C19orf33

Summary

C19orf33 (chromosome 19 open reading frame 33, HGNC:16668) is a protein-coding gene on chromosome 19q13.2, encoding Immortalization up-regulated protein (Q9GZP8).

The protein encoded by this gene has been shown to be upregulated in SV40-immortalized fibroblasts as well as in endometrial carcinoma cells. The encoded protein is found primarily in the nucleus. This protein may play a role in placental development and diseases such as pre-eclampsia. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 64073 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_033520

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16668
Approved symbol	C19orf33
Name	chromosome 19 open reading frame 33
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	IMUP-1, IMUP-2, H2RSP, IMUP
Ensembl gene	ENSG00000167644
Ensembl biotype	protein_coding
OMIM	619711
Entrez	64073

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000301246, ENST00000588605, ENST00000589986, ENST00000591852, ENST00000870637

RefSeq mRNA: 2 — MANE Select: NM_033520 NM_001317801, NM_033520

CCDS: CCDS12511, CCDS82344

Canonical transcript exons

ENST00000301246 — 4 exons

Exon	Start	End
ENSE00002868661	38304845	38305006
ENSE00002964887	38304251	38304283
ENSE00003669537	38304624	38304686
ENSE00003679241	38304375	38304490

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.58.

FANTOM5 (CAGE): breadth broad, TPM avg 56.8615 / max 1580.6513, expressed in 826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175611	53.0905	803
175610	3.5499	451
175612	0.2212	146

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.58	gold quality
mucosa of transverse colon	UBERON:0004991	99.26	gold quality
esophagus mucosa	UBERON:0002469	99.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.04	gold quality
skin of abdomen	UBERON:0001416	98.91	gold quality
zone of skin	UBERON:0000014	98.82	gold quality
skin of leg	UBERON:0001511	98.78	gold quality
duodenum	UBERON:0002114	98.62	gold quality
right uterine tube	UBERON:0001302	98.14	gold quality
upper lobe of left lung	UBERON:0008952	97.30	gold quality
minor salivary gland	UBERON:0001830	97.28	gold quality
rectum	UBERON:0001052	97.09	gold quality
right lung	UBERON:0002167	96.96	gold quality
saliva-secreting gland	UBERON:0001044	96.34	gold quality
tibial nerve	UBERON:0001323	95.43	gold quality
vagina	UBERON:0000996	94.96	gold quality
apex of heart	UBERON:0002098	94.26	gold quality
lung	UBERON:0002048	93.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.75	gold quality
fallopian tube	UBERON:0003889	93.63	gold quality
transverse colon	UBERON:0001157	93.50	gold quality
gall bladder	UBERON:0002110	93.50	gold quality
small intestine	UBERON:0002108	93.23	gold quality
monocyte	CL:0000576	92.01	gold quality
body of stomach	UBERON:0001161	91.57	gold quality
leukocyte	CL:0000738	91.15	gold quality
sural nerve	UBERON:0015488	90.73	gold quality
stomach	UBERON:0000945	90.47	gold quality
metanephros cortex	UBERON:0010533	90.26	gold quality
esophagus	UBERON:0001043	89.22	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	2227.43
E-MTAB-8410	yes	2119.35
E-MTAB-8495	yes	1566.90
E-MTAB-8221	yes	1286.95
E-MTAB-9906	yes	1285.51
E-HCAD-1	yes	272.57
E-MTAB-8142	yes	95.07
E-CURD-114	yes	63.75
E-MTAB-10287	yes	30.73
E-GEOD-125970	yes	29.93
E-MTAB-6701	yes	19.89
E-HCAD-10	yes	17.77
E-GEOD-130148	yes	10.31
E-CURD-11	no	92.19
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 9)

• H2RSP and H2RSP/HAI-2 chimeric peptides might function as a transcriptional regulatory peptide at the nucleus. (PMID:11606055)
• results showed the up-regulation of IMUP-1 and IMUP-2 in human ovarian epithelial tumors and suggested that the altered mRNA level of these molecules is possibly associated with ovarian tumorigenesis (PMID:14981917)
• Nuclear translocation of H2RSP may be related to a signaling involved in the transition from cellular proliferation to differentiation in experimental murine colitis. (PMID:16189703)
• Our findings suggest that the balance between hepsin and its inhibitor, HAI-2, may have prognostic value in RCC. (PMID:17309599)
• These findings demonstrate the up-regulation of imup-1 and imup-2 in human endometrial carcinomas and indicate that these molecules play a role in endometrial carcinogenesis in both Korean and Japanese patients. (PMID:18507030)
• results suggest that IMUP-2 expression is specifically elevated in preterm pre-eclampsia and under hypoxic conditions, and that IMUP-2 induces apoptosis of the trophoblast (PMID:20432246)
• Hypoxia-induced down-regulation of XIAP mediates apoptosis in trophoblasts through interaction with increased IMUP-2; this mechanism underlies the pathogenesis of pre-eclampsia. (PMID:22886722)
• Immortalization-upregulated protein promotes pancreatic cancer progression by regulating NPM1/FHL1-mediated cell-cycle-checkpoint protein activity. (PMID:35142956)
• Unraveling dedifferentiation and metastasis traces in pancreatic ductal adenocarcinoma ductal cells: Insights from single-cell RNA sequencing analysis of ITGB4 and C19orf33. (PMID:38071887)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	2200002D01Rik	ENSMUSG00000030587
rattus_norvegicus	C1h19orf33	ENSRNOG00000056651

Protein

Protein identifiers

Immortalization up-regulated protein — Q9GZP8 (reviewed: Q9GZP8)

Alternative names: Hepatocyte growth factor activator inhibitor type 2-related small protein

All UniProt accessions (1): Q9GZP8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9GZP8-1	1, IMUP-1	yes
Q9GZP8-2	2, IMUP-2

RefSeq proteins (2): NP_001304730, NP_277055* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026621	IMUP	Family

Pfam: PF15761

UniProt features (7 total): compositionally biased region 2, modified residue 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZP8-F1	62.92	0.00

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 (2): 1, 29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, AP1_01, AP1_Q4_01, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, TGANTCA_AP1_C, GOMF_SINGLE_STRANDED_DNA_BINDING, GOCC_NUCLEOLUS, DODD_NASOPHARYNGEAL_CARCINOMA_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_UP, FIGUEROA_AML_METHYLATION_CLUSTER_6_UP, JOHNSTONE_PARVB_TARGETS_3_UP, LEE_BMP2_TARGETS_UP, KATSANOU_ELAVL1_TARGETS_UP, ANDERSEN_CHOLANGIOCARCINOMA_CLASS2, DLX6_TARGET_GENES

GO Biological Process (1): biological_process (GO:0008150)

GO Molecular Function (0):

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

242 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C19orf33	SPINT2	O43291	860
C19orf33	PPP1R14A	Q96A00	770
C19orf33	OR14A16	Q8NHC5	433
C19orf33	PPP1R12A	O14974	428
C19orf33	PPP1CB	P37140	424
C19orf33	MUC21	Q5SSG8	408
C19orf33	IFI27	P40305	393
C19orf33	C3orf52	Q5BVD1	350
C19orf33	PGCKA1	Q8IY42	339
C19orf33	C6orf89	Q6UWU4	323
C19orf33	KIAA1328	Q86T90	317
C19orf33	ZNF560	Q96MR9	312
C19orf33	COXFA4L3	Q9C002	310
C19orf33	TMEM52	Q8NDY8	306
C19orf33	NF2	P35240	303

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SUN2	PIP	psi-mi:“MI:0914”(association)	0.530

BioGRID (24): C19orf33 (Affinity Capture-MS), C19orf33 (Affinity Capture-MS), C19orf33 (Co-fractionation), C19orf33 (Co-fractionation), C19orf33 (Co-fractionation), C19orf33 (Co-fractionation), C19orf33 (Co-fractionation), C19orf33 (Co-fractionation), C19orf33 (Co-fractionation), C19orf33 (Co-fractionation), C19orf33 (Co-fractionation), C19orf33 (Co-fractionation), RAB3GAP2 (Co-fractionation), WDR55 (Co-fractionation), GTF3C5 (Co-fractionation)

ESM2 similar proteins: A0JLT2, A2A6A1, A4RD36, A7MB40, E9Q6J5, F4I5N6, F4IVV0, F4J424, O00257, O55187, O88573, O88778, P02686, P04370, P08855, P10636, P10637, P19332, P27321, P30658, P49342, P51125, P81558, Q03111, Q14781, Q4G0F8, Q4VC05, Q505I5, Q58CQ0, Q5FVI4, Q5I034, Q5JSZ5, Q5S6V2, Q5XFY4, Q5YCV9, Q5YCW0, Q5YCW1, Q5ZLM8, Q7TT28, Q8C551

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

453 predictions. Top by Δscore:

Variant	Effect	Δscore
19:38304373:A:AG	acceptor_gain	1.0000
19:38304374:G:GG	acceptor_gain	1.0000
19:38304687:GTAA:G	donor_loss	1.0000
19:38304828:T:TA	acceptor_gain	1.0000
19:38304279:AGCAG:A	donor_loss	0.9900
19:38304280:GCAGG:G	donor_loss	0.9900
19:38304281:CAG:C	donor_loss	0.9900
19:38304281:CAGG:C	donor_loss	0.9900
19:38304282:AGG:A	donor_loss	0.9900
19:38304282:AGGT:A	donor_loss	0.9900
19:38304283:GG:G	donor_loss	0.9900
19:38304284:G:A	donor_loss	0.9900
19:38304284:GTG:G	donor_loss	0.9900
19:38304285:T:A	donor_loss	0.9900
19:38304369:CCACA:C	acceptor_loss	0.9900
19:38304370:CACA:C	acceptor_loss	0.9900
19:38304371:ACAG:A	acceptor_loss	0.9900
19:38304372:CA:C	acceptor_loss	0.9900
19:38304373:AGCCC:A	acceptor_loss	0.9900
19:38304374:G:A	acceptor_loss	0.9900
19:38304374:GC:G	acceptor_gain	0.9900
19:38304374:GCC:G	acceptor_gain	0.9900
19:38304374:GCCCT:G	acceptor_gain	0.9900
19:38304487:AAAGG:A	donor_loss	0.9900
19:38304488:AAGG:A	donor_loss	0.9900
19:38304488:AAGGT:A	donor_loss	0.9900
19:38304489:AGGT:A	donor_loss	0.9900
19:38304489:AGGTA:A	donor_loss	0.9900
19:38304490:GGT:G	donor_loss	0.9900
19:38304490:GGTA:G	donor_loss	0.9900

AlphaMissense

696 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:38304657:A:C	S58R	0.952
19:38304659:C:A	S58R	0.952
19:38304659:C:G	S58R	0.952
19:38304651:A:C	S56R	0.937
19:38304653:C:A	S56R	0.937
19:38304653:C:G	S56R	0.937
19:38304654:A:C	S57R	0.933
19:38304656:C:A	S57R	0.933
19:38304656:C:G	S57R	0.933
19:38304663:A:C	S60R	0.893
19:38304665:C:A	S60R	0.893
19:38304665:C:G	S60R	0.893
19:38304268:T:C	F3L	0.845
19:38304270:C:A	F3L	0.845
19:38304270:C:G	F3L	0.845
19:38304269:T:C	F3S	0.760
19:38304375:C:A	A8D	0.746
19:38304658:G:T	S58I	0.677
19:38304283:G:C	A8P	0.676
19:38304904:A:C	K87N	0.670
19:38304904:A:T	K87N	0.670
19:38304275:T:A	L5Q	0.659
19:38304910:G:C	K89N	0.654
19:38304910:G:T	K89N	0.654
19:38304664:G:T	S60I	0.644
19:38304652:G:T	S56I	0.633
19:38304652:G:A	S56N	0.628
19:38304655:G:T	S57I	0.623
19:38304895:G:C	K84N	0.607
19:38304895:G:T	K84N	0.607

dbSNP variants (sampled 300 via entrez): RS1001529252 (19:38302907 G>A,C), RS1001943255 (19:38304813 C>T), RS1002851812 (19:38303428 G>A), RS1002897851 (19:38303679 T>C), RS1004716533 (19:38303881 C>A,T), RS1005334176 (19:38304449 G>A,T), RS1007177708 (19:38304148 G>A,T), RS1007729002 (19:38302465 C>A,T), RS1008597693 (19:38303073 A>C,G,T), RS1008701954 (19:38304775 A>G), RS1010171789 (19:38303905 CT>C), RS1010337850 (19:38303194 T>C,G), RS1014471548 (19:38302541 G>T), RS1014598450 (19:38303896 C>T), RS1014934901 (19:38302822 T>A)

Disease associations

OMIM: gene MIM:619711 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004599_150	Mean platelet volume	9.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	decreases expression, increases expression, increases methylation	2
Cyclosporine	increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
tetrathiomolybdate	decreases expression	1
nickel sulfate	decreases expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arbutin	decreases expression	1
Carbamazepine	affects expression	1
Diazinon	decreases methylation	1
Diethylhexyl Phthalate	increases expression	1
Furaldehyde	increases expression, affects cotreatment	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Smoke	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1LQ	Abcam HeLa C19orf33 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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