C3orf49

Summary

C3orf49 (chromosome 3 open reading frame 49, HGNC:25190) is a protein-coding gene on chromosome 3p14.1, encoding Putative uncharacterized protein C3orf49 (Q96BT1). It is a selective cancer dependency (DepMap: 13.7% of cell lines).

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 13.7% of screened cell lines
• MANE Select transcript: NM_001355236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25190
Approved symbol	C3orf49
Name	chromosome 3 open reading frame 49
Location	3p14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163632
Ensembl biotype	protein_coding
Entrez	132200

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000295896, ENST00000491896, ENST00000647022, ENST00000673037

RefSeq mRNA: 1 — MANE Select: NM_001355236 NM_001355236

CCDS: CCDS87102

Canonical transcript exons

ENST00000295896 — 7 exons

Exon	Start	End
ENSE00001076786	63831680	63831844
ENSE00001125434	63823250	63823569
ENSE00001366230	63845023	63845082
ENSE00001533812	63848364	63848636
ENSE00003667395	63831110	63831223
ENSE00003678219	63827601	63827725
ENSE00003889690	63819299	63819596

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 80.61.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0561 / max 99.9489, expressed in 2 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37143	0.0251	1
37142	0.0197	2
37141	0.0114	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.61	gold quality
secondary oocyte	CL:0000655	73.05	silver quality
prefrontal cortex	UBERON:0000451	66.59	gold quality
cerebellar hemisphere	UBERON:0002245	65.04	gold quality
cerebellar cortex	UBERON:0002129	65.03	gold quality
oocyte	CL:0000023	64.86	gold quality
superficial temporal artery	UBERON:0001614	64.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	64.00	gold quality
cerebellum	UBERON:0002037	63.70	gold quality
Brodmann (1909) area 9	UBERON:0013540	63.12	gold quality
calcaneal tendon	UBERON:0003701	63.03	gold quality
muscle of leg	UBERON:0001383	62.28	gold quality
gastrocnemius	UBERON:0001388	62.26	gold quality
sperm	CL:0000019	61.59	silver quality
frontal cortex	UBERON:0001870	59.84	gold quality
adrenal tissue	UBERON:0018303	59.78	gold quality
neocortex	UBERON:0001950	59.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	58.87	gold quality
right frontal lobe	UBERON:0002810	58.54	gold quality
anterior cingulate cortex	UBERON:0009835	58.36	gold quality
primary visual cortex	UBERON:0002436	58.13	gold quality
smooth muscle tissue	UBERON:0001135	57.68	gold quality
esophagus squamous epithelium	UBERON:0006920	57.68	gold quality
corpus callosum	UBERON:0002336	56.98	gold quality
epithelium of nasopharynx	UBERON:0001951	56.95	gold quality
vena cava	UBERON:0004087	56.85	gold quality
occipital lobe	UBERON:0002021	56.81	gold quality
gingival epithelium	UBERON:0001949	56.68	gold quality
skin of hip	UBERON:0001554	55.91	gold quality
descending thoracic aorta	UBERON:0002345	55.90	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.68

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 13.7% of screened cell lines.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gm11100	ENSMUSG00000079357
rattus_norvegicus	C15h3orf49	ENSRNOG00000027633
drosophila_melanogaster	CG11929	FBGN0031620

Protein

Protein identifiers

Putative uncharacterized protein C3orf49 — Q96BT1 (reviewed: Q96BT1)

All UniProt accessions (4): Q96BT1, A0A2R8Y7G4, A0A2R8YD18, A0A5F9ZI70

RefSeq proteins (1): NP_001342165* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR055322	C3orf49-like	Family

UniProt features (2 total): chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BT1-F1	61.01	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, CCANNAGRKGGC_UNKNOWN, chr3p14, TGGAAA_NFAT_Q4_01, SOX10_TARGET_GENES, HBZ_TARGET_GENES, MXD1_TARGET_GENES, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_0.5H_ACT_CD4_TCELL_DN, RYCACNNRNNRNCAG_UNKNOWN, GSE40666_UNTREATED_VS_IFNA_STIM_EFFECTOR_CD8_TCELL_90MIN_UP, GSE20727_DNFB_ALLERGEN_VS_ROS_INH_AND_DNFB_ALLERGEN_TREATED_DC_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

48 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C3orf49	ZNF823	P16415	521
C3orf49	THOC7	Q6I9Y2	433
C3orf49	MT1F	P04733	305
C3orf49	NRGN	Q92686	287
C3orf49	ENPP1	P22413	227
C3orf49	NDNF	Q8TB73	178
C3orf49	COL2A1	P02458	167
C3orf49	EPYC	Q99645	165
C3orf49	SPRR2A	P35326	159
C3orf49	SPRR3	Q9UBC9	159
C3orf49	S100A2	P29034	153
C3orf49	FARP2	O94887	0
C3orf49	A0A0A6YYI9	A0A0A6YYI9	0
C3orf49	CENPB	P07199	0
C3orf49	UBTF	P17480	0
C3orf49	BPTF	Q12830	0
C3orf49	STX3	Q13277	0
C3orf49	DPYSL3	Q14195	0

IntAct

3 interactions, top by confidence:

A	B	Type	Score
C3orf49	DPYSL3	psi-mi:“MI:0915”(physical association)	0.400
C3orf49	FARP2	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A1B0GUA6, A2AHC3, A2APA5, A2ARZ3, A3KP40, A5WUN7, A6H5Y1, D3Z8E6, D3ZJ47, D4AEC2, E9Q309, F5H4B4, O60303, Q08AD1, Q0P5X5, Q32LN6, Q3KQW7, Q3TCJ8, Q3V036, Q3ZAV0, Q4R815, Q5CZC0, Q5JX69, Q5T5Y3, Q5VT06, Q60664, Q66H35, Q6IRN6, Q6ZVD7, Q7PCK7, Q8BZJ8, Q8C4J0, Q8C636, Q8CB14, Q8CCG1, Q8IYD9, Q8K3V7, Q8R2H7, Q8WWI1, Q96BT1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1958 predictions. Top by Δscore:

Variant	Effect	Δscore
3:63819582:G:GT	donor_gain	1.0000
3:63819583:A:T	donor_gain	1.0000
3:63819593:AAAG:A	donor_loss	1.0000
3:63819595:AGGT:A	donor_loss	1.0000
3:63819596:GGT:G	donor_loss	1.0000
3:63819598:T:G	donor_loss	1.0000
3:63827596:T:A	acceptor_gain	1.0000
3:63831203:G:GG	donor_gain	1.0000
3:63831754:GT:G	donor_gain	1.0000
3:63831826:G:GT	donor_gain	1.0000
3:63831826:G:T	donor_gain	1.0000
3:63834200:C:CC	acceptor_gain	1.0000
3:63835152:A:AC	donor_gain	1.0000
3:63835152:ACTTT:A	donor_gain	1.0000
3:63835153:C:CC	donor_gain	1.0000
3:63835153:CTTTC:C	donor_gain	1.0000
3:63835156:T:A	donor_gain	1.0000
3:63835220:CCAG:C	acceptor_gain	1.0000
3:63835221:CAG:C	acceptor_gain	1.0000
3:63835221:CAGC:C	acceptor_gain	1.0000
3:63835222:AGC:A	acceptor_loss	1.0000
3:63835224:C:CC	acceptor_gain	1.0000
3:63835225:T:A	acceptor_loss	1.0000
3:63835226:G:C	acceptor_gain	1.0000
3:63835226:G:GC	acceptor_gain	1.0000
3:63835229:T:TC	acceptor_gain	1.0000
3:63835328:T:C	donor_gain	1.0000
3:63835388:TCCC:T	acceptor_loss	1.0000
3:63835389:CC:C	acceptor_gain	1.0000
3:63835390:CC:C	acceptor_gain	1.0000

AlphaMissense

1911 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:63831690:T:C	L232P	0.973
3:63831747:T:C	L251P	0.972
3:63831797:T:C	F268L	0.969
3:63831799:C:A	F268L	0.969
3:63831799:C:G	F268L	0.969
3:63831723:T:C	L243P	0.962
3:63831736:A:C	R247S	0.958
3:63831736:A:T	R247S	0.958
3:63831780:T:C	L262P	0.952
3:63831740:G:C	A249P	0.950
3:63831798:T:C	F268S	0.949
3:63831713:T:C	S240P	0.948
3:63831777:T:C	I261T	0.948
3:63831767:G:T	G258W	0.943
3:63831213:T:C	L225P	0.935
3:63831767:G:A	G258R	0.934
3:63831767:G:C	G258R	0.934
3:63831777:T:G	I261S	0.934
3:63823251:T:A	W43R	0.926
3:63823251:T:C	W43R	0.926
3:63831793:A:C	K266N	0.921
3:63831793:A:T	K266N	0.921
3:63831755:T:C	C254R	0.917
3:63831714:C:T	S240F	0.916
3:63831768:G:A	G258E	0.914
3:63831768:G:T	G258V	0.914
3:63831798:T:G	F268C	0.908
3:63831726:T:C	L244P	0.906
3:63831788:T:C	S265P	0.905
3:63831789:C:T	S265F	0.897

dbSNP variants (sampled 300 via entrez): RS1000074512 (3:63835748 A>C), RS1000096696 (3:63806162 T>G), RS1000120340 (3:63848844 T>C), RS1000126641 (3:63836040 T>G), RS1000161965 (3:63830783 TCTTA>T), RS1000183844 (3:63822255 G>A,C), RS1000207184 (3:63779517 A>G,T), RS1000234474 (3:63831006 A>C,G), RS1000291921 (3:63783341 C>T), RS1000374389 (3:63843151 C>T), RS1000387014 (3:63824381 C>T), RS1000387201 (3:63815529 G>A), RS1000400993 (3:63783726 A>G,T), RS1000487293 (3:63807871 A>C,G), RS1000630319 (3:63844028 G>A)

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

10 associations (top):

Study	Trait	p-value
GCST002539_49	Schizophrenia	1.000000e-08
GCST006803_106	Schizophrenia	1.000000e-10
GCST008595_34	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-08
GCST010698_66	Subcortical volume (min-P)	1.000000e-16
GCST010699_21	Brain morphology (min-P)	9.000000e-10
GCST010701_75	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_127	Subcortical volume (MOSTest)	4.000000e-09
GCST010703_71	Brain morphology (MOSTest)	3.000000e-08
GCST90002398_124	Neutrophil count	2.000000e-09
GCST90002407_49	White blood cell count	5.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004346	neuroimaging measurement
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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