C3orf70

Summary

C3orf70 (chromosome 3 open reading frame 70, HGNC:33731) is a protein-coding gene on chromosome 3q27.2, encoding UPF0524 protein C3orf70 (A6NLC5). May play a role in neuronal and neurobehavioral development.

Predicted to be involved in circadian behavior and nervous system development.

Source: NCBI Gene 285382 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 9 total — 1 pathogenic
• MANE Select transcript: NM_001025266

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33731
Approved symbol	C3orf70
Name	chromosome 3 open reading frame 70
Location	3q27.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000187068
Ensembl biotype	protein_coding
Entrez	285382

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000335012

RefSeq mRNA: 1 — MANE Select: NM_001025266 NM_001025266

CCDS: CCDS33900

Canonical transcript exons

ENST00000335012 — 2 exons

Exon	Start	End
ENSE00001334396	185076838	185083563
ENSE00001334397	185152628	185153060

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 97.04.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5386 / max 54.2742, expressed in 631 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45910	1.4014	501
45909	0.7634	341
45908	0.3737	138

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	97.04	gold quality
cauda epididymis	UBERON:0004360	95.82	gold quality
seminal vesicle	UBERON:0000998	92.95	gold quality
subthalamic nucleus	UBERON:0001906	91.85	gold quality
entorhinal cortex	UBERON:0002728	91.84	gold quality
tibia	UBERON:0000979	91.64	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.98	gold quality
pons	UBERON:0000988	90.79	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.25	gold quality
medial globus pallidus	UBERON:0002477	90.16	gold quality
medulla oblongata	UBERON:0001896	90.15	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.78	gold quality
globus pallidus	UBERON:0001875	89.54	gold quality
substantia nigra pars compacta	UBERON:0001965	89.52	gold quality
urethra	UBERON:0000057	89.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.91	gold quality
inferior vagus X ganglion	UBERON:0005363	88.45	gold quality
superior vestibular nucleus	UBERON:0007227	88.21	gold quality
adult organism	UBERON:0007023	87.88	gold quality
postcentral gyrus	UBERON:0002581	87.75	gold quality
ventral tegmental area	UBERON:0002691	87.65	gold quality
vena cava	UBERON:0004087	87.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.27	gold quality
parotid gland	UBERON:0001831	87.01	gold quality
parietal lobe	UBERON:0001872	86.88	gold quality
middle temporal gyrus	UBERON:0002771	86.81	gold quality
superior frontal gyrus	UBERON:0002661	86.60	gold quality
ileal mucosa	UBERON:0000331	86.25	gold quality
nipple	UBERON:0002030	85.93	gold quality
lateral globus pallidus	UBERON:0002476	85.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.70
E-MTAB-7249	no	15.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

209 targeting C3orf70, 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-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 1)

• An Epithelial-Mesenchymal Transition (EMT) Preoperative Nomogram for Prediction of Lymph Node Metastasis in Bladder Cancer (BLCA). (PMID:33204364)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	C9H3orf70	ENSDARG00000061664
danio_rerio	C9H3orf70	ENSDARG00000091513
mus_musculus	2510009E07Rik	ENSMUSG00000043391
rattus_norvegicus	C11h3orf70	ENSRNOG00000063811

Protein

Protein identifiers

UPF0524 protein C3orf70 — A6NLC5 (reviewed: A6NLC5)

All UniProt accessions (1): A6NLC5

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in neuronal and neurobehavioral development.

Similarity. Belongs to the UPF0524 family.

RefSeq proteins (1): NP_001020437* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029670	UPF0524_fam	Family

Pfam: PF15823

UniProt features (3 total): chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NLC5-F1	52.56	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 164 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_BEHAVIOR, GOZGIT_ESR1_TARGETS_DN, AAGCCAT_MIR135A_MIR135B, FOSTER_TOLERANT_MACROPHAGE_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_RHYTHMIC_BEHAVIOR, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GTCAGGA_MIR378, TTTGCAC_MIR19A_MIR19B, GAVIN_FOXP3_TARGETS_CLUSTER_P2, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, ATGTAGC_MIR221_MIR222, AAGCACA_MIR218

GO Biological Process (2): nervous system development (GO:0007399), circadian behavior (GO:0048512)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
rhythmic behavior	1
circadian rhythm	1

Protein interactions and networks

STRING

188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C3orf70	PRR19	A6NJB7	514
C3orf70	ZFP69B	Q9UJL9	507
C3orf70	CCDC73	Q6ZRK6	480
C3orf70	MB21D2	Q8IYB1	471
C3orf70	TBC1D12	O60347	447
C3orf70	MROH2B	Q7Z745	418
C3orf70	ELFN2	Q5R3F8	415
C3orf70	LRRC10B	A6NIK2	399
C3orf70	FAM133A	Q8N9E0	395
C3orf70	POC1A	Q8NBT0	376
C3orf70	DEDD2	Q8WXF8	376
C3orf70	CYTH4	Q9UIA0	370
C3orf70	WDR26	Q9H7D7	370
C3orf70	CNIH4	Q9P003	370
C3orf70	CREG2	Q8IUH2	369

IntAct

16 interactions, top by confidence:

A	B	Type	Score
C3orf70	AKT1	psi-mi:“MI:0915”(physical association)	0.450
AKT1	C3orf70	psi-mi:“MI:2364”(proximity)	0.450
SMAD4	C3orf70	psi-mi:“MI:2364”(proximity)	0.270
SPOP	C3orf70	psi-mi:“MI:2364”(proximity)	0.270
C3orf70	SPOP	psi-mi:“MI:2364”(proximity)	0.270
EGFR	C3orf70	psi-mi:“MI:2364”(proximity)	0.270
C3orf70	PTEN	psi-mi:“MI:2364”(proximity)	0.270
C3orf70	PTPN11	psi-mi:“MI:2364”(proximity)	0.270
C3orf70	TP53	psi-mi:“MI:2364”(proximity)	0.270
C3orf70	BRAF	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (2): C3orf70 (Affinity Capture-MS), C3orf70 (Biochemical Activity)

ESM2 similar proteins: A3KNX6, A4IGV6, A4QNW7, A6NLC5, A7E369, B3DHS1, B4Q0P5, O36397, P04605, P05909, P14353, P15835, P17759, P18098, P19507, P20880, P24109, P24433, P29169, P97440, Q03233, Q09382, Q0P4S0, Q1LV19, Q1LY84, Q2M2T8, Q4R309, Q53QV2, Q5M7L2, Q5M948, Q5RD13, Q5T7R7, Q5ZM46, Q6AX58, Q6AXY9, Q6DFB0, Q6GQU0, Q74124, Q7T346, Q87042

Diamond homologs: A3KNX6, A6NLC5, A7E369, Q1LY84, Q6GQU0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
152989	GRCh38/hg38 3q27.2(chr3:185151277-185558406)x1	Pathogenic

SpliceAI

703 predictions. Top by Δscore:

Variant	Effect	Δscore
3:185152626:A:AC	donor_gain	1.0000
3:185152627:C:CC	donor_gain	1.0000
3:185131989:A:AC	donor_gain	0.9900
3:185131990:C:CC	donor_gain	0.9900
3:185131990:CAAG:C	donor_gain	0.9900
3:185152620:CGACT:C	donor_loss	0.9900
3:185152621:GACTT:G	donor_loss	0.9900
3:185152622:ACTT:A	donor_loss	0.9900
3:185152623:CT:C	donor_loss	0.9900
3:185152624:TTACA:T	donor_loss	0.9900
3:185152625:TAC:T	donor_loss	0.9900
3:185152626:A:AG	donor_loss	0.9900
3:185152627:C:CT	donor_loss	0.9900
3:185152627:CA:C	donor_gain	0.9900
3:185083559:TTTGC:T	acceptor_gain	0.9800
3:185132450:AATG:A	donor_gain	0.9800
3:185152627:CAG:C	donor_gain	0.9800
3:185082993:T:TA	donor_gain	0.9700
3:185083564:C:CC	acceptor_gain	0.9700
3:185152354:C:A	donor_gain	0.9700
3:185152627:CAGT:C	donor_gain	0.9700
3:185152638:T:TA	donor_gain	0.9700
3:185083077:T:C	donor_gain	0.9600
3:185083562:GCCTG:G	acceptor_loss	0.9600
3:185083563:CCTG:C	acceptor_loss	0.9600
3:185083564:C:T	acceptor_loss	0.9600
3:185083565:T:G	acceptor_loss	0.9600
3:185132194:T:C	acceptor_gain	0.9600
3:185132450:A:AC	donor_gain	0.9600
3:185152371:C:CA	donor_gain	0.9600

AlphaMissense

1653 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:185152635:C:A	W63C	0.997
3:185152635:C:G	W63C	0.997
3:185152637:A:G	W63R	0.996
3:185152637:A:T	W63R	0.996
3:185152639:C:T	G62E	0.996
3:185152653:C:A	W57C	0.996
3:185152653:C:G	W57C	0.996
3:185152719:G:C	F35L	0.996
3:185152719:G:T	F35L	0.996
3:185152721:A:G	F35L	0.996
3:185152632:A:C	C64W	0.995
3:185152655:A:G	W57R	0.995
3:185152655:A:T	W57R	0.995
3:185152639:C:A	G62V	0.994
3:185152648:C:T	C59Y	0.994
3:185152670:A:G	C52R	0.994
3:185083338:C:A	G141V	0.993
3:185083353:A:T	V136D	0.993
3:185152633:C:G	C64S	0.993
3:185152634:A:G	C64R	0.993
3:185152634:A:T	C64S	0.993
3:185152640:C:G	G62R	0.993
3:185152640:C:T	G62R	0.993
3:185152647:A:C	C59W	0.993
3:185152665:G:C	F53L	0.993
3:185152665:G:T	F53L	0.993
3:185152667:A:G	F53L	0.993
3:185152669:C:G	C52S	0.992
3:185152670:A:T	C52S	0.992
3:185152694:A:G	C44R	0.992

dbSNP variants (sampled 300 via entrez): RS1000028759 (3:185105964 A>G), RS1000047123 (3:185132162 C>G), RS1000055843 (3:185105760 G>A,C), RS1000069573 (3:185078782 T>C), RS1000080539 (3:185078500 G>A), RS1000092817 (3:185128736 T>C), RS1000143216 (3:185144882 T>A,C), RS1000218756 (3:185098631 AAAT>A), RS1000227683 (3:185126034 T>C), RS1000292583 (3:185152731 G>A,C), RS1000295171 (3:185090093 TTCCTC>T), RS1000296134 (3:185083264 C>G,T), RS1000329907 (3:185128858 TC>T), RS1000477758 (3:185116734 G>C), RS1000499978 (3:185095765 T>A)

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

2 associations (top):

Study	Trait	p-value
GCST000856_3	Major depressive disorder	5.000000e-06
GCST003558_1	Major depressive disorder	5.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	8
mercuric bromide	decreases expression, affects cotreatment	2
Estradiol	increases expression, affects binding	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation, affects cotreatment, affects methylation	1
trichostatin A	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Leflunomide	decreases expression	1
Arsenic	affects methylation	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Silver	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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