UniProtKB/Swiss-Prot O43541: Variant p.Ala325Thr

Mothers against decapentaplegic homolog 6
Gene: SMAD6
Feedback?

Variant information Variant position:

325 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Alanine (A) to Threonine (T) at position 325 (A325T, p.Ala325Thr). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from small size and hydrophobic (A) to medium size and polar (T) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In CRS7; found in a patient with congenital mitral valve prolapse; uncertain significance; no effect on inhibition of BMP signaling pathway. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs199822239 [ dbSNP | Ensembl ]

Sequence information Variant position:

325 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

496 The length of the canonical sequence.
Location on the sequence:

ATNSLITAPGEFSDASMSPD A TKPSHWCSVAYWEHRTRVGR The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         ATNSLITAPGEFSDASMSPDATKPSHWCSVAYWEHRTRVGR

Mouse                         ATNSLITAPGEFSDASMSPDATKPSHWCSVAYWEHRTRVGR

Chicken                       ATNSPNVTPGEFSDASTSPDAVKRSHWCNVAYWEHRTRVGR

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 496	Mothers against decapentaplegic homolog 6
Alternative sequence	318 – 338	DASMSPDATKPSHWCSVAYWE -> AADAGIGSRGNRGLESSVPCS. In isoform D.

Literature citations
Nonsynonymous variants in the SMAD6 gene predispose to congenital cardiovascular malformation.
Tan H.L.; Glen E.; Topf A.; Hall D.; O'Sullivan J.J.; Sneddon L.; Wren C.; Avery P.; Lewis R.J.; ten Dijke P.; Arthur H.M.; Goodship J.A.; Keavney B.D.;
Hum. Mutat. 33:720-727(2012)
Cited for: INVOLVEMENT IN CONGENITAL CARDIOVASCULAR MALFORMATIONS; INVOLVEMENT IN AOVD2; VARIANT THR-325; VARIANTS AOVD2 LEU-415 AND PHE-484; CHARACTERIZATION OF VARIANTS AOVD2 LEU-415 AND PHE-484; FUNCTION; SMAD6 variants in craniosynostosis: genotype and phenotype evaluation.
Calpena E.; Cuellar A.; Bala K.; Swagemakers S.M.A.; Koelling N.; McGowan S.J.; Phipps J.M.; Balasubramanian M.; Cunningham M.L.; Douzgou S.; Lattanzi W.; Morton J.E.V.; Shears D.; Weber A.; Wilson L.C.; Lord H.; Lester T.; Johnson D.; Wall S.A.; Twigg S.R.F.; Mathijssen I.M.J.; Boardman-Pretty F.; Boyadjiev S.A.; Wilkie A.O.M.;
Genet. Med. 22:1498-1506(2020)
Cited for: VARIANTS CRS7 ARG-14; ASN-36; 42-ARG--ARG-496 DEL; CYS-85; CYS-88; VAL-98; LEU-113; LYS-171; PRO-224; MET-239; ASN-242; ARG-244; ARG-261; LEU-263; 279-TYR--ARG-496 DEL; THR-325; THR-333; CYS-365; ARG-390; ARG-395; ARG-473 AND LYS-489; CHARACTERIZATION OF VARIANTS CRS7 ARG-14; ASN-36; CYS-85; CYS-88; VAL-98; LEU-113; LYS-171; PRO-224; MET-239; ASN-242; ARG-244; ARG-261; LEU-263; THR-325; THR-333; ARG-390; ARG-395; ARG-473 AND LYS-489; Homozygous SMAD6 variants in two unrelated patients with craniosynostosis and radioulnar synostosis.
Luyckx I.; Walton I.S.; Boeckx N.; Van Schil K.; Pang C.; De Praeter M.; Lord H.; Watson C.M.; Bonthron D.T.; Van Laer L.; Wilkie A.O.M.; Loeys B.;
J. Med. Genet. 61:363-368(2024)
Cited for: VARIANTS GLY-195 AND LYS-273; CHARACTERIZATION OF VARIANTS GLY-195; LYS-273; THR-325 AND PHE-484;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.