DPPA5

Summary

DPPA5 (developmental pluripotency associated 5, HGNC:19201) is a protein-coding gene on chromosome 6q13, encoding Developmental pluripotency-associated 5 protein (A6NC42). Involved in the maintenance of embryonic stem (ES) cell pluripotency. It is a selective cancer dependency (DepMap: 15.1% of cell lines).

This gene encodes a protein that may function in the control of cell pluripotency and early embryogenesis. Expression of this gene is a specific marker for pluripotent stem cells. Pseudogenes of this gene are located on the short arm of chromosome 10 and the long arm of chromosomes 14 and 19.

Source: NCBI Gene 340168 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 17 total
• Cancer dependency (DepMap): dependent in 15.1% of screened cell lines
• MANE Select transcript: NM_001025290

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19201
Approved symbol	DPPA5
Name	developmental pluripotency associated 5
Location	6q13
Locus type	gene with protein product
Status	Approved
Aliases	Esg1
Ensembl gene	ENSG00000203909
Ensembl biotype	protein_coding
OMIM	611111
Entrez	340168

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000370370

RefSeq mRNA: 1 — MANE Select: NM_001025290 NM_001025290

CCDS: CCDS34483

Canonical transcript exons

ENST00000370370 — 3 exons

Exon	Start	End
ENSE00001452497	73353063	73353378
ENSE00001452502	73353853	73354032
ENSE00001452522	73354114	73354276

Expression profiles

Bgee: expression breadth broad, 37 present calls, max score 99.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2665 / max 180.8255, expressed in 22 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74356	0.2483	17
204058	0.0182	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.98	gold quality
oocyte	CL:0000023	99.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.18	gold quality
vena cava	UBERON:0004087	59.35	gold quality
sperm	CL:0000019	56.00	gold quality
substantia nigra pars reticulata	UBERON:0001966	54.06	gold quality
lateral globus pallidus	UBERON:0002476	54.05	gold quality
testis	UBERON:0000473	49.45	gold quality
right testis	UBERON:0004534	48.53	gold quality
palpebral conjunctiva	UBERON:0001812	48.34	silver quality
lower lobe of lung	UBERON:0008949	48.00	silver quality
left testis	UBERON:0004533	47.69	gold quality
quadriceps femoris	UBERON:0001377	46.22	gold quality
vastus lateralis	UBERON:0001379	45.98	gold quality
cardia of stomach	UBERON:0001162	45.63	gold quality
nipple	UBERON:0002030	45.56	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	43.50	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
subthalamic nucleus	UBERON:0001906	43.33	gold quality
deltoid	UBERON:0001476	43.18	gold quality
ventral tegmental area	UBERON:0002691	43.13	gold quality
layer of synovial tissue	UBERON:0007616	43.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	42.66	gold quality
jejunum	UBERON:0002115	42.52	gold quality
body of tongue	UBERON:0011876	42.52	gold quality
buccal mucosa cell	CL:0002336	42.47	gold quality
pharyngeal mucosa	UBERON:0000355	42.22	gold quality
globus pallidus	UBERON:0001875	42.11	gold quality
biceps brachii	UBERON:0001507	41.66	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	3926.61
E-MTAB-10018	yes	3259.80
E-MTAB-6819	yes	2091.70
E-MTAB-8060	yes	1388.63
E-ANND-3	no	0.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZFP42

miRNA regulators (miRDB)

14 targeting DPPA5, 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-3148	99.97	75.06	6478
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-1912-5P	97.94	67.98	832
HSA-MIR-618	97.62	67.46	861
HSA-MIR-6892-5P	97.27	68.60	847
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 15.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• Dppa5 is specifically and differentially expressed in human cells that have pluripotency and can be used as a marker of pluripotent stem cells. (PMID:15790765)
• Our study provides new insight into the function of DPPA5 and NANOG regulation in human pluripotent stem cell . (PMID:26661329)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dppa5a	ENSMUSG00000060461
rattus_norvegicus	Dppa5l1	ENSRNOG00000060610
rattus_norvegicus		ENSRNOG00000071290
rattus_norvegicus		ENSRNOG00000073791
rattus_norvegicus		ENSRNOG00000081106

Paralogs (2): KHDC1 (ENSG00000135314), KHDC1L (ENSG00000256980)

Protein

Protein identifiers

Developmental pluripotency-associated 5 protein — A6NC42 (reviewed: A6NC42)

Alternative names: Embryonal stem cell-specific gene 1 protein

All UniProt accessions (1): A6NC42

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the maintenance of embryonic stem (ES) cell pluripotency. Dispensable for self-renewal of pluripotent ES cells and establishment of germ cells. Associates with specific target mRNAs.

Subcellular location. Cytoplasm.

Induction. Down-regulated in differentiated embryonic stem (ESC) cells, compared with strong expression in undifferentiated ESC cells.

Similarity. Belongs to the KHDC1 family.

RefSeq proteins (1): NP_001020461* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031952	MOEP19_KH-like	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily

Pfam: PF16005

UniProt features (2 total): chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NC42-F1	88.63	0.75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 26 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOMF_MRNA_BINDING, MIKKELSEN_PLURIPOTENT_STATE_UP, DELACROIX_RAR_BOUND_ES, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GCNP_SHH_UP_LATE.V1_DN, NKX2_3_TARGET_GENES, MIR5582_3P, MIR4668_5P, MIR4446_5P, MIR6081, MIR4468, MIR1912_5P, chr6q13

GO Biological Process (1): regulation of gene expression (GO:0010468)

GO Molecular Function (2): mRNA binding (GO:0003729), RNA binding (GO:0003723)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	1
regulation of macromolecule biosynthetic process	1
RNA binding	1
nucleic acid binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPPA5	KHDC1	Q4VXA5	980
DPPA5	DPPA3	Q6W0C5	796
DPPA5	NANOG	Q9H9S0	755
DPPA5	UTF1	Q5T230	621
DPPA5	DPPA2	Q7Z7J5	620
DPPA5	DPPA4	Q7L190	603
DPPA5	GDF3	Q9NR23	599
DPPA5	ZFP42	Q96MM3	593
DPPA5	KLF17	Q5JT82	588
DPPA5	LIN28A	Q9H9Z2	588
DPPA5	POU5F1	P31359	537
DPPA5	TFCP2L1	Q9NZI6	533
DPPA5	SOX2	P48431	528
DPPA5	KLF4	P78338	519
DPPA5	DNMT3L	Q9UJW3	480

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DPPA5	DNM1L	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): DNM1L (Affinity Capture-MS)

ESM2 similar proteins: A0JNQ6, A6NC42, A6NGQ2, A6NGR9, A6QP75, A7E3N7, A9X185, E1BDF2, E9PGG2, F6SZT2, P0C7A0, P85965, Q06VW1, Q0ZFW8, Q14DK4, Q3UK37, Q3UV16, Q3ZBN4, Q400G9, Q4VXA5, Q587J8, Q5JSQ8, Q60953, Q60I26, Q60I27, Q6NUI2, Q6ZUX3, Q810I0, Q8BH06, Q8C0R7, Q8IWB1, Q8IWY9, Q8IYX4, Q8K4C2, Q8N6L0, Q8N7F7, Q8NCV1, Q8TE82, Q91WA6, Q95JV3

Diamond homologs: A0JNQ6, A6NC42, A6NGQ2, A9X185, Q06VW1, Q0ZFW8, Q9CWE6, F6SZT2, P85965, Q587J8, Q9CQS7, D3ZVV1, Q9CWU5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

292 predictions. Top by Δscore:

Variant	Effect	Δscore
6:73353848:CTCA:C	donor_loss	1.0000
6:73353850:CA:C	donor_loss	1.0000
6:73353851:A:AG	donor_loss	1.0000
6:73353852:CCTC:C	donor_loss	1.0000
6:73354030:GGCC:G	acceptor_loss	1.0000
6:73354033:C:CC	acceptor_gain	1.0000
6:73354033:C:CG	acceptor_loss	1.0000
6:73354109:CTCA:C	donor_loss	1.0000
6:73354110:TCACC:T	donor_loss	1.0000
6:73354111:CACCG:C	donor_loss	1.0000
6:73354112:A:AC	donor_gain	1.0000
6:73354112:A:T	donor_loss	1.0000
6:73354113:C:CA	donor_loss	1.0000
6:73354113:C:CC	donor_gain	1.0000
6:73353852:CCTCG:C	donor_gain	0.9900
6:73354028:CGGGC:C	acceptor_gain	0.9900
6:73354030:GGC:G	acceptor_gain	0.9900
6:73354107:CACT:C	donor_loss	0.9900
6:73354108:ACTC:A	donor_loss	0.9900
6:73354031:GC:G	acceptor_gain	0.9800
6:73354032:CC:C	acceptor_gain	0.9800
6:73354036:T:TC	acceptor_gain	0.9800
6:73354138:TCTGG:T	donor_gain	0.9800
6:73354029:GGGC:G	acceptor_gain	0.9700
6:73354113:CCGAA:C	donor_gain	0.9600
6:73353386:A:T	acceptor_gain	0.9500
6:73354113:CCG:C	donor_gain	0.9500
6:73354113:CCGA:C	donor_gain	0.9500
6:73353385:C:CT	acceptor_gain	0.9400
6:73354036:T:C	acceptor_gain	0.9300

AlphaMissense

745 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:73354001:C:A	E48D	0.965
6:73354001:C:G	E48D	0.965
6:73353992:G:C	S51R	0.958
6:73353992:G:T	S51R	0.958
6:73353994:T:G	S51R	0.958
6:73354189:A:G	W13R	0.955
6:73354189:A:T	W13R	0.955
6:73353897:A:G	M83T	0.934
6:73353936:A:T	V70D	0.927
6:73354187:C:A	W13C	0.920
6:73354187:C:G	W13C	0.920
6:73354002:T:A	E48V	0.917
6:73353901:A:G	W82R	0.912
6:73353901:A:T	W82R	0.912
6:73353914:C:A	K77N	0.909
6:73353914:C:G	K77N	0.909
6:73354114:C:G	G38R	0.906
6:73353894:A:T	L84H	0.903
6:73353931:C:G	G72R	0.898
6:73354115:G:C	F37L	0.896
6:73354115:G:T	F37L	0.896
6:73354117:A:G	F37L	0.896
6:73353981:A:T	L55H	0.892
6:73353883:C:G	A88P	0.887
6:73353930:C:T	G72D	0.887
6:73353899:C:A	W82C	0.882
6:73353899:C:G	W82C	0.882
6:73354149:A:G	F26S	0.881
6:73353902:C:A	K81N	0.878
6:73353902:C:G	K81N	0.878

dbSNP variants (sampled 300 via entrez): RS1001435008 (6:73353570 C>CG), RS1002525626 (6:73354613 T>C), RS1002738363 (6:73353195 A>T), RS1003578524 (6:73355622 G>GATA), RS1003934147 (6:73356072 A>G), RS1004791113 (6:73354595 A>C), RS1005448674 (6:73355608 C>T), RS1006587328 (6:73352718 A>C), RS1010248664 (6:73353348 G>A), RS1011497543 (6:73352773 G>A), RS1014561980 (6:73352855 A>G), RS1014619714 (6:73354243 C>G), RS1015511976 (6:73355614 T>G), RS1015981113 (6:73355344 A>C), RS1016320326 (6:73353599 C>A)

Disease associations

OMIM: gene MIM:611111 | disease phenotypes: MIM:142623

GenCC curated gene-disease

Mondo (1): Hirschsprung disease (MONDO:0018309)

Orphanet (1): Hirschsprung disease (Orphanet:388)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
trichostatin A	affects cotreatment, increases expression	3
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
bisphenol A	affects cotreatment, decreases expression, increases expression	1
perfluorooctane sulfonic acid	decreases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	affects methylation	1
Butyrates	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT03660176	PHASE3	UNKNOWN	Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung’s Disease
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT00671684	PHASE1/PHASE2	UNKNOWN	Endoscopic Mucosal Resection (EMR) for Diagnosis of Hirschsprung’s Disease
NCT01985646	EARLY_PHASE1	COMPLETED	A Trial on Conservative Treatment for Infants’ Hirschsprung Disease
NCT00478712	Not specified	RECRUITING	Hirschsprung Disease Genetic Study
NCT01515501	Not specified	COMPLETED	Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01927809	Not specified	UNKNOWN	Genetic Mosaicism in Hirschsprung’s Disease
NCT02193685	Not specified	UNKNOWN	Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease
NCT02216994	Not specified	UNKNOWN	A New Scoring System Improves Diagnostic Accuracy of Intestinal Dysganglionosis –a Prospective Study
NCT02296008	Not specified	COMPLETED	3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders
NCT02776176	Not specified	UNKNOWN	Enhanced Recovery After Surgery In Hirschsprung Disease
NCT02857205	Not specified	COMPLETED	MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung’s Associated EnteroColitis
NCT03269812	Not specified	UNKNOWN	Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease
NCT03406741	Not specified	COMPLETED	Neuropsychological Development and Functional Outcome Sin Children With Hirschsprung Disease at School Age
NCT03626350	Not specified	ACTIVE_NOT_RECRUITING	Prospective Evaluation of the Efficacy and Safety of Submucosal Endoscopy
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04106947	Not specified	UNKNOWN	Transition of Care for Patients With Hirschsprung Disease and Anorectal Malformations
NCT04149093	Not specified	UNKNOWN	The Association Between Calretinin and the Function of Ganglion Cells in Hirschsprung Disease
NCT04150120	Not specified	COMPLETED	eHealth as an Aid for Facilitating and Supporting Self-management in Families With Long-term Childhood Illness
NCT04213976	Not specified	UNKNOWN	Ostomy in Continuity or Conventional Ileostomy: a Retrospective Multicentric Analysis
NCT04476225	Not specified	COMPLETED	Induced Pluripotent Stem Cells for Disease Research
NCT04598841	Not specified	COMPLETED	Nutrition Support for Hirschsprung Disease
NCT04622410	Not specified	RECRUITING	Registry for Hirschsprung Disease of the BELAPS
NCT04624334	Not specified	TERMINATED	Non-invasive Assessment of Colonic Motility
NCT04713085	Not specified	COMPLETED	Sacral Neuromodulation in Children and Adolescents
NCT04730128	Not specified	COMPLETED	Translation and Validation of a Disease-specific Questionnaire for Hirschsprung’s Disease in Danish Patients
NCT04837963	Not specified	COMPLETED	Does Hirschsprung Disease Increase the Risk of Febrile Urinary Tract Infection in Children
NCT04957667	Not specified	COMPLETED	Scintigraphic Defecography for Evaluation of Functional Outcome in an Adult Hirschsprung Population
NCT05038345	Not specified	TERMINATED	Hirschsprung Disease Trends in the United States: Analysis of the National Inpatient Sample
NCT05044741	Not specified	COMPLETED	Risk Factors of Perforated HSCR in Neonates
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems
NCT05307419	Not specified	UNKNOWN	Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease
NCT05450991	Not specified	RECRUITING	Long-term Qualitative and Quantitative Outcomes of Children With Hirschsprung’s Disease and Anorectal Malformations
NCT05655845	Not specified	UNKNOWN	Risk Factors for Bowel Dysfunction at Preschool and Early Childhood Age in Children With Hirschsprung Disease
NCT06072976	Not specified	RECRUITING	The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies