C3orf38

Summary

C3orf38 (chromosome 3 open reading frame 38, HGNC:28384) is a protein-coding gene on chromosome 3p11.1, encoding Uncharacterized protein C3orf38 (Q5JPI3). May be involved in apoptosis regulation. It is a selective cancer dependency (DepMap: 28.0% of cell lines).

Involved in positive regulation of apoptotic process. Located in nucleus.

Source: NCBI Gene 285237 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 16 total — 2 pathogenic
• Cancer dependency (DepMap): dependent in 28.0% of screened cell lines
• MANE Select transcript: NM_173824

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28384
Approved symbol	C3orf38
Name	chromosome 3 open reading frame 38
Location	3p11.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC26717
Ensembl gene	ENSG00000179021
Ensembl biotype	protein_coding
Entrez	285237

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000318887, ENST00000464919, ENST00000485219, ENST00000486971, ENST00000895149, ENST00000895150

RefSeq mRNA: 1 — MANE Select: NM_173824 NM_173824

CCDS: CCDS2921

Canonical transcript exons

ENST00000318887 — 3 exons

Exon	Start	End
ENSE00001219843	88153230	88153471
ENSE00001219855	88149959	88150185
ENSE00001936859	88156021	88157965

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 97.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6862 / max 528.5169, expressed in 1805 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37461	15.6741	1793
37457	3.7912	1239
37460	2.4336	1347
37459	0.3862	162
37458	0.2588	108
37462	0.1422	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.64	gold quality
sperm	CL:0000019	95.16	gold quality
oocyte	CL:0000023	92.81	gold quality
monocyte	CL:0000576	89.93	gold quality
leukocyte	CL:0000738	89.73	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.16	gold quality
calcaneal tendon	UBERON:0003701	88.92	gold quality
tendon	UBERON:0000043	87.16	gold quality
bone marrow	UBERON:0002371	87.04	gold quality
left testis	UBERON:0004533	86.74	gold quality
testis	UBERON:0000473	86.70	gold quality
right testis	UBERON:0004534	86.55	gold quality
adrenal tissue	UBERON:0018303	86.53	gold quality
ganglionic eminence	UBERON:0004023	86.32	gold quality
bone marrow cell	CL:0002092	86.18	gold quality
ventricular zone	UBERON:0003053	85.75	gold quality
islet of Langerhans	UBERON:0000006	85.47	gold quality
esophagus squamous epithelium	UBERON:0006920	85.02	gold quality
germinal epithelium of ovary	UBERON:0001304	84.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.61	gold quality
jejunal mucosa	UBERON:0000399	84.55	gold quality
amniotic fluid	UBERON:0000173	84.53	gold quality
pancreatic ductal cell	CL:0002079	84.21	silver quality
palpebral conjunctiva	UBERON:0001812	84.18	gold quality
granulocyte	CL:0000094	84.13	gold quality
tendon of biceps brachii	UBERON:0008188	84.13	silver quality
lymph node	UBERON:0000029	84.05	gold quality
smooth muscle tissue	UBERON:0001135	84.01	gold quality
rectum	UBERON:0001052	83.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

112 targeting C3orf38, 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-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 28.0% of screened cell lines.

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	C9H3orf38	ENSDARG00000076798
mus_musculus	4930453N24Rik	ENSMUSG00000059920
rattus_norvegicus	C11h3orf38	ENSRNOG00000000720
rattus_norvegicus	AABR07000292.1	ENSRNOG00000011399
rattus_norvegicus	Cxh3orf38	ENSRNOG00000038965
drosophila_melanogaster	CG13876	FBGN0035109

Protein

Protein identifiers

Uncharacterized protein C3orf38 — Q5JPI3 (reviewed: Q5JPI3)

All UniProt accessions (2): Q5JPI3, E9PFZ1

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in apoptosis regulation.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JPI3-1	1	yes
Q5JPI3-2	2

RefSeq proteins (1): NP_776185* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026698	UPF_C3orf38	Family
IPR032710	NTF2-like_dom_sf	Homologous_superfamily

Pfam: PF15008

UniProt features (4 total): chain 1, splice variant 1, initiator methionine 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JPI3-F1	76.42	0.40

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): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, ZHENG_BOUND_BY_FOXP3, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B, NUYTTEN_NIPP1_TARGETS_DN, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, FIGUEROA_AML_METHYLATION_CLUSTER_6_UP, ALKBH3_TARGET_GENES, DIDO1_TARGET_GENES, E2F2_TARGET_GENES, FEV_TARGET_GENES, HHEX_TARGET_GENES, HMG20B_TARGET_GENES

GO Biological Process (2): apoptotic process (GO:0006915), positive regulation of apoptotic process (GO:0043065)

GO Molecular Function (0):

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C3orf38	ZNF654	Q8IZM8	666
C3orf38	CGGBP1	Q9UFW8	605
C3orf38	THOC3	Q96J01	494
C3orf38	MAP10	Q9P2G4	433
C3orf38	NPM3	O75607	417
C3orf38	NUDT19	A8MXV4	370
C3orf38	C14orf39	Q8N1H7	370
C3orf38	HTR1F	P30939	369
C3orf38	ILRUN	Q9H6K1	368
C3orf38	JSRP1	Q96MG2	366
C3orf38	PIGZ	Q86VD9	365
C3orf38	ARL6IP1	Q15041	364
C3orf38	FHIT	P49789	350
C3orf38	NIT1	Q86X76	350
C3orf38	LRFN4	Q6PJG9	348

IntAct

16 interactions, top by confidence:

A	B	Type	Score
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
DNAJB4	SYNM	psi-mi:“MI:0914”(association)	0.530
BAG4	DNAJC13	psi-mi:“MI:0914”(association)	0.530
HSPA2	DNAJC13	psi-mi:“MI:0914”(association)	0.530
C3orf38	SLC19A3	psi-mi:“MI:0915”(physical association)	0.370
BAG1	PSMD11	psi-mi:“MI:0914”(association)	0.350
HSPA2	HGS	psi-mi:“MI:0914”(association)	0.350
TMEM87A	PC	psi-mi:“MI:0914”(association)	0.350
TCEAL5	C3orf38	psi-mi:“MI:0914”(association)	0.350
HSPA8	SBNO1	psi-mi:“MI:0914”(association)	0.350
BAG2	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
C3orf38	DNAJB5	psi-mi:“MI:0914”(association)	0.350
HSPA8	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
LY86	MAP2K7	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): C3orf38 (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), C3orf38 (Two-hybrid), C3orf38 (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), HSPA1A (Affinity Capture-MS), ALAS1 (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), HSPA2 (Affinity Capture-MS)

ESM2 similar proteins: A0JPF9, A1A5Q7, A2RT67, A2RUS2, A4D126, A5PKL6, A6NCI4, A6QPR9, D4ACE5, E9PYK3, F1ND48, Q05AA6, Q09M05, Q13474, Q15061, Q32PJ3, Q3TTL0, Q3UMR0, Q3UVV9, Q3UY96, Q498D5, Q49MI3, Q4R6Y8, Q4U2V3, Q502W6, Q5F204, Q5JPI3, Q5M8J0, Q5REW9, Q5RL51, Q5XIJ6, Q6DJG6, Q6RI63, Q7TNH6, Q7TPQ3, Q80V94, Q8BSE0, Q8CEL2, Q8IZC4, Q8N392

Diamond homologs: Q0VCL9, Q3TTL0, Q5JPI3, Q66H33

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of HSF1-mediated heat shock response	5	46.4×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	6	32.6×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
155598	GRCh38/hg38 3p12.3-11.1(chr3:74649382-89495681)x1	Pathogenic
57802	GRCh38/hg38 3p12.2-11.1(chr3:82912987-90179222)x1	Pathogenic

SpliceAI

466 predictions. Top by Δscore:

Variant	Effect	Δscore
3:88150182:CAAGG:C	donor_loss	1.0000
3:88150183:AAGGT:A	donor_loss	1.0000
3:88150186:G:C	donor_loss	1.0000
3:88150187:T:G	donor_loss	1.0000
3:88150915:A:G	acceptor_gain	1.0000
3:88153225:TCTA:T	acceptor_loss	1.0000
3:88153226:CTA:C	acceptor_loss	1.0000
3:88153227:TAG:T	acceptor_loss	1.0000
3:88153228:A:AG	acceptor_gain	1.0000
3:88153228:A:AT	acceptor_loss	1.0000
3:88153229:G:GG	acceptor_gain	1.0000
3:88153229:GAT:G	acceptor_gain	1.0000
3:88153468:ACAG:A	donor_gain	1.0000
3:88156015:A:AG	acceptor_gain	1.0000
3:88149962:A:T	donor_gain	0.9900
3:88150186:G:GG	donor_gain	0.9900
3:88150916:G:GG	acceptor_gain	0.9900
3:88153217:A:AG	acceptor_gain	0.9900
3:88153228:A:T	acceptor_gain	0.9900
3:88153228:AGAT:A	acceptor_gain	0.9900
3:88153229:G:T	acceptor_gain	0.9900
3:88153229:GA:G	acceptor_gain	0.9900
3:88153229:GATG:G	acceptor_gain	0.9900
3:88153229:GATGC:G	acceptor_gain	0.9900
3:88153472:G:GG	donor_gain	0.9900
3:88156009:T:TA	acceptor_gain	0.9900
3:88156016:A:G	acceptor_gain	0.9900
3:88156019:A:AG	acceptor_gain	0.9900
3:88156020:G:GC	acceptor_gain	0.9900
3:88156020:GCA:G	acceptor_gain	0.9900

AlphaMissense

2174 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:88156364:T:A	V240D	0.998
3:88156144:T:A	W167R	0.997
3:88156144:T:C	W167R	0.997
3:88153245:T:A	I50K	0.996
3:88156160:T:C	F172S	0.996
3:88156441:T:A	W266R	0.996
3:88156441:T:C	W266R	0.996
3:88156463:T:C	L273P	0.996
3:88153283:C:A	R63S	0.995
3:88156078:T:C	F145L	0.995
3:88156080:C:A	F145L	0.995
3:88156080:C:G	F145L	0.995
3:88153245:T:G	I50R	0.994
3:88156357:G:T	G238W	0.994
3:88156358:G:A	G238E	0.994
3:88156393:T:C	F250L	0.994
3:88156395:T:A	F250L	0.994
3:88156395:T:G	F250L	0.994
3:88153308:T:A	I71K	0.993
3:88156159:T:C	F172L	0.993
3:88156161:C:A	F172L	0.993
3:88156161:C:G	F172L	0.993
3:88156178:T:C	L178P	0.993
3:88156412:T:C	L256P	0.993
3:88153284:G:C	R63P	0.992
3:88153293:T:A	V66D	0.992
3:88156146:G:C	W167C	0.992
3:88156146:G:T	W167C	0.992
3:88153368:T:C	L91P	0.991
3:88156079:T:C	F145S	0.991

dbSNP variants (sampled 300 via entrez): RS1000826514 (3:88149424 G>A,T), RS1001532077 (3:88157523 C>A), RS1001542184 (3:88157884 A>G), RS1002315140 (3:88152590 G>A), RS1002652148 (3:88154207 T>A), RS1002722628 (3:88153835 T>C), RS1004223883 (3:88152579 G>A,T), RS1004340052 (3:88152278 T>C), RS1004562818 (3:88154096 AT>A,ATT), RS1004675893 (3:88153766 G>T), RS1006383497 (3:88154979 C>T), RS1006546930 (3:88149885 T>G), RS1008218735 (3:88151425 T>A), RS1008557382 (3:88153005 T>A,C), RS1009871679 (3:88151319 T>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

11 associations (top):

Study	Trait	p-value
GCST000924_2	Response to acetaminophen (hepatotoxicity)	2.000000e-07
GCST003773_2	Loneliness (multivariate analysis)	7.000000e-06
GCST005149_6	Colorectal cancer	1.000000e-06
GCST007094_110	Diastolic blood pressure	1.000000e-07
GCST007098_49	Diastolic blood pressure	1.000000e-08
GCST007099_5	Systolic blood pressure	4.000000e-06
GCST009723_4	Vertical cup-disc ratio (adjusted for vertical disc diameter)	8.000000e-10
GCST009724_32	Vertical cup-disc ratio (multi-trait analysis)	1.000000e-13
GCST010988_105	Adult body size	6.000000e-10
GCST012053_5	Weight	1.000000e-07
GCST90000047_53	Age at first sexual intercourse	1.000000e-17

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007865	loneliness measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0006939	cup-to-disc ratio measurement
EFO:0004338	body weight
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	7
trichostatin A	affects cotreatment, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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