C2orf81

Summary

C2orf81 (chromosome 2 open reading frame 81, HGNC:34350) is a protein-coding gene on chromosome 2p13.1, encoding Uncharacterized protein C2orf81 (A6NN90). It is a selective cancer dependency (DepMap: 16.9% of cell lines).

Predicted to be involved in regulation of DNA-templated transcription. Predicted to be located in nucleus.

Source: NCBI Gene 388963 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 5 total
• Cancer dependency (DepMap): dependent in 16.9% of screened cell lines
• MANE Select transcript: NM_001316764

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34350
Approved symbol	C2orf81
Name	chromosome 2 open reading frame 81
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	LOC388963, hCG40743
Ensembl gene	ENSG00000284308
Ensembl biotype	protein_coding
Entrez	388963

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000290390, ENST00000612891, ENST00000638555, ENST00000640331, ENST00000640371, ENST00000640868, ENST00000684111

RefSeq mRNA: 4 — MANE Select: NM_001316764 NM_001145054, NM_001316764, NM_001316765, NM_001316766

CCDS: CCDS86853, CCDS92782

Canonical transcript exons

ENST00000684111 — 3 exons

Exon	Start	End
ENSE00001474483	74416011	74416241
ENSE00003917703	74421543	74421619
ENSE00003919675	74414177	74415927

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 95.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.9172 / max 133.3829, expressed in 1501 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29191	3.3845	803
29194	3.1212	1073
29192	0.3292	196
29193	0.0824	34

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	95.91	gold quality
cerebellar vermis	UBERON:0004720	95.73	gold quality
quadriceps femoris	UBERON:0001377	94.05	gold quality
thymus	UBERON:0002370	91.89	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	85.67	gold quality
right testis	UBERON:0004534	84.66	gold quality
left testis	UBERON:0004533	84.65	gold quality
testis	UBERON:0000473	84.11	gold quality
pituitary gland	UBERON:0000007	83.66	gold quality
adenohypophysis	UBERON:0002196	82.90	gold quality
fallopian tube	UBERON:0003889	79.39	gold quality
ventricular zone	UBERON:0003053	73.82	gold quality
endocervix	UBERON:0000458	72.90	gold quality
stromal cell of endometrium	CL:0002255	72.58	gold quality
granulocyte	CL:0000094	72.15	gold quality
body of uterus	UBERON:0009853	72.10	gold quality
Ammon’s horn	UBERON:0001954	72.00	gold quality
myometrium	UBERON:0001296	71.87	gold quality
temporal lobe	UBERON:0001871	71.82	gold quality
amygdala	UBERON:0001876	71.80	gold quality
hypothalamus	UBERON:0001898	71.61	gold quality
metanephros cortex	UBERON:0010533	71.57	gold quality
apex of heart	UBERON:0002098	71.46	gold quality
caudate nucleus	UBERON:0001873	71.37	gold quality
right frontal lobe	UBERON:0002810	70.83	gold quality
nucleus accumbens	UBERON:0001882	70.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.54	gold quality
prefrontal cortex	UBERON:0000451	70.44	gold quality
brain	UBERON:0000955	70.38	gold quality
frontal cortex	UBERON:0001870	70.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting C2orf81, 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-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-4794	96.47	65.53	1063
HSA-MIR-664A-5P	95.84	64.93	949

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.9% of screened cell lines.

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	1700003E16Rik	ENSMUSG00000030030

Protein

Protein identifiers

Uncharacterized protein C2orf81 — A6NN90 (reviewed: A6NN90)

All UniProt accessions (7): A6NN90, A0A1W2PPJ4, A0A1W2PQG2, A0A1W2PRV2, A0A1W2PSA2, A0A804HJ35, G3XAA6

RefSeq proteins (4): NP_001138526, NP_001303693, NP_001303694, NP_001303695 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028042	DUF4639	Family

Pfam: PF15479

UniProt features (9 total): region of interest 5, compositionally biased region 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NN90-F1	51.42	0.09

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 242

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 10 (showing top): DODD_NASOPHARYNGEAL_CARCINOMA_DN, chr2p13, GSE13485_CTRL_VS_DAY1_YF17D_VACCINE_PBMC_DN, GAO_ESOPHAGUS_25W_C1_CILIATED_EPITHELIAL_CELLS, TRAVAGLINI_LUNG_CILIATED_CELL, TRAVAGLINI_LUNG_PROXIMAL_CILIATED_CELL, GSE19825_NAIVE_VS_DAY3_EFF_CD8_TCELL_UP, GSE5679_CTRL_VS_RARA_AGONIST_AM580_TREATED_DC_UP, GSE21546_WT_VS_SAP1A_KO_DP_THYMOCYTES_DN, GSE21927_SPLENIC_VS_TUMOR_MONOCYTES_FROM_C26GM_TUMOROUS_MICE_BALBC_UP

GO Biological Process (1): regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (0):

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2841 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C2orf81	CCDC154	A6NI56	644
C2orf81	STMP1	E0CX11	620
C2orf81	IQCN	Q9H0B3	606
C2orf81	CCDC142	Q17RM4	592
C2orf81	GOLGA6L7	A0A1B0GV03	571
C2orf81	JAKMIP3	Q5VZ66	530
C2orf81	OR5J2	Q8NH18	479
C2orf81	VWA5B2	Q8N398	477
C2orf81	TTC31	Q49AM3	476
C2orf81	MYO3B	Q8WXR4	463
C2orf81	WDR54	Q9H977	447
C2orf81	ELOA2	Q8IYF1	447
C2orf81	ZNF658	Q5TYW1	433
C2orf81	RHBDF1	Q96CC6	430
C2orf81	DQX1	Q8TE96	428

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A096LP49, A2A7Y5, A2VE02, A5D7I0, A6NE82, A6NJB7, A6NN90, A8NIX5, B1ASB6, Q05AH6, Q0P5M0, Q149B8, Q2KIS6, Q2NL68, Q3SY00, Q3TQ03, Q4R736, Q5JXC2, Q5M844, Q5RCJ6, Q5RCQ2, Q5VZ46, Q5XIK6, Q66JV7, Q6AXP4, Q6NS69, Q6PAC4, Q6ZMY3, Q76N32, Q7TN08, Q7Z572, Q7Z591, Q80TS7, Q80VW7, Q80X53, Q86Y26, Q8BHP2, Q8BZW2, Q8C0D9, Q8C5V8

Diamond homologs: A6NN90, A8NIX5, Q6AXP4, Q9DAQ4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

244 predictions. Top by Δscore:

Variant	Effect	Δscore
2:74415924:TGCA:T	acceptor_gain	1.0000
2:74415928:C:CC	acceptor_gain	1.0000
2:74416237:TGCCT:T	acceptor_gain	1.0000
2:74416238:GCCT:G	acceptor_gain	1.0000
2:74416239:CCTC:C	acceptor_gain	1.0000
2:74416240:CT:C	acceptor_gain	1.0000
2:74416241:TC:T	acceptor_loss	1.0000
2:74416242:C:CC	acceptor_gain	1.0000
2:74415926:CA:C	acceptor_gain	0.9900
2:74416010:CCTG:C	donor_gain	0.9900
2:74416244:G:C	acceptor_gain	0.9900
2:74416244:G:GC	acceptor_gain	0.9900
2:74416251:C:CT	acceptor_gain	0.9900
2:74416252:A:T	acceptor_gain	0.9800
2:74416238:GCCTC:G	acceptor_gain	0.9700
2:74416239:CCTCT:C	acceptor_gain	0.9700
2:74416240:CTCT:C	acceptor_gain	0.9700
2:74416005:GCCCA:G	donor_loss	0.9500
2:74416006:CCCAC:C	donor_loss	0.9500
2:74416007:CCACC:C	donor_loss	0.9500
2:74416008:CA:C	donor_loss	0.9500
2:74416009:ACC:A	donor_loss	0.9500
2:74416011:C:G	donor_loss	0.9500
2:74416242:CTGT:C	acceptor_gain	0.9500
2:74415927:AC:A	acceptor_loss	0.9400
2:74415928:C:CA	acceptor_loss	0.9400
2:74415929:T:G	acceptor_loss	0.9400
2:74416243:T:A	acceptor_gain	0.9400
2:74415923:ATGCA:A	acceptor_gain	0.9300
2:74415930:G:C	acceptor_loss	0.9300

AlphaMissense

3916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:74415865:G:C	F101L	0.993
2:74415865:G:T	F101L	0.993
2:74415867:A:G	F101L	0.993
2:74415916:G:C	F84L	0.989
2:74415916:G:T	F84L	0.989
2:74415918:A:G	F84L	0.989
2:74415777:A:G	W131R	0.988
2:74415777:A:T	W131R	0.988
2:74415775:C:A	W131C	0.987
2:74415775:C:G	W131C	0.987
2:74415873:A:G	W99R	0.986
2:74415873:A:T	W99R	0.986
2:74415817:C:A	W117C	0.982
2:74415817:C:G	W117C	0.982
2:74415819:A:G	W117R	0.982
2:74415819:A:T	W117R	0.982
2:74416121:A:G	W44R	0.981
2:74416121:A:T	W44R	0.981
2:74415866:A:G	F101S	0.980
2:74415894:C:G	A92P	0.978
2:74416197:C:A	K18N	0.969
2:74416197:C:G	K18N	0.969
2:74415903:C:G	A89P	0.966
2:74416119:C:A	W44C	0.965
2:74416119:C:G	W44C	0.965
2:74415871:C:A	W99C	0.961
2:74415871:C:G	W99C	0.961
2:74415917:A:G	F84S	0.958
2:74415768:C:G	G134R	0.956
2:74415783:C:G	D129H	0.952

dbSNP variants (sampled 300 via entrez): RS1000002846 (2:74415088 G>A,T), RS1000603634 (2:74416706 T>C), RS1000909908 (2:74419041 C>A), RS1002221556 (2:74419107 G>C), RS1002510898 (2:74420131 C>A), RS1002573971 (2:74418726 T>C), RS1002607428 (2:74421694 G>C), RS1003403291 (2:74414842 G>A,C), RS1003455696 (2:74414531 A>G), RS1003660238 (2:74422741 C>A,T), RS1003885818 (2:74414815 G>A,T), RS1003937984 (2:74415124 C>T), RS1004461004 (2:74421633 G>A,C,T), RS1004470860 (2:74421397 G>A,T), RS1004471688 (2:74421163 T>C)

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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	increases expression	1
ferrous chloride	decreases expression	1
abrine	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Endosulfan	decreases expression	1
Rotenone	decreases expression	1
Smoke	increases abundance, increases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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