C5orf22

Summary

C5orf22 (chromosome 5 open reading frame 22, HGNC:25639) is a protein-coding gene on chromosome 5p13.3, encoding UPF0489 protein C5orf22 (Q49AR2).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 20 total — 1 pathogenic
• MANE Select transcript: NM_018356

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25639
Approved symbol	C5orf22
Name	chromosome 5 open reading frame 22
Location	5p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11193
Ensembl gene	ENSG00000082213
Ensembl biotype	protein_coding
Entrez	55322

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 4 nonsense_mediated_decay, 3 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000325366, ENST00000504464, ENST00000504866, ENST00000507818, ENST00000510530, ENST00000510659, ENST00000511208, ENST00000513967, ENST00000515409, ENST00000517780, ENST00000926221

RefSeq mRNA: 1 — MANE Select: NM_018356 NM_018356

CCDS: CCDS3895

Canonical transcript exons

ENST00000325366 — 9 exons

Exon	Start	End
ENSE00001844074	31552773	31555053
ENSE00003525421	31538260	31538689
ENSE00003555735	31551293	31551432
ENSE00003643718	31541281	31541402
ENSE00003644259	31532301	31532473
ENSE00003649458	31540949	31541011
ENSE00003667586	31545646	31545712
ENSE00003691445	31534272	31534417
ENSE00003786752	31535744	31535893

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.9827 / max 239.3115, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55964	18.9576	1813
55965	0.0251	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.08	gold quality
oocyte	CL:0000023	94.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.13	gold quality
biceps brachii	UBERON:0001507	90.86	gold quality
hair follicle	UBERON:0002073	89.28	silver quality
mucosa of sigmoid colon	UBERON:0004993	89.16	gold quality
epithelium of nasopharynx	UBERON:0001951	89.03	gold quality
colonic mucosa	UBERON:0000317	88.84	gold quality
skeletal muscle tissue	UBERON:0001134	87.91	gold quality
calcaneal tendon	UBERON:0003701	87.59	gold quality
gastrocnemius	UBERON:0001388	87.03	gold quality
muscle of leg	UBERON:0001383	87.01	gold quality
choroid plexus epithelium	UBERON:0003911	86.93	gold quality
palpebral conjunctiva	UBERON:0001812	86.92	gold quality
muscle organ	UBERON:0001630	86.91	gold quality
muscle tissue	UBERON:0002385	86.84	gold quality
heart right ventricle	UBERON:0002080	86.75	gold quality
deltoid	UBERON:0001476	86.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.46	gold quality
vastus lateralis	UBERON:0001379	86.26	silver quality
bone marrow cell	CL:0002092	86.05	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.69	gold quality
tibialis anterior	UBERON:0001385	85.66	gold quality
myocardium	UBERON:0002349	85.62	gold quality
lateral nuclear group of thalamus	UBERON:0002736	85.52	gold quality
adrenal tissue	UBERON:0018303	85.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.36	gold quality
embryo	UBERON:0000922	85.34	gold quality
bone marrow	UBERON:0002371	85.28	gold quality
CA1 field of hippocampus	UBERON:0003881	85.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

129 targeting C5orf22, 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-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AT-5P	99.96	70.83	2666
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-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
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

Literature-anchored findings (GeneRIF, showing 1)

• A Proteomic Connectivity Map for Characterizing the Tumor Adaptive Response to Small Molecule Chemical Perturbagens. (PMID:31846293)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	C2H5orf22	ENSDARG00000011723
mus_musculus	6030458C11Rik	ENSMUSG00000022195
rattus_norvegicus	C2h5orf22	ENSRNOG00000022745
drosophila_melanogaster	MESR6	FBGN0036846

Protein

Protein identifiers

UPF0489 protein C5orf22 — Q49AR2 (reviewed: Q49AR2)

All UniProt accessions (4): Q49AR2, B4DR92, E5RFG1, E5RHP8

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the UPF0489 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q49AR2-1	1	yes
Q49AR2-2	2
Q49AR2-3	3

RefSeq proteins (1): NP_060826* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024131	FlmR/OhkR-like	Family

Pfam: PF12640

UniProt features (9 total): splice variant 3, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q49AR2-F1	85.16	0.75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, RYTTCCTG_ETS2_B, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, BIDUS_METASTASIS_UP, MARSON_BOUND_BY_E2F4_UNSTIMULATED, BOYAULT_LIVER_CANCER_SUBCLASS_G3_UP, BROWNE_HCMV_INFECTION_48HR_UP, STAMBOLSKY_TARGETS_OF_MUTATED_TP53_UP, JOHNSTONE_PARVB_TARGETS_3_DN, TERAO_AOX4_TARGETS_SKIN_DN, PURBEY_TARGETS_OF_CTBP1_AND_SATB1_DN, LIM_MAMMARY_STEM_CELL_DN

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

1000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C5orf22	SAYSD1	Q9NPB0	580
C5orf22	TPGS2	Q68CL5	562
C5orf22	TRMT13	Q9NUP7	541
C5orf22	RGS3	P49796	537
C5orf22	TRPM6	Q9BX84	455
C5orf22	PRR3	P79522	448
C5orf22	PIGH	Q14442	437
C5orf22	BDNF	P23560	429
C5orf22	NXT2	Q9NPJ8	424
C5orf22	TMEM267	Q0VDI3	397
C5orf22	SPANXN1	Q5VSR9	397
C5orf22	SPRYD7	Q5W111	370
C5orf22	IFFO1	Q0D2I5	368
C5orf22	ZNF250	P15622	366
C5orf22	SPRING1	Q9H741	350

IntAct

33 interactions, top by confidence:

A	B	Type	Score
C5orf22	WBP11	psi-mi:“MI:0915”(physical association)	0.800
WBP11	PQBP1	psi-mi:“MI:0914”(association)	0.800
SURF2	RPL5	psi-mi:“MI:0914”(association)	0.800
WBP11	C5orf22	psi-mi:“MI:0915”(physical association)	0.800
OSM	IL6ST	psi-mi:“MI:0914”(association)	0.760
ELOF1	C5orf22	psi-mi:“MI:0915”(physical association)	0.670
C5orf22	ELOF1	psi-mi:“MI:0915”(physical association)	0.670
C5orf22	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
XAGE1A	THAP12	psi-mi:“MI:0914”(association)	0.530
SURF2	HEXIM1	psi-mi:“MI:0914”(association)	0.530
NOL9	IPO5	psi-mi:“MI:0914”(association)	0.530
SURF2	KPNA6	psi-mi:“MI:0914”(association)	0.350
DEF8	DPYSL4	psi-mi:“MI:0914”(association)	0.350
WBP11	PQBP1	psi-mi:“MI:0914”(association)	0.350
CDC14B	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
SPON1	AHCYL1	psi-mi:“MI:0914”(association)	0.350
CTAG2	PCNT	psi-mi:“MI:0914”(association)	0.350
NOBOX	CDK2	psi-mi:“MI:0914”(association)	0.350
FOXE3	C1QBP	psi-mi:“MI:0914”(association)	0.350
PQBP1	ANK3	psi-mi:“MI:0914”(association)	0.350
PQBP1	C5orf22	psi-mi:“MI:0914”(association)	0.350
C5orf22	ELOF1	psi-mi:“MI:0915”(physical association)	0.000
C5orf22	DDIT4L	psi-mi:“MI:0915”(physical association)	0.000
C5orf22	WBP11	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): C5orf22 (Affinity Capture-MS), C5orf22 (Affinity Capture-MS), ELOF1 (Two-hybrid), C5orf22 (Two-hybrid), C5orf22 (Affinity Capture-MS), C5orf22 (Affinity Capture-MS), C5orf22 (Affinity Capture-MS), C5orf22 (Affinity Capture-MS), C5orf22 (Affinity Capture-MS), C5orf22 (Negative Genetic), C5orf22 (Synthetic Lethality), C5orf22 (Affinity Capture-MS), WBP11 (Two-hybrid), ELOF1 (Two-hybrid), DDIT4L (Two-hybrid)

ESM2 similar proteins: A2AUU0, A3KMI0, E7F654, F1MAB7, P33279, P59114, Q08DH3, Q0P5B2, Q13686, Q28H30, Q3T131, Q3T9Z9, Q49AR2, Q4R8E0, Q5R5W9, Q5R6T6, Q5U2S3, Q5ZLL7, Q62240, Q63185, Q6DTM3, Q6NXH8, Q6NZP1, Q6P1Q9, Q6PAE6, Q6PD74, Q6ZUJ8, Q7SZF1, Q7TNN8, Q7Z3E5, Q8BGC1, Q8BMD7, Q8BMK1, Q8CHK4, Q8K3E5, Q8N6Q8, Q8TE76, Q8W5R2, Q92993, Q96IZ6

Diamond homologs: Q28H30, Q49AR2, Q5R5W9, Q6PAE6, Q7SZF1, Q8BGC1

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	5
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
147643	GRCh38/hg38 5p13.3(chr5:31208753-32173244)x3	Pathogenic

SpliceAI

1623 predictions. Top by Δscore:

Variant	Effect	Δscore
5:31534269:CAGGT:C	acceptor_loss	1.0000
5:31534270:A:AG	acceptor_gain	1.0000
5:31534270:A:C	acceptor_loss	1.0000
5:31534271:G:GG	acceptor_gain	1.0000
5:31534271:GGTT:G	acceptor_gain	1.0000
5:31534321:GTAAT:G	donor_gain	1.0000
5:31534326:G:GG	donor_gain	1.0000
5:31535069:G:GT	donor_gain	1.0000
5:31535070:A:T	donor_gain	1.0000
5:31535742:A:AG	acceptor_gain	1.0000
5:31535743:G:GG	acceptor_gain	1.0000
5:31535743:GA:G	acceptor_gain	1.0000
5:31535743:GAGA:G	acceptor_gain	1.0000
5:31535890:TCAG:T	donor_loss	1.0000
5:31535891:CAG:C	donor_loss	1.0000
5:31535892:AGG:A	donor_loss	1.0000
5:31535893:GGT:G	donor_loss	1.0000
5:31535894:GT:G	donor_loss	1.0000
5:31535895:T:A	donor_loss	1.0000
5:31538258:AG:A	acceptor_gain	1.0000
5:31538259:GG:G	acceptor_gain	1.0000
5:31538617:G:T	donor_gain	1.0000
5:31541008:AGAGG:A	donor_loss	1.0000
5:31541009:GAG:G	donor_gain	1.0000
5:31541009:GAGG:G	donor_loss	1.0000
5:31541011:GGTAT:G	donor_loss	1.0000
5:31541012:G:GA	donor_loss	1.0000
5:31541013:T:A	donor_loss	1.0000
5:31541401:GG:G	donor_gain	1.0000
5:31541402:GG:G	donor_gain	1.0000

AlphaMissense

2918 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:31535763:T:A	W83R	0.998
5:31535763:T:C	W83R	0.998
5:31538646:A:T	D255V	0.998
5:31535823:T:A	W103R	0.997
5:31535823:T:C	W103R	0.997
5:31538646:A:C	D255A	0.997
5:31538647:T:A	D255E	0.997
5:31538647:T:G	D255E	0.997
5:31551306:G:A	G358D	0.997
5:31534345:A:T	D52V	0.996
5:31534360:T:C	L57P	0.996
5:31535808:T:A	W98R	0.996
5:31535808:T:C	W98R	0.996
5:31538665:T:A	N261K	0.996
5:31538665:T:G	N261K	0.996
5:31538669:T:C	F263L	0.996
5:31538671:C:A	F263L	0.996
5:31538671:C:G	F263L	0.996
5:31552794:T:G	C407W	0.996
5:31534338:C:G	H50D	0.995
5:31534350:C:G	H54D	0.995
5:31534357:A:T	D56V	0.995
5:31535762:T:A	N82K	0.995
5:31535762:T:G	N82K	0.995
5:31538646:A:G	D255G	0.995
5:31551294:T:A	V354D	0.995
5:31551302:G:C	A357P	0.995
5:31551303:C:A	A357D	0.995
5:31534346:C:A	D52E	0.994
5:31534346:C:G	D52E	0.994

dbSNP variants (sampled 300 via entrez): RS1000130906 (5:31549779 G>A), RS1000210208 (5:31543126 C>A), RS1000267384 (5:31549392 C>G), RS1000448397 (5:31551332 C>T), RS1000660907 (5:31543477 G>A), RS1000946695 (5:31543902 T>C), RS1000986523 (5:31538075 G>A), RS1001039103 (5:31537563 C>G,T), RS1001053777 (5:31550608 C>A), RS1001147591 (5:31544511 A>G), RS1001515570 (5:31544378 T>C), RS1001770571 (5:31530419 A>T), RS1001921965 (5:31549921 A>T), RS1002011016 (5:31555323 A>C,G), RS1002108861 (5:31543009 GA>G)

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

1 associations (top):

Study	Trait	p-value
GCST006991_2	Cerebrospinal fluid t-tau levels in Alzheimer’s disease dementia	9.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004760	t-tau measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10035440	C5orf22		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	2
TAK-243	increases sumoylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	decreases expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
potassium chromate(VI)	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Etoposide	affects response to substance	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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