UniProtKB/Swiss-Prot Q14444: Variant p.Ile373Lys

Caprin-1
Gene: CAPRIN1
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Variant information Variant position:

373 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 Isoleucine (I) to Lysine (K) at position 373 (I373K, p.Ile373Lys). 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 hydrophobic (I) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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:

Found in a patient with a neurodevelopmental disorder; uncertain significance; decreased function in stress granule formation shown by rescue assays in transfected CAPRIN1-deficient cells; impaired interaction with G3BP1 and G3BP2. Any additional useful information about the variant.

Sequence information Variant position:

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

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

LVRRQRVQDLMAQMQGPYNF I QDSMLDFENQTLDPAIVSAQ 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                         LVRRQRVQDLMAQMQ-----------GPYNFIQDSMLD--------------------------------------FENQT-------------------LDPAIVSAQ

Mouse                         LVRRQRVQDLMAQMQ-----------GPYNFIQDSMLD---

Rat                           LVRRQRVQDLMAQMQ-----------GPYNFIQDSMLD---

Bovine                        LVRRQRVQDLMAQMQ-----------GPYNFIQDSMLD---

Drosophila                    GIQAPQTPQQQQFMQHSRPLAEVLGTGRFHFLQDSELDNPE

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	2 – 709	Caprin-1
Region	360 – 381	G3BP1-binding
Mutagenesis	370 – 370	Y -> AGPVWDERHKSCTMNQ. Abolished interaction with G3BP1.
Mutagenesis	372 – 372	F -> AGILPVWYDERHKSCTMNQ. Abolished interaction with G3BP1 and ability to promote stress granule formation.
Mutagenesis	373 – 373	I -> AGPVDERHKSCTMNQ. Abolished interaction with G3BP1.
Mutagenesis	373 – 373	I -> F. Increased interaction with G3BP1.
Mutagenesis	376 – 376	S -> AGILPVFERHTMQ. Abolished interaction with G3BP1.
Mutagenesis	376 – 376	S -> C. Increased interaction with G3BP1.
Mutagenesis	377 – 377	M -> FY. Increased interaction with G3BP1.
Mutagenesis	377 – 377	M -> GPK. Abolished interaction with G3BP1.

Literature citations
De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders.
Jia X.; Zhang S.; Tan S.; Du B.; He M.; Qin H.; Chen J.; Duan X.; Luo J.; Chen F.; Ouyang L.; Wang J.; Chen G.; Yu B.; Zhang G.; Zhang Z.; Lyu Y.; Huang Y.; Jiao J.; Chen J.Y.H.; Swoboda K.J.; Agolini E.; Novelli A.; Leoni C.; Zampino G.; Cappuccio G.; Brunetti-Pierri N.; Gerard B.; Ginglinger E.; Richer J.; McMillan H.; White-Brown A.; Hoekzema K.; Bernier R.A.; Kurtz-Nelson E.C.; Earl R.K.; Meddens C.; Alders M.; Fuchs M.; Caumes R.; Brunelle P.; Smol T.; Kuehl R.; Day-Salvatore D.L.; Monaghan K.G.; Morrow M.M.; Eichler E.E.; Hu Z.; Yuan L.; Tan J.; Xia K.; Shen Y.; Guo H.;
Sci. Adv. 8:eabo7112-eabo7112(2022)
Cited for: FUNCTION; INTERACTION WITH G3BP1 AND G3BP1; VARIANTS LYS-373; HIS-446 AND PRO-484; CHARACTERIZATION OF VARIANTS LYS-373; HIS-446 AND PRO-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.