C4orf33

Summary

C4orf33 (chromosome 4 open reading frame 33, HGNC:27025) is a protein-coding gene on chromosome 4q28.2, encoding UPF0462 protein C4orf33 (Q8N1A6).

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 20 total — 1 pathogenic
• MANE Select transcript: NM_001099783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27025
Approved symbol	C4orf33
Name	chromosome 4 open reading frame 33
Location	4q28.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33703
Ensembl gene	ENSG00000151470
Ensembl biotype	protein_coding
Entrez	132321

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 retained_intron

ENST00000281146, ENST00000425929, ENST00000502360, ENST00000502887, ENST00000508622, ENST00000508673, ENST00000859483, ENST00000859484, ENST00000859485, ENST00000859486, ENST00000859487, ENST00000859488, ENST00000911334, ENST00000911335, ENST00000911336, ENST00000911337, ENST00000911338, ENST00000911339, ENST00000956407

RefSeq mRNA: 2 — MANE Select: NM_001099783 NM_001099783, NM_173487

CCDS: CCDS3741

Canonical transcript exons

ENST00000425929 — 6 exons

Exon	Start	End
ENSE00001205230	129111686	129116637
ENSE00003842813	129096152	129096209
ENSE00003889393	129109473	129109672
ENSE00003892319	129102602	129102791
ENSE00003893662	129106587	129106647
ENSE00003896241	129109307	129109358

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 88.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4952 / max 162.8225, expressed in 1675 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49648	6.0228	1238
49649	4.3738	1510
49650	0.0986	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	88.99	gold quality
leukocyte	CL:0000738	88.23	gold quality
rectum	UBERON:0001052	86.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.09	gold quality
adrenal tissue	UBERON:0018303	83.69	gold quality
duodenum	UBERON:0002114	83.49	gold quality
islet of Langerhans	UBERON:0000006	83.33	gold quality
gall bladder	UBERON:0002110	81.25	gold quality
cerebellar cortex	UBERON:0002129	81.12	gold quality
cerebellar hemisphere	UBERON:0002245	81.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.38	gold quality
right adrenal gland cortex	UBERON:0035827	80.22	gold quality
cerebellum	UBERON:0002037	80.03	gold quality
colonic mucosa	UBERON:0000317	79.97	gold quality
bone marrow cell	CL:0002092	79.85	gold quality
right adrenal gland	UBERON:0001233	79.48	gold quality
left adrenal gland cortex	UBERON:0035825	79.47	gold quality
left adrenal gland	UBERON:0001234	79.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.18	gold quality
granulocyte	CL:0000094	79.02	gold quality
pancreas	UBERON:0001264	78.69	gold quality
jejunal mucosa	UBERON:0000399	78.54	gold quality
spinal cord	UBERON:0002240	78.22	gold quality
left ovary	UBERON:0002119	78.19	gold quality
adrenal gland	UBERON:0002369	78.18	gold quality
bronchial epithelial cell	CL:0002328	78.10	gold quality
adrenal cortex	UBERON:0001235	78.09	gold quality
mucosa of transverse colon	UBERON:0004991	77.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

94 targeting C4orf33, 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-432-3P	100.00	67.86	705
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	C1H4orf33	ENSDARG00000017985
mus_musculus	D3Ertd751e	ENSMUSG00000025766
rattus_norvegicus	C2h4orf33	ENSRNOG00000038330
caenorhabditis_elegans		WBGENE00007882

Protein

Protein identifiers

UPF0462 protein C4orf33 — Q8N1A6 (reviewed: Q8N1A6)

All UniProt accessions (4): D6RD26, D6RIS3, D6RIT3, Q8N1A6

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the UPF0462 family.

RefSeq proteins (2): NP_001093253, NP_775758 (=MANE)

Domains & families (InterPro)

UniProt features (7 total): sequence variant 4, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N1A6-F1	95.50	0.95

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): KOYAMA_SEMA3B_TARGETS_UP, NF1_Q6_01, CREB_Q3, ACEVEDO_LIVER_CANCER_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, chr4q28, MTF1_Q4, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_UP, ELF2_TARGET_GENES, EMX1_TARGET_GENES, HES2_TARGET_GENES, ID2_TARGET_GENES, NR1D1_TARGET_GENES, MIR153_5P

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

222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C4orf33	SYNRG	Q9UMZ2	496
C4orf33	TAF11	Q15544	493
C4orf33	CCDC185	Q8N715	479
C4orf33	KHDRBS2	Q5VWX1	460
C4orf33	GPATCH11	Q8N954	446
C4orf33	PCDH10	Q9P2E7	427
C4orf33	ZFP37	Q9Y6Q3	418
C4orf33	BTAF1	O14981	389
C4orf33	CDH18	Q13634	383
C4orf33	SLC31A2	O15432	378
C4orf33	SFT2D1	Q8WV19	377
C4orf33	PCDH17	O14917	374
C4orf33	ZFAND1	Q8TCF1	370
C4orf33	TMEM60	Q9H2L4	370
C4orf33	BASP1	P80723	368

IntAct

26 interactions, top by confidence:

A	B	Type	Score
C4orf33	VAC14	psi-mi:“MI:0915”(physical association)	0.830
VAC14	C4orf33	psi-mi:“MI:0915”(physical association)	0.830
C4orf33	TRIP13	psi-mi:“MI:0915”(physical association)	0.780
TRIP13	C4orf33	psi-mi:“MI:0915”(physical association)	0.780
C4orf33	CASP6	psi-mi:“MI:0915”(physical association)	0.560
C4orf33	LAMP2	psi-mi:“MI:0915”(physical association)	0.560
C4orf33	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
ECE1	C4orf33	psi-mi:“MI:0915”(physical association)	0.370
C4orf33	VAC14	psi-mi:“MI:0915”(physical association)	0.000
C4orf33	TRIP13	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): C4orf33 (Two-hybrid), C4orf33 (Two-hybrid), DCXR (Co-fractionation), C4orf33 (Positive Genetic), C4orf33 (Two-hybrid), C4orf33 (Two-hybrid), C4orf33 (Two-hybrid), C4orf33 (Affinity Capture-RNA), EEA1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2AV36, A3AZW5, A4IF69, A4IG42, A6QQV6, E1BVR9, F1RET2, O02791, P52019, P54803, P57075, Q08BV2, Q28GP0, Q32PY6, Q3U3W5, Q3UDE2, Q3V3E1, Q4R3W5, Q5F204, Q5IH14, Q5M845, Q5RGQ2, Q5T8I9, Q5U4E8, Q5ZI67, Q5ZIB9, Q6DIZ0, Q6EE23, Q6GML1, Q6P2P2, Q6P2T7, Q6P7I0, Q6PCI6, Q75W54, Q7Z3D6, Q7ZU91, Q8BGG7, Q8BGN2, Q8CFC1, Q8N1A6

Diamond homologs: Q28GP0, Q5M845, Q6P2T7, Q8BGN2, Q8N1A6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	9
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57367	GRCh38/hg38 4q28.2-31.21(chr4:128119872-142431375)x1	Pathogenic

SpliceAI

1139 predictions. Top by Δscore:

Variant	Effect	Δscore
4:129102788:GAAG:G	donor_gain	1.0000
4:129102789:AAGGT:A	donor_loss	1.0000
4:129102792:G:GA	donor_loss	1.0000
4:129102793:T:G	donor_loss	1.0000
4:129106582:A:AG	acceptor_gain	1.0000
4:129106585:A:G	acceptor_gain	1.0000
4:129109668:GATTT:G	donor_gain	1.0000
4:129100308:G:GG	donor_gain	0.9900
4:129101633:A:AG	donor_gain	0.9900
4:129102596:TTTTA:T	acceptor_loss	0.9900
4:129102597:TTTA:T	acceptor_loss	0.9900
4:129102599:TA:T	acceptor_loss	0.9900
4:129102599:TAGA:T	acceptor_gain	0.9900
4:129102600:A:AG	acceptor_gain	0.9900
4:129102600:A:AT	acceptor_loss	0.9900
4:129102600:AGAGA:A	acceptor_gain	0.9900
4:129102601:G:GG	acceptor_gain	0.9900
4:129102601:GA:G	acceptor_gain	0.9900
4:129102601:GAGA:G	acceptor_gain	0.9900
4:129102790:AG:A	donor_gain	0.9900
4:129102791:GG:G	donor_gain	0.9900
4:129102792:G:GG	donor_gain	0.9900
4:129106583:A:G	acceptor_gain	0.9900
4:129106586:G:GA	acceptor_gain	0.9900
4:129106586:GTT:G	acceptor_gain	0.9900
4:129106648:G:GG	donor_gain	0.9900
4:129109456:A:AG	acceptor_gain	0.9900
4:129109457:C:G	acceptor_gain	0.9900
4:129109459:T:G	acceptor_gain	0.9900
4:129109472:GCAA:G	acceptor_gain	0.9900

AlphaMissense

1317 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:129106598:T:C	F65L	0.933
4:129106600:T:A	F65L	0.933
4:129106600:T:G	F65L	0.933
4:129109518:T:A	W114R	0.932
4:129109518:T:C	W114R	0.932
4:129109581:T:C	F135L	0.925
4:129109583:T:A	F135L	0.925
4:129109583:T:G	F135L	0.925
4:129109620:G:C	A148P	0.905
4:129111702:T:C	F171L	0.897
4:129111704:C:A	F171L	0.897
4:129111704:C:G	F171L	0.897
4:129106601:T:C	F66L	0.892
4:129106603:C:A	F66L	0.892
4:129106603:C:G	F66L	0.892
4:129109577:T:A	N133K	0.887
4:129109577:T:G	N133K	0.887
4:129109520:G:C	W114C	0.885
4:129109520:G:T	W114C	0.885
4:129106633:A:C	E76D	0.877
4:129106633:A:T	E76D	0.877
4:129109572:T:C	F132L	0.875
4:129109574:C:A	F132L	0.875
4:129109574:C:G	F132L	0.875
4:129109671:T:C	F165L	0.861
4:129111686:C:A	F165L	0.861
4:129111686:C:G	F165L	0.861
4:129106594:A:C	E63D	0.859
4:129106594:A:T	E63D	0.859
4:129102635:T:A	W9R	0.858

dbSNP variants (sampled 300 via entrez): RS1000044094 (4:129107095 C>T), RS1000513379 (4:129112270 A>G), RS1000599268 (4:129116052 A>AG), RS1000671430 (4:129115814 A>ATG), RS1000857991 (4:129093234 C>T), RS10008622 (4:129114596 G>A), RS1000911638 (4:129093447 G>A,C), RS1000916102 (4:129109128 A>G), RS10009430 (4:129109608 C>T), RS1001027976 (4:129105629 T>G), RS1001103428 (4:129098809 T>C), RS1001238116 (4:129106107 A>G), RS1001442593 (4:129105813 T>C), RS1001525421 (4:129098623 G>A), RS1001870757 (4:129103101 G>A,T)

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

15 associations (top):

Study	Trait	p-value
GCST002783_177	Body mass index	1.000000e-06
GCST002783_281	Body mass index	1.000000e-06
GCST002783_75	Body mass index	3.000000e-07
GCST004735_22	Epstein-Barr virus copy number in lymphoblastoid cell lines	1.000000e-06
GCST004863_140	Mosquito bite size	4.000000e-08
GCST005833_2	Remission after SSRI treatment in MDD or openness	4.000000e-07
GCST007326_38	Number of sexual partners	4.000000e-10
GCST007576_262	Chronotype	1.000000e-10
GCST008830_14	Neurofibrillary tangles	3.000000e-06
GCST009733_169	Urinary metabolite levels in chronic kidney disease	6.000000e-18
GCST010922_3	Hip bone mineral density and total body fat mass (bivariate analysis)	6.000000e-09
GCST010988_77	Adult body size	2.000000e-10
GCST010989_244	Body size at age 10	1.000000e-11
GCST012020_3	Serum metabolite levels	7.000000e-22
GCST90002409_36	Childhood body mass index	3.000000e-06

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008378	mosquito bite reaction size measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007914	openness measurement
EFO:0008328	chronotype measurement
EFO:0006797	neurofibrillary tangles measurement
EFO:0005116	urinary metabolite measurement
EFO:0007702	hip bone mineral density
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	5
methylmercuric chloride	decreases expression	3
Acetaminophen	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
potassium chromate(VI)	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation	1
Vorinostat	increases expression	1
Vehicle Emissions	decreases reaction, decreases expression	1
Cisplatin	increases expression	1
Drugs, Chinese Herbal	increases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Naphthoquinones	increases expression	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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