Variant position:  175

Type of variant:  Disease [Disclaimer: Variants classification is intended for research purposes only, not for clinical and diagnostic use. The label disease variant is assigned according to literature reports on probable disease-association that can be based on theoretical reasons. This label must not be considered as a definitive proof for the pathogenic role of a variant.]

Residue change:  From Arginine (R) to Histidine (H) at position 175 (R175H, p.Arg175His).

Physico-chemical properties:  Change from large size and basic (R) to medium size and polar (H)

BLOSUM score:  0

Involvement in disease:  Li-Fraumeni syndrome (LFS) [MIM:151623]: An autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. {ECO:0000269|PubMed:10484981, ECO:0000269|PubMed:1565144, ECO:0000269|PubMed:1737852, ECO:0000269|PubMed:1933902, ECO:0000269|PubMed:1978757, ECO:0000269|PubMed:2259385, ECO:0000269|PubMed:7887414, ECO:0000269|PubMed:8825920, ECO:0000269|PubMed:9452042}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Variant description:  In LFS; germline mutation and in sporadic cancers; somatic mutation; does not induce SNAI1 degradation; reduces interaction with ZNF385A.

Other resources:  

• Variant rs28934578 [ dbSNP | Ensembl ]

Variant position:  175

Protein sequence length:  393

Location on the sequence:   TRVRAMAIYKQSQHMTEVVR  R CPHHERCSDSDGLAPPQHLI

Residue conservation: 

Human                         TRVRAMAIYKQSQHMTEVVRRCPHHERCSD-SDGLAPPQHLI

                              TCVRAMAIYKKSEFVTEVVRRCPHHERCSDSSDGLAPPQHL

Rhesus macaque                SRVRAMAIYKQSQHMTEVVRRCPHHERCSD-SDGLAPPQHL

Mouse                         SRVRAMAIYKKSQHMTEVVRRCPHHERCSD-GDGLAPPQHL

Rat                           TRVRAMAIYKKSQHMTEVVRRCPHHERCSD-GDGLAPPQHL

Pig                           TRVRAMAIYKKSEYMTEVVRRCPHHERSSDYSDGLAPPQHL

Bovine                        TRVRAMAIYKKLEHMTEVVRRCPHHERSSDYSDGLAPPQHL

Rabbit                        TRVRAMAIYKKSQHMTEVVRRCPHHERCSD-SDGLAPPQHL

Sheep                         TRVRAMAIYKKLEHMTEVVRRSPHHERSSDYSDGLAPPQHL

Cat                           TCVRAMAIYKKSEFMTEVVRRCPHHERCPDSSDGLAPPQHL

Chicken                       SSLRAVAVYKKSEHVAEVVRRCPHHERCGGGTDGLAPAQHL

Xenopus laevis                SILRATAVYKKSEHVAEVVKRCPHHERSVEPGEDAAPPSHL

Zebrafish                     SVVRATAIYKKSEHVAEVVRRCPHHERTPD-GDNLAPAGHL

Sequence annotation in neighborhood:  

Hzf Determines cell survival upon genotoxic stress by modulating p53 transactivation.
Das S.; Raj L.; Zhao B.; Kimura Y.; Bernstein A.; Aaronson S.A.; Lee S.W.;
Cell 130:624-637(2007)
Cited for: INTERACTION WITH ZNF385A; CHARACTERIZATION OF VARIANTS ALA-143; HIS-175 AND PRO-175;

p53 inhibits tumor cell invasion via the degradation of snail protein in hepatocellular carcinoma.
Lim S.O.; Kim H.; Jung G.;
FEBS Lett. 584:2231-2236(2010)
Cited for: INTERACTION WITH SNAI1; CHARACTERIZATION OF VARIANTS LEU-110; PRO-155; HIS-175; SER-232; SER-249; HIS-273 AND TRP-282; MUTAGENESIS OF ARG-248;

p53 gene mutations in Barrett's epithelium and esophageal cancer.
Casson A.G.; Mukhopadhyay T.; Cleary K.R.; Ro J.Y.; Levin B.; Roth J.A.;
Cancer Res. 51:4495-4499(1991)
Cited for: VARIANTS SPORADIC CANCERS LEU-152; ALA-155; HIS-175; PHE-176 AND HIS-273;

Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome.
Frebourg T.; Barbier N.; Yan Y.-X.; Garber J.E.; Dreyfus M.; Fraumeni J.F. Jr.; Li F.P.; Friend S.H.;
Am. J. Hum. Genet. 56:608-615(1995)
Cited for: VARIANTS LFS HIS-175; ARG-193; GLN-248; CYS-273 AND TYR-275;

An extended Li-Fraumeni kindred with gastric carcinoma and a codon 175 mutation in TP53.
Varley J.M.; McGrown G.; Thorncroft M.; Tricker K.J.; Teare M.D.; Santibanez-Koref M.F.; Houlston R.S.; Martin J.; Birch J.M.; Evans D.G.R.;
J. Med. Genet. 32:942-945(1995)
Cited for: VARIANT LFS HIS-175;

The consensus coding sequences of human breast and colorectal cancers.
Sjoeblom T.; Jones S.; Wood L.D.; Parsons D.W.; Lin J.; Barber T.D.; Mandelker D.; Leary R.J.; Ptak J.; Silliman N.; Szabo S.; Buckhaults P.; Farrell C.; Meeh P.; Markowitz S.D.; Willis J.; Dawson D.; Willson J.K.V.; Gazdar A.F.; Hartigan J.; Wu L.; Liu C.; Parmigiani G.; Park B.H.; Bachman K.E.; Papadopoulos N.; Vogelstein B.; Kinzler K.W.; Velculescu V.E.;
Science 314:268-274(2006)
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-134; PHE-157; CYS-163; HIS-175; ARG-177; ARG-193; PRO-213; PHE-241; PHE-242; GLN-248; TRP-248; SER-249; TRP-267; LYS-271; CYS-273; HIS-273; LEU-273; SER-278; ILE-280 AND HIS-281;