OSR2

Summary

OSR2 (odd-skipped related transciption factor 2, HGNC:15830) is a protein-coding gene on chromosome 8q22.2, encoding Protein odd-skipped-related 2 (Q8N2R0). May be involved in the development of the mandibular molar tooth germ at the bud stage.

OSR2 is a mammalian homolog of the Drosophila odd-skipped family of transcription factors (Lan et al., 2004 [PubMed 15175245]).

Source: NCBI Gene 116039 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 46 total — 1 pathogenic
• MANE Select transcript: NM_001142462

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15830
Approved symbol	OSR2
Name	odd-skipped related transciption factor 2
Location	8q22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90037
Ensembl gene	ENSG00000164920
Ensembl biotype	protein_coding
OMIM	611297
Entrez	116039

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000297565, ENST00000435298, ENST00000457907, ENST00000518199, ENST00000520722, ENST00000520791, ENST00000520951, ENST00000521044, ENST00000522510, ENST00000523368, ENST00000874773, ENST00000874775, ENST00000951284, ENST00000951285, ENST00000951286

RefSeq mRNA: 4 — MANE Select: NM_001142462 NM_001142462, NM_001286841, NM_001394683, NM_053001

CCDS: CCDS47901, CCDS47902, CCDS69520

Canonical transcript exons

ENST00000297565 — 4 exons

Exon	Start	End
ENSE00001088653	98950656	98950755
ENSE00002112727	98944442	98944823
ENSE00003672820	98948839	98949608
ENSE00003931867	98951519	98952100

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 98.71.

FANTOM5 (CAGE): breadth broad, TPM avg 3.4947 / max 166.1639, expressed in 657 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89943	3.4299	651
89944	0.0648	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	98.71	gold quality
body of uterus	UBERON:0009853	98.36	gold quality
endocervix	UBERON:0000458	98.29	gold quality
left uterine tube	UBERON:0001303	98.04	gold quality
seminal vesicle	UBERON:0000998	97.69	gold quality
right ovary	UBERON:0002118	97.19	gold quality
urethra	UBERON:0000057	97.09	gold quality
decidua	UBERON:0002450	96.73	gold quality
ectocervix	UBERON:0012249	96.70	gold quality
right uterine tube	UBERON:0001302	96.09	gold quality
nipple	UBERON:0002030	95.94	gold quality
cauda epididymis	UBERON:0004360	95.88	gold quality
oocyte	CL:0000023	95.72	gold quality
left ovary	UBERON:0002119	95.69	gold quality
caput epididymis	UBERON:0004358	95.56	gold quality
endometrium	UBERON:0001295	95.49	gold quality
uterus	UBERON:0000995	95.29	gold quality
synovial joint	UBERON:0002217	95.05	gold quality
myometrium	UBERON:0001296	94.95	gold quality
mucosa of stomach	UBERON:0001199	93.52	gold quality
skin of hip	UBERON:0001554	93.41	gold quality
vagina	UBERON:0000996	93.11	gold quality
adult organism	UBERON:0007023	92.79	gold quality
corpus epididymis	UBERON:0004359	92.73	gold quality
female reproductive system	UBERON:0000474	92.53	gold quality
ovary	UBERON:0000992	92.33	gold quality
tibial nerve	UBERON:0001323	92.32	gold quality
penis	UBERON:0000989	92.15	gold quality
saphenous vein	UBERON:0007318	91.34	gold quality
uterine cervix	UBERON:0000002	91.13	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	718.26
E-MTAB-6701	yes	136.78
E-MTAB-10287	yes	112.32
E-GEOD-134144	yes	50.41
E-GEOD-125970	yes	14.71
E-CURD-112	yes	5.80
E-GEOD-124263	no	998.32
E-MTAB-8381	no	399.11
E-CURD-11	no	39.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
PAX8

JASPAR motifs

Motif	Name	Family
MA1646.1	OSR2	More than 3 adjacent zinc fingers
MA1646.2	OSR2	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:28473536

Upstream regulators (CollecTRI, top): ATF2, CEBPA, CEBPG, PAX9, RUNX2, SMAD3

miRNA regulators (miRDB)

56 targeting OSR2, 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-3924	100.00	72.09	2394
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6791-5P	99.16	65.92	1844

Literature-anchored findings (GeneRIF, showing 3)

• Results found that OSR2, VAV3, and PPFIA3 were significantly hypermethylated in gastric cancer (GC) patients offering a good alternative in a simple, promising, and noninvasive detection of GC. (PMID:27143812)
• A comprehensive molecular characterization of the 8q22.2 region reveals the prognostic relevance of OSR2 mRNA in muscle invasive bladder cancer. (PMID:33711044)
• Osr2 functions as a biomechanical checkpoint to aggravate CD8[+] T cell exhaustion in tumor. (PMID:38744281)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	osr2	ENSDARG00000038006
mus_musculus	Osr2	ENSMUSG00000022330
rattus_norvegicus	Osr2	ENSRNOG00000011136
drosophila_melanogaster	drm	FBGN0024244
caenorhabditis_elegans		WBGENE00003845

Paralogs (1): OSR1 (ENSG00000143867)

Protein

Protein identifiers

Protein odd-skipped-related 2 — Q8N2R0 (reviewed: Q8N2R0)

All UniProt accessions (4): E5RGY8, E5RH04, E5RH47, Q8N2R0

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the development of the mandibular molar tooth germ at the bud stage.

Subcellular location. Nucleus.

Similarity. Belongs to the Odd C2H2-type zinc-finger protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N2R0-1	1, OSR2A	yes
Q8N2R0-2	2, OSR2B
Q8N2R0-3	3

RefSeq proteins (4): NP_001135934, NP_001273770, NP_001381612, NP_443727 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050717	C2H2-ZF_Transcription_Reg	Family

Pfam: PF00096

UniProt features (12 total): zinc finger region 5, sequence conflict 2, splice variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N2R0-F1	61.81	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BROWNE_HCMV_INFECTION_6HR_DN, BENPORATH_ES_WITH_H3K27ME3, GOBP_METANEPHROS_DEVELOPMENT, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GGGNRMNNYCAT_UNKNOWN, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_HINDLIMB_MORPHOGENESIS, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GOZGIT_ESR1_TARGETS_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP

GO Biological Process (32): negative regulation of transcription by RNA polymerase II (GO:0000122), urogenital system development (GO:0001655), metanephros development (GO:0001656), mesonephros development (GO:0001823), chondrocyte differentiation (GO:0002062), pattern specification process (GO:0007389), positive regulation of cell population proliferation (GO:0008284), embryo development ending in birth or egg hatching (GO:0009792), positive regulation of gene expression (GO:0010628), cell differentiation (GO:0030154), positive regulation of bone mineralization (GO:0030501), osteoblast proliferation (GO:0033687), embryonic forelimb morphogenesis (GO:0035115), embryonic hindlimb morphogenesis (GO:0035116), embryonic skeletal limb joint morphogenesis (GO:0036023), middle ear morphogenesis (GO:0042474), odontogenesis (GO:0042476), embryonic digit morphogenesis (GO:0042733), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic skeletal system morphogenesis (GO:0048704), pronephros development (GO:0048793), positive regulation of epithelial cell proliferation (GO:0050679), roof of mouth development (GO:0060021), embryonic skeletal joint morphogenesis (GO:0060272), head development (GO:0060322), bone morphogenesis (GO:0060349), eyelid development in camera-type eye (GO:0061029), stem cell proliferation (GO:0072089), embryonic skeletal joint development (GO:0072498), positive regulation of stem cell proliferation (GO:2000648), cell population proliferation (GO:0008283)

GO Molecular Function (8): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
embryonic limb morphogenesis	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	2
kidney development	2
cell population proliferation	2
embryonic morphogenesis	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
negative regulation of DNA-templated transcription	1
system development	1
renal system development	1
cell differentiation	1
cartilage development	1
multicellular organism development	1
multicellular organismal process	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
embryo development	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
cellular developmental process	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
forelimb morphogenesis	1
hindlimb morphogenesis	1
limb joint morphogenesis	1
embryonic skeletal joint morphogenesis	1
ear morphogenesis	1
animal organ morphogenesis	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
transcription cis-regulatory region binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSR2	MSX1	P28360	862
OSR2	FOXL2	P58012	798
OSR2	PAX9	P55771	790
OSR2	PITX2	Q99697	747
OSR2	BMP4	P12644	628
OSR2	BARX1	Q9HBU1	583
OSR2	PRRX1	P54821	555
OSR2	FOXC1	Q12948	545
OSR2	TGFB3	P10600	543
OSR2	HAND2	P61296	542
OSR2	LGALS4	P56470	541
OSR2	SIX1	Q15475	540
OSR2	MSX2	P35548	512
OSR2	FOXE1	O00358	509
OSR2	SHOX2	O60902	463

IntAct

6 interactions, top by confidence:

A	B	Type	Score
OSR2	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
PSMA3	OSR2	psi-mi:“MI:0915”(physical association)	0.560
OSR2	SCGN	psi-mi:“MI:0914”(association)	0.350
LIMS1	OSR2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): OSR2 (Two-hybrid), OSR2 (Reconstituted Complex), OSR2 (Affinity Capture-RNA), KRTAP6-1 (Two-hybrid), OSR2 (Two-hybrid), TLE3 (Affinity Capture-MS), SCGN (Affinity Capture-MS), OSR2 (Proximity Label-MS), OSR2 (Affinity Capture-RNA)

ESM2 similar proteins: A0JPB4, A0PJY2, B0K011, O08876, O15090, O57415, O62651, O70237, O75626, O95863, P19544, P22561, P41183, P49952, P55878, P86413, Q02085, Q08DS3, Q0IHB8, Q0P4W9, Q0VDQ9, Q25C93, Q28G88, Q2TAR3, Q2VWH6, Q32NK7, Q3MHQ4, Q3T135, Q3UH06, Q567J8, Q5T0B9, Q5VTD9, Q5XJQ7, Q60636, Q62255, Q66JF8, Q6AY34, Q6DBW0, Q6NRM0, Q804Q5

Diamond homologs: B0K011, E9Q6W4, P23803, P41995, P86413, Q08DS3, Q0IHB8, Q32NK7, Q3T135, Q567J8, Q5XJQ7, Q62255, Q66JF8, Q6AY34, Q7PN68, Q8I7Z8, Q8N2R0, Q8TAX0, Q8WUU4, Q91ZD1, Q9BXA9, Q9N5X6, Q9UJQ4, Q9VQS6, Q9VQS7, Q9VQU9, Q9WVG7, B0X9H6, O75362, O77459, P28698, P31509, P60319, P80944, Q01798, Q02026, Q02027, Q292R5, Q29419, Q3US17

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	33
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3245432	NC_000008.10:g.(?99594279)(100513908_?)del	Pathogenic

SpliceAI

793 predictions. Top by Δscore:

Variant	Effect	Δscore
8:98949586:C:T	donor_gain	1.0000
8:98949605:ACAGG:A	donor_loss	1.0000
8:98949607:AGGTG:A	donor_loss	1.0000
8:98949609:G:GC	donor_loss	1.0000
8:98944819:GGGAG:G	donor_gain	0.9900
8:98944820:GGAG:G	donor_gain	0.9900
8:98944820:GGAGG:G	donor_gain	0.9900
8:98944821:GAG:G	donor_gain	0.9900
8:98944821:GAGG:G	donor_gain	0.9900
8:98944823:GGTG:G	donor_loss	0.9900
8:98944824:G:GA	donor_loss	0.9900
8:98944824:G:GG	donor_gain	0.9900
8:98948153:C:CA	acceptor_gain	0.9900
8:98949609:G:GG	donor_gain	0.9900
8:98950650:TTTCA:T	acceptor_loss	0.9900
8:98950651:TTCA:T	acceptor_loss	0.9900
8:98950652:TCAGA:T	acceptor_loss	0.9900
8:98950653:CAGAT:C	acceptor_loss	0.9900
8:98950654:A:AG	acceptor_gain	0.9900
8:98950654:AGA:A	acceptor_loss	0.9900
8:98950655:G:GG	acceptor_gain	0.9900
8:98950655:GATAC:G	acceptor_gain	0.9900
8:98950752:GCAG:G	donor_gain	0.9900
8:98950754:AGGT:A	donor_loss	0.9900
8:98950756:GT:G	donor_loss	0.9900
8:98950757:T:A	donor_loss	0.9900
8:98944806:T:TA	donor_gain	0.9800
8:98948151:T:TA	acceptor_gain	0.9800
8:98948154:G:A	acceptor_gain	0.9800
8:98950646:T:A	acceptor_loss	0.9700

AlphaMissense

2064 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:98949577:T:C	F209L	1.000
8:98949579:C:A	F209L	1.000
8:98949579:C:G	F209L	1.000
8:98949596:T:C	L215P	1.000
8:98950708:T:C	F237L	1.000
8:98950710:T:A	F237L	1.000
8:98950710:T:G	F237L	1.000
8:98951555:T:C	F265L	1.000
8:98951557:T:A	F265L	1.000
8:98951557:T:G	F265L	1.000
8:98951639:T:C	F293L	1.000
8:98951641:C:A	F293L	1.000
8:98951641:C:G	F293L	1.000
8:98951646:G:C	R295P	1.000
8:98949472:T:C	C174R	0.999
8:98949481:T:A	C177S	0.999
8:98949481:T:C	C177R	0.999
8:98949482:G:A	C177Y	0.999
8:98949482:G:C	C177S	0.999
8:98949493:T:C	F181L	0.999
8:98949495:T:A	F181L	0.999
8:98949495:T:G	F181L	0.999
8:98949520:C:A	H190N	0.999
8:98949520:C:G	H190D	0.999
8:98949522:T:A	H190Q	0.999
8:98949522:T:G	H190Q	0.999
8:98949534:C:A	H194Q	0.999
8:98949534:C:G	H194Q	0.999
8:98949556:T:C	C202R	0.999
8:98949565:T:C	C205R	0.999

dbSNP variants (sampled 300 via entrez): RS1000129398 (8:98944489 C>G,T), RS1000315856 (8:98947909 G>T), RS1000368330 (8:98948117 C>A,T), RS1000467525 (8:98942977 G>A), RS1000914058 (8:98942882 A>T), RS1001564135 (8:98950122 G>T), RS1001594635 (8:98948328 C>A), RS1001595161 (8:98950459 C>G), RS1001894241 (8:98949988 A>C,G,T), RS1001902619 (8:98948534 G>T), RS1001933772 (8:98948663 A>G), RS1001945638 (8:98943481 C>T), RS1002023965 (8:98943391 T>G), RS1003611492 (8:98947687 G>A,T), RS1003947363 (8:98950573 C>A,T)

Disease associations

OMIM: gene MIM:611297 | disease phenotypes: MIM:216550

GenCC curated gene-disease

Mondo (1): Cohen syndrome (MONDO:0008999)

Orphanet (1): Cohen syndrome (Orphanet:193)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536438	Cohen syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	4
Cisplatin	affects cotreatment, increases expression, decreases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
Calcitriol	affects cotreatment, increases expression	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Estradiol	decreases expression, increases expression, decreases reaction	2
Progesterone	decreases reaction, increases expression	2
Smoke	decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol A	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
beta-lapachone	decreases expression, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
dinophysistoxin 1	increases expression	1
azaspiracid	decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression, decreases expression	1
7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one	increases expression	1
NSC 689534	affects binding, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_HC86	HEK293 eGFP-OSR2	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01907555	Not specified	COMPLETED	Clinical, Molecular and Physiopathological Study of Cohen Syndrome and Cohen-like Syndromes