0.9800
6:169705615:CCA:C	donor_gain	0.9700
6:169705721:TTGG:T	acceptor_gain	0.9700
6:169705724:GCTGG:G	acceptor_loss	0.9700
6:169705725:CT:C	acceptor_loss	0.9700
6:169705726:T:A	acceptor_loss	0.9700
6:169705733:G:C	acceptor_loss	0.9700
6:169705614:A:AC	donor_gain	0.9600
6:169705615:C:CC	donor_gain	0.9600
6:169705723:GGCT:G	acceptor_gain	0.9600
6:169705724:GCTG:G	acceptor_gain	0.9600
6:169705721:TTGGC:T	acceptor_gain	0.9500
6:169705722:TGGCT:T	acceptor_gain	0.9500
6:169705722:TGG:T	acceptor_gain	0.9400
6:169705725:C:A	acceptor_gain	0.9400
6:169705608:ATACT:A	donor_loss	0.9300
6:169705609:TACTT:T	donor_loss	0.9300
6:169705610:AC:A	donor_loss	0.9300
6:169705611:CTT:C	donor_loss	0.9300
6:169705612:TTACC:T	donor_loss	0.9300
6:169705613:T:TC	donor_loss	0.9300
6:169705614:A:T	donor_loss	0.9300
6:169705720:TTTG:T	acceptor_gain	0.9300
6:169705723:GG:G	acceptor_gain	0.9300
6:169705607:AATAC:A	donor_loss	0.9200
6:169705615:CCACT:C	donor_gain	0.9200
6:169705322:C:CC	acceptor_gain	0.8800
6:169705770:C:CC	acceptor_gain	0.8800
6:169705319:GGCC:G	acceptor_loss	0.8700

AlphaMissense

1234 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:169702698:T:A	V80D	0.999
6:169702719:C:A	P87H	0.999
6:169702818:G:A	G120E	0.999
6:169702659:T:A	L67H	0.998
6:169702679:G:A	G74R	0.998
6:169702679:G:C	G74R	0.998
6:169702680:G:A	G74E	0.998
6:169702680:G:T	G74V	0.998
6:169702806:T:A	I116N	0.998
6:169702809:G:A	G117D	0.998
6:169702812:T:A	V118D	0.998
6:169702822:C:A	H121Q	0.998
6:169702822:C:G	H121Q	0.998
6:169702838:A:C	S127R	0.998
6:169702840:C:A	S127R	0.998
6:169702840:C:G	S127R	0.998
6:169702844:T:C	F129L	0.998
6:169702846:C:A	F129L	0.998
6:169702846:C:G	F129L	0.998
6:169702694:T:G	Y79D	0.997
6:169702724:T:C	F89L	0.997
6:169702726:C:A	F89L	0.997
6:169702726:C:G	F89L	0.997
6:169702814:T:G	Y119D	0.997
6:169702614:G:T	G52V	0.996
6:169702629:T:C	L57P	0.996
6:169702635:T:C	L59P	0.996
6:169702670:A:C	S71R	0.996
6:169702672:C:A	S71R	0.996
6:169702672:C:G	S71R	0.996

dbSNP variants (sampled 300 via entrez): RS1000023966 (6:169704969 G>A,C,T), RS1000127001 (6:169701914 G>A,T), RS1000192868 (6:169702414 C>T), RS1000233806 (6:169700830 T>C), RS1000499157 (6:169701722 G>A,C), RS1002304922 (6:169701661 C>T), RS1002494170 (6:169703985 T>C), RS1002680230 (6:169701371 G>A,T), RS1003010021 (6:169701996 A>G,T), RS1003046856 (6:169700402 C>T), RS1003167116 (6:169702065 G>A,C,T), RS1003432244 (6:169703257 A>G), RS1003941829 (6:169704218 C>G), RS1004372299 (6:169704334 G>C,T), RS1004838109 (6:169700974 CACTAGGTAA>C)

Disease associations

OMIM: gene MIM:616987 | disease phenotypes: MIM:619000

GenCC curated gene-disease

Mondo (2): intellectual developmental disorder with seizures and language delay (MONDO:0033559), multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042)

Orphanet (1): Multiple congenital anomalies/dysmorphic syndrome (Orphanet:68341)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001255_3	Type 1 diabetes	8.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
avobenzone	decreases expression	1
corosolic acid	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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