Variant VAR_007736 | SNPeffect 4.0

Phenotypic summary of VAR_007736

Compact overview of VAR_007736
UniProt ID	Gene	Mutation	Mutation type	Disease	OMIM	dbSNP
EGR2_HUMAN	EGR2	D355V	Disease	Charcot-Marie-Tooth disease type 1D (CMT1D)	607678	No dbSNP entry

Short stretch summary of VAR_007736
Predictor	Predicted regions overview	Comparison to WT	Stretches in variant	Stretches in WT
Tango		0 No change	1	1
Waltz		0 No change	4	4
Limbo		0 No change	6	6
Domain composition of EGR2_HUMAN
Database	Domain composition	Residue details
PFAM		DUF3446 (Residues 94-184), zf-C2H2 (Residues 340-364), zf-C2H2 (Residues 370-392), zf-C2H2 (Residues 398-420)
SMART		ZnF_C2H2 (Residues 340-364), ZnF_C2H2 (Residues 370-392), ZnF_C2H2 (Residues 398-420)

Structure stability summary of VAR_007736
Variant	Stability change	Effect	Structure	Stability frequency histogram
D355V	0.63 kcal/mol	Slightly reduced stability

TANGO aggregation

Graphical comparison of TANGO regions in variant and wild type
Protein	Predicted regions overview	TANGO regions	Total score
Variant		1	239
Wild type		1	239

TANGO regions in wild type and variant
Wild type TANGO regions
N-term gatekeepers	TANGO region	C-term gatekeepers	Start	End	Score
CYPEG	IINIVSAGIL	QGVTS	112	121	19
Variant protein TANGO regions
N-term gatekeepers	TANGO region	C-term gatekeepers	Start	End	Score
CYPEG	IINIVSAGIL	QGVTS	112	121	19

Difference in TANGO aggregation between wild type and variant
	This graph plots the per-residue TANGO aggregation score difference between the wild type protein and this variant. From left to right, all residue TANGO score differences from the N-terminus to the C-terminus are plotted. A flat line indicates that the variant does not alter the aggregation profile of the protein. Positive peaks indicate increased aggregation tendency due to this variant. Negative peaks indicate decreased aggregation tendency due to this variant.

Difference in TANGO aggregation between wild type and variant

This graph plots the per-residue TANGO aggregation score difference between the wild type protein and this variant.
From left to right, all residue TANGO score differences from the N-terminus to the C-terminus are plotted.
A flat line indicates that the variant does not alter the aggregation profile of the protein.
Positive peaks indicate increased aggregation tendency due to this variant.
Negative peaks indicate decreased aggregation tendency due to this variant.

TANGO aggregation profile score plot
	This graph plots the per-residue TANGO aggregation score of the variant protein. From left to right, all residue scores from the N-terminus to the C-terminus are plotted

Molecular visualization of TANGO aggregation-prone regions
Wild type EGR2_HUMAN	Variant VAR_007736
These two molecular images show the TANGO aggregation-prone regions as red colored segments. The left image represents the wild type protein, the right represents the variant protein. If both images are the same, it implies that the introduced variant amino acid does not alter the TANGO aggregation tendency. In any other case, the images allow structural interpretation of gained or lost aggregation-prone regions due to the variant amino acid. The structural location of the variant residue is colored in yellow. Click on the images to get a larger view and to download the original.

Molecular visualization of TANGO aggregation-prone regions

Wild type EGR2_HUMAN

Variant VAR_007736

These two molecular images show the TANGO aggregation-prone regions as red colored segments. The left image represents the wild type protein, the right represents the variant protein.
If both images are the same, it implies that the introduced variant amino acid does not alter the TANGO aggregation tendency. In any other case, the images allow structural interpretation of gained or lost aggregation-prone regions due to the variant amino acid.
The structural location of the variant residue is colored in yellow. Click on the images to get a larger view and to download the original.

WALTZ amylogenicity

Graphical comparison of WALTZ regions in variant and wild type
Protein	Predicted regions overview	WALTZ regions	Total score
Variant		4	1123
Wild type		4	1123

WALTZ regions in wild type and variant
Wild type WALTZ regions
N-term gatekeepers	WALTZ region	C-term gatekeepers	Start	End	Score
EDLAA	TSVTIF	PNAEL	34	39	9
SAPRN	QTFTYM	GKFSI	88	93	41
SCYPE	GIINIV	SAGIL	111	116	89
AAAAA	AAAAYN	PHHLP	306	311	42
Variant protein WALTZ regions
N-term gatekeepers	WALTZ region	C-term gatekeepers	Start	End	Score
EDLAA	TSVTIF	PNAEL	34	39	9
SAPRN	QTFTYM	GKFSI	88	93	41
SCYPE	GIINIV	SAGIL	111	116	89
AAAAA	AAAAYN	PHHLP	306	311	42

Difference in WALTZ amylogenicity between wild type and variant
	This graph plots the per-residue WALTZ amylogenic score difference between the wild type protein and this variant. From left to right, all residue WALTZ score differences from the N-terminus to the C-terminus are plotted. A flat line indicates that the variant does not alter the amylogenic profile of the protein. Positive peaks indicate increased amylogenic tendency due to this variant. Negative peaks indicate decreased amylogenic tendency due to this variant.

Difference in WALTZ amylogenicity between wild type and variant

This graph plots the per-residue WALTZ amylogenic score difference between the wild type protein and this variant.
From left to right, all residue WALTZ score differences from the N-terminus to the C-terminus are plotted.
A flat line indicates that the variant does not alter the amylogenic profile of the protein.
Positive peaks indicate increased amylogenic tendency due to this variant.
Negative peaks indicate decreased amylogenic tendency due to this variant.

WALTZ amylogenic profile score plot
	This graph plots the per-residue WALTZ amylogenic score of the variant protein. From left to right, all residue scores from the N-terminus to the C-terminus are plotted

Molecular visualization of WALTZ amylogenic regions
Wild type EGR2_HUMAN	Variant VAR_007736
These two molecular images show the WALTZ amylogenic regions as blue colored segments. The left image represents the wild type protein, the right represents the variant protein. If both images are the same, it implies that the introduced variant amino acid does not alter the WALTZ amyloid-forming tendency. In any other case, the images allow structural interpretation of gained or lost amylogenic regions due to the variant amino acid. The structural location of the variant residue is colored in yellow. Click on the images to get a larger view and to download the original.

Molecular visualization of WALTZ amylogenic regions

Wild type EGR2_HUMAN

Variant VAR_007736

These two molecular images show the WALTZ amylogenic regions as blue colored segments. The left image represents the wild type protein, the right represents the variant protein.
If both images are the same, it implies that the introduced variant amino acid does not alter the WALTZ amyloid-forming tendency. In any other case, the images allow structural interpretation of gained or lost amylogenic regions due to the variant amino acid.
The structural location of the variant residue is colored in yellow. Click on the images to get a larger view and to download the original.

LIMBO chaperone binding

Graphical comparison of LIMBO regions in variant and wild type
Protein	Predicted regions overview	LIMBO regions	Total score
Variant		6	4781
Wild type		6	4781

LIMBO regions in wild type and variant
Wild type LIMBO regions
N-term gatekeepers	WALTZ region	C-term gatekeepers	Start	End	Score
LAATS	VTIFPNAE	LGGPF	36	43	99
VSAPR	NQTFTYMG	KFSID	87	94	94
TQPDL	DHLYSPPP	PPPPY	162	169	100
CPLDT	LRVPPPLT	PLSTI	256	263	100
SDELT	RHIRIHTG	HKPFQ	359	366	100
KRHTK	IHLRQKER	KSSAP	419	426	100
Variant protein LIMBO regions
N-term gatekeepers	WALTZ region	C-term gatekeepers	Start	End	Score
LAATS	VTIFPNAE	LGGPF	36	43	99
VSAPR	NQTFTYMG	KFSID	87	94	94
TQPDL	DHLYSPPP	PPPPY	162	169	100
CPLDT	LRVPPPLT	PLSTI	256	263	100
SVELT	RHIRIHTG	HKPFQ	359	366	100
KRHTK	IHLRQKER	KSSAP	419	426	100

Difference in LIMBO chaperone binding between wild type and variant
	This graph plots the per-residue LIMBO chaperone binding difference between the wild type protein and this variant. From left to right, all residue LIMBO score differences from the N-terminus to the C-terminus are plotted. A flat line indicates that the variant does not alter the chaperone binding profile of the protein. Positive peaks indicate increased predicted chaperone binding due to this variant. Negative peaks indicate decreased predicted chaperone binding due to this variant.

Difference in LIMBO chaperone binding between wild type and variant

This graph plots the per-residue LIMBO chaperone binding difference between the wild type protein and this variant.
From left to right, all residue LIMBO score differences from the N-terminus to the C-terminus are plotted.
A flat line indicates that the variant does not alter the chaperone binding profile of the protein.
Positive peaks indicate increased predicted chaperone binding due to this variant.
Negative peaks indicate decreased predicted chaperone binding due to this variant.

LIMBO chaperone binding score plot
	This graph plots the per-residue LIMBO chaperone binding score of the variant protein. From left to right, all residue scores from the N-terminus to the C-terminus are plotted

Molecular visualization of LIMBO chaperone binding regions
Wild type EGR2_HUMAN	Variant VAR_007736
These two molecular images show the LIMBO chaperone binding regions as magenta colored segments. The left image represents the wild type protein, the right represents the variant protein. If both images are the same, it implies that the introduced variant amino acid does not alter the LIMBO chaperone binding properties. In any other case, the images allow structural interpretation of gained or lost chaperone binding regions due to the variant amino acid. The structural location of the variant residue is colored in yellow. Click on the images to get a larger view and to download the original.

Molecular visualization of LIMBO chaperone binding regions

Wild type EGR2_HUMAN

Variant VAR_007736

These two molecular images show the LIMBO chaperone binding regions as magenta colored segments. The left image represents the wild type protein, the right represents the variant protein.
If both images are the same, it implies that the introduced variant amino acid does not alter the LIMBO chaperone binding properties. In any other case, the images allow structural interpretation of gained or lost chaperone binding regions due to the variant amino acid.
The structural location of the variant residue is colored in yellow. Click on the images to get a larger view and to download the original.

FOLDX structural profile

There is currently no structural information available to make the required analyses.

Functional sites, structural features and cellular processing

Functional sites and structural features
Feature	This residue
Catalytic site	No
Secondary structure	No secondary structure information available
Transmembrane topology	No TM regions in this protein

Cellular processing
Feature	Affected by variant
Signal peptide	No
Farnesylation anchor	No
N-Myristoylation anchor	No
Geranylgeranyl transferase Type 1 anchor	No
Geranylgeranyl transferase Type 2 anchor	No
Glycosylphosphatidylinositol (GPI) anchor	No
Peroxisomal targeting signal PTS1	No
Subcellular location	No

All mutations from EGR2_HUMAN

8 mutations listed

Variant	UniProt ID	Mutation	Disease	Mutation Type	dWALTZ	dLIMBO	ddG
VAR_007735	EGR2_HUMAN	I268N	Congenital hypomyelination neuropathy (CHN)	Disease	-2	0	N.A.
VAR_007736	EGR2_HUMAN	D355V	Charcot-Marie-Tooth disease type 1D (CMT1D)	Disease	0	0	0.63
VAR_009875	EGR2_HUMAN	R381H	Charcot-Marie-Tooth disease type 1D (CMT1D)	Disease	0	0	-0.46
VAR_009874	EGR2_HUMAN	R359W	Dejerine-Sottas syndrome (DSS)	Disease	1	1	-1.07
VAR_029959	EGR2_HUMAN	D383Y	Charcot-Marie-Tooth disease type 1D (CMT1D)	Disease	0	-411	2
VAR_029958	EGR2_HUMAN	R381C	Charcot-Marie-Tooth disease type 1D (CMT1D)	Disease	0	0	-1.19
VAR_007738	EGR2_HUMAN	R409W	Charcot-Marie-Tooth disease type 1D (CMT1D)	Disease	0	0	0.06
VAR_009874	EGR2_HUMAN	R359W	Charcot-Marie-Tooth disease type 1D (CMT1D)	Disease	1	1	N.A.