Mapping SNPs GLA

^{by Benjamin Drexler and Fabian Grandke}

Introduction

This task is about point mutations in our protein GLA. We searched for SNP data in public databases. The results were mapped to the sequence to get an overview of their distribution. The different properties of the databases have been taken into account.

Databases

Two databases have been used to do research about SNPs in our protein: HGMD and DbSNP.

HGMD

Human Gene Mutation Database (HGMD) is a database maintained by the Institute of Medical Genetics in Cardiff.

The table below shows the different types of mutations that are listed in HGMD:

Mutation Type	Number of Mutations	Describtion
Missense/nonsense	344	different amino acid/stop codon
Splicing	26	different splice site
Regulatory	1	substitutions cause regulatory abnormalities
Small deletions	69	micro-deletions (20 bp or less)
Small insertions	28	micro-insertions (20 bp or less)
Small indels	8	micro-indels (20 bp or less)
Gross deletions	14	deletions in regions of data with variable quality
Gross insertions/duplications	1	insertions/duplications in regions of data with variable quality
Complex rearrangements	3	sequence is not continuous
Repeat variations	0	variations of the sequence are repeated

The professional version provides many more mutations. The mutations in the free version are at least 2.5 years old (date of publication).

The table below shows all missense and nonsense mutations from HGMD. To gather them, we searched HGMD for gla, chose the drop-down option "Gene symbol", copied&pasted the text from the website into a file ,and parsed out the required information.

Position	Amino Acids	Codons
1	Met->Thr	ATG-ACG
1	Met->Arg	ATG-AGG
1	Met->Ile	ATGc-ATA
14	Leu->Pro	CTT-CCT
16	Leu->Pro	CTT-CCT
18	Phe->Ser	TTC-TCC
19	Leu->Pro	CTG-CCG
20	Ala->Pro	gGCC-CCC
31	Ala->Val	GCA-GTA
32	Leu->Pro	CTG-CCG
34	Asn->Ser	AAT-AGT
34	Asn->Lys	AATg-AAG
35	Gly->Arg	tGGA-AGA
40	Pro->Leu	CCT-CTT
40	Pro->Ser	gCCT-TCT
41	Thr->Ile	ACC-ATC
42	Met->Thr	ATG-ACG
42	Met->Leu	cATG-CTG
42	Met->Val	cATG-GTG
43	Gly->Asp	GGC-GAC
43	Gly->Val	GGC-GTC
43	Gly->Arg	gGGC-CGC
44	Trp->Ter	TGG-TAG
46	His->Arg	CAC-CGC
46	His->Tyr	gCAC-TAC
47	Trp->Gly	cTGG-GGG
47	Trp->Leu	TGG-TTG
48	Glu->Lys	gGAG-AAG
49	Arg->Pro	CGC-CCC
49	Arg->Leu	CGC-CTC
49	Arg->Ser	gCGC-AGC
49	Arg->Gly	gCGC-GGC
50	Phe->Cys	TTC-TGC
51	Met->Lys	ATG-AAG
51	Met->Ile	ATGt-ATA
52	Cys->Arg	gTGC-CGC
52	Cys->Ser	TGC-TCC
52	Cys->Ter	TGCa-TGA
54	Leu->Pro	CTT-CCT
56	Cys->Gly	cTGC-GGC
56	Cys->Tyr	TGC-TAC
56	Cys->Phe	TGC-TTC
56	Cys->Ter	TGCc-TGA
59	Glu->Lys	aGAG-AAG
63	Cys->Tyr	TGC-TAC
66	Glu->Gly	GAG-GGG
66	Glu->Lys	tGAG-AAG
66	Glu->Gln	tGAG-CAG
68	Leu->Phe	gCTC-TTC
72	Met->Arg	ATG-AGG
72	Met->Ile	ATGg-ATA
72	Met->Val	gATG-GTG
73	Ala->Val	GCA-GTA
76	Met->Thr	ATG-ACG
78	Ser->Ter	TCA-TGA
79	Glu->Ter	aGAA-TAA
81	Trp->Ter	TGG-TAG
81	Trp->Ser	TGG-TCG
85	Gly->Asp	GGT-GAT
86	Tyr->Cys	TAT-TGT
86	Tyr->Ter	TATg-TAG
88	Tyr->Asp	gTAC-GAC
89	Leu->Pro	CTC-CCC
89	Leu->Arg	CTC-CGC
91	Ile->Thr	ATT-ACT
92	Asp->Asn	tGAT-AAT
92	Asp->His	tGAT-CAT
92	Asp->Tyr	tGAT-TAT
93	Asp->Gly	GAC-GGC
93	Asp->Val	GAC-GTC
93	Asp->Asn	tGAC-AAC
94	Cys->Tyr	TGT-TAT
94	Cys->Ser	TGT-TCT
95	Trp->Ter	TGG-TAG
95	Trp->Ser	TGG-TCG
97	Ala->Val	GCT-GTT
97	Ala->Pro	gGCT-CCT
99	Gln->Ter	cCAA-TAA
100	Arg->Lys	AGA-AAA
100	Arg->Thr	AGA-ACA
102	Ser->Ter	TCA-TGA
103	Glu->Gln	aGAA-CAA
106	Leu->Arg	CTT-CGT
107	Gln->Ter	tCAG-TAG
112	Arg->His	CGC-CAC
112	Arg->Ser	gCGC-AGC
112	Arg->Cys	gCGC-TGC
113	Phe->Leu	cTTT-CTT
113	Phe->Ser	TTT-TCT
118	Arg->Cys	tCGC-TGC
119	Gln->Ter	cCAG-TAG
121	Ala->Pro	aGCT-CCT
125	His->Pro	CAC-CCC
126	Ser->Gly	cAGC-GGC
127	Lys->Ter	cAAA-TAA
128	Gly->Glu	GGA-GAA
129	Leu->Pro	CTG-CCG
131	Leu->Pro	CTA-CCA
132	Gly->Arg	aGGG-AGG
134	Tyr->Ser	TAT-TCT
134	Tyr->Ter	TATg-TAG
135	Ala->Val	GCA-GTA
136	Asp->His	aGAT-CAT
138	Gly->Glu	GGA-GAA
138	Gly->Arg	tGGA-AGA
141	Thr->Ile	ACC-ATC
142	Cys->Arg	cTGC-CGC
142	Cys->Tyr	TGC-TAC
142	Cys->Ter	TGCg-TGA
142	Cys->Trp	TGCg-TGG
143	Ala->Thr	cGCA-ACA
143	Ala->Pro	cGCA-CCA
144	Gly->Val	GGC-GTC
146	Pro->Ser	cCCT-TCT
147	Gly->Arg	tGGG-AGG
148	Ser->Asn	AGT-AAT
148	Ser->Arg	AGTt-AGG
151	Tyr->Ter	TACt-TAG
152	Tyr->Ter	TACg-TAA
155	Asp->His	tGAT-CAT
156	Ala->Val	GCC-GTC
156	Ala->Thr	tGCC-ACC
157	Gln->Ter	cCAG-TAG
162	Trp->Arg	cTGG-CGG
162	Trp->Ter	TGG-TAG
162	Trp->Cys	TGGg-TGC
163	Gly->Val	GGA-GTA
165	Asp->His	aGAT-CAT
165	Asp->Val	GAT-GTT
166	Leu->Val	tCTG-GTG
167	Leu->Pro	CTA-CCA
168	Lys->Arg	AAA-AGA
169	Phe->Ser	TTT-TCT
170	Asp->Val	GAT-GTT
170	Asp->His	tGAT-CAT
171	Gly->Asp	GGT-GAT
171	Gly->Arg	tGGT-CGT
172	Cys->Tyr	TGT-TAT
172	Cys->Phe	TGT-TTT
172	Cys->Trp	TGTt-TGG
172	Cys->Arg	tTGT-CGT
172	Cys->Gly	tTGT-GGT
173	Tyr->Ter	TACt-TAA
177	Leu->Ter	TTG-TAG
183	Gly->Asp	GGT-GAT
183	Gly->Ser	tGGT-AGT
187	Met->Thr	ATG-ACG
187	Met->Val	cATG-GTG
191	Leu->Gln	CTG-CAG
191	Leu->Pro	CTG-CCG
194	Thr->Ile	ACT-ATT
199	Val->Met	tGTG-ATG
201	Ser->Tyr	TCC-TAC
201	Ser->Phe	TCC-TTC
202	Cys->Tyr	TGT-TAT
202	Cys->Trp	TGTg-TGG
204	Trp->Ter	TGG-TAG
205	Pro->Arg	CCT-CGT
205	Pro->Leu	CCT-CTT
205	Pro->Thr	gCCT-ACT
207	Tyr->Ser	TAT-TCT
215	Asn->Ser	AAT-AGT
216	Tyr->Asp	tTAT-GAT
220	Arg->Ter	cCGA-TGA
221	Gln->Ter	aCAG-TAG
222	Tyr->Ter	TACt-TAA
223	Cys->Arg	cTGC-CGC
223	Cys->Gly	cTGC-GGC
223	Cys->Tyr	TGC-TAC
224	Asn->Ser	AAT-AGT
224	Asn->Asp	cAAT-GAT
225	His->Arg	CAC-CGC
226	Trp->Arg	cTGG-CGG
226	Trp->Ter	TGG-TAG
226	Trp->Cys	TGGc-TGT
227	Arg->Gln	CGA-CAA
227	Arg->Ter	gCGA-TGA
230	Ala->Thr	tGCT-ACT
231	Asp->Val	GAC-GTC
231	Asp->Asn	tGAC-AAC
234	Asp->Glu	GATt-GAG
234	Asp->Tyr	tGAT-TAT
235	Ser->Cys	TCC-TGC
235	Ser->Phe	TCC-TTC
236	Trp->Arg	cTGG-CGG
236	Trp->Ter	TGG-TAG
236	Trp->Leu	TGG-TTG
236	Trp->Cys	TGGa-TGC
239	Ile->Thr	ATA-ACA
242	Ile->Asn	ATC-AAC
243	Leu->Phe	TTGg-TTC
244	Asp->Asn	gGAC-AAC
244	Asp->His	gGAC-CAC
245	Trp->Ter	TGG-TAG
247	Ser->Pro	aTCT-CCT
247	Ser->Cys	TCT-TGT
250	Gln->Ter	cCAG-TAG
251	Glu->Ter	gGAG-TAG
257	Ala->Pro	tGCT-CCT
258	Gly->Val	GGA-GTA
258	Gly->Arg	tGGA-CGA
259	Pro->Arg	CCA-CGA
259	Pro->Leu	CCA-CTA
260	Gly->Ala	GGG-GCG
261	Gly->Asp	GGT-GAT
262	Trp->Ter	TGG-TAG
262	Trp->Cys	TGGa-TGC
263	Asn->Ser	AAT-AGT
264	Asp->Val	GAC-GTC
264	Asp->Tyr	tGAC-TAC
265	Pro->Arg	CCA-CGA
265	Pro->Leu	CCA-CTA
266	Asp->Asn	aGAT-AAT
266	Asp->His	aGAT-CAT
266	Asp->Val	GAT-GTT
266	Asp->Glu	GATa-GAA
267	Met->Arg	ATG-AGG
267	Met->Ile	ATGg-ATA
268	Leu->Ser	TTA-TCA
269	Val->Met	aGTG-ATG
269	Val->Ala	GTG-GCG
270	Ile->Thr	ATT-ACT
271	Gly->Val	GGC-GTC
271	Gly->Ser	tGGC-AGC
271	Gly->Cys	tGGC-TGC
272	Asn->Lys	AACt-AAA
276	Ser->Asn	AGC-AAC
276	Ser->Gly	cAGC-GGC
277	Trp->Ter	TGG-TAG
279	Gln->Arg	CAG-CGG
279	Gln->His	CAGc-CAC
279	Gln->Glu	tCAG-GAG
280	Gln->His	CAAg-CAT
280	Gln->Lys	gCAA-AAA
282	Thr->Ala	aACT-GCT
282	Thr->Asn	ACT-AAT
283	Gln->Pro	CAG-CCG
284	Met->Thr	ATG-ACG
285	Ala->Asp	GCC-GAC
285	Ala->Pro	gGCC-CCC
287	Trp->Gly	cTGG-GGG
287	Trp->Ter	TGGg-TGA
287	Trp->Cys	TGGg-TGT
288	Ala->Asp	GCT-GAT
288	Ala->Pro	gGCT-CCT
289	Ile->Ser	ATC-AGC
289	Ile->Phe	tATC-TTC
290	Met->Ile	ATGg-ATA
292	Ala->Thr	tGCT-ACT
293	Pro->Thr	tCCT-ACT
293	Pro->Ala	tCCT-GCT
293	Pro->Ser	tCCT-TCT
294	Leu->Ter	TTA-TGA
296	Met->Ile	ATGt-ATA
296	Met->Val	cATG-GTG
297	Ser->Cys	TCT-TGT
297	Ser->Phe	TCT-TTT
298	Asn->Ser	AAT-AGT
298	Asn->Lys	AATg-AAG
298	Asn->His	tAAT-CAT
300	Leu->Phe	cCTC-TTC
300	Leu->His	CTC-CAC
301	Arg->Gly	cCGA-GGA
301	Arg->Ter	cCGA-TGA
301	Arg->Gln	CGA-CAA
301	Arg->Pro	CGA-CCA
303	Ile->Asn	ATC-AAC
306	Gln->Ter	tCAA-TAA
308	Lys->Asn	AAAg-AAT
310	Leu->Phe	tCTC-TTC
312	Gln->Arg	CAG-CGG
312	Gln->His	CAGg-CAT
313	Asp->Tyr	gGAT-TAT
316	Val->Glu	GTA-GAA
317	Ile->Asn	ATT-AAT
317	Ile->Thr	ATT-ACT
320	Asn->Ile	AAT-ATT
320	Asn->Lys	AATc-AAG
320	Asn->Tyr	cAAT-TAT
321	Gln->Arg	CAG-CGG
321	Gln->Leu	CAG-CTG
321	Gln->Glu	tCAG-GAG
321	Gln->Ter	tCAG-TAG
325	Gly->Asp	GGC-GAC
327	Gln->Lys	gCAA-AAA
327	Gln->Glu	gCAA-GAA
328	Gly->Arg	aGGG-AGG
328	Gly->Ala	GGG-GCG
328	Gly->Val	GGG-GTG
330	Gln->Ter	cCAG-TAG
333	Gln->Ter	aCAG-TAG
338	Glu->Lys	tGAA-AAA
338	Glu->Ter	tGAA-TAA
340	Trp->Arg	gTGG-CGG
340	Trp->Ter	TGGg-TGA
341	Glu->Asp	GAAc-GAC
341	Glu->Lys	gGAA-AAA
342	Arg->Ter	aCGA-TGA
342	Arg->Gln	CGA-CAA
344	Leu->Pro	CTC-CCC
345	Ser->Pro	cTCA-CCA
348	Ala->Pro	aGCC-CCC
349	Trp->Ter	TGG-TAG
350	Ala->Pro	gGCT-CCT
352	Ala->Asp	GCT-GAT
355	Asn->Lys	AACc-AAA
356	Arg->Trp	cCGG-TGG
357	Gln->Ter	gCAG-TAG
358	Glu->Ala	GAG-GCG
358	Glu->Gly	GAG-GGG
358	Glu->Lys	gGAG-AAG
360	Gly->Ser	tGGT-AGT
360	Gly->Cys	tGGT-TGT
361	Gly->Arg	tGGA-AGA
362	Pro->Leu	CCT-CTT
363	Arg->His	CGC-CAC
363	Arg->Cys	tCGC-TGC
365	Tyr->Ter	TATa-TAA
373	Gly->Ser	gGGT-AGT
373	Gly->Asp	GGT-GAT
377	Ala->Asp	GCC-GAC
378	Cys->Arg	cTGT-CGT
378	Cys->Tyr	TGT-TAT
382	Cys->Tyr	TGC-TAC
382	Cys->Trp	TGCt-TGG
384	Ile->Asn	ATC-AAC
385	Thr->Pro	cACA-CCA
386	Gln->Ter	aCAG-TAG
386	Gln->Pro	CAG-CCG
398	Glu->Lys	tGAA-AAA
398	Glu->Ter	tGAA-TAA
399	Trp->Ter	TGG-TAG
401	Ser->Ter	TCA-TGA
403	Leu->Ser	TTA-TCA
407	Ile->Lys	ATA-AAA
409	Pro->Thr	tCCC-ACC
409	Pro->Ala	tCCC-GCC
409	Pro->Ser	tCCC-TCC
410	Thr->Lys	ACA-AAA
410	Thr->Pro	cACA-CCA
410	Thr->Ala	cACA-GCA
411	Gly->Asp	GGC-GAC
414	Leu->Ser	TTG-TCG
415	Leu->Pro	CTT-CCT

dbSNP

We used DbSNP to search for silent mutations, as they are not listed in HGMD (because the do not lead to a disease). The query "synonymous-codon"[Function_Class] AND gla[GENE] AND "human"[ORGN] AND "snp"[SNP_CLASS] only output two results, these are listed in the table below. Insertions and deletions have not been taken into account, because they usually cause frameshifts, that means that the reading frame of the transcription is changed. Thus the mutation does not only course the change of a single amino acid, but it most probably changes the whole protein sequence. Additionally the new reading frame my read a stop codon and the transcription is terminated to early or the normal stop codon is missed and the sequence gets to long. In all cases the mutation can not be mapped to the initial sequence and thus is excluded from this task.

Identifier	AA-Position	Triplet	Allele	Residue
rs77934640	143	GCA -> GCG	A -> G	A -> A
rs74795363	112	CGC -> CGT	C -> T	R -> R

Mutation Map

The results from the database searches were mapped to the sequence and highlighted with different colors. As many mutations from HGMD occur at the same amino acid position in the sequence, there are less red or blue letters than mutations in the table in the HGMD section.

• red: missense/nonsense mutation (HGMD)
• blue: as well missense/nonsense as silent mutation

MQLRNPELHL GCALALRFLA LVSWDIPGAR ALDNGLARTP TMGWLHWERF
MCNLDCQEEP DSCISEKLFM EMAELMVSEG WKDAGYEYLC IDDCWMAPQR
DSEGRLQADP QRFPHGIRQL ANYVHSKGLK LGIYADVGNK TCAGFPGSFG
YYDIDAQTFA DWGVDLLKFD GCYCDSLENL ADGYKHMSLA LNRTGRSIVY
SCEWPLYMWP FQKPNYTEIR QYCNHWRNFA DIDDSWKSIK SILDWTSFNQ
ERIVDVAGPG GWNDPDMLVI GNFGLSWNQQ VTQMALWAIM AAPLFMSNDL
RHISPQAKAL LQDKDVIAIN QDPLGKQGYQ LRQGDNFEVW ERPLSGLAWA
VAMINRQEIG GPRSYTIAVA SLGKGVACNP ACFITQLLPV KRKLGFYEWT
SRLRSHINPT GTVLLQLENT MQMSLKDLL

Additionally, we mapped the mutations to the structure of α-galactosidase (see figure 1). For this, we used the PDB structure 1R47. We applied the same color scheme as above. It should be noted that this structure does not include the signal peptide (residues 1 to 31, see UniProt).

Figure 1: The PDB structures 1R47 in cartoon representation. The residues are colored by the following scheme. Gray: no annoated mutation in HGMD or DbSNP, red: a missense/nonsense mutation according to HGMD, blue: this residue can cause a missense/nonsense mutation or a silent mutation as well.

References

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