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UniProtKB/Swiss-Prot P38935: Variant p.Thr221Ala

DNA-binding protein SMUBP-2
Gene: IGHMBP2
Variant information

Variant position:  221
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Threonine (T) to Alanine (A) at position 221 (T221A, p.Thr221Ala).
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 medium size and polar (T) to small size and hydrophobic (A)
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 HMN6; severe reduction of ATPase activity and loss of helicase activity on RNA duplices.
Any additional useful information about the variant.



Sequence information

Variant position:  221
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  993
The length of the canonical sequence.

Location on the sequence:   LFALSQKELAIIHGPPGTGK  T TTVVEIILQAVKQGLKVLCC
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                         LFALSQKELAIIHGPPGTGKTTTVVEIILQAVKQGLKVLCC

Mouse                         SFALAQKELAIIHGPPGTGKTTTVVEIILQAVKQGLKVLCC

Rat                           SFALAQKEVAIIHGPPGTGKTTTVVEIILQAVKQGLKVLCC

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.

TypePositionsDescription
Chain 2 – 993 DNA-binding protein SMUBP-2
Nucleotide binding 214 – 221 ATP
Helix 220 – 233


Literature citations

IGHMBP2 is a ribosome-associated helicase inactive in the neuromuscular disorder distal SMA type 1 (DSMA1).
Guenther U.P.; Handoko L.; Laggerbauer B.; Jablonka S.; Chari A.; Alzheimer M.; Ohmer J.; Ploettner O.; Gehring N.; Sickmann A.; von Au K.; Schuelke M.; Fischer U.;
Hum. Mol. Genet. 18:1288-1300(2009)
Cited for: FUNCTION AS AN ATP-DEPENDENT HELICASE; INTERACTION WITH RIBOSOMES; CHARACTERIZATION OF VARIANTS HMN6 ARG-196; ALA-221; ARG-241; LYS-382; PRO-445; ILE-493; ASN-565; ILE-583 AND HIS-603;

Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1).
Grohmann K.; Varon R.; Stolz P.; Schuelke M.; Janetzki C.; Bertini E.; Bushby K.; Muntoni F.; Ouvrier R.; Van Maldergem L.; Goemans N.M.L.A.; Lochmueller H.; Eichholz S.; Adams C.; Bosch F.; Grattan-Smith P.; Navarro C.; Neitzel H.; Polster T.; Topaloglu H.; Steglich C.; Guenther U.P.; Zerres K.; Rudnik-Schoeneborn S.; Huebner C.;
Ann. Neurol. 54:719-724(2003)
Cited for: VARIANTS HMN6 PRO-192; ALA-221; ARG-241; LYS-334; PRO-361; PRO-364; LYS-382; PRO-426; ASN-565; LYS-572 DEL; PRO-577; ILE-583; CYS-586; HIS-603; CYS-637 AND GLU-974;

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.