DPPA3

Summary

DPPA3 (developmental pluripotency associated 3, HGNC:19199) is a protein-coding gene on chromosome 12p13.31, encoding Developmental pluripotency-associated protein 3 (Q6W0C5). Primordial germ cell (PGCs)-specific protein involved in epigenetic chromatin reprogramming in the zygote following fertilization.

This gene encodes a protein that in mice may function as a maternal factor during the preimplantation stage of development. In mice, this gene may play a role in transcriptional repression, cell division, and maintenance of cell pluripotentiality. In humans, related intronless loci are located on chromosomes 14 and X.

Source: NCBI Gene 359787 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 31 total
• MANE Select transcript: NM_199286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19199
Approved symbol	DPPA3
Name	developmental pluripotency associated 3
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	Stella, Pgc7
Ensembl gene	ENSG00000187569
Ensembl biotype	protein_coding
OMIM	608408
Entrez	359787

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000345088, ENST00000934351

RefSeq mRNA: 1 — MANE Select: NM_199286 NM_199286

CCDS: CCDS8582

Canonical transcript exons

ENST00000345088 — 4 exons

Exon	Start	End
ENSE00001379988	7716198	7716239
ENSE00001383367	7711433	7711652
ENSE00001388108	7716967	7717559
ENSE00001391180	7715183	7715427

Expression profiles

Bgee: expression breadth broad, 19 present calls, max score 91.25.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.0942 / max 2988.3179, expressed in 87 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123917	3.9866	82
123918	0.4118	16
206569	0.3667	13
123916	0.2281	10
206568	0.0962	10
206567	0.0049	3

Top tissues by expression

121 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	91.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.85	gold quality
duodenum	UBERON:0002114	45.56	gold quality
granulocyte	CL:0000094	42.39	silver quality
ventricular zone	UBERON:0003053	40.55	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
right testis	UBERON:0004534	36.46	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
leukocyte	CL:0000738	35.85	silver quality
monocyte	CL:0000576	35.83	silver quality
blood	UBERON:0000178	35.69	silver quality
testis	UBERON:0000473	35.68	gold quality
muscle tissue	UBERON:0002385	35.58	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
bone marrow	UBERON:0002371	34.23	gold quality
left testis	UBERON:0004533	33.18	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
liver	UBERON:0002107	30.53	gold quality
right ovary	UBERON:0002118	30.35	gold quality
islet of Langerhans	UBERON:0000006	30.32	silver quality
lymph node	UBERON:0000029	30.30	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
ovary	UBERON:0000992	29.80	gold quality
smooth muscle tissue	UBERON:0001135	29.69	silver quality
prefrontal cortex	UBERON:0000451	29.40	gold quality
placenta	UBERON:0001987	28.75	silver quality
tonsil	UBERON:0002372	28.67	gold quality
left ovary	UBERON:0002119	28.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	262.77
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting DPPA3, 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-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-188-5P	97.89	67.01	756
HSA-MIR-6866-3P	97.38	66.94	748
HSA-MIR-610	96.84	67.98	905
HSA-MIR-3651	95.62	64.67	287
HSA-MIR-4732-5P	90.07	64.77	412

Literature-anchored findings (GeneRIF, showing 12)

• In mice, this gene may play a role in oogenesis and primordial germ cell development. (PMID:11900980)
• In mice, a targeted mutation results in reduced female fertility and may function as a mammalian maternal effect gene. (PMID:14654002)
• In mice, knockout experiments show this gene may be a maternal factor in cleavage stage embryogenesis. (PMID:15018652)
• human adult tissue-specific transcripts originate via retrotransposition of the pluripotent cell-specific gene, Dppa3 (PMID:16291741)
• These results demonstrate that PGC7/Stella is indispensable for the maintenance of methylation involved in epigenetic reprogramming after fertilization. (PMID:17143267)
• a role for STELLA in facilitating germline and endodermal differentiation of human ES cells (PMID:23457636)
• Considering that impaired DNA methylation profiles are associated with various developmental or disease phenomena, Stella may be a powerful tool with which to study the biological effects of global DNA hypomethylation (PMID:25280994)
• Data suggest enforced expression of Stella into normal cells induces not only global DNA demethylation but also neoplastic transformation and increases metastatic ability; these changes involve altered regulation of neoplastic gene expression. (PMID:26608031)
• Super-enhancers at the Nanog locus differentially regulate neighboring pluripotency-associated genes, in particular, DPPA3. (PMID:27681417)
• We conclude that heterogeneous population of the HEK293T cells might be easily shifted towards expression of the pluripotency markers by ectopic expression of the SON factors or by growth in serum depleted media. (PMID:27794480)
• Stella employs a multilayered mechanism to achieve robust UHRF1 inhibition, which involves the dissociation from chromatin and cytoplasmic sequestration of UHRF1. (PMID:31018966)
• Structure of human DPPA3 bound to the UHRF1 PHD finger reveals its functional and structural differences from mouse DPPA3. (PMID:38898124)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dppa3	ENSMUSG00000046323
rattus_norvegicus	Dppa3l1	ENSRNOG00000022376
rattus_norvegicus	Dppa3	ENSRNOG00000022950
rattus_norvegicus	AABR07048770.1	ENSRNOG00000031344
rattus_norvegicus	AABR07015759.1	ENSRNOG00000033640
rattus_norvegicus	LOC120096971	ENSRNOG00000042103
rattus_norvegicus		ENSRNOG00000075403
rattus_norvegicus		ENSRNOG00000079045
rattus_norvegicus		ENSRNOG00000083650
rattus_norvegicus		ENSRNOG00000084024

Protein

Protein identifiers

Developmental pluripotency-associated protein 3 — Q6W0C5 (reviewed: Q6W0C5)

Alternative names: Stella-related protein

All UniProt accessions (1): Q6W0C5

UniProt curated annotations — full annotation on UniProt →

Function. Primordial germ cell (PGCs)-specific protein involved in epigenetic chromatin reprogramming in the zygote following fertilization. In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in protection of DNA methylation in the maternal pronucleus by preventing conversion of 5mC to 5hmC: specifically recognizes and binds histone H3 dimethylated at ‘Lys-9’ (H3K9me2) on maternal genome, and protects maternal genome from TET3-mediated conversion to 5hmC and subsequent DNA demethylation. Does not bind paternal chromatin, which is mainly packed into protamine and does not contain much H3K9me2 mark. Also protects imprinted loci that are marked with H3K9me2 in mature sperm from DNA demethylation in early embryogenesis. May be important for the totipotent/pluripotent states continuing through preimplantation development. Also involved in chromatin condensation in oocytogenesis.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Low expression in testis, ovary and thymus. Expressed in embryonic stem and carcinoma cells. Highly expressed in testicular germ cell tumors.

Domain organisation. Mediates binding to H3K9me2 via N-terminal region, while ability to exclude TET3 from the maternal pronucleus requires the C-terminal part.

RefSeq proteins (1): NP_954980* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029096	Dppa3	Family

Pfam: PF15549

UniProt features (9 total): region of interest 2, sequence conflict 2, helix 2, chain 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8XV8	X-RAY DIFFRACTION	2.05
8XV7	X-RAY DIFFRACTION	2.25
8WMS	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6W0C5-F1	63.46	0.00

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9821002	Chromatin modifications during the maternal to zygotic transition (MZT)

MSigDB gene sets: 47 (showing top): KORKOLA_EMBRYONAL_CARCINOMA_UP, CORRE_MULTIPLE_MYELOMA_UP, CONRAD_GERMLINE_STEM_CELL, YAMAZAKI_TCEB3_TARGETS_DN, GOBP_CHROMATIN_REMODELING, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOCC_PRONUCLEUS, CAMPS_COLON_CANCER_COPY_NUMBER_DN, MATZUK_MATERNAL_EFFECT, KORKOLA_SEMINOMA_UP, MIKKELSEN_ES_ICP_WITH_H3K4ME3, GOCC_FEMALE_PRONUCLEUS, GOCC_MALE_PRONUCLEUS, MIR548G_3P

GO Biological Process (2): epigenetic programing of female pronucleus (GO:0044726), chromatin organization (GO:0006325)

GO Molecular Function (3): histone H3K9me2/3 reader activity (GO:0062072), protein binding (GO:0005515), obsolete methylated histone binding (GO:0035064)

GO Cellular Component (3): female pronucleus (GO:0001939), nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
epigenetic programming in the zygotic pronuclei	1
cellular component organization	1
histone H3 reader activity	1
binding	1
pronucleus	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

758 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPPA3	NANOG	Q9H9S0	807
DPPA3	PRDM1	O75626	802
DPPA3	DPPA5	A6NC42	796
DPPA3	POU5F1	P31359	786
DPPA3	LIN28A	Q9H9Z2	751
DPPA3	ZFP57	Q9NU63	747
DPPA3	LIN28B	Q6ZN17	745
DPPA3	KLF4	P78338	740
DPPA3	SOX2	P48431	738
DPPA3	UTF1	Q5T230	737
DPPA3	DAZL	Q92904	728
DPPA3	PRDM14	Q9GZV8	717
DPPA3	ZFP42	Q96MM3	696
DPPA3	GDF3	Q9NR23	694
DPPA3	UHRF1	Q96T88	675

IntAct

45 interactions, top by confidence:

A	B	Type	Score
DYNLL1	DPPA3	psi-mi:“MI:0915”(physical association)	0.560
KRT76	DPPA3	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG4	DPPA3	psi-mi:“MI:0915”(physical association)	0.560
DPPA3	KRT27	psi-mi:“MI:0915”(physical association)	0.560
DPPA3	DYNLL2	psi-mi:“MI:0915”(physical association)	0.560
	DPPA3	psi-mi:“MI:0915”(physical association)	0.560
ZNF618	DPPA3	psi-mi:“MI:0915”(physical association)	0.560
DPPA3	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
DPPA3	HAUS7	psi-mi:“MI:0915”(physical association)	0.560
DPPA3	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
DEPDC5	DPPA3	psi-mi:“MI:0915”(physical association)	0.560
DPPA3	TRIB3	psi-mi:“MI:0915”(physical association)	0.560
NUP62	DPPA3	psi-mi:“MI:0915”(physical association)	0.560
DPPA3	CFTR	psi-mi:“MI:0915”(physical association)	0.370
DPPA3	TBKBP1	psi-mi:“MI:0914”(association)	0.350
DPPA3	PYGM	psi-mi:“MI:0914”(association)	0.350
DPPA3	DYNLL1	psi-mi:“MI:0915”(physical association)	0.000
DPPA3	KRT76	psi-mi:“MI:0915”(physical association)	0.000
	DPPA3	psi-mi:“MI:0915”(physical association)	0.000
DPPA3	ZNF618	psi-mi:“MI:0915”(physical association)	0.000
DPPA3	TFIP11	psi-mi:“MI:0915”(physical association)	0.000
DPPA3	NUP62	psi-mi:“MI:0915”(physical association)	0.000
DPPA3	PLEKHG4	psi-mi:“MI:0915”(physical association)	0.000
DPPA3	KRT27	psi-mi:“MI:0915”(physical association)	0.000
DPPA3	DYNLL2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): DPPA3 (Proximity Label-MS), DPPA3 (Affinity Capture-MS), DPPA3 (Two-hybrid), DPPA3 (Two-hybrid), DPPA3 (Two-hybrid), DPPA3 (Two-hybrid), DPPA3 (Two-hybrid), DPPA3 (Two-hybrid), DPPA3 (Two-hybrid), DPPA3 (Two-hybrid), PLEKHG4 (Two-hybrid), SYCE1L (Two-hybrid), NUP62 (Two-hybrid), HAUS7 (Two-hybrid), DYNLL2 (Two-hybrid)

ESM2 similar proteins: A0A1B0GU33, A0A1B0GUV7, A6NGY3, A6ZT44, F5HHT4, G2TRR6, H3BU77, O13894, O54835, O89085, P0C2W9, P0C6G1, P0C6G2, P0C6G3, P0C6G4, P0C6G5, P0C733, P0DON5, P0DON6, P14976, P16722, P27262, P27271, P28979, P29887, P38612, P38839, Q05105, Q08588, Q1KN14, Q1KN19, Q1X6Y3, Q1X6Y4, Q1X6Z0, Q2YDL7, Q5R5R7, Q5ZK14, Q67621, Q6W0C5, Q88891

Diamond homologs: Q6IMK0, Q6W0C5, Q8QZY3, A9Q1J7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

430 predictions. Top by Δscore:

Variant	Effect	Δscore
12:7711648:TTCAG:T	donor_gain	1.0000
12:7711649:TCAGG:T	donor_loss	1.0000
12:7711651:AGG:A	donor_loss	1.0000
12:7711652:GGTA:G	donor_loss	1.0000
12:7711653:G:GG	donor_gain	1.0000
12:7711654:T:A	donor_loss	1.0000
12:7715177:TTTCA:T	acceptor_loss	1.0000
12:7715178:TTCA:T	acceptor_loss	1.0000
12:7715180:CA:C	acceptor_loss	1.0000
12:7715181:A:AG	acceptor_gain	1.0000
12:7715181:AG:A	acceptor_gain	1.0000
12:7715181:AGG:A	acceptor_gain	1.0000
12:7715181:AGGG:A	acceptor_gain	1.0000
12:7715182:G:A	acceptor_loss	1.0000
12:7715182:G:GC	acceptor_gain	1.0000
12:7715182:GG:G	acceptor_gain	1.0000
12:7715182:GGG:G	acceptor_gain	1.0000
12:7715182:GGGG:G	acceptor_gain	1.0000
12:7715182:GGGGC:G	acceptor_gain	1.0000
12:7716192:A:AG	acceptor_gain	1.0000
12:7716192:AT:A	acceptor_gain	1.0000
12:7716193:T:G	acceptor_gain	1.0000
12:7716193:T:TA	acceptor_gain	1.0000
12:7716196:A:AG	acceptor_gain	1.0000
12:7716197:G:GG	acceptor_gain	1.0000
12:7711649:TCAG:T	donor_gain	0.9900
12:7711651:AG:A	donor_gain	0.9900
12:7711652:GG:G	donor_gain	0.9900
12:7715327:A:G	donor_gain	0.9900
12:7715348:GAGGA:G	donor_gain	0.9900

AlphaMissense

1027 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:7717000:T:C	F135L	0.957
12:7717002:C:A	F135L	0.957
12:7717002:C:G	F135L	0.957
12:7716982:T:C	F129L	0.954
12:7716984:C:A	F129L	0.954
12:7716984:C:G	F129L	0.954
12:7717020:G:C	W141C	0.920
12:7717020:G:T	W141C	0.920
12:7716988:T:C	C131R	0.900
12:7715358:A:C	R86S	0.895
12:7715358:A:T	R86S	0.895
12:7717003:T:A	C136S	0.883
12:7717004:G:C	C136S	0.883
12:7715360:C:T	T87I	0.868
12:7717018:T:A	W141R	0.861
12:7717018:T:C	W141R	0.861
12:7716988:T:A	C131S	0.849
12:7716989:G:C	C131S	0.849
12:7716994:T:C	C133R	0.847
12:7717003:T:C	C136R	0.827
12:7717035:T:A	N146K	0.825
12:7717035:T:G	N146K	0.825
12:7716996:C:G	C133W	0.821
12:7715231:T:C	L44S	0.814
12:7716990:T:G	C131W	0.814
12:7716983:T:G	F129C	0.809
12:7717022:A:G	D142G	0.803
12:7716983:T:C	F129S	0.800
12:7717019:G:T	W141L	0.800
12:7716994:T:A	C133S	0.798

dbSNP variants (sampled 300 via entrez): RS1000359829 (12:7714155 G>A), RS1001070848 (12:7713627 T>C), RS1001696805 (12:7714191 C>G,T), RS1001750834 (12:7714530 T>C,G), RS1002030407 (12:7713065 C>T), RS1002082847 (12:7713301 G>T), RS1002756740 (12:7715626 T>A), RS1003073223 (12:7710881 TAA>T,TA), RS1003451508 (12:7710531 C>A), RS1003560166 (12:7715225 G>A), RS1003632276 (12:7709698 C>A), RS1004089356 (12:7710052 G>A), RS1004383664 (12:7716066 G>T), RS1004933698 (12:7712828 C>T), RS1005287822 (12:7713014 C>T)

Disease associations

OMIM: gene MIM:608408 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003245_6	White matter hyperintensities in ischemic stroke	2.000000e-06
GCST004641_1	Borderline personality disorder	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005665	white matter hyperintensity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
decabromobiphenyl ether	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
potassium chromate(VI)	decreases expression	1
bisphenol S	increases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation	1
Butyrates	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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