C21orf58

Summary

C21orf58 (chromosome 21 open reading frame 58, HGNC:1300) is a protein-coding gene on chromosome 21q22.3, encoding Uncharacterized protein C21orf58 (P58505).

At a glance

• Clinical variants (ClinVar): 33 total — 4 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_058180

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1300
Approved symbol	C21orf58
Name	chromosome 21 open reading frame 58
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000160298
Ensembl biotype	protein_coding
Entrez	54058

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000291691, ENST00000397679, ENST00000397680, ENST00000397682, ENST00000397683, ENST00000417060, ENST00000445935, ENST00000472607, ENST00000475776, ENST00000491666, ENST00000851029, ENST00000894108, ENST00000956568

RefSeq mRNA: 5 — MANE Select: NM_058180 NM_001286462, NM_001286463, NM_001286476, NM_001286477, NM_058180

CCDS: CCDS13735, CCDS68229

Canonical transcript exons

ENST00000291691 — 8 exons

Exon	Start	End
ENSE00001051246	46314716	46314880
ENSE00002244793	46311456	46311567
ENSE00003530408	46317208	46317268
ENSE00003567971	46315474	46315547
ENSE00003583756	46302485	46302576
ENSE00003603708	46322639	46323870
ENSE00003625644	46318012	46318220
ENSE00004283468	46301130	46302154

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 98.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5292 / max 93.5903, expressed in 1363 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190933	8.2133	1348
190930	0.1483	44
190932	0.1158	34
190931	0.0518	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.37	gold quality
bronchial epithelial cell	CL:0002328	90.51	gold quality
bronchus	UBERON:0002185	88.69	gold quality
ventricular zone	UBERON:0003053	88.44	gold quality
pituitary gland	UBERON:0000007	87.83	gold quality
oviduct epithelium	UBERON:0004804	87.10	gold quality
adenohypophysis	UBERON:0002196	86.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.45	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.53	gold quality
trabecular bone tissue	UBERON:0002483	85.21	silver quality
ganglionic eminence	UBERON:0004023	84.20	gold quality
tendon of biceps brachii	UBERON:0008188	82.80	gold quality
fallopian tube	UBERON:0003889	82.69	gold quality
mucosa of transverse colon	UBERON:0004991	80.16	gold quality
bone marrow cell	CL:0002092	78.83	gold quality
left testis	UBERON:0004533	78.33	gold quality
right testis	UBERON:0004534	78.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.52	gold quality
bone marrow	UBERON:0002371	77.41	gold quality
colonic epithelium	UBERON:0000397	76.80	gold quality
lower esophagus mucosa	UBERON:0035834	76.79	gold quality
right lung	UBERON:0002167	75.88	gold quality
testis	UBERON:0000473	75.87	gold quality
stromal cell of endometrium	CL:0002255	75.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.19	gold quality
islet of Langerhans	UBERON:0000006	74.76	gold quality
buccal mucosa cell	CL:0002336	74.59	silver quality
granulocyte	CL:0000094	74.56	gold quality
apex of heart	UBERON:0002098	73.79	gold quality
esophagus mucosa	UBERON:0002469	73.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	29.18
E-MTAB-10287	yes	26.30
E-ANND-3	yes	10.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting C21orf58, 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-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-4782-5P	98.35	69.33	1474
HSA-MIR-5706	98.35	69.33	1463
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-6781-3P	97.44	66.85	970
HSA-MIR-2682-3P	97.10	66.16	840

Literature-anchored findings (GeneRIF, showing 1)

• Targeting C21orf58 is a Novel Treatment Strategy of Hepatocellular Carcinoma by Disrupting the Formation of JAK2/C21orf58/STAT3 Complex. (PMID:38342622)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	zgc:112416	ENSDARG00000044549
mus_musculus	2610028H24Rik	ENSMUSG00000009114
rattus_norvegicus	C20h21orf58	ENSRNOG00000012714

Protein

Protein identifiers

Uncharacterized protein C21orf58 — P58505 (reviewed: P58505)

All UniProt accessions (4): P58505, C9JH41, H0YCB6, H7C1T9

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in skin and fetal lung.

Isoforms (3)

UniProt ID	Names	Canonical?
P58505-1	1	yes
P58505-2	2
P58505-3	3

RefSeq proteins (5): NP_001273391, NP_001273392, NP_001273405, NP_001273406, NP_478060* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027904	DUF4587	Domain
IPR038915	PRR29-like	Family

Pfam: PF15248

UniProt features (8 total): splice variant 3, region of interest 2, chain 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P58505-F1	60.77	0.19

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): WANG_CLIM2_TARGETS_UP, YY1_Q6, YY1_02, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, chr21q22, GATGKMRGCG_UNKNOWN, MYB_Q5_01, GCCATNTTG_YY1_Q6, YGCGYRCGC_UNKNOWN, AHR_Q5, MARSON_BOUND_BY_E2F4_UNSTIMULATED, AAGWWRNYGGC_UNKNOWN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP, NRF1_Q6

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C21orf58	YBEY	P58557	577
C21orf58	ZNF526	Q8TF50	543
C21orf58	SCAF4	O95104	500
C21orf58	KRTAP19-2	Q3LHN2	477
C21orf58	SPATC1L	Q9H0A9	475
C21orf58	MAP3K7CL	P57077	447
C21orf58	MCM3AP	O60318	434
C21orf58	SMIM11	P58511	400
C21orf58	KIAA1614	Q5VZ46	399
C21orf58	FAM124A	Q86V42	392
C21orf58	MTRES1	Q9P0P8	391
C21orf58	M0QY95	M0QY95	376
C21orf58	FAM186A	A6NE01	370
C21orf58	KLHDC7A	Q5VTJ3	370
C21orf58	PLCXD2	Q0VAA5	369

IntAct

5 interactions, top by confidence:

A	B	Type	Score
C21orf58	MTUS2	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
C21orf58	MTA2	psi-mi:“MI:0914”(association)	0.350
C21orf58	GRB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): C21orf58 (Two-hybrid), C21orf58 (Two-hybrid), C21orf58 (Two-hybrid), C21orf58 (Two-hybrid), C21orf58 (Two-hybrid), C21orf58 (Two-hybrid), C21orf58 (Two-hybrid), C21orf58 (Two-hybrid), SPTA1 (Two-hybrid), KRT27 (Two-hybrid), POLR1C (Two-hybrid), MKRN3 (Two-hybrid), CCDC125 (Two-hybrid), KRT35 (Two-hybrid), C21orf58 (Affinity Capture-MS)

ESM2 similar proteins: A1L443, A2A9T0, A2IDD5, A6NNL0, A7E346, A7MCY6, B1AL46, D6RGH6, E9PGG2, F5GYI3, O14836, P0C7W0, P58505, Q0X0E2, Q0ZCJ7, Q2KI80, Q2M3G4, Q3SYZ3, Q3SZL6, Q3TVI4, Q4KLY2, Q5F267, Q5FVJ4, Q5FVM5, Q5JXC2, Q5R8C5, Q5SW24, Q5T7N3, Q5VT03, Q5VZR2, Q68CJ9, Q6DG50, Q6PJ61, Q6ZN01, Q7TN08, Q7TNF9, Q80VJ8, Q8BRJ3, Q8BX43, Q8IVF1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	11
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1456137	NC_000021.8:g.(?47699887)(47787074_?)del	Pathogenic
1701429	GRCh37/hg19 21q22.3(chr21:47533920-48084286)x1	Pathogenic
4279456	GRCh37/hg19 21q22.3(chr21:47682081-47721739)x1	Pathogenic
59069	GRCh38/hg38 21q22.3(chr21:45801860-46670405)x1	Pathogenic
253347	GRCh37/hg19 21q22.3(chr21:46682125-48090317)x3	Likely pathogenic
253363	GRCh37/hg19 21q22.3(chr21:47550596-48080926)x1	Likely pathogenic
816184	GRCh37/hg19 21q22.3(chr21:46749869-48097372)x1	Likely pathogenic

SpliceAI

1790 predictions. Top by Δscore:

Variant	Effect	Δscore
21:46302574:TGT:T	acceptor_gain	0.9900
21:46302577:C:CC	acceptor_gain	0.9900
21:46311454:ACCTT:A	donor_gain	0.9900
21:46311455:CCTTC:C	donor_gain	0.9900
21:46317202:TCTCA:T	donor_loss	0.9900
21:46317203:CTCAC:C	donor_loss	0.9900
21:46317204:TCA:T	donor_loss	0.9900
21:46317205:CACC:C	donor_loss	0.9900
21:46317206:ACC:A	donor_loss	0.9900
21:46317207:C:CA	donor_loss	0.9900
21:46317207:CCTGG:C	donor_gain	0.9900
21:46317266:CTT:C	acceptor_gain	0.9900
21:46317269:C:CC	acceptor_gain	0.9900
21:46322588:C:CT	donor_gain	0.9900
21:46323048:C:CA	donor_gain	0.9900
21:46302572:CATGT:C	acceptor_gain	0.9800
21:46302575:GT:G	acceptor_gain	0.9800
21:46302575:GTCTG:G	acceptor_loss	0.9800
21:46302576:TC:T	acceptor_loss	0.9800
21:46302578:T:A	acceptor_loss	0.9800
21:46311469:TCCTG:T	donor_gain	0.9800
21:46322813:T:TA	donor_gain	0.9800
21:46323047:TC:T	donor_gain	0.9800
21:46323048:CC:C	donor_gain	0.9800
21:46323720:ATG:A	donor_gain	0.9800
21:46324280:AAG:A	donor_loss	0.9800
21:46324281:AG:A	donor_loss	0.9800
21:46324283:GT:G	donor_loss	0.9800
21:46302478:AGCCT:A	donor_loss	0.9700
21:46302479:GCCTA:G	donor_loss	0.9700

AlphaMissense

2030 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:46311460:C:A	K239N	0.995
21:46311460:C:G	K239N	0.995
21:46302567:T:A	E244V	0.984
21:46302564:A:G	L245P	0.981
21:46302558:A:G	L247P	0.979
21:46311461:T:A	K239M	0.971
21:46302561:A:G	L246P	0.969
21:46302548:G:C	N250K	0.965
21:46302548:G:T	N250K	0.965
21:46311456:C:G	D241H	0.962
21:46302551:C:A	Q249H	0.961
21:46302551:C:G	Q249H	0.961
21:46302538:G:C	H254D	0.960
21:46315490:A:G	L143P	0.958
21:46311466:A:C	S237R	0.956
21:46311466:A:T	S237R	0.956
21:46311468:T:G	S237R	0.956
21:46302525:A:G	L258P	0.954
21:46302549:T:A	N250I	0.953
21:46302547:C:G	A251P	0.952
21:46302528:A:T	V257D	0.951
21:46311464:A:T	I238N	0.948
21:46311458:T:A	E240V	0.947
21:46302568:C:T	E244K	0.946
21:46315478:A:G	L147P	0.945
21:46315498:C:A	R140S	0.945
21:46315498:C:G	R140S	0.945
21:46302576:T:A	D241V	0.943
21:46311462:T:C	K239E	0.942
21:46311464:A:G	I238T	0.942

dbSNP variants (sampled 300 via entrez): RS1000079133 (21:46320426 T>C), RS1000107250 (21:46323809 G>A,T), RS1000156510 (21:46320226 C>G,T), RS1000291316 (21:46324504 A>G), RS1000292264 (21:46303290 G>C), RS1000410052 (21:46300076 T>C), RS1000541747 (21:46315224 G>A,T), RS1000598928 (21:46323888 G>A), RS1000641965 (21:46320205 T>A,C), RS1000642637 (21:46303610 G>A), RS1000900191 (21:46304237 A>G), RS1001051987 (21:46319913 A>T), RS1001164278 (21:46325057 G>A,T), RS1001221277 (21:46312901 A>G), RS1001242868 (21:46302411 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	3
sodium arsenite	affects expression, decreases expression, increases expression	3
Valproic Acid	affects cotreatment, decreases expression, increases methylation	3
entinostat	affects expression, affects cotreatment, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
dicrotophos	increases expression	1
zinc chromate	increases abundance, decreases expression	1
ethylene dichloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
NSC 689534	affects binding, decreases expression	1
NSC668394	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cannabidiol	decreases expression	1
Copper	affects binding, decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Gallic Acid	decreases expression	1
Gasoline	increases abundance, affects cotreatment, decreases expression	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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