C8orf34

Summary

C8orf34 (chromosome 8 open reading frame 34, HGNC:30905) is a protein-coding gene on chromosome 8q13.2, encoding Uncharacterized protein C8orf34 (Q49A92).

This gene encodes a protein that is related to the cyclic AMP dependent protein kinase regulators. Naturally occurring mutations in this gene are associated with an increased risk for severe toxicities, such as diarrhea and neutropenia, in patients undergoing chemotherapeutic treatment.

Source: NCBI Gene 116328 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 14 total — 1 pathogenic
• MANE Select transcript: NM_052958

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30905
Approved symbol	C8orf34
Name	chromosome 8 open reading frame 34
Location	8q13.2
Locus type	gene with protein product
Status	Approved
Aliases	vest-1, VEST1
Ensembl gene	ENSG00000165084
Ensembl biotype	protein_coding
Entrez	116328

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000325233, ENST00000337103, ENST00000348340, ENST00000349492, ENST00000518515, ENST00000518698, ENST00000521406, ENST00000523686, ENST00000860815, ENST00000860816, ENST00000924297, ENST00000924298

RefSeq mRNA: 7 — MANE Select: NM_052958 NM_001195639, NM_001349476, NM_001349477, NM_001349478, NM_001349479, NM_001349480, NM_052958

CCDS: CCDS6203

Canonical transcript exons

ENST00000518698 — 14 exons

Exon	Start	End
ENSE00001090166	68468692	68468820
ENSE00001149900	68521799	68521971
ENSE00001716480	68330955	68331339
ENSE00002099197	68818239	68819023
ENSE00003464017	68708994	68709079
ENSE00003465397	68446329	68446460
ENSE00003469331	68439499	68439646
ENSE00003484098	68640376	68640511
ENSE00003508881	68532983	68533149
ENSE00003621032	68721361	68721437
ENSE00003640451	68815886	68815945
ENSE00003651188	68787443	68787536
ENSE00003654672	68488023	68488051
ENSE00003691856	68776399	68776449

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 95.12.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5283 / max 113.2824, expressed in 305 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89250	0.6525	222
89248	0.2100	92
89247	0.1911	72
89251	0.1816	81
89249	0.1602	77
89252	0.1329	63

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.12	gold quality
oviduct epithelium	UBERON:0004804	91.34	gold quality
bronchial epithelial cell	CL:0002328	89.86	gold quality
bronchus	UBERON:0002185	87.87	gold quality
right uterine tube	UBERON:0001302	85.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.35	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.28	gold quality
ascending aorta	UBERON:0001496	77.17	gold quality
thoracic aorta	UBERON:0001515	77.04	gold quality
pigmented layer of retina	UBERON:0001782	76.34	gold quality
fallopian tube	UBERON:0003889	75.30	gold quality
descending thoracic aorta	UBERON:0002345	74.89	gold quality
prefrontal cortex	UBERON:0000451	74.57	gold quality
right coronary artery	UBERON:0001625	74.34	gold quality
pons	UBERON:0000988	71.86	gold quality
cerebellar cortex	UBERON:0002129	70.52	gold quality
aorta	UBERON:0000947	70.41	gold quality
cerebellar hemisphere	UBERON:0002245	70.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	69.72	gold quality
left coronary artery	UBERON:0001626	69.64	gold quality
cerebellum	UBERON:0002037	69.57	gold quality
hypothalamus	UBERON:0001898	68.63	gold quality
right lung	UBERON:0002167	68.63	gold quality
coronary artery	UBERON:0001621	68.42	gold quality
ganglionic eminence	UBERON:0004023	68.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	68.33	gold quality
Ammon’s horn	UBERON:0001954	68.10	gold quality
corpus callosum	UBERON:0002336	67.97	gold quality
caudate nucleus	UBERON:0001873	67.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	103.65
E-ANND-3	yes	6.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting C8orf34, 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-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
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
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

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	C24H8orf34	ENSDARG00000095034
mus_musculus	A830018L16Rik	ENSMUSG00000057715
rattus_norvegicus	C5h8orf34	ENSRNOG00000005375

Protein

Protein identifiers

Uncharacterized protein C8orf34 — Q49A92 (reviewed: Q49A92)

Alternative names: Protein VEST-1

All UniProt accessions (3): A0A2P0CTR9, E5RJD9, Q49A92

UniProt curated annotations — full annotation on UniProt →

Isoforms (4)

UniProt ID	Names	Canonical?
Q49A92-6	1	yes
Q49A92-2	2
Q49A92-3	3
Q49A92-4	4

RefSeq proteins (7): NP_001182568, NP_001336405, NP_001336406, NP_001336407, NP_001336408, NP_001336409, NP_443190* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040687	DUF5586	Family

Pfam: PF17824

UniProt features (14 total): splice variant 6, region of interest 4, sequence variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q49A92-F1	57.20	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 86 (showing top): EVI1_05, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, ACTTTAT_MIR1425P, MODULE_48, MODULE_95, MODULE_455, chr8q13, TGGAAA_NFAT_Q4_01, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MEISSNER_NPC_HCP_WITH_H3K4ME2, MODULE_163, HMGA1_TARGET_GENES, ZIM3_TARGET_GENES, MIR153_5P, MIR607

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C8orf34	TEX55	Q96M34	506
C8orf34	C19orf18	Q8NEA5	447
C8orf34	EFCAB10	A6NFE3	430
C8orf34	OR1E2	P47887	419
C8orf34	ANKUB1	A6NFN9	419
C8orf34	ZNF562	Q6V9R5	380
C8orf34	MINDY4B	A8MYZ0	380
C8orf34	BAIAP2L1	Q9UHR4	365
C8orf34	OR1E1	P30953	359
C8orf34	SPATA31G1	Q5VYM1	358
C8orf34	DNAJC5B	Q9UF47	355
C8orf34	BPNT2	Q9NX62	353
C8orf34	CATIP	Q7Z7H3	349
C8orf34	ROPN1B	Q9BZX4	348
C8orf34	CCDC47	Q96A33	343

IntAct

6 interactions, top by confidence:

A	B	Type	Score
ASB7	POLR3A	psi-mi:“MI:0914”(association)	0.530
C8orf34	CNDP2	psi-mi:“MI:0915”(physical association)	0.400
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (18): C8orf34 (Two-hybrid), C8orf34 (Two-hybrid), C8orf34 (Two-hybrid), ASB7 (Affinity Capture-MS), C8orf34 (Affinity Capture-MS), CNDP2 (Affinity Capture-MS), C8orf34 (Two-hybrid), C8orf34 (Two-hybrid), ZNF319 (Two-hybrid), TCEANC (Two-hybrid), MCRS1 (Two-hybrid), ZNF655 (Two-hybrid), UTP14C (Two-hybrid), C8orf34 (Affinity Capture-MS), C8orf34 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GV85, A0A1L8HTT5, A2ALI5, A2BDC9, A4IFM1, A7YWL5, B0BN13, B5X1Q3, B5X216, B6ZI38, O35181, O60279, P07141, P09603, P0C7U0, P20934, P28906, P56975, Q0IIY7, Q1XFL1, Q28270, Q2T9L4, Q3UH99, Q3USH1, Q498S6, Q49A92, Q4V9H3, Q4W8E7, Q5JTD0, Q5U2P6, Q64314, Q68DK7, Q69ZB8, Q6P1B3, Q6PDM1, Q6ZSJ9, Q7TSX9, Q8C6Z1, Q8C8T7, Q8CAE9

Diamond homologs: A3KP40, Q49A92, Q8BZJ8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	6
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
57153	GRCh38/hg38 8q13.2-13.3(chr8:68488015-71476177)x1	Pathogenic

SpliceAI

4969 predictions. Top by Δscore:

Variant	Effect	Δscore
8:68439490:T:TA	acceptor_gain	1.0000
8:68439496:CA:C	acceptor_loss	1.0000
8:68439497:A:AC	acceptor_loss	1.0000
8:68439497:A:AG	acceptor_gain	1.0000
8:68439497:AG:A	acceptor_gain	1.0000
8:68439498:G:GT	acceptor_gain	1.0000
8:68439498:GG:G	acceptor_gain	1.0000
8:68439498:GGA:G	acceptor_gain	1.0000
8:68439498:GGAA:G	acceptor_gain	1.0000
8:68439498:GGAAT:G	acceptor_gain	1.0000
8:68439643:TCAGG:T	donor_loss	1.0000
8:68439645:AGG:A	donor_loss	1.0000
8:68439647:G:GC	donor_loss	1.0000
8:68446461:G:GG	donor_gain	1.0000
8:68446466:G:GT	donor_gain	1.0000
8:68468689:T:G	acceptor_gain	1.0000
8:68468818:GAA:G	donor_gain	1.0000
8:68468821:G:GG	donor_gain	1.0000
8:68521938:A:T	donor_gain	1.0000
8:68521967:GGAAG:G	donor_gain	1.0000
8:68521968:G:GT	donor_gain	1.0000
8:68521969:A:T	donor_gain	1.0000
8:68530651:C:G	donor_gain	1.0000
8:68530680:G:GG	donor_gain	1.0000
8:68532981:A:AG	acceptor_gain	1.0000
8:68532982:G:GT	acceptor_gain	1.0000
8:68532982:GC:G	acceptor_gain	1.0000
8:68532982:GCT:G	acceptor_gain	1.0000
8:68532982:GCTT:G	acceptor_gain	1.0000
8:68532982:GCTTA:G	acceptor_gain	1.0000

AlphaMissense

3510 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:68439551:T:C	L127P	1.000
8:68439515:T:C	L115S	0.999
8:68439551:T:A	L127H	0.999
8:68439551:T:G	L127R	0.999
8:68439563:T:C	L131P	0.999
8:68640495:T:C	C409R	0.999
8:68640497:T:G	C409W	0.999
8:68640504:T:C	C412R	0.999
8:68331308:T:C	L99P	0.998
8:68331334:T:C	F108L	0.998
8:68331335:T:G	F108C	0.998
8:68331336:T:A	F108L	0.998
8:68331336:T:G	F108L	0.998
8:68439506:T:C	M112T	0.998
8:68439507:G:A	M112I	0.998
8:68439507:G:C	M112I	0.998
8:68439507:G:T	M112I	0.998
8:68439539:C:A	P123Q	0.998
8:68439563:T:A	L131H	0.998
8:68533037:G:C	K331N	0.998
8:68533037:G:T	K331N	0.998
8:68533045:T:C	L334P	0.998
8:68640391:T:C	L374S	0.998
8:68640487:T:C	L406P	0.998
8:68640493:T:A	I408N	0.998
8:68640493:T:C	I408T	0.998
8:68640493:T:G	I408S	0.998
8:68640496:G:A	C409Y	0.998
8:68640504:T:A	C412S	0.998
8:68640505:G:C	C412S	0.998

dbSNP variants (sampled 300 via entrez): RS1000005405 (8:68737926 C>G), RS1000006597 (8:68696560 A>G,T), RS1000015831 (8:68803265 T>C), RS1000016777 (8:68718987 A>G), RS1000026863 (8:68345682 C>T), RS1000036538 (8:68738331 C>A,T), RS1000044233 (8:68687247 A>G), RS1000045166 (8:68816764 T>G), RS1000055282 (8:68733980 T>C), RS1000055548 (8:68744755 T>G), RS1000056931 (8:68425682 A>G), RS1000057827 (8:68649178 C>A,T), RS1000061406 (8:68480701 C>G,T), RS1000063925 (8:68402985 T>C), RS1000067515 (8:68514765 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

13 associations (top):

Study	Trait	p-value
GCST001144_6	Dupuytren’s disease	2.000000e-13
GCST001558_1	Response to irinotecan in non-small-cell lung cancer	9.000000e-06
GCST001762_450	Obesity-related traits	3.000000e-07
GCST001762_482	Obesity-related traits	5.000000e-06
GCST002932_19	Manganese levels	9.000000e-06
GCST008156_44	Hip circumference adjusted for BMI	1.000000e-06
GCST010170_6	Neonatal total 25-hydroxyvitamin D levels (maternal genetic effect)	3.000000e-06
GCST010867_68	Coronary artery disease	2.000000e-08
GCST011743_77	HDL cholesterol levels in HIV infection	7.000000e-06
GCST90020025_1010	Waist-to-hip ratio adjusted for BMI	4.000000e-08
GCST90020026_615	Hip index	3.000000e-08
GCST90020026_616	Hip index	5.000000e-09
GCST90020027_1367	Waist-hip index	3.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture
EFO:0004736	aspartate aminotransferase measurement
EFO:0005116	urinary metabolite measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0005939	parental genotype effect measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1517114	Toxicity	3	irinotecan	Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1517114	C8orf34	3	0.00	1	irinotecan

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	6
bisphenol A	decreases methylation, affects cotreatment, increases expression	2
trichostatin A	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
benzo(e)pyrene	increases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	increases expression, affects cotreatment	1
Malathion	decreases expression	1
Methapyrilene	increases methylation	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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