SETSIP

Summary

SETSIP (SET like protein, HGNC:42937) is a protein-coding gene on chromosome 1p22.1, encoding Protein SETSIP (P0DME0). Plays a role as a transcriptional activator involved in the early stage of somatic cell reprogramming.

Enables chromatin binding activity. Involved in endothelial cell differentiation and positive regulation of transcription by RNA polymerase II. Located in cytoplasm; lipid droplet; and nucleoplasm.

Source: NCBI Gene 646817 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total — 1 pathogenic
• MANE Select transcript: NM_001287737

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:42937
Approved symbol	SETSIP
Name	SET like protein
Location	1p22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000230667
Ensembl biotype	protein_coding
Entrez	646817

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000596516

RefSeq mRNA: 1 — MANE Select: NM_001287737 NM_001287737

CCDS: CCDS72821

Canonical transcript exons

ENST00000596516 — 1 exons

Exon	Start	End
ENSE00003976296	92074533	92075411

Expression profiles

Bgee: expression breadth broad, 28 present calls, max score 85.74.

Top tissues by expression

101 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	85.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.07	gold quality
cortical plate	UBERON:0005343	50.27	gold quality
ganglionic eminence	UBERON:0004023	49.39	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	44.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	42.59	gold quality
prefrontal cortex	UBERON:0000451	41.01	gold quality
primary visual cortex	UBERON:0002436	40.42	silver quality
stromal cell of endometrium	CL:0002255	40.36	silver quality
frontal cortex	UBERON:0001870	40.10	gold quality
cerebral cortex	UBERON:0000956	39.69	gold quality
right frontal lobe	UBERON:0002810	39.03	gold quality
putamen	UBERON:0001874	38.19	silver quality
anterior cingulate cortex	UBERON:0009835	37.82	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
nucleus accumbens	UBERON:0001882	35.46	gold quality
mucosa of stomach	UBERON:0001199	34.66	gold quality
calcaneal tendon	UBERON:0003701	34.63	gold quality
brain	UBERON:0000955	34.53	gold quality
caudate nucleus	UBERON:0001873	33.44	silver quality
islet of Langerhans	UBERON:0000006	33.18	gold quality
bone marrow	UBERON:0002371	33.08	gold quality
leukocyte	CL:0000738	32.54	silver quality
amygdala	UBERON:0001876	32.53	silver quality
temporal lobe	UBERON:0001871	32.52	silver quality
placenta	UBERON:0001987	32.48	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
monocyte	CL:0000576	31.73	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.00

Regulation

Is transcription factor: no

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspy	ENSDARG00000005015
danio_rerio	nap1l4a	ENSDARG00000070560
mus_musculus	Set	ENSMUSG00000054766
rattus_norvegicus	Setsip	ENSRNOG00000062793
rattus_norvegicus		ENSRNOG00000090603
drosophila_melanogaster	Set	FBGN0014879
drosophila_melanogaster	Nap1	FBGN0015268
drosophila_melanogaster	CG3708	FBGN0040345
drosophila_melanogaster	mil	FBGN0267366
caenorhabditis_elegans		WBGENE00005007
caenorhabditis_elegans		WBGENE00017075

Paralogs (19): SET (ENSG00000119335), TSPY2 (ENSG00000168757), NAP1L5 (ENSG00000177432), TSPYL6 (ENSG00000178021), TSPYL5 (ENSG00000180543), TSPYL2 (ENSG00000184205), NAP1L3 (ENSG00000186310), NAP1L2 (ENSG00000186462), NAP1L1 (ENSG00000187109), TSPYL4 (ENSG00000187189), TSPYL1 (ENSG00000189241), NAP1L4 (ENSG00000205531), TSPY3 (ENSG00000228927), TSPY8 (ENSG00000229549), TSPY4 (ENSG00000233803), TSPY10 (ENSG00000236424), TSPY9 (ENSG00000238074), TSPY1 (ENSG00000258992), (ENSG00000293164)

Protein

Protein identifiers

Protein SETSIP — P0DME0 (reviewed: P0DME0)

Alternative names: SET pseudogene protein 18, SET similar protein, Similar to SET translocation protein

All UniProt accessions (1): P0DME0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role as a transcriptional activator involved in the early stage of somatic cell reprogramming. Promotes the differentiation of protein-induced pluripotent stem (PiPS) cells into endothelial cells and the formation of vascular-like tubes (in vitro). Involved in the transcription induction of vascular endothelial-cadherin (VE-cadherin) expression. Associates to the VE-cadherin gene promoter.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in endothelial cell (EC) and protein-induced pluripotent stem (PiPS) endothelial cell (EC) (at protein level).

Induction. Up-regulated during protein-induced pluripotent stem (PiPS) endothelial cell differention. Up-regulated by VEGFA and POU2F1 (at protein level).

Miscellaneous. Gene prediction based on conservation data. Probable retrogene derived from SET transcript.

Similarity. Belongs to the nucleosome assembly protein (NAP) family.

Isoforms (2)

UniProt ID	Names	Canonical?
P0DME0-2	2	yes
P0DME0-1	1

RefSeq proteins (1): NP_001274666* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002164	NAP	Family
IPR037231	NAP-like_sf	Homologous_superfamily

Pfam: PF00956

UniProt features (7 total): region of interest 2, compositionally biased region 2, chain 1, coiled-coil region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DME0-F1	78.97	0.57

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ENDOTHELIUM_DEVELOPMENT, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOBP_CHROMATIN_REMODELING, chr1p22, GOMF_CHROMATIN_BINDING, GOMF_HISTONE_BINDING, GOBP_NUCLEOSOME_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOCC_LIPID_DROPLET, GOBP_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_RNA_METABOLIC_PROCESS, GOBP_CHROMATIN_ORGANIZATION, GOBP_PROTEIN_CONTAINING_COMPLEX_ORGANIZATION, GOBP_ENDOTHELIAL_CELL_DIFFERENTIATION

GO Biological Process (4): nucleosome assembly (GO:0006334), endothelial cell differentiation (GO:0045446), positive regulation of transcription by RNA polymerase II (GO:0045944), cell differentiation (GO:0030154)

GO Molecular Function (2): chromatin binding (GO:0003682), histone binding (GO:0042393)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lipid droplet (GO:0005811)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
endothelium development	1
epithelial cell differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cellular developmental process	1
binding	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

474 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SETSIP	FAM229A	H3BQW9	544
SETSIP	C19orf73	Q9NVV2	506
SETSIP	NPM3	O75607	420
SETSIP	DENND10	Q8TCE6	417
SETSIP	CIMIP2A	Q6J272	398
SETSIP	ANP32A	P39687	380
SETSIP	OR11H12	B2RN74	373
SETSIP	MYO15B	Q96JP2	367
SETSIP	OR11H1	Q8NG94	323
SETSIP	MALRD1	Q5VYJ5	316
SETSIP	LY6G5C	Q5SRR4	284
SETSIP	TAS2R14	Q9NYV8	270
SETSIP	TPR	P12270	269
SETSIP	OTOG	Q6ZRI0	255
SETSIP	RHO	P08100	253

IntAct

13 interactions, top by confidence:

A	B	Type	Score
SGO1	USP12	psi-mi:“MI:0914”(association)	0.530
	TUBA4A	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ZNF20	ZNF316	psi-mi:“MI:0914”(association)	0.350
ZNF567	IPO8	psi-mi:“MI:0914”(association)	0.350
ZNF627	POLR1C	psi-mi:“MI:0914”(association)	0.350
ZNF90	SETSIP	psi-mi:“MI:0914”(association)	0.350
ARMC9	PRMT5	psi-mi:“MI:0914”(association)	0.350
DYRK2	POLRMT	psi-mi:“MI:2364”(proximity)	0.270
DYRK2	HNRNPCL2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (33): SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Affinity Capture-MS), SETSIP (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: G3V9R8, O35381, O43423, O60812, O77768, O88978, P07910, P0DME0, P19600, P39687, P49911, P50503, P51122, P97822, Q01105, Q1RMR5, Q28XE2, Q32KP2, Q3SZC6, Q4KLJ8, Q4R3F0, Q5F4A3, Q5RA82, Q5REE1, Q5UAK0, Q5XIE0, Q5ZKT9, Q5ZLF0, Q5ZMN0, Q63945, Q64G17, Q6A1I3, Q6NUW5, Q6P1U7, Q6PAF6, Q7ZUP0, Q7ZY40, Q86X45, Q8AVC1, Q8HY67

Diamond homologs: A0A494C1R9, A2ZX50, A6NKD2, B8AEC1, B8B2R4, B8B4K9, B9FU45, F4JEI8, O19110, O59797, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0DME0, P53997, P78920, Q01105, Q01534, Q0P5N2, Q18240, Q5R5G8, Q5VND6, Q63945, Q69JW2, Q69ZB3, Q70Z17, Q70Z18, Q70Z19, Q7TQI8, Q86VY4, Q8N831, Q8VD63, Q94K07, Q9BE64, Q9CA59, Q9EQU5, Q9H0U9, Q9H2G4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1707481	NM_001287737.2(SETSIP):c.648G>A (p.Glu216=)	Pathogenic

SpliceAI

256 predictions. Top by Δscore:

Variant	Effect	Δscore
1:92074683:T:TA	donor_gain	0.7200
1:92074636:T:TA	donor_gain	0.7100
1:92074608:ATCC:A	donor_gain	0.6800
1:92074641:C:A	donor_gain	0.6400
1:92074647:A:AC	donor_gain	0.6300
1:92074819:T:TA	donor_gain	0.6300
1:92074879:T:TA	donor_gain	0.6300
1:92074569:C:A	donor_gain	0.6200
1:92074768:T:C	donor_gain	0.6200
1:92074835:T:TA	donor_gain	0.6200
1:92074564:T:TA	donor_gain	0.6100
1:92074863:TGA:T	donor_gain	0.5900
1:92074884:T:A	donor_gain	0.5900
1:92074540:T:C	donor_gain	0.5700
1:92074603:T:TA	donor_gain	0.5700
1:92074719:C:CC	acceptor_gain	0.5700
1:92074646:CA:C	donor_gain	0.5600
1:92075263:T:TA	donor_gain	0.5600
1:92074552:T:TA	donor_gain	0.5500
1:92074687:T:TA	donor_gain	0.5500
1:92074560:T:A	donor_gain	0.5400
1:92074535:AGT:A	donor_gain	0.5300
1:92074639:T:TA	donor_gain	0.5300
1:92074545:T:A	donor_gain	0.5200
1:92074763:A:AC	donor_gain	0.5200
1:92074764:C:CC	donor_gain	0.5200
1:92074555:T:TA	donor_gain	0.5100
1:92074608:AT:A	donor_gain	0.5100
1:92074645:TCATC:T	donor_gain	0.5100
1:92074829:G:GA	donor_gain	0.5100

AlphaMissense

2047 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:92074989:A:C	F151L	0.854
1:92074989:A:T	F151L	0.854
1:92074991:A:G	F151L	0.854
1:92075028:A:C	F138L	0.818
1:92075028:A:T	F138L	0.818
1:92075030:A:G	F138L	0.818
1:92074944:A:C	F166L	0.795
1:92074944:A:T	F166L	0.795
1:92074946:A:G	F166L	0.795
1:92074971:A:C	F157L	0.785
1:92074971:A:T	F157L	0.785
1:92074973:A:G	F157L	0.785
1:92075115:A:C	F109L	0.774
1:92075115:A:T	F109L	0.774
1:92075117:A:G	F109L	0.774
1:92075172:A:C	F90L	0.759
1:92075172:A:T	F90L	0.759
1:92075174:A:G	F90L	0.759
1:92074794:A:C	F216L	0.750
1:92074794:A:T	F216L	0.750
1:92074796:A:G	F216L	0.750
1:92074895:A:G	W183R	0.746
1:92074895:A:T	W183R	0.746
1:92074995:A:C	F149L	0.725
1:92074995:A:T	F149L	0.725
1:92074997:A:G	F149L	0.725
1:92075130:A:C	F104L	0.720
1:92075130:A:T	F104L	0.720
1:92075132:A:G	F104L	0.720
1:92074950:T:A	K164N	0.711

dbSNP variants (sampled 300 via entrez): RS1001978342 (1:92074109 A>G), RS1003725553 (1:92076162 T>C), RS1003806059 (1:92076402 A>G), RS1003868396 (1:92075746 T>G), RS1004200954 (1:92075859 C>G,T), RS1005091956 (1:92074349 ACT>A), RS1006528452 (1:92074453 GAAA>G,GA,GAA,GAAAA,GAAAAA,GAAAAAA), RS1007647573 (1:92076029 A>G), RS1008310931 (1:92076905 C>T), RS1008653332 (1:92077207 C>T), RS1009543799 (1:92076191 G>A), RS1009802991 (1:92076439 C>T), RS1009945456 (1:92074678 TCTC>T), RS1010881534 (1:92076377 A>AT), RS1010933983 (1:92076070 C>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:618106

GenCC curated gene-disease

Mondo (1): intellectual disability, autosomal dominant 58 (MONDO:0020847)

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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
fluorene-9-bisphenol	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Estradiol	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Dronabinol	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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