UniProtKB/Swiss-Prot Q9HBA0: Variant p.Arg269His

Transient receptor potential cation channel subfamily V member 4
Gene: TRPV4
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Variant information Variant position:

269 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 269 (R269H, p.Arg269His). 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 HMND8 and CMT2C; increased agonist-induced channel activity and increased basal intracellular calcium concentration; slightly decreased protein stability and ATP-binding; decreases binding to membranes enriched in phosphatidylinositol-2,4-bisphosphate; causes increased cell death. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs267607144 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

RCKHYVELLVAQGADVHAQA R GRFFQPKDEGGYFYFGELPL 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                         RCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPL

Mouse                         RCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPL

Rat                           RCKHYVELLVAQGADVHAQARGRFFQPKDEGGYFYFGELPL

Chicken                       RCKHYVELLVEKGADVHAQARGRFFQPKDEGGYFYFGELPL

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 – 871	Transient receptor potential cation channel subfamily V member 4
Topological domain	1 – 469	Cytoplasmic
Modified residue	253 – 253	Phosphotyrosine
Alternative sequence	239 – 285	Missing. In isoform 4 and isoform 6.
Mutagenesis	251 – 251	K -> E. No effect on channel activity. No effect on interaction with membranes enriched in phosphatidylinositol-2,4-bisphosphate.

Literature citations
TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P.
Takahashi N.; Hamada-Nakahara S.; Itoh Y.; Takemura K.; Shimada A.; Ueda Y.; Kitamata M.; Matsuoka R.; Hanawa-Suetsugu K.; Senju Y.; Mori M.X.; Kiyonaka S.; Kohda D.; Kitao A.; Mori Y.; Suetsugu S.;
Nat. Commun. 5:4994-4994(2014)
Cited for: FUNCTION; TRANSPORTER ACTIVITY; ACTIVITY REGULATION; SUBCELLULAR LOCATION; DOMAIN; MUTAGENESIS OF LYS-251; ASN-296; HIS-299 AND LYS-344; CHARACTERIZATION OF VARIANTS CMT2C CYS-232; HIS-269; TRP-315 AND HIS-316; Structural and biochemical consequences of disease-causing mutations in the ankyrin repeat domain of the human TRPV4 channel.
Inada H.; Procko E.; Sotomayor M.; Gaudet R.;
Biochemistry 51:6195-6206(2012)
Cited for: X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 149-397 ALONE AND IN COMPLEX WITH ATP; MUTAGENESIS OF PHE-231; CHARACTERIZATION OF VARIANTS MTD ARG-197; PHE-199; ALA-295; PHE-331; THR-331 AND PHE-342; CHARACTERIZATION OF VARIANTS SMDK LYS-278 AND GLY-333; CHARACTERIZATION OF VARIANTS CMT2C CYS-232; HIS-269; TRP-315 AND CYS-316; CHARACTERIZATION OF VARIANT SPSMA CYS-316; CHARACTERIZATION OF VARIANT LYS-183; CHARACTERIZATION OF VARIANTS HMND8 CYS-232 AND HIS-269; Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C.
Auer-Grumbach M.; Olschewski A.; Papic L.; Kremer H.; McEntagart M.E.; Uhrig S.; Fischer C.; Frohlich E.; Balint Z.; Tang B.; Strohmaier H.; Lochmuller H.; Schlotter-Weigel B.; Senderek J.; Krebs A.; Dick K.J.; Petty R.; Longman C.; Anderson N.E.; Padberg G.W.; Schelhaas H.J.; van Ravenswaaij-Arts C.M.; Pieber T.R.; Crosby A.H.; Guelly C.;
Nat. Genet. 42:160-164(2010)
Cited for: VARIANTS CMT2C TRP-315 AND CYS-316; VARIANT HMND8 HIS-269; SUBCELLULAR LOCATION; Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4.
Deng H.X.; Klein C.J.; Yan J.; Shi Y.; Wu Y.; Fecto F.; Yau H.J.; Yang Y.; Zhai H.; Siddique N.; Hedley-Whyte E.T.; Delong R.; Martina M.; Dyck P.J.; Siddique T.;
Nat. Genet. 42:165-169(2010)
Cited for: VARIANT CMT2C HIS-269; VARIANT SPSMA CYS-316; SUBCELLULAR LOCATION; Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.
Landoure G.; Zdebik A.A.; Martinez T.L.; Burnett B.G.; Stanescu H.C.; Inada H.; Shi Y.; Taye A.A.; Kong L.; Munns C.H.; Choo S.S.; Phelps C.B.; Paudel R.; Houlden H.; Ludlow C.L.; Caterina M.J.; Gaudet R.; Kleta R.; Fischbeck K.H.; Sumner C.J.;
Nat. Genet. 42:170-174(2010)
Cited for: VARIANTS CMT2C CYS-269 AND HIS-269; CHARACTERIZATION OF VARIANTS CMT2C CYS-269 AND HIS-269; FUNCTION; TRANSPORTER ACTIVITY; TRPV4 mutations and cytotoxic hypercalcemia in axonal Charcot-Marie-Tooth neuropathies.
Klein C.J.; Shi Y.; Fecto F.; Donaghy M.; Nicholson G.; McEntagart M.E.; Crosby A.H.; Wu Y.; Lou H.; McEvoy K.M.; Siddique T.; Deng H.X.; Dyck P.J.;
Neurology 76:887-894(2011)
Cited for: VARIANTS CMT2C CYS-232 AND HIS-316; CHARACTERIZATION OF VARIANTS CMT2C CYS-232; CYS-269; HIS-269 AND HIS-316;

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.