C4orf46

Summary

C4orf46 (chromosome 4 open reading frame 46, HGNC:27320) is a protein-coding gene on chromosome 4q32.1, encoding Renal cancer differentiation gene 1 protein (Q504U0).

This gene encodes a small, conserved protein of unknown function that is expressed in a variety of tissues. There are pseudogenes for this gene on chromosomes 6, 8, 16, and X. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 201725 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 22 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001008393

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27320
Approved symbol	C4orf46
Name	chromosome 4 open reading frame 46
Location	4q32.1
Locus type	gene with protein product
Status	Approved
Aliases	LOC201725, RCDG1
Ensembl gene	ENSG00000205208
Ensembl biotype	protein_coding
OMIM	616210
Entrez	201725

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000379205, ENST00000508457, ENST00000508836, ENST00000933936

RefSeq mRNA: 1 — MANE Select: NM_001008393 NM_001008393

CCDS: CCDS34088

Canonical transcript exons

ENST00000379205 — 2 exons

Exon	Start	End
ENSE00001480066	158666675	158669768
ENSE00001480069	158671616	158671887

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 92.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7213 / max 110.7990, expressed in 1759 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54609	9.7025	1701
54608	0.8761	529
54611	0.8244	425
54610	0.3183	142

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	92.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.35	gold quality
ganglionic eminence	UBERON:0004023	84.28	gold quality
endothelial cell	CL:0000115	83.65	gold quality
ventricular zone	UBERON:0003053	83.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.54	gold quality
stromal cell of endometrium	CL:0002255	81.46	gold quality
bone marrow	UBERON:0002371	79.57	gold quality
calcaneal tendon	UBERON:0003701	79.56	gold quality
endometrium	UBERON:0001295	78.91	gold quality
monocyte	CL:0000576	78.75	gold quality
testis	UBERON:0000473	78.73	gold quality
leukocyte	CL:0000738	78.54	gold quality
right testis	UBERON:0004534	78.08	gold quality
islet of Langerhans	UBERON:0000006	77.90	gold quality
cortical plate	UBERON:0005343	77.88	gold quality
left testis	UBERON:0004533	77.65	gold quality
smooth muscle tissue	UBERON:0001135	77.64	gold quality
bone marrow cell	CL:0002092	76.17	gold quality
rectum	UBERON:0001052	76.10	gold quality
oviduct epithelium	UBERON:0004804	75.82	gold quality
adrenal tissue	UBERON:0018303	75.63	gold quality
vermiform appendix	UBERON:0001154	75.54	gold quality
thymus	UBERON:0002370	75.13	gold quality
uterus	UBERON:0000995	74.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.00	gold quality
gall bladder	UBERON:0002110	73.85	gold quality
pancreas	UBERON:0001264	73.46	gold quality
lymph node	UBERON:0000029	73.16	gold quality
body of uterus	UBERON:0009853	72.98	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

158 targeting C4orf46, 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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4533	100.00	69.48	2758
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478
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-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867

Literature-anchored findings (GeneRIF, showing 1)

• A reduction in RCDG1 expression may be associated with the oncogenesis of renal cell carcinoma and the differentiation of clear cell renal cell carcinoma. (PMID:25059753)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	4930579G24Rik	ENSMUSG00000027811
rattus_norvegicus	C2h4orf46	ENSRNOG00000010071

Protein

Protein identifiers

Renal cancer differentiation gene 1 protein — Q504U0 (reviewed: Q504U0)

All UniProt accessions (2): Q504U0, D6RFF4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in the kidney, in epithelial cells in both proximal tubules and distal convoluted tubules.

RefSeq proteins (1): NP_001008394* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031457	RCDG1	Family

Pfam: PF15725

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-Q504U0-F1	80.81	0.56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): chr4q32, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, WEI_MYCN_TARGETS_WITH_E_BOX, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, SENESE_HDAC1_TARGETS_UP, ZHENG_BOUND_BY_FOXP3, SENESE_HDAC1_AND_HDAC2_TARGETS_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, TOYOTA_TARGETS_OF_MIR34B_AND_MIR34C, JOHNSTONE_PARVB_TARGETS_3_DN, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_UP, BANP_TARGET_GENES, HES2_TARGET_GENES, MIER1_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C4orf46	RD3L	P0DJH9	631
C4orf46	BHLHA9	Q7RTU4	587
C4orf46	NSUN6	Q8TEA1	419
C4orf46	OIP5	O43482	374
C4orf46	MTFR2	Q6P444	374
C4orf46	MLF1	P58340	371
C4orf46	ZPBP	Q9BS86	368
C4orf46	SLC5A10	A0PJK1	348
C4orf46	P3H4	Q92791	325
C4orf46	DIAPH3	Q9NSV4	310
C4orf46	TPST1	O60507	302
C4orf46	NAP1L5	Q96NT1	301
C4orf46	CENPBD1P	B2RD01	290
C4orf46	COX17	Q14061	283
C4orf46	GMPPA	Q96IJ6	282

IntAct

50 interactions, top by confidence:

A	B	Type	Score
C4orf46	CDR2	psi-mi:“MI:0915”(physical association)	0.870
CDR2	C4orf46	psi-mi:“MI:0915”(physical association)	0.870
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
KXD1	C4orf46	psi-mi:“MI:0915”(physical association)	0.720
C4orf46	KXD1	psi-mi:“MI:0915”(physical association)	0.720
C4orf46	CDR2L	psi-mi:“MI:0915”(physical association)	0.670
TFPT	C4orf46	psi-mi:“MI:0915”(physical association)	0.560
C4orf46	TFPT	psi-mi:“MI:0915”(physical association)	0.560
C4orf46	PICK1	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	C4orf46	psi-mi:“MI:0915”(physical association)	0.560
C4orf46	BLOC1S6	psi-mi:“MI:0915”(physical association)	0.560
HUS1	C4orf46	psi-mi:“MI:0915”(physical association)	0.560
KIF2B	BACH1	psi-mi:“MI:0914”(association)	0.530
CDR2	IGSF3	psi-mi:“MI:0914”(association)	0.530
C4orf46	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CDR2	IGSF3	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TFPT	KRBA1	psi-mi:“MI:0914”(association)	0.350
CDR2L	SNAP29	psi-mi:“MI:0914”(association)	0.350
C4orf46	PICK1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): C4orf46 (Two-hybrid), C4orf46 (Two-hybrid), C4orf46 (Two-hybrid), C4orf46 (Affinity Capture-MS), C4orf46 (Affinity Capture-MS), C4orf46 (Affinity Capture-MS), C4orf46 (Two-hybrid), C4orf46 (Two-hybrid), C4orf46 (Two-hybrid), C4orf46 (Two-hybrid), C4orf46 (Two-hybrid), C4orf46 (Two-hybrid), C4orf46 (Two-hybrid), C4orf46 (Affinity Capture-MS), C4orf46 (Affinity Capture-MS)

ESM2 similar proteins: A0JPN6, A4IIZ9, A5WUL3, D4AE48, O57595, O75081, P0DPB3, P0DPB4, P49140, P53349, P68943, P85299, Q0II83, Q0IIJ3, Q13233, Q15528, Q1LZ89, Q2KHX9, Q2TBN4, Q3SZV2, Q3ULM0, Q3UUX7, Q4ZIN3, Q504U0, Q5BJU7, Q5E9K2, Q5FVG6, Q5M853, Q5NVG8, Q5RKN3, Q5XIX8, Q62276, Q62925, Q68EF0, Q6GQ95, Q800L3, Q80XH1, Q86XL3, Q8AVJ1, Q8CIV2

Diamond homologs: Q0II83, Q3UUX7, Q504U0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	10
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
58047	GRCh38/hg38 4q32.1(chr4:156252927-160451424)x3	Pathogenic
155554	GRCh38/hg38 4q32.1-32.2(chr4:156499748-163386407)x3	Likely pathogenic

SpliceAI

395 predictions. Top by Δscore:

Variant	Effect	Δscore
4:158669765:CTGC:C	acceptor_gain	1.0000
4:158669769:C:CC	acceptor_gain	1.0000
4:158669769:CTA:C	acceptor_loss	1.0000
4:158671614:A:AC	donor_gain	1.0000
4:158671615:C:CA	donor_gain	1.0000
4:158671615:CGT:C	donor_gain	1.0000
4:158671615:CGTCT:C	donor_gain	1.0000
4:158669766:TGC:T	acceptor_gain	0.9900
4:158669767:GC:G	acceptor_gain	0.9900
4:158669768:CC:C	acceptor_gain	0.9900
4:158670568:AGCT:A	donor_gain	0.9900
4:158671542:AG:A	donor_gain	0.9900
4:158671610:ACTC:A	donor_loss	0.9900
4:158671612:TCACG:T	donor_loss	0.9900
4:158671613:CACGT:C	donor_loss	0.9900
4:158671614:ACG:A	donor_loss	0.9900
4:158671614:ACGT:A	donor_gain	0.9900
4:158671615:C:A	donor_loss	0.9900
4:158671615:CG:C	donor_gain	0.9900
4:158671615:CGTC:C	donor_gain	0.9900
4:158671638:T:TA	donor_gain	0.9900
4:158671572:C:A	donor_gain	0.9800
4:158671606:C:CT	donor_gain	0.9800
4:158671609:CACT:C	donor_loss	0.9700
4:158671607:C:CT	donor_gain	0.9600
4:158671610:A:AC	donor_gain	0.9600
4:158671611:C:CC	donor_gain	0.9600
4:158671571:T:TA	donor_gain	0.9500
4:158671608:ACACT:A	donor_loss	0.9500
4:158672010:CGG:C	donor_gain	0.9500

AlphaMissense

716 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:158669650:A:G	L102S	0.995
4:158669663:A:G	W98R	0.990
4:158669663:A:T	W98R	0.990
4:158669673:G:C	F94L	0.988
4:158669673:G:T	F94L	0.988
4:158669675:A:G	F94L	0.988
4:158669671:A:T	L95H	0.987
4:158669661:C:A	W98C	0.985
4:158669661:C:G	W98C	0.985
4:158669671:A:G	L95P	0.985
4:158669653:A:G	L101P	0.982
4:158669738:C:G	A73P	0.979
4:158669674:A:G	F94S	0.978
4:158669642:C:G	G105R	0.976
4:158669659:C:G	R99P	0.976
4:158669681:C:G	A92P	0.974
4:158669662:C:G	W98S	0.971
4:158669649:C:A	L102F	0.964
4:158669649:C:G	L102F	0.964
4:158669641:C:T	G105D	0.961
4:158669650:A:C	L102W	0.961
4:158669725:A:T	V77E	0.960
4:158669704:A:G	L84P	0.959
4:158669642:C:A	G105C	0.955
4:158671623:A:C	I60S	0.952
4:158669662:C:A	W98L	0.951
4:158669693:A:G	C88R	0.951
4:158669746:A:G	L70P	0.951
4:158669755:A:G	L67S	0.951
4:158669646:T:A	K103N	0.948

dbSNP variants (sampled 300 via entrez): RS1000012048 (4:158667896 C>T), RS1000113510 (4:158672157 G>A,C), RS1000252680 (4:158667641 C>T), RS1001221143 (4:158672382 A>G), RS1001337610 (4:158666308 G>C), RS1001688592 (4:158666380 C>T), RS1001852331 (4:158666578 T>C,G), RS1001927485 (4:158666196 G>A), RS10024549 (4:158666828 C>T), RS1002527185 (4:158669717 G>C), RS1003937543 (4:158671352 G>T), RS1004083151 (4:158667625 T>C), RS1004250444 (4:158668306 A>G,T), RS1004805197 (4:158667941 T>C), RS1005476086 (4:158671269 G>A)

Disease associations

OMIM: gene MIM:616210 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): megacolon (MONDO:0001273)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008531	Megacolon	C06.405.469.158.701

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases expression	3
Benzo(a)pyrene	increases expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
triphenyl phosphate	affects expression	1
potassium chromate(VI)	decreases expression	1
resorcinol	increases expression	1
phenethyl isothiocyanate	decreases expression	1
chromium hexavalent ion	affects expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, decreases expression	1
Azathioprine	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Catechin	affects cotreatment, increases expression	1
Coumestrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Lead	affects expression	1
N-Nitrosopyrrolidine	decreases expression	1
Nickel	increases expression	1
Oxygen	decreases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04340856	Not specified	COMPLETED	Retrospective, Uncontrolled Cohort Study on the Therapy of Chronic Megalon
NCT07470892	Not specified	NOT_YET_RECRUITING	Preoperative Fish Oil PN and Prognosis After Constipation Surgery