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UniProtKB/Swiss-Prot A6NHR9: Variant p.His348Arg

Structural maintenance of chromosomes flexible hinge domain-containing protein 1
Gene: SMCHD1
Chromosomal location: 18p11.32
Variant information

Variant position:  348
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 Histidine (H) to Arginine (R) at position 348 (H348R, p.His348Arg).
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 (H) to large size and basic (R)
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

Involvement in disease:  Bosma arhinia microphthalmia syndrome (BAMS) [MIM:603457]: An autosomal dominant syndrome characterized by severe hypoplasia of the nose, palatal abnormalities, hypoplasia of the eyes, sensory abnormalities of taste and smell, hypogonadotropic hypogonadism with cryptorchidism, and normal intelligence. {ECO:0000269|PubMed:28067909, ECO:0000269|PubMed:28067911, ECO:0000269|PubMed:29748383}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In BAMS; no change in protein abundance; does not affect ATPase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  348
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2005
The length of the canonical sequence.

Location on the sequence:   QPEHIQYLKNYFHLWTRQLA  H IYHYYIHGPKGNEIRTSKEV
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                         QPEHIQYLKNYFHLWTRQLAHIYHYYIHGPKGNEIRTSKEV

Mouse                         QPEHIQYLKNYLHLWTRQLTHIYHYYIHGPKGNEISTAKAI

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 – 2005 Structural maintenance of chromosomes flexible hinge domain-containing protein 1
Region 111 – 702 ATPase activity domain
Alternative sequence 1 – 1065 Missing. In isoform 3.


Literature citations

SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome.
Shaw N.D.; Brand H.; Kupchinsky Z.A.; Bengani H.; Plummer L.; Jones T.I.; Erdin S.; Williamson K.A.; Rainger J.; Stortchevoi A.; Samocha K.; Currall B.B.; Dunican D.S.; Collins R.L.; Willer J.R.; Lek A.; Lek M.; Nassan M.; Pereira S.; Kammin T.; Lucente D.; Silva A.; Seabra C.M.; Chiang C.; An Y.; Ansari M.; Rainger J.K.; Joss S.; Smith J.C.; Lippincott M.F.; Singh S.S.; Patel N.; Jing J.W.; Law J.R.; Ferraro N.; Verloes A.; Rauch A.; Steindl K.; Zweier M.; Scheer I.; Sato D.; Okamoto N.; Jacobsen C.; Tryggestad J.; Chernausek S.; Schimmenti L.A.; Brasseur B.; Cesaretti C.; Garcia-Ortiz J.E.; Buitrago T.P.; Silva O.P.; Hoffman J.D.; Muehlbauer W.; Ruprecht K.W.; Loeys B.L.; Shino M.; Kaindl A.M.; Cho C.H.; Morton C.C.; Meehan R.R.; van Heyningen V.; Liao E.C.; Balasubramanian R.; Hall J.E.; Seminara S.B.; Macarthur D.; Moore S.A.; Yoshiura K.I.; Gusella J.F.; Marsh J.A.; Graham J.M. Jr.; Lin A.E.; Katsanis N.; Jones P.L.; Crowley W.F. Jr.; Davis E.E.; FitzPatrick D.R.; Talkowski M.E.;
Nat. Genet. 49:238-248(2017)
Cited for: INVOLVEMENT IN BAMS; VARIANTS BAMS PRO-107; LYS-129; ASN-135; CYS-135; ILE-135; ASP-136; GLU-137; HIS-139; PHE-141; VAL-171; GLY-242; ARG-345; ARG-348; LEU-400; VAL-420; GLN-473; LYS-523; SER-524 AND GLN-552; CHARACTERIZATION OF VARIANTS BAMS PRO-107; LYS-129; ASN-135; CYS-135; ILE-135; ASP-136; GLU-137; HIS-139; PHE-141; VAL-171; GLY-242; ARG-345; ARG-348; LEU-400; VAL-420; GLN-473; LYS-523; SER-524 AND GLN-552;

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development.
Gordon C.T.; Xue S.; Yigit G.; Filali H.; Chen K.; Rosin N.; Yoshiura K.I.; Oufadem M.; Beck T.J.; McGowan R.; Magee A.C.; Altmueller J.; Dion C.; Thiele H.; Gurzau A.D.; Nuernberg P.; Meschede D.; Muehlbauer W.; Okamoto N.; Varghese V.; Irving R.; Sigaudy S.; Williams D.; Ahmed S.F.; Bonnard C.; Kong M.K.; Ratbi I.; Fejjal N.; Fikri M.; Elalaoui S.C.; Reigstad H.; Bole-Feysot C.; Nitschke P.; Ragge N.; Levy N.; Tuncbilek G.; Teo A.S.; Cunningham M.L.; Sefiani A.; Kayserili H.; Murphy J.M.; Chatdokmaiprai C.; Hillmer A.M.; Wattanasirichaigoon D.; Lyonnet S.; Magdinier F.; Javed A.; Blewitt M.E.; Amiel J.; Wollnik B.; Reversade B.;
Nat. Genet. 49:249-255(2017)
Cited for: VARIANTS BAMS SER-134; ASN-135; CYS-135; GLY-136; SER-342; ARG-348; VAL-420; GLU-518 AND GLN-552; CHARACTERIZATION OF VARIANTS BAMS SER-134; CYS-135; GLY-136 AND VAL-420; CHARACTERIZATION OF VARIANTS FSHD2 CYS-353 AND MET-527;

FSHD2- and BAMS-associated mutations confer opposing effects on SMCHD1 function.
Gurzau A.D.; Chen K.; Xue S.; Dai W.; Lucet I.S.; Ly T.T.N.; Reversade B.; Blewitt M.E.; Murphy J.M.;
J. Biol. Chem. 293:9841-9853(2018)
Cited for: VARIANTS FSHD2 PHE-194; ASP-263; CYS-283; CYS-353; GLU-478; MET-527 AND SER-690; VARIANTS BAMS ASN-135; GLU-137; SER-342; ARG-348; VAL-420; GLN-473; GLU-518; LYS-523 AND GLN-552; CHARACTERIZATION OF VARIANTS FSHD2 PHE-194; ASP-263; CYS-283; CYS-353; GLU-478; MET-527 AND SER-690; CHARACTERIZATION OF VARIANTS BAMS ASN-135; GLU-137; SER-342; ARG-348; VAL-420; GLN-473; GLU-518; LYS-523 AND GLN-552; FUNCTION; CATALYTIC ACTIVITY;

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.