Reviewed, UniProtKB/Swiss-Prot P19544 (WT1_HUMAN)

Names and origin

Protein names

Recommended name:
    Wilms tumor protein
Alternative name(s):
    WT33

Gene names

Name:

WT1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	449 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Potential role in transcriptional regulation. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'.
Subunit structure	Interacts with WTIP By similarity. Interacts with ZNF224 via the zinc-finger region. Interacts with WTAP and SRY.
Subcellular location	Nucleus.
Tissue specificity	Expressed in the kidney and a subset of hematopoietic cells.
Involvement in disease	Defects in WT1 are the cause of Frasier syndrome (FS) [MIM:136680]. FS is characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant. Ref.32 Defects in WT1 are a cause of Wilms tumor--aniridia--genitourinary anomalies--mental retardation syndrome (WAGR syndrome) [MIM:194072]. Defects in WT1 are the cause of Wilms tumor 1 (WT1) [MIM:194070]. WT is an embryonal malignancy of the kidney that affects approximately 1 in 10'000 infants and young children. It occurs both in sporadic and hereditary forms. Ref.18 Ref.28 Ref.29 Ref.37 Defects in WT1 are the cause of Denys-Drash syndrome (DDS) [MIM:194080]. DDS is a typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic. Ref.29 Ref.9 Ref.10 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.27 Ref.30 Ref.33 Ref.34 Ref.35 Ref.36 Ref.40 Defects in WT1 are the cause of isolated diffuse mesangial sclerosis (IDMS) [MIM:256370]. IDMS is an early-onset nephrotic syndrome occurring in the absence of other abnormalities and resulting in renal failure. Inheritance is autosomal recessive. Ref.29 Ref.34 Defects in WT1 are a cause of Meacham syndrome [MIM:608978]. Meacham syndrome is a rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities. Ref.41 Defects in WT1 are a cause of hypospadias. Hypospadias is a common malformation in which the urethra opens on the ventral side of the penis. It is considered a complex disorder with both genetic and environmental factors involved in the pathogenesis. Hypospadias can occur alone on an apparently multifactorial basis or as part of syndromes. A chromosomal aberration involving WT1 may be a cause of desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with EWSR1.
Sequence similarities	Belongs to the EGR C2H2-type zinc-finger protein family. Contains 4 C2H2-type zinc fingers.

Ontologies

Keywords
Biological process	Cell cycle Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Disease mutation
Domain	Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Anti-oncogene
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of cell cycle Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: MGI transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Non-traceable author statement. Source: UniProtKB
Molecular function	transcription factor activity Ref.8 Ref.16 Non-traceable author statement. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P19544-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P19544-2)

The sequence of this isoform differs from the canonical sequence as follows:
     250-266: Missing.
     408-410: Missing.

Isoform 3 (identifier: P19544-3)

The sequence of this isoform differs from the canonical sequence as follows:
     250-266: Missing.

Isoform 4 (identifier: P19544-4)

The sequence of this isoform differs from the canonical sequence as follows:
     408-410: Missing.

Isoform 5 (identifier: P19544-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MQDPASTCVPEPASQHTLRSGPGCLQQPEQQGVRDPGGIWAKLGAAEASAERLQGRRSRGASGSEPQQM
     250-266: Missing.
     408-410: Missing.

Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 449

449

Wilms tumor protein

PRO_0000047131

Regions

Zinc finger

323 – 347

25

C2H2-type 1

Zinc finger

353 – 377

25

C2H2-type 2

Zinc finger

383 – 405

23

C2H2-type 3

Zinc finger

414 – 438

25

C2H2-type 4

Compositional bias

27 – 83

57

Pro-rich

Natural variations

Alternative sequence

1

1

M → MQDPASTCVPEPASQHTLRS GPGCLQQPEQQGVRDPGGIW AKLGAAEASAERLQGRRSRG ASGSEPQQM in isoform 5.

VSP_026675

Alternative sequence

250 – 266

17

Missing in isoform 2, isoform 3 and isoform 5.

VSP_006866

Alternative sequence

408 – 410

3

Missing in isoform 2, isoform 4 and isoform 5.

VSP_006867

Natural variant

131

1

A → T in hypospadias. Ref.38

VAR_043798

Natural variant

181

1

P → S in WT1. dbSNP rs2234584. Ref.28 Ref.37

VAR_007739

Natural variant

223

1

S → N in WT1. Ref.29

VAR_007740

Natural variant

253

1

G → A in WT1. Ref.28

VAR_007741

Natural variant

273

1

S → G in mesothelioma. Ref.24

VAR_007742

Natural variant

312

1

R → Q in IDMS. Ref.34

VAR_015053

Natural variant

330

1

C → Y in DDS. Ref.10

VAR_007743

Natural variant

342

1

M → R in DDS. Ref.34

VAR_015054

Natural variant

355

1

C → G in WT1. Ref.37

VAR_043799

Natural variant

355

1

C → Y in DDS. Ref.30 Ref.34

VAR_015055

Natural variant

360

1

C → G in DDS. Ref.23

VAR_007744

Natural variant

360

1

C → Y in DDS. Ref.23

VAR_043800

Natural variant

364

1

F → L in nephrotic syndrome. Ref.31

VAR_043801

Natural variant

366

1

R → C in WT1, DDS and Meacham syndrome.

VAR_007745

Natural variant

366

1

R → H in DDS and WT1.

VAR_007746

Natural variant

366

1

R → L in DDS. Ref.29 Ref.26 Ref.30 Ref.34

VAR_043802

Natural variant

369

1

Q → P in DDS. Ref.35

VAR_043803

Natural variant

373

1

H → Q in DDS and WT1.

VAR_007747

Natural variant

373

1

H → Y in DDS. Ref.27

VAR_015056

Natural variant

377

1

H → R in DDS. Ref.25

VAR_015057

Natural variant

377

1

H → Y in IDMS. Ref.29

VAR_007748

Natural variant

379

1

G → C in nephrotic syndrome. Ref.31

VAR_043804

Natural variant

383

1

F → L in IDMS. Ref.29

VAR_007749

Natural variant

385

1

C → R in DDS. Ref.30 Ref.34

VAR_015058

Natural variant

388

1

C → F in DDS. Ref.34 Ref.36

VAR_015059

Natural variant

388

1

C → R in nephrotic syndrome. Ref.34 Ref.36 Ref.39

VAR_043805

Natural variant

388

1

C → Y in DDS. Ref.34 Ref.36

VAR_043806

Natural variant

392

1

F → L in FS. Ref.32

VAR_015060

Natural variant

394

1

R → L in WT1. Ref.37

VAR_043807

Natural variant

394

1

R → P in DDS. Ref.29 Ref.10 Ref.22 Ref.23 Ref.34

VAR_043808

Natural variant

394

1

R → Q in DDS. Ref.29 Ref.10 Ref.22 Ref.23 Ref.34

VAR_015061

Natural variant

394

1

R → W in DDS, WT1 and Meacham syndrome.

VAR_007750

Natural variant

396

1

D → G in DDS. Ref.33 Ref.34

VAR_007752

Natural variant

396

1

D → N in DDS and IDMS.

VAR_007751

Natural variant

396

1

D → Y in DDS. Ref.33 Ref.34

VAR_043809

Natural variant

397

1

H → P in nephrotic syndrome. Ref.39

VAR_043810

Natural variant

398

1

L → P in DDS. Ref.29 Ref.22

VAR_015062

Natural variant

401

1

H → Y in DDS. Ref.21

VAR_043811

Natural variant

405

1

H → R in DDS. Ref.40

VAR_043812

Experimental info

Sequence conflict

288

1

I → M in AAH32861. Ref.7

Sequence conflict

365

1

S → F in AAA36810. Ref.6

Sequence conflict

365

1

S → F in AAB33443. Ref.8

Sequence conflict

387

1

T → A in CAA43819. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

449

Helix Strand Turn

Details...

Beta strand

386 – 388

3

Beta strand

391 – 394

4

Helix

395 – 402

8

Turn

403 – 405

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1991. Version 2. Checksum: 11C7FA3D485096B2	FASTA	449	49,188
	10 20 30 40 50 60 MGSDVRDLNA LLPAVPSLGG GGGCALPVSG AAQWAPVLDF APPGASAYGS LGGPAPPPAP 70 80 90 100 110 120 PPPPPPPPHS FIKQEPSWGG AEPHEEQCLS AFTVHFSGQF TGTAGACRYG PFGPPPPSQA 130 140 150 160 170 180 SSGQARMFPN APYLPSCLES QPAIRNQGYS TVTFDGTPSY GHTPSHHAAQ FPNHSFKHED 190 200 210 220 230 240 PMGQQGSLGE QQYSVPPPVY GCHTPTDSCT GSQALLLRTP YSSDNLYQMT SQLECMTWNQ 250 260 270 280 290 300 MNLGATLKGV AAGSSSSVKW TEGQSNHSTG YESDNHTTPI LCGAQYRIHT HGVFRGIQDV 310 320 330 340 350 360 RRVPGVAPTL VRSASETSEK RPFMCAYPGC NKRYFKLSHL QMHSRKHTGE KPYQCDFKDC 370 380 390 400 410 420 ERRFSRSDQL KRHQRRHTGV KPFQCKTCQR KFSRSDHLKT HTRTHTGKTS EKPFSCRWPS 430 440 CQKKFARSDE LVRHHNMHQR NMTKLQLAL
	Isoform 2. Checksum: C2F9912E0A4DA3DB	FASTA	429	47,195
	10 20 30 40 50 60 MGSDVRDLNA LLPAVPSLGG GGGCALPVSG AAQWAPVLDF APPGASAYGS LGGPAPPPAP 70 80 90 100 110 120 PPPPPPPPHS FIKQEPSWGG AEPHEEQCLS AFTVHFSGQF TGTAGACRYG PFGPPPPSQA 130 140 150 160 170 180 SSGQARMFPN APYLPSCLES QPAIRNQGYS TVTFDGTPSY GHTPSHHAAQ FPNHSFKHED 190 200 210 220 230 240 PMGQQGSLGE QQYSVPPPVY GCHTPTDSCT GSQALLLRTP YSSDNLYQMT SQLECMTWNQ 250 260 270 280 290 300 MNLGATLKGH STGYESDNHT TPILCGAQYR IHTHGVFRGI QDVRRVPGVA PTLVRSASET 310 320 330 340 350 360 SEKRPFMCAY PGCNKRYFKL SHLQMHSRKH TGEKPYQCDF KDCERRFSRS DQLKRHQRRH 370 380 390 400 410 420 TGVKPFQCKT CQRKFSRSDH LKTHTRTHTG EKPFSCRWPS CQKKFARSDE LVRHHNMHQR NMTKLQLAL
	Isoform 3. Checksum: 1ACA6CE3563DA9D2	FASTA	432	47,511
	10 20 30 40 50 60 MGSDVRDLNA LLPAVPSLGG GGGCALPVSG AAQWAPVLDF APPGASAYGS LGGPAPPPAP 70 80 90 100 110 120 PPPPPPPPHS FIKQEPSWGG AEPHEEQCLS AFTVHFSGQF TGTAGACRYG PFGPPPPSQA 130 140 150 160 170 180 SSGQARMFPN APYLPSCLES QPAIRNQGYS TVTFDGTPSY GHTPSHHAAQ FPNHSFKHED 190 200 210 220 230 240 PMGQQGSLGE QQYSVPPPVY GCHTPTDSCT GSQALLLRTP YSSDNLYQMT SQLECMTWNQ 250 260 270 280 290 300 MNLGATLKGH STGYESDNHT TPILCGAQYR IHTHGVFRGI QDVRRVPGVA PTLVRSASET 310 320 330 340 350 360 SEKRPFMCAY PGCNKRYFKL SHLQMHSRKH TGEKPYQCDF KDCERRFSRS DQLKRHQRRH 370 380 390 400 410 420 TGVKPFQCKT CQRKFSRSDH LKTHTRTHTG KTSEKPFSCR WPSCQKKFAR SDELVRHHNM 430 HQRNMTKLQL AL
	Isoform 4. Checksum: 8CE7FC116A41DA04	FASTA	446	48,872
	10 20 30 40 50 60 MGSDVRDLNA LLPAVPSLGG GGGCALPVSG AAQWAPVLDF APPGASAYGS LGGPAPPPAP 70 80 90 100 110 120 PPPPPPPPHS FIKQEPSWGG AEPHEEQCLS AFTVHFSGQF TGTAGACRYG PFGPPPPSQA 130 140 150 160 170 180 SSGQARMFPN APYLPSCLES QPAIRNQGYS TVTFDGTPSY GHTPSHHAAQ FPNHSFKHED 190 200 210 220 230 240 PMGQQGSLGE QQYSVPPPVY GCHTPTDSCT GSQALLLRTP YSSDNLYQMT SQLECMTWNQ 250 260 270 280 290 300 MNLGATLKGV AAGSSSSVKW TEGQSNHSTG YESDNHTTPI LCGAQYRIHT HGVFRGIQDV 310 320 330 340 350 360 RRVPGVAPTL VRSASETSEK RPFMCAYPGC NKRYFKLSHL QMHSRKHTGE KPYQCDFKDC 370 380 390 400 410 420 ERRFSRSDQL KRHQRRHTGV KPFQCKTCQR KFSRSDHLKT HTRTHTGEKP FSCRWPSCQK 430 440 KFARSDELVR HHNMHQRNMT KLQLAL
	Isoform 5. Checksum: EF68A3182252372B	FASTA	497	54,288
	10 20 30 40 50 60 MQDPASTCVP EPASQHTLRS GPGCLQQPEQ QGVRDPGGIW AKLGAAEASA ERLQGRRSRG 70 80 90 100 110 120 ASGSEPQQMG SDVRDLNALL PAVPSLGGGG GCALPVSGAA QWAPVLDFAP PGASAYGSLG 130 140 150 160 170 180 GPAPPPAPPP PPPPPPHSFI KQEPSWGGAE PHEEQCLSAF TVHFSGQFTG TAGACRYGPF 190 200 210 220 230 240 GPPPPSQASS GQARMFPNAP YLPSCLESQP AIRNQGYSTV TFDGTPSYGH TPSHHAAQFP 250 260 270 280 290 300 NHSFKHEDPM GQQGSLGEQQ YSVPPPVYGC HTPTDSCTGS QALLLRTPYS SDNLYQMTSQ 310 320 330 340 350 360 LECMTWNQMN LGATLKGHST GYESDNHTTP ILCGAQYRIH THGVFRGIQD VRRVPGVAPT 370 380 390 400 410 420 LVRSASETSE KRPFMCAYPG CNKRYFKLSH LQMHSRKHTG EKPYQCDFKD CERRFSRSDQ 430 440 450 460 470 480 LKRHQRRHTG VKPFQCKTCQ RKFSRSDHLK THTRTHTGEK PFSCRWPSCQ KKFARSDELV 490 RHHNMHQRNM TKLQLAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping." Gessler M., Poustka A., Cavenee W., Neve R.L., Orkin S.H., Bruns G.A.P. Nature 343:774-778(1990) [PubMed: 2154702] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal kidney.
[2]	"Alternative splicing and genomic structure of the Wilms tumor gene WT1." Haber D.A., Sohn R.L., Buckler A.J., Pelletier J., Call K.M., Housman D.E. Proc. Natl. Acad. Sci. U.S.A. 88:9618-9622(1991) [PubMed: 1658787] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), ALTERNATIVE SPLICING. Tissue: Placenta.
[3]	"The genomic organization and expression of the WT1 gene." Gessler M., Konig A., Bruns G.A.P. Genomics 12:807-813(1992) [PubMed: 1572653] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 4).
[4]	NIEHS SNPs program Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus." Call K.M., Glaser T., Ito C.Y., Buckler A.J., Pelletier J., Haber D.A., Rose E.A., Kral A., Yeger H., Lewis W.H., Jones C., Housman D.E. Cell 60:509-520(1990) [PubMed: 2154335] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-449 (ISOFORMS 2/5).
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 148-449 (ISOFORM 4). Tissue: Testis.
[8]	"High affinity binding sites for the Wilms' tumour suppressor protein WT1." Hamilton T.B., Barilla K.C., Romaniuk P.J. Nucleic Acids Res. 23:277-284(1995) [PubMed: 7862533] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 301-449. Tissue: Fetal kidney.
[9]	"Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome." Pelletier J., Bruening W., Kashtan C.E., Mauer S.M., Manivel J.C., Striegel J.E., Houghton D.C., Junien C., Habib R., Fouser L., Fine R.N., Silverman B.L., Haber D.A., Housman D.E. Cell 67:437-447(1991) [PubMed: 1655284] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 385-405, VARIANTS DDS.
[10]	"Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development." Bruening W., Bardeesy N., Silverman B.L., Cohn R.A., Machin G.A., Aronson A.J., Housman D., Pelletier J. Nat. Genet. 1:144-148(1992) [PubMed: 1302008] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 385-405, VARIANTS DDS TYR-330; PRO-394 AND TRP-394.
[11]	"Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development." Buckler A.J., Pelletier J., Haber D.A., Glaser T., Housman D.E. Mol. Cell. Biol. 11:1707-1712(1991) [PubMed: 1671709] [Abstract] Cited for: IDENTIFICATION OF START CODON, ALTERNATIVE SPLICING.
[12]	"Identification of WTAP, a novel Wilms' tumour 1-associating protein." Little N.A., Hastie N.D., Davies R.C. Hum. Mol. Genet. 9:2231-2239(2000) [PubMed: 11001926] [Abstract] Cited for: INTERACTION WITH WTAP.
[13]	"Inhibition of Wilms tumor 1 transactivation by bone marrow zinc finger 2, a novel transcriptional repressor." Lee T.H., Lwu S., Kim J., Pelletier J. J. Biol. Chem. 277:44826-44837(2002) [PubMed: 12239212] [Abstract] Cited for: INTERACTION WITH ZNF224.
[14]	"Transcriptional activity of testis-determining factor SRY is modulated by the Wilms' tumor 1 gene product, WT1." Matsuzawa-Watanabe Y., Inoue J., Semba K. Oncogene 22:7900-7904(2003) [PubMed: 12970737] [Abstract] Cited for: INTERACTION WITH SRY.
[15]	"WT1: a novel tumor suppressor gene inactivated in Wilms' tumor." Haber D.A., Buckler A.J. New Biol. 4:97-106(1992) [PubMed: 1313285] [Abstract] Cited for: REVIEW.
[16]	"The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor." Rauscher F.J. III FASEB J. 7:896-903(1993) [PubMed: 8393820] [Abstract] Cited for: REVIEW.
[17]	"WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour." Pelletier J., Bruening W., Li F.P., Haber D.A., Glaser T., Housman D.E. Nature 353:431-434(1991) [PubMed: 1654525] [Abstract] Cited for: INVOLVEMENT IN WAGR SYNDROME.
[18]	"Zinc finger point mutations within the WT1 gene in Wilms tumor patients." Little M.H., Prosser J., Condie A., Smith P.J., van Heyningen V., Hastie N.D. Proc. Natl. Acad. Sci. U.S.A. 89:4791-4795(1992) [PubMed: 1317572] [Abstract] Cited for: VARIANT WT1 CYS-366.
[19]	"Constitutional mutations in the WT1 gene in patients with Denys-Drash syndrome." Baird P.N., Santos A., Groves N., Jadresic L., Cowell J.K. Hum. Mol. Genet. 1:301-305(1992) [PubMed: 1338906] [Abstract] Cited for: VARIANTS DDS.
[20]	"Evidence that WT1 mutations in Denys-Drash syndrome patients may act in a dominant-negative fashion." Little M.H., Williamson K.A., Mannens M., Kelsey A., Gosden C., Hastie N.D., van Heyningen V. Hum. Mol. Genet. 2:259-264(1993) [PubMed: 8388765] [Abstract] Cited for: VARIANTS DDS.
[21]	"A novel zinc finger mutation in a patient with Denys-Drash syndrome." Baird P.N., Cowell J.K. Hum. Mol. Genet. 2:2193-2194(1993) [PubMed: 8111391] [Abstract] Cited for: VARIANT DDS TYR-401.
[22]	"Molecular analysis of two Japanese cases of Denys-Drash syndrome." Tsuda M., Sakiyama T., Kitagawa T., Watanabe S., Watanabe T., Takahashi S., Kawaguchi H., Ito K. J. Inherit. Metab. Dis. 16:876-880(1993) [PubMed: 8295405] [Abstract] Cited for: VARIANTS DDS TRP-394 AND PRO-398.
[23]	"Mutational screening of the Wilms's tumour gene, WT1, in males with genital abnormalities." Clarkson P.A., Davies H.R., Williams D.M., Chaudhary R., Hughes I.A., Patterson M.N. J. Med. Genet. 30:767-772(1993) [PubMed: 8411073] [Abstract] Cited for: VARIANTS DDS TYR-360 AND TRP-394.
[24]	"The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma." Park S., Schalling M., Bernard A., Maheswaran S., Shipley G.C., Roberts D., Fletcher J., Shipman R., Rheinwald J., Demetri G., Griffin J., Minden M., Housman D.E., Haber D.A. Nat. Genet. 4:415-420(1993) [PubMed: 8401592] [Abstract] Cited for: VARIANT MESOTHELIOMA GLY-273.
[25]	"WT1 mutations in patients with Denys-Drash syndrome: a novel mutation in exon 8 and paternal allele origin." Nordenskjold A., Friedman E., Anvret M. Hum. Genet. 93:115-120(1994) [PubMed: 8112732] [Abstract] Cited for: VARIANT DDS ARG-377.
[26]	"A newly identified exonic mutation of the WT1 gene in a patient with Denys-Drash syndrome." Tsuda M., Sakiyama T., Owada M., Chiba Y. Acta Paediatr. Jpn. Overseas Ed. 38:265-266(1996) [PubMed: 8741319] [Abstract] Cited for: VARIANT DDS LEU-366.
[27]	"A novel mutation H373Y in the Wilms' tumor suppressor gene, WT1, associated with Denys-Drash syndrome." Ghahremani M., Chan C.B., Bistritzer T., Aladjem M.M., Tieder M., Pelletier J. Hum. Hered. 46:336-338(1996) [PubMed: 8956030] [Abstract] Cited for: VARIANT DDS TYR-373.
[28]	"Correlation of germ-line mutations and two-hit inactivation of the WT1 gene with Wilms tumors of stromal-predominant histology." Schumacher V., Schneider S., Figge A., Wildhardt G., Harms D., Schmidt D., Weirich A., Ludwig R., Royer-Pokora B. Proc. Natl. Acad. Sci. U.S.A. 94:3972-3977(1997) [PubMed: 9108089] [Abstract] Cited for: VARIANTS WT1 SER-181 AND ALA-253.
[29]	"Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database." Jeanpierre C., Denamur E., Henry I., Cabanis M.-O., Luce S., Cecille A., Elion J., Peuchmaur M., Loirat C., Niaudet P., Gubler M.-C., Junien C. Am. J. Hum. Genet. 62:824-833(1998) [PubMed: 9529364] [Abstract] Cited for: VARIANTS IDMS TYR-377; LEU-383 AND ASN-396, VARIANTS DDS CYS-366; GLN-394; TRP-394 AND PRO-398, VARIANT WT1 ASN-223.
[30]	"Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome?" Kikuchi H., Takata A., Akasaka Y., Fukuzawa R., Yoneyama H., Kurosawa Y., Honda M., Kamiyama Y., Hata J. J. Med. Genet. 35:45-48(1998) [PubMed: 9475094] [Abstract] Cited for: VARIANTS DDS TYR-355; HIS-366 AND ARG-385.
[31]	"Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations." Schumacher V., Schaerer K., Wuehl E., Altrogge H., Bonzel K.-E., Guschmann M., Neuhaus T.J., Pollastro R.M., Kuwertz-Broeking E., Bulla M., Tondera A.-M., Mundel P., Helmchen U., Waldherr R., Weirich A., Royer-Pokora B. Kidney Int. 53:1594-1600(1998) [PubMed: 9607189] [Abstract] Cited for: VARIANTS NEPHROTIC SYNDROME LEU-364; HIS-366; CYS-379; ARG-385; GLN-394; TRP-394 AND ASN-396.
[32]	"Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome." Kohsaka T., Tagawa M., Takekoshi Y., Yanagisawa H., Tadokoro K., Yamada M. Hum. Mutat. 14:466-470(1999) [PubMed: 10571943] [Abstract] Cited for: VARIANT FS LEU-392.
[33]	"Novel WT1 exon 9 mutation (D396Y) in a patient with early onset Denys Drash syndrome." Little M., Carman G., Donaldson E. Hum. Mutat. 15:389-389(2000) [PubMed: 10738002] [Abstract] Cited for: VARIANT DDS TYR-396.
[34]	"Constitutional WT1 correlate with clinical features in children with progressive nephropathy." Takata A., Kikuchi H., Fukuzawa R., Ito S., Honda M., Hata J. J. Med. Genet. 37:698-701(2000) [PubMed: 11182928] [Abstract] Cited for: VARIANTS DDS ARG-342; TYR-355; HIS-366; ARG-385; PHE-388; TRP-394 AND ASN-396, VARIANT IDMS GLN-312.
[35]	"A novel missense mutation of the WT1 gene causing Denys-Drash syndrome with exceptionally mild renal manifestations." Ohta S., Ozawa T., Izumino K., Sakuragawa N., Fuse H. J. Urol. 163:1857-1858(2000) [PubMed: 10799199] [Abstract] Cited for: VARIANT DDS PRO-369.
[36]	"Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome." Swiatecka-Urban A., Mokrzycki M.H., Kaskel F., Da Silva F., Denamur E. Pediatr. Nephrol. 16:627-630(2001) [PubMed: 11519891] [Abstract] Cited for: VARIANT DDS TYR-388.
[37]	"Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development." Royer-Pokora B., Beier M., Henzler M., Alam R., Schumacher V., Weirich A., Huff V. Am. J. Med. Genet. A 127:249-257(2004) [PubMed: 15150775] [Abstract] Cited for: VARIANTS WT1 SER-181; GLY-355; CYS-366; HIS-366; GLN-373; TRP-394 AND LEU-394.
[38]	"Mutation analysis of five candidate genes in Chinese patients with hypospadias." Wang Y., Li Q., Xu J., Liu Q., Wang W., Lin Y., Ma F., Chen T., Li S., Shen Y. Eur. J. Hum. Genet. 12:706-712(2004) [PubMed: 15266301] [Abstract] Cited for: VARIANT HYPOSPADIAS THR-131.
[39]	"Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome." Members of the APN study group Ruf R.G., Schultheiss M., Lichtenberger A., Karle S.M., Zalewski I., Mucha B., Everding A.S., Neuhaus T., Patzer L., Plank C., Haas J.P., Ozaltin F., Imm A., Fuchshuber A., Bakkaloglu A., Hildebrandt F. Kidney Int. 66:564-570(2004) [PubMed: 15253707] [Abstract] Cited for: VARIANTS NEPHROTIC SYNDROME ARG-388 AND PRO-397.
[40]	"A novel mutation of WT1 exon 9 in a patient with Denys-Drash syndrome and pyloric stenosis." Hu M., Craig J., Howard N., Kan A., Chaitow J., Little D., Alexander S.I. Pediatr. Nephrol. 19:1160-1163(2004) [PubMed: 15349765] [Abstract] Cited for: VARIANT DDS ARG-405.
[41]	"WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations." Suri M., Kelehan P., O'neill D., Vadeyar S., Grant J., Ahmed S.F., Tolmie J., McCann E., Lam W., Smith S., FitzPatrick D., Hastie N.D., Reardon W. Am. J. Med. Genet. A 143:2312-2320(2007) [PubMed: 17853480] [Abstract] Cited for: VARIANTS MEACHAM SYNDROME CYS-366 AND TRP-394.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X51630 mRNA. Translation: CAA35956.1. Different initiation.
M80232 , M80217, M80218, M80219, M80220, M80221, M80228, M80229, M80231 Genomic DNA. Translation: AAA61299.1.
X61631 , X61632, X61633, X61634, X61635, X61636, X61637, X61638 Genomic DNA. Translation: CAA43819.1.
AY245105 Genomic DNA. Translation: AAO61088.1.
AL049692 Genomic DNA. Translation: CAC39220.2.
M30393 mRNA. Translation: AAA36810.1.
BC032861 mRNA. Translation: AAH32861.1. Different initiation.
S75264 mRNA. Translation: AAB33443.1. Different initiation.
S61515 Genomic DNA. Translation: AAB20110.1.
S61522 Genomic DNA. Translation: AAB20111.1.
S61524 Genomic DNA. Translation: AAB20112.1.
S60755 Genomic DNA. Translation: AAC60605.1.

IPI

IPI00019517.
IPI00215679.
IPI00374173.
IPI00550100.
IPI00853526.

PIR

A38080.

RefSeq

NP_000369.3.
NP_077742.2.
NP_077743.2.
NP_077744.3.

UniGene

Hs.591980

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LU6	model	-	A	310-449	[»]
1XF7	NMR	-	A	381-407	[»]
2G7T	model	-	A	310-449	[»]
2G7V	model	-	A	310-449	[»]
2G7W	model	-	A	310-449	[»]
2G7X	model	-	A	310-449	[»]
2PRT	X-ray	3.15	A	318-438	[»]

ModBase

Search...

PTM databases

PhosphoSite

P19544.

Genome annotation databases

Ensembl

ENSG00000184937. Homo sapiens. [Contig view]

GeneID

7490.

KEGG

hsa:7490.

Organism-specific databases

GeneCards

GC11M032365.

H-InvDB

HIX0000516.
HIX0009531.

HGNC

HGNC:12796. WT1.

MIM

136680. phenotype.
194070. phenotype.
194072. phenotype.
194080. phenotype.
256370. phenotype.
607102. gene.
608978. phenotype.

Orphanet

220. Denys-Drash syndrome.
347. Frasier syndrome.
3097. Meacham syndrome.
804. Mesangial sclerosis, diffuse.
654. Nephroblastoma.
84271. Nephrotic syndrome, idiopathic, steroid-resistant, sporadic.
93220. Nephrotic syndrome, idiopathic, steroid-resistant, with diffuse mesangial sclerosis, sporadic.
893. WAGR syndrome.

PharmGKB

PA37395.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P19544.

HOVERGEN

P19544.

Enzyme and pathway databases

Pathway_Interaction_DB

telomerasepathway. Regulation of Telomerase.

Gene expression databases

ArrayExpress

P19544.

Bgee

P19544.

CleanEx

HS_WT1.

GermOnline

ENSG00000184937. Homo sapiens.

Family and domain databases

InterPro

IPR000976. Wilms_tumour.
IPR017987. Wilms_tumour_rgn_bac.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]

Gene3D

G3DSA:3.30.160.60. Znf_C2H2/integrase_DNA-bd. 4 hits.

Pfam

PF02165. WT1. 1 hit.
PF00096. zf-C2H2. 4 hits.
[Graphical view]

PRINTS

PR00049. WILMSTUMOUR.

ProDom

PD000003. Znf_C2H2. 2 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00355. ZnF_C2H2. 4 hits.
[Graphical view]

PROSITE

PS00028. ZINC_FINGER_C2H2_1. 4 hits.
PS50157. ZINC_FINGER_C2H2_2. 4 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

29336.

SOURCE

Search...

Entry information

Entry name

WT1_HUMAN

Accession

Primary (citable) accession number: P19544
Secondary accession number(s): Q15881 , Q16256, Q16575, Q8IYZ5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	August 1, 1991
Last modified:	June 16, 2009
This is version 128 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)