C19orf84

Summary

C19orf84 (chromosome 19 open reading frame 84, HGNC:27112) is a protein-coding gene on chromosome 19q13.41, encoding piRNA-mediated silencing protein C19orf84 (I3L1E1). Protein adapter involved in piRNA-directed transposon methylation by connecting PIWIL4-piRNA and DNA methylation machineries.

Predicted to be involved in transposable element silencing by piRNA-mediated DNA methylation. Predicted to be located in nucleoplasm.

Source: NCBI Gene 147646 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001193623

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27112
Approved symbol	C19orf84
Name	chromosome 19 open reading frame 84
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000262874
Ensembl biotype	protein_coding
Entrez	147646

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000570516, ENST00000574814

RefSeq mRNA: 1 — MANE Select: NM_001193623 NM_001193623

CCDS: CCDS58676

Canonical transcript exons

ENST00000574814 — 2 exons

Exon	Start	End
ENSE00002661880	51388289	51389509
ENSE00002669126	51390478	51390591

Expression profiles

Bgee: expression breadth broad, 71 present calls, max score 92.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5251 / max 65.4073, expressed in 166 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182404	0.2985	131
182405	0.1898	83
182403	0.0197	8
182406	0.0171	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.57	gold quality
cardia of stomach	UBERON:0001162	86.63	silver quality
right testis	UBERON:0004534	85.44	gold quality
left testis	UBERON:0004533	84.96	gold quality
testis	UBERON:0000473	83.37	gold quality
epithelium of nasopharynx	UBERON:0001951	81.15	gold quality
vena cava	UBERON:0004087	79.23	gold quality
superficial temporal artery	UBERON:0001614	78.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	77.99	gold quality
inferior vagus X ganglion	UBERON:0005363	77.95	gold quality
body of tongue	UBERON:0011876	77.84	gold quality
saphenous vein	UBERON:0007318	77.41	gold quality
pericardium	UBERON:0002407	77.20	gold quality
pharyngeal mucosa	UBERON:0000355	77.04	gold quality
pons	UBERON:0000988	76.75	gold quality
nipple	UBERON:0002030	76.70	gold quality
substantia nigra pars compacta	UBERON:0001965	76.65	gold quality
trachea	UBERON:0003126	76.61	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.93	gold quality
thymus	UBERON:0002370	75.73	gold quality
renal medulla	UBERON:0000362	75.61	gold quality
pylorus	UBERON:0001166	75.08	gold quality
cerebellar vermis	UBERON:0004720	75.04	gold quality
synovial joint	UBERON:0002217	74.69	gold quality
layer of synovial tissue	UBERON:0007616	73.20	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	73.13	gold quality
mammary duct	UBERON:0001765	72.56	gold quality
penis	UBERON:0000989	72.43	gold quality
urethra	UBERON:0000057	70.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

77 targeting C19orf84, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7G-5P	99.98	72.37	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6766-5P	99.68	67.70	2325

Literature-anchored findings (GeneRIF, showing 1)

• C19ORF84 connects piRNA and DNA methylation machineries to defend the mammalian germ line. (PMID:38359823)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gm38999	ENSMUSG00000118553
rattus_norvegicus	C1h19orf84	ENSRNOG00000068198

Protein

Protein identifiers

piRNA-mediated silencing protein C19orf84 — I3L1E1 (reviewed: I3L1E1)

All UniProt accessions (2): I3L1E1, K7EN44

UniProt curated annotations — full annotation on UniProt →

Function. Protein adapter involved in piRNA-directed transposon methylation by connecting PIWIL4-piRNA and DNA methylation machineries. The PIWIL4-piRNA pathway plays a central role during spermatogenesis by directing transposon DNA methylation and silencing, thereby preventing their mobilization, which is essential for the germline integrity.

Subunit / interactions. Interacts with SPOCD1.

Subcellular location. Nucleus. Nucleoplasm.

RefSeq proteins (1): NP_001180552* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR040606	C19orf84	Family

Pfam: PF17703

UniProt features (7 total): compositionally biased region 4, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-I3L1E1-F1	58.32	0.00

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)

MSigDB gene sets: 38 (showing top): GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOBP_TRANSPOSITION, REACTOME_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, NCOA2_TARGET_GENES, MIR6825_5P, MIR6780B_5P, MIR4725_3P, MIR4441, MIR4271, MIR4270, MIR6716_5P

GO Biological Process (2): transposable element silencing by piRNA-mediated DNA methylation (GO:0141196), transposable element silencing (GO:0010526)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): nucleoplasm (GO:0005654), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of endogenous retroelements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transposable element silencing by heterochromatin formation	1
gene silencing by piRNA-directed DNA methylation	1
negative regulation of gene expression	1
retrotransposition	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0U1RRK4, A0A1W2PPE3, A0A1W2PR82, A0A2R8Y2Y2, A0A494C0N9, A0A494C0Y3, A0JNN8, A6NF83, A6NHQ4, A6QPM6, A8E4L3, A8MTW9, B2KGE5, C9JVW0, I3L1E1, O43541, O75474, O75638, P0C7X2, P70339, P89439, Q02080, Q05215, Q12950, Q3SYB3, Q5T230, Q5VV16, Q6NZ36, Q6NZY7, Q6P1X6, Q6VB84, Q6VUC0, Q6VUP9, Q6ZSJ8, Q7RTU5, Q7TNS8, Q80WY3, Q86SI9, Q86UU5, Q8K025

Diamond homologs: H3BKT1, I3L1E1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

158 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51390496:T:TA	donor_gain	0.9900
19:51390476:AC:A	donor_gain	0.9800
19:51390477:CC:C	donor_gain	0.9800
19:51389506:GTTCC:G	acceptor_loss	0.9700
19:51389507:TTCCT:T	acceptor_loss	0.9700
19:51389508:TCC:T	acceptor_loss	0.9700
19:51389509:CCTA:C	acceptor_loss	0.9700
19:51389510:C:CC	acceptor_gain	0.9700
19:51389510:CTAGA:C	acceptor_loss	0.9700
19:51389511:T:A	acceptor_loss	0.9700
19:51390532:CGTAT:C	donor_gain	0.9700
19:51390536:T:C	donor_gain	0.9700
19:51389505:TGTTC:T	acceptor_gain	0.9600
19:51390531:A:AC	donor_gain	0.9600
19:51390532:C:CC	donor_gain	0.9600
19:51389508:TC:T	acceptor_gain	0.9500
19:51389509:CC:C	acceptor_gain	0.9500
19:51389507:TTC:T	acceptor_gain	0.8900
19:51390471:GTCTC:G	donor_loss	0.8900
19:51390472:TCTCA:T	donor_loss	0.8900
19:51390473:CT:C	donor_loss	0.8900
19:51390474:TCACC:T	donor_loss	0.8900
19:51390475:C:CA	donor_loss	0.8900
19:51390476:A:AA	donor_loss	0.8900
19:51389516:C:CT	acceptor_gain	0.8700
19:51390469:TTGTC:T	donor_loss	0.8700
19:51390470:TGTCT:T	donor_loss	0.8700
19:51389506:GTTC:G	acceptor_gain	0.8500
19:51390476:A:AC	donor_gain	0.8300
19:51390477:C:CC	donor_gain	0.8300

AlphaMissense

1157 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51389360:T:A	D62V	0.986
19:51389369:A:T	I59K	0.982
19:51389354:A:T	L64H	0.974
19:51389333:G:T	A71D	0.971
19:51389369:A:C	I59R	0.971
19:51389360:T:G	D62A	0.967
19:51389361:C:A	D62Y	0.962
19:51389369:A:G	I59T	0.959
19:51389375:A:T	V57E	0.953
19:51389361:C:G	D62H	0.952
19:51389342:A:G	L68P	0.950
19:51389345:A:G	L67P	0.950
19:51388999:C:A	W182C	0.949
19:51388999:C:G	W182C	0.949
19:51389334:C:G	A71P	0.946
19:51389330:A:G	L72P	0.939
19:51389354:A:C	L64R	0.939
19:51389359:G:C	D62E	0.939
19:51389359:G:T	D62E	0.939
19:51389366:C:G	R60P	0.938
19:51389335:G:C	S70R	0.935
19:51389335:G:T	S70R	0.935
19:51389337:T:G	S70R	0.935
19:51389360:T:C	D62G	0.933
19:51389381:A:T	V55D	0.932
19:51389372:G:T	P58H	0.929
19:51389342:A:C	L68R	0.924
19:51389354:A:G	L64P	0.923
19:51389342:A:T	L68Q	0.922
19:51389367:G:T	R60S	0.921

dbSNP variants (sampled 300 via entrez): RS1000110447 (19:51389792 C>T), RS1000505187 (19:51390220 A>C,T), RS1002586608 (19:51388223 C>A,T), RS1004118253 (19:51389385 A>C), RS1004637088 (19:51390458 G>A,C), RS1005069438 (19:51391041 T>C), RS1005533111 (19:51390705 A>G), RS1005629095 (19:51392014 C>A,G,T), RS1006055041 (19:51391846 T>A), RS1006478640 (19:51392247 G>A,T), RS1006818476 (19:51387885 A>G), RS1007945810 (19:51392292 C>A), RS1008545976 (19:51389852 A>G), RS1008828667 (19:51390103 C>G,T), RS1008888987 (19:51388273 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
Fulvestrant	increases methylation	1
Lipopolysaccharides	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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