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UniProtKB/Swiss-Prot P63267: Variant p.Arg40His

Actin, gamma-enteric smooth muscle
Gene: ACTG2
Variant information

Variant position:  40
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Arginine (R) to Histidine (H) at position 40 (R40H, p.Arg40His).
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 large size and basic (R) to medium size and polar (H)
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 VSCM1 and MMIHS5.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  40
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  376
The length of the canonical sequence.

Location on the sequence:   AGFAGDDAPRAVFPSIVGRP  R HQGVMVGMGQKDSYVGDEAQ
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                         AGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQ

Mouse                         AGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQ

Rat                           AGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQ

Bovine                        AGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQ

Chicken                       AGFAGDDAPRAVFPSIVGRPRHQGVMVGMGQKDSYVGDEAQ

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 – 376 Actin, gamma-enteric smooth muscle, intermediate form
Chain 3 – 376 Actin, gamma-enteric smooth muscle
Modified residue 45 – 45 Methionine (R)-sulfoxide
Modified residue 48 – 48 Methionine (R)-sulfoxide
Cross 51 – 51 Isoglutamyl lysine isopeptide (Lys-Glu) (interchain with E-271); by Vibrio toxins RtxA and VgrG1


Literature citations

Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2) gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome.
Wangler M.F.; Gonzaga-Jauregui C.; Gambin T.; Penney S.; Moss T.; Chopra A.; Probst F.J.; Xia F.; Yang Y.; Werlin S.; Eglite I.; Kornejeva L.; Bacino C.A.; Baldridge D.; Neul J.; Lehman E.L.; Larson A.; Beuten J.; Muzny D.M.; Jhangiani S.; Gibbs R.A.; Lupski J.R.; Beaudet A.;
PLoS Genet. 10:E1004258-E1004258(2014)
Cited for: VARIANTS MMIHS5 CYS-40; HIS-40; ASN-134; CYS-178; HIS-178 AND CYS-257; VARIANTS VSCM1 HIS-40; THR-45; GLY-63; LEU-110 AND ASP-198; INVOLVEMENT IN MMIHS5; INVOLVEMENT IN VSCM1;

Diagnosis of chronic intestinal pseudo-obstruction and megacystis by sequencing the ACTG2 gene.
Milunsky A.; Baldwin C.; Zhang X.; Primack D.; Curnow A.; Milunsky J.;
J. Pediatr. Gastroenterol. Nutr. 65:384-387(2017)
Cited for: VARIANTS MMIHS5 HIS-40 AND CYS-257; INVOLVEMENT IN MMIHS5;

Variants in ACTG2 underlie a substantial number of Australasian patients with primary chronic intestinal pseudo-obstruction.
Ravenscroft G.; Pannell S.; O'Grady G.; Ong R.; Ee H.C.; Faiz F.; Marns L.; Goel H.; Kumarasinghe P.; Sollis E.; Sivadorai P.; Wilson M.; Magoffin A.; Nightingale S.; Freckmann M.L.; Kirk E.P.; Sachdev R.; Lemberg D.A.; Delatycki M.B.; Kamm M.A.; Basnayake C.; Lamont P.J.; Amor D.J.; Jones K.; Schilperoort J.; Davis M.R.; Laing N.G.;
Neurogastroenterol. Motil. 30:e13371-e13371(2018)
Cited for: VARIANTS VSCM1 HIS-40; LEU-148 AND CYS-257; VARIANT MMIHS5 CYS-40;

Novel ACTG2 variants disclose allelic heterogeneity and bi-allelic inheritance in pediatric chronic intestinal pseudo-obstruction.
Matera I.; Bordo D.; Di Duca M.; Lerone M.; Santamaria G.; Pongiglione M.; Lezo A.; Diamanti A.; Spagnuolo M.I.; Pini Prato A.; Alberti D.; Mattioli G.; Gandullia P.; Ceccherini I.;
Clin. Genet. 99:430-436(2021)
Cited for: VARIANT MMIHS5 HIS-40; VARIANTS VSCM1 GLN-41; PHE-143; ARG-149; ASP-196 AND CYS-257; VARIANT TRP-336;

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.