Variant position:  176

Type of variant:  LP/P [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 Tyrosine (Y) to Cysteine (C) at position 176 (Y176C, p.Tyr176Cys).

Physico-chemical properties:  Change from large size and aromatic (Y) to medium size and polar (C)

BLOSUM score:  -2

Variant description:  In FAP2; loss of DNA glycosylase activity; decreased DNA binding; loss of function in DNA repair.

Other resources:  

• Variant rs34612342 [ dbSNP | Ensembl ]

Variant position:  176

Protein sequence length:  546

Location on the sequence:   LQDLASASLEEVNQLWAGLG  Y YSRGRRLQEGARKVVEELGG

Residue conservation: 

Human                         LQDLASASLEEVNQLWAGLGYYSRGRRLQEGARKVVEELGG

Mouse                         LQDLASASLEEVNQLWSGLGYYSRGRRLQEGARKVVEELGG

Rat                           LQDLASASLEEVNQLWSGLGYYSRGRRLQEGARKVVEELGG

Sequence annotation in neighborhood:  

Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors.
Al-Tassan N.; Chmiel N.H.; Maynard J.; Fleming N.; Livingston A.L.; Williams G.T.; Hodges A.K.; Davies D.R.; David S.S.; Sampson J.R.; Cheadle J.P.;
Nat. Genet. 30:227-232(2002)
Cited for: VARIANTS FAP2 CYS-176 AND ASP-393;

Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH.
Sampson J.R.; Dolwani S.; Jones S.; Eccles D.; Ellis A.; Evans D.G.; Frayling I.; Jordan S.; Maher E.R.; Mak T.; Maynard J.; Pigatto F.; Shaw J.; Cheadle J.P.;
Lancet 362:39-41(2003)
Cited for: VARIANTS FAP2 ARG-128; CYS-176 AND ASP-393;

Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH.
Sieber O.M.; Lipton L.; Crabtree M.; Heinimann K.; Fidalgo P.; Phillips R.K.S.; Bisgaard M.-L.; Orntoft T.F.; Aaltonen L.A.; Hodgson S.V.; Thomas H.J.W.; Tomlinson I.P.M.;
N. Engl. J. Med. 348:791-799(2003)
Cited for: VARIANTS FAP2 CYS-176 AND ASP-393; VARIANTS MET-22; HIS-335 AND PHE-512;

Mutations of APC and MYH in unrelated Italian patients with adenomatous polyposis coli.
Aceto G.; Curia M.C.; Veschi S.; De Lellis L.; Mammarella S.; Catalano T.; Stuppia L.; Palka G.; Valanzano R.; Tonelli F.; Casale V.; Stigliano V.; Cetta F.; Battista P.; Mariani-Costantini R.; Cama A.;
Hum. Mutat. 26:394-394(2005)
Cited for: VARIANTS FAP2 CYS-176; HIS-242; TRP-271; PRO-385; ASP-393; CYS-423 AND GLU-477 DEL; VARIANTS MET-22 AND HIS-335;

Low frequency of AXIN2 mutations and high frequency of MUTYH mutations in patients with multiple polyposis.
Lejeune S.; Guillemot F.; Triboulet J.P.; Cattan S.; Mouton C.; Porchet N.; Manouvrier S.; Buisine M.P.;
Hum. Mutat. 27:1064-1064(2006)
Cited for: VARIANTS FAP2 CYS-176; SER-177; VAL-280; LEU-292; PRO-385 AND ASP-393; VARIANTS MET-22; HIS-335 AND PHE-512;

Prevalence of MYH germline mutations in Swiss APC mutation-negative polyposis patients.
Russell A.M.; Zhang J.; Luz J.; Hutter P.; Chappuis P.O.; Berthod C.R.; Maillet P.; Mueller H.; Heinimann K.;
Int. J. Cancer 118:1937-1940(2006)
Cited for: VARIANTS FAP2 ILE-TRP-148 INS; CYS-176; GLN-182; VAL-220; HIS-242 AND ASP-393; VARIANTS MET-22 AND HIS-335;

MUTYH-associated polyposis: 70 of 71 patients with biallelic mutations present with an attenuated or atypical phenotype.
Aretz S.; Uhlhaas S.; Goergens H.; Siberg K.; Vogel M.; Pagenstecher C.; Mangold E.; Caspari R.; Propping P.; Friedl W.;
Int. J. Cancer 119:807-814(2006)
Cited for: VARIANTS FAP2 LEU-154; CYS-176; HIS-179; HIS-242; TRP-271; LEU-292; CYS-306; ASP-393; LEU-402; CYS-423; GLU-477 DEL AND PHE-490;

Heterogeneous molecular mechanisms underlie attenuated familial adenomatous polyposis.
Cattaneo F.; Molatore S.; Mihalatos M.; Apessos A.; Venesio T.; Bione S.; Grignani P.; Nasioulas G.; Ranzani G.N.;
Genet. Med. 9:836-841(2007)
Cited for: VARIANTS FAP2 CYS-176; CYS-179; TRP-182 AND ASP-393;

Functional analysis of MUTYH mutated proteins associated with familial adenomatous polyposis.
D'Agostino V.G.; Minoprio A.; Torreri P.; Marinoni I.; Bossa C.; Petrucci T.C.; Albertini A.M.; Ranzani G.N.; Bignami M.; Mazzei F.;
DNA Repair 9:700-707(2010)
Cited for: CHARACTERIZATION OF VARIANTS FAP2 ILE-TRP-148 INS; CYS-176; TRP-182; ASP-393 AND GLU-477 DEL; FUNCTION; CATALYTIC ACTIVITY;

MUTYH mutations associated with familial adenomatous polyposis: functional characterization by a mammalian cell-based assay.
Molatore S.; Russo M.T.; D'Agostino V.G.; Barone F.; Matsumoto Y.; Albertini A.M.; Minoprio A.; Degan P.; Mazzei F.; Bignami M.; Ranzani G.N.;
Hum. Mutat. 31:159-166(2010)
Cited for: VARIANTS FAP2 ILE-TRP-148 INS; TRP-182 AND GLU-477 DEL; CHARACTERIZATION OF VARIANTS FAP2 ILE-TRP-148 INS; CYS-176; TRP-182; ASP-393 AND GLU-477 DEL;

Adenine DNA glycosylase activity of 14 human MutY homolog (MUTYH) variant proteins found in patients with colorectal polyposis and cancer.
Goto M.; Shinmura K.; Nakabeppu Y.; Tao H.; Yamada H.; Tsuneyoshi T.; Sugimura H.;
Hum. Mutat. 31:E1861-E1874(2010)
Cited for: CHARACTERIZATION OF VARIANTS FAP2 CYS-176; HIS-179; VAL-220; VAL-280; CYS-306; PRO-385; ASP-393; LEU-402 AND GLU-477 DEL; CHARACTERIZATION OF VARIANTS GLU-72; VAL-370 AND PHE-512; FUNCTION; MUTAGENESIS OF ASP-233;

Functional complementation assay for 47 MUTYH variants in a MutY-disrupted Escherichia coli strain.
Komine K.; Shimodaira H.; Takao M.; Soeda H.; Zhang X.; Takahashi M.; Ishioka C.;
Hum. Mutat. 36:704-711(2015)
Cited for: CHARACTERIZATION OF VARIANTS FAP2 LEU-18; HIS-125; ARG-128; LEU-154; CYS-176; CYS-179; HIS-179; GLN-182; GLU-186; VAL-220; TRP-238; HIS-242; TRP-271; GLU-283; LEU-292; CYS-306; THR-377; PRO-385; ASP-393; LEU-402; MET-417; CYS-423; ASP-470; THR-470; GLU-477 DEL; THR-486 AND PHE-490; CHARACTERIZATION OF VARIANTS GASC SER-402 AND ARG-411; CHARACTERIZATION OF VARIANTS MET-22; ASP-25; ARG-100; ASN-102; VAL-224; MET-231; CYS-242; PHE-243; TRP-287; HIS-335; ARG-335; GLN-434; PRO-434; GLU-500; PHE-512; LEU-513; MET-526 AND GLN-531; FUNCTION; SUBCELLULAR LOCATION;