ALS2 (alsin Rho guanine nucleotide exchange factor ALS2)

Gene

• Entrez ID: 57679
• Gene name: Alsin Rho guanine nucleotide exchange factor ALS2
• Gene symbol: ALS2
• Synonyms (NCBI Gene): ALS2CR6, ALSJ, IAHSP, PLSJ
• Chromosome: 2
• Chromosome location: 2q33.1
• Summary: The protein encoded by this gene contains an ATS1/RCC1-like domain, a RhoGEF domain, and a vacuolar protein sorting 9 (VPS9) domain, all of which are guanine-nucleotide exchange factors that activate members of the Ras superfamily of GTPases. The protein

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs61745503	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, non coding transcript variant, coding sequence variant, upstream transcript variant, genic upstream transcript variant, 5 prime UTR variant
rs61757691	T>C	Conflicting-interpretations-of-pathogenicity, likely-benign, uncertain-significance	Coding sequence variant, missense variant, genic downstream transcript variant, non coding transcript variant
rs121908137	G>A,T	Pathogenic	Non coding transcript variant, coding sequence variant, stop gained, genic downstream transcript variant, synonymous variant
rs121908138	C>T	Pathogenic	Non coding transcript variant, upstream transcript variant, coding sequence variant, missense variant, genic upstream transcript variant
rs121908139	G>A	Pathogenic	Non coding transcript variant, 5 prime UTR variant, coding sequence variant, stop gained, genic downstream transcript variant
rs185911369	G>A	Likely-benign, uncertain-significance, conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, intron variant
rs190369242	G>C	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Genic downstream transcript variant, upstream transcript variant, missense variant, genic upstream transcript variant, coding sequence variant, non coding transcript variant, 5 prime UTR variant
rs202219507	T>A	Likely-pathogenic, uncertain-significance	Coding sequence variant, non coding transcript variant, genic downstream transcript variant, missense variant
rs369577952	A>C,G	Pathogenic	Genic upstream transcript variant, 5 prime UTR variant, stop gained, genic downstream transcript variant, non coding transcript variant, synonymous variant, upstream transcript variant, coding sequence variant
rs386134173	T>-	Pathogenic	Genic upstream transcript variant, non coding transcript variant, 5 prime UTR variant, coding sequence variant, frameshift variant
rs386134174	T>-	Pathogenic	Upstream transcript variant, genic upstream transcript variant, non coding transcript variant, coding sequence variant, frameshift variant
rs386134175	AT>-	Pathogenic	Genic upstream transcript variant, non coding transcript variant, 5 prime UTR variant, coding sequence variant, frameshift variant
rs386134176	CT>-	Pathogenic	Non coding transcript variant, 5 prime UTR variant, coding sequence variant, genic downstream transcript variant, frameshift variant
rs386134178	C>T	Pathogenic	Missense variant, non coding transcript variant, 5 prime UTR variant, coding sequence variant, genic downstream transcript variant
rs386134179	->ACTGC	Pathogenic	Non coding transcript variant, 5 prime UTR variant, coding sequence variant, genic downstream transcript variant, frameshift variant
rs386134180	C>A	Pathogenic	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, stop gained
rs386134181	AG>-	Pathogenic	Non coding transcript variant, 5 prime UTR variant, coding sequence variant, genic downstream transcript variant, frameshift variant
rs386134182	T>A	Pathogenic	Genic downstream transcript variant, splice acceptor variant
rs386134183	AT>-	Pathogenic	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, frameshift variant
rs386134184	T>C	Pathogenic	Genic downstream transcript variant, splice acceptor variant
rs386134185	C>-	Pathogenic	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, frameshift variant
rs386134186	C>G	Pathogenic	Intron variant, genic downstream transcript variant
rs386134187	T>-	Pathogenic	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, stop gained
rs386134188	A>-	Pathogenic	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, frameshift variant
rs387906316	C>A	Pathogenic	Genic downstream transcript variant, splice acceptor variant
rs587777132	G>A,T	Pathogenic, likely-pathogenic	Genic downstream transcript variant, synonymous variant, stop gained, non coding transcript variant, coding sequence variant
rs730882255	C>A	Pathogenic	Genic downstream transcript variant, 5 prime UTR variant, stop gained, non coding transcript variant, coding sequence variant
rs730882256	->C	Pathogenic	Non coding transcript variant, genic downstream transcript variant, coding sequence variant, frameshift variant
rs746255868	G>A	Likely-pathogenic	Genic upstream transcript variant, stop gained, non coding transcript variant, coding sequence variant, upstream transcript variant
rs757972700	T>A	Pathogenic	Stop gained, genic downstream transcript variant, coding sequence variant, non coding transcript variant
rs761291489	C>T	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, non coding transcript variant, missense variant
rs767350733	G>A	Pathogenic, likely-pathogenic	Genic downstream transcript variant, non coding transcript variant, coding sequence variant, stop gained
rs797044934	G>A	Pathogenic	Genic downstream transcript variant, non coding transcript variant, stop gained, coding sequence variant
rs863225293	G>A	Likely-pathogenic, pathogenic	Genic downstream transcript variant, non coding transcript variant, stop gained, coding sequence variant
rs863225294	G>T	Likely-pathogenic, pathogenic	5 prime UTR variant, coding sequence variant, stop gained, non coding transcript variant, genic downstream transcript variant
rs878855058	CTCT>-	Pathogenic	5 prime UTR variant, coding sequence variant, frameshift variant, non coding transcript variant, genic downstream transcript variant
rs1057523547	C>G,T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, genic upstream transcript variant, missense variant, upstream transcript variant
rs1057524355	C>G	Likely-pathogenic	Splice acceptor variant, genic downstream transcript variant
rs1060503672	C>T	Likely-pathogenic	Splice acceptor variant, genic downstream transcript variant
rs1064793583	CTTT>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant, genic upstream transcript variant, upstream transcript variant
rs1064797281	C>T	Likely-pathogenic	Coding sequence variant, stop gained, non coding transcript variant, genic downstream transcript variant
rs1553506317	->GTGCGTGGAG	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant, genic downstream transcript variant
rs1553511680	G>A	Pathogenic	Stop gained, genic downstream transcript variant, coding sequence variant, 5 prime UTR variant, non coding transcript variant
rs1574655402	C>-	Likely-pathogenic	Splice acceptor variant, non coding transcript variant, genic downstream transcript variant, coding sequence variant
rs1574698048	C>A	Pathogenic	Stop gained, non coding transcript variant, genic downstream transcript variant, coding sequence variant
rs1574748038	C>A	Likely-pathogenic	Non coding transcript variant, stop gained, genic downstream transcript variant, 5 prime UTR variant, coding sequence variant
rs1574786170	CTGACAGT>-	Likely-pathogenic	Frameshift variant, non coding transcript variant, 5 prime UTR variant, coding sequence variant, genic upstream transcript variant
rs1574786641	G>-	Pathogenic	Non coding transcript variant, stop gained, 5 prime UTR variant, coding sequence variant, genic upstream transcript variant
rs1574787779	G>A	Pathogenic, likely-pathogenic	Non coding transcript variant, genic upstream transcript variant, stop gained, coding sequence variant, upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT047362	hsa-miR-34a-5p	CLASH	23622248
MIRT038866	hsa-miR-93-3p	CLASH	23622248
MIRT036325	hsa-miR-1229-3p	CLASH	23622248
MIRT779185	hsa-miR-203	CLIP-seq
MIRT779186	hsa-miR-205	CLIP-seq
MIRT779187	hsa-miR-21	CLIP-seq
MIRT779188	hsa-miR-216a	CLIP-seq
MIRT779189	hsa-miR-216b	CLIP-seq
MIRT779190	hsa-miR-23a	CLIP-seq
MIRT779191	hsa-miR-23b	CLIP-seq
MIRT779192	hsa-miR-23c	CLIP-seq
MIRT779193	hsa-miR-3122	CLIP-seq
MIRT779194	hsa-miR-3192	CLIP-seq
MIRT779195	hsa-miR-362-5p	CLIP-seq
MIRT779196	hsa-miR-3689a-3p	CLIP-seq
MIRT779197	hsa-miR-3689c	CLIP-seq
MIRT779198	hsa-miR-369-3p	CLIP-seq
MIRT779199	hsa-miR-374a	CLIP-seq
MIRT779200	hsa-miR-374b	CLIP-seq
MIRT779201	hsa-miR-3913-5p	CLIP-seq
MIRT779202	hsa-miR-3929	CLIP-seq
MIRT779203	hsa-miR-4263	CLIP-seq
MIRT779204	hsa-miR-4419b	CLIP-seq
MIRT779205	hsa-miR-4478	CLIP-seq
MIRT779206	hsa-miR-4494	CLIP-seq
MIRT779207	hsa-miR-4683	CLIP-seq
MIRT779208	hsa-miR-4724-3p	CLIP-seq
MIRT779209	hsa-miR-4728-5p	CLIP-seq
MIRT779210	hsa-miR-4799-5p	CLIP-seq
MIRT779211	hsa-miR-485-5p	CLIP-seq
MIRT779212	hsa-miR-490-3p	CLIP-seq
MIRT779213	hsa-miR-499a-5p	CLIP-seq
MIRT779214	hsa-miR-500b	CLIP-seq
MIRT779215	hsa-miR-501-5p	CLIP-seq
MIRT779216	hsa-miR-548c-3p	CLIP-seq
MIRT779217	hsa-miR-576-5p	CLIP-seq
MIRT779218	hsa-miR-590-5p	CLIP-seq
MIRT779219	hsa-miR-1323	CLIP-seq
MIRT779220	hsa-miR-145	CLIP-seq
MIRT779221	hsa-miR-1825	CLIP-seq
MIRT779222	hsa-miR-186	CLIP-seq
MIRT779223	hsa-miR-199a-5p	CLIP-seq
MIRT779224	hsa-miR-199b-5p	CLIP-seq
MIRT779225	hsa-miR-3133	CLIP-seq
MIRT779226	hsa-miR-3137	CLIP-seq
MIRT779227	hsa-miR-3155	CLIP-seq
MIRT779228	hsa-miR-3155b	CLIP-seq
MIRT779229	hsa-miR-3202	CLIP-seq
MIRT779230	hsa-miR-4427	CLIP-seq
MIRT779231	hsa-miR-4452	CLIP-seq
MIRT779232	hsa-miR-4476	CLIP-seq
MIRT779233	hsa-miR-4639-3p	CLIP-seq
MIRT779234	hsa-miR-4680-3p	CLIP-seq
MIRT779235	hsa-miR-4769-3p	CLIP-seq
MIRT779236	hsa-miR-4778-3p	CLIP-seq
MIRT779237	hsa-miR-4785	CLIP-seq
MIRT779238	hsa-miR-484	CLIP-seq
MIRT779239	hsa-miR-518a-5p	CLIP-seq
MIRT779240	hsa-miR-527	CLIP-seq
MIRT779241	hsa-miR-548o	CLIP-seq
MIRT779242	hsa-miR-630	CLIP-seq
MIRT1930012	hsa-miR-1273e	CLIP-seq
MIRT779188	hsa-miR-216a	CLIP-seq
MIRT779189	hsa-miR-216b	CLIP-seq
MIRT779193	hsa-miR-3122	CLIP-seq
MIRT1930013	hsa-miR-3664-3p	CLIP-seq
MIRT1930014	hsa-miR-3670	CLIP-seq
MIRT779196	hsa-miR-3689a-3p	CLIP-seq
MIRT779197	hsa-miR-3689c	CLIP-seq
MIRT779201	hsa-miR-3913-5p	CLIP-seq
MIRT779202	hsa-miR-3929	CLIP-seq
MIRT779204	hsa-miR-4419b	CLIP-seq
MIRT1930015	hsa-miR-4433	CLIP-seq
MIRT1930016	hsa-miR-4459	CLIP-seq
MIRT779205	hsa-miR-4478	CLIP-seq
MIRT779209	hsa-miR-4728-5p	CLIP-seq
MIRT1930017	hsa-miR-4768-3p	CLIP-seq
MIRT779211	hsa-miR-485-5p	CLIP-seq
MIRT779220	hsa-miR-145	CLIP-seq
MIRT2170775	hsa-miR-1197	CLIP-seq
MIRT2170776	hsa-miR-1282	CLIP-seq
MIRT2170777	hsa-miR-1305	CLIP-seq
MIRT2170778	hsa-miR-2110	CLIP-seq
MIRT2170779	hsa-miR-3144-5p	CLIP-seq
MIRT2170780	hsa-miR-3150a-3p	CLIP-seq
MIRT2170781	hsa-miR-3191	CLIP-seq
MIRT779229	hsa-miR-3202	CLIP-seq
MIRT1930013	hsa-miR-3664-3p	CLIP-seq
MIRT2170782	hsa-miR-3664-5p	CLIP-seq
MIRT2170783	hsa-miR-3692	CLIP-seq
MIRT2170784	hsa-miR-4260	CLIP-seq
MIRT2170785	hsa-miR-4264	CLIP-seq
MIRT2170786	hsa-miR-4436a	CLIP-seq
MIRT2170787	hsa-miR-4475	CLIP-seq
MIRT779232	hsa-miR-4476	CLIP-seq
MIRT2170788	hsa-miR-4533	CLIP-seq
MIRT2170789	hsa-miR-4652-5p	CLIP-seq
MIRT2170790	hsa-miR-4704-3p	CLIP-seq
MIRT2170791	hsa-miR-4717-3p	CLIP-seq
MIRT2170792	hsa-miR-4719	CLIP-seq
MIRT2170793	hsa-miR-4742-3p	CLIP-seq
MIRT2170794	hsa-miR-4797-3p	CLIP-seq
MIRT2170795	hsa-miR-4802-3p	CLIP-seq
MIRT2170796	hsa-miR-507	CLIP-seq
MIRT2170797	hsa-miR-510	CLIP-seq
MIRT779239	hsa-miR-518a-5p	CLIP-seq
MIRT779240	hsa-miR-527	CLIP-seq
MIRT2170798	hsa-miR-557	CLIP-seq
MIRT2170799	hsa-miR-873	CLIP-seq
MIRT2384101	hsa-miR-1262	CLIP-seq
MIRT2384102	hsa-miR-4701-3p	CLIP-seq
MIRT2384103	hsa-miR-508-5p	CLIP-seq
MIRT2384104	hsa-miR-542-3p	CLIP-seq
MIRT2384105	hsa-miR-661	CLIP-seq
MIRT2384106	hsa-miR-766	CLIP-seq
MIRT779188	hsa-miR-216a	CLIP-seq
MIRT779189	hsa-miR-216b	CLIP-seq
MIRT779193	hsa-miR-3122	CLIP-seq
MIRT2443593	hsa-miR-3613-3p	CLIP-seq
MIRT2443594	hsa-miR-3667-5p	CLIP-seq
MIRT779196	hsa-miR-3689a-3p	CLIP-seq
MIRT779197	hsa-miR-3689c	CLIP-seq
MIRT2443595	hsa-miR-371-5p	CLIP-seq
MIRT2443596	hsa-miR-371b-5p	CLIP-seq
MIRT779201	hsa-miR-3913-5p	CLIP-seq
MIRT779202	hsa-miR-3929	CLIP-seq
MIRT779204	hsa-miR-4419b	CLIP-seq
MIRT779205	hsa-miR-4478	CLIP-seq
MIRT779209	hsa-miR-4728-5p	CLIP-seq
MIRT779211	hsa-miR-485-5p	CLIP-seq
MIRT2443597	hsa-miR-495	CLIP-seq
MIRT779188	hsa-miR-216a	CLIP-seq
MIRT779189	hsa-miR-216b	CLIP-seq
MIRT779193	hsa-miR-3122	CLIP-seq
MIRT779196	hsa-miR-3689a-3p	CLIP-seq
MIRT779197	hsa-miR-3689c	CLIP-seq
MIRT779201	hsa-miR-3913-5p	CLIP-seq
MIRT779209	hsa-miR-4728-5p	CLIP-seq
MIRT2473441	hsa-miR-1183	CLIP-seq
MIRT2473442	hsa-miR-1200	CLIP-seq
MIRT2473443	hsa-miR-1273f	CLIP-seq
MIRT2170777	hsa-miR-1305	CLIP-seq
MIRT2473444	hsa-miR-143	CLIP-seq
MIRT2473445	hsa-miR-3064-3p	CLIP-seq
MIRT2473446	hsa-miR-3148	CLIP-seq
MIRT779229	hsa-miR-3202	CLIP-seq
MIRT2473447	hsa-miR-3671	CLIP-seq
MIRT2473448	hsa-miR-3688-3p	CLIP-seq
MIRT2473449	hsa-miR-3935	CLIP-seq
MIRT2473450	hsa-miR-411	CLIP-seq
MIRT2473451	hsa-miR-4324	CLIP-seq
MIRT779232	hsa-miR-4476	CLIP-seq
MIRT2473452	hsa-miR-4659a-3p	CLIP-seq
MIRT2473453	hsa-miR-4659b-3p	CLIP-seq
MIRT2473454	hsa-miR-4682	CLIP-seq
MIRT2473455	hsa-miR-4693-5p	CLIP-seq
MIRT2473456	hsa-miR-4694-3p	CLIP-seq
MIRT2473457	hsa-miR-4708-5p	CLIP-seq
MIRT2473458	hsa-miR-4770	CLIP-seq
MIRT779236	hsa-miR-4778-3p	CLIP-seq
MIRT2473459	hsa-miR-4793-5p	CLIP-seq
MIRT2473460	hsa-miR-522	CLIP-seq
MIRT2473461	hsa-miR-544b	CLIP-seq
MIRT2473462	hsa-miR-577	CLIP-seq
MIRT2473463	hsa-miR-607	CLIP-seq
MIRT2473441	hsa-miR-1183	CLIP-seq
MIRT2170777	hsa-miR-1305	CLIP-seq
MIRT779229	hsa-miR-3202	CLIP-seq
MIRT2473447	hsa-miR-3671	CLIP-seq
MIRT2473449	hsa-miR-3935	CLIP-seq
MIRT2473450	hsa-miR-411	CLIP-seq
MIRT779232	hsa-miR-4476	CLIP-seq
MIRT2473455	hsa-miR-4693-5p	CLIP-seq
MIRT2473456	hsa-miR-4694-3p	CLIP-seq
MIRT779236	hsa-miR-4778-3p	CLIP-seq
MIRT2674943	hsa-miR-487a	CLIP-seq
MIRT2473460	hsa-miR-522	CLIP-seq
MIRT2473462	hsa-miR-577	CLIP-seq
MIRT2473463	hsa-miR-607	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001662	Process	Behavioral fear response	IEA
GO:0001726	Component	Ruffle	IEA
GO:0001726	Component	Ruffle	ISS
GO:0001881	Process	Receptor recycling	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IBA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IDA	15247254
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IDA	12837691, 16049005
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005096	Function	GTPase activator activity	IDA	12837691, 15247254
GO:0005515	Function	Protein binding	IPI	21300063, 33961781
GO:0005634	Component	Nucleus	IDA	12837691
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005769	Component	Early endosome	IDA	12837691
GO:0005813	Component	Centrosome	IBA
GO:0005813	Component	Centrosome	IDA	16085057
GO:0005813	Component	Centrosome	IEA
GO:0005829	Component	Cytosol	IDA	12837691
GO:0005829	Component	Cytosol	TAS
GO:0006979	Process	Response to oxidative stress	IEA
GO:0007032	Process	Endosome organization	NAS	12837691
GO:0007041	Process	Lysosomal transport	IDA	12837691
GO:0007528	Process	Neuromuscular junction development	IEA
GO:0007626	Process	Locomotory behavior	IEA
GO:0008104	Process	Intracellular protein localization	IEA
GO:0014069	Component	Postsynaptic density	IEA
GO:0016050	Process	Vesicle organization	IEA
GO:0016197	Process	Endosomal transport	IBA
GO:0016197	Process	Endosomal transport	IEA
GO:0030027	Component	Lamellipodium	IEA
GO:0030027	Component	Lamellipodium	ISS
GO:0030425	Component	Dendrite	IBA
GO:0030425	Component	Dendrite	IDA	15371724
GO:0030425	Component	Dendrite	IEA
GO:0030426	Component	Growth cone	ISS
GO:0031267	Function	Small GTPase binding	IBA
GO:0031267	Function	Small GTPase binding	IDA	12837691, 15247254
GO:0031267	Function	Small GTPase binding	NAS	16670179
GO:0031982	Component	Vesicle	IDA	12837691
GO:0032991	Component	Protein-containing complex	IDA	15247254
GO:0035022	Process	Positive regulation of Rac protein signal transduction	IC	16049005
GO:0035249	Process	Synaptic transmission, glutamatergic	IEA
GO:0042802	Function	Identical protein binding	IDA	15247254
GO:0042803	Function	Protein homodimerization activity	IPI	15247254
GO:0043197	Component	Dendritic spine	IEA
GO:0043231	Component	Intracellular membrane-bounded organelle	IBA
GO:0043539	Function	Protein serine/threonine kinase activator activity	IDA	16049005
GO:0043547	Process	Positive regulation of GTPase activity	IDA	16049005
GO:0045860	Process	Positive regulation of protein kinase activity	IDA	16049005
GO:0048812	Process	Neuron projection morphogenesis	IDA	16049005
GO:0051036	Process	Regulation of endosome size	IEP	15247254
GO:0051260	Process	Protein homooligomerization	IDA	15247254
GO:0065008	Process	Regulation of biological quality	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099072	Process	Regulation of postsynaptic membrane neurotransmitter receptor levels	IEA

Other IDs

• MIM: 606352
• HGNC: 443
• e!Ensembl: ENSG00000003393

Protein

• UniProt ID: Q96Q42
• Protein name: Alsin (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 6 protein) (Amyotrophic lateral sclerosis 2 protein)
• Protein function: May act as a GTPase regulator. Controls survival and growth of spinal motoneurons (By similarity).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00415	RCC1	109 → 165	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	170 → 216	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	527 → 574	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00621	RhoGEF	694 → 882	RhoGEF domain	Domain
  PF02493	MORN	1049 → 1071	MORN repeat	Repeat
  PF02493	MORN	1072 → 1094	MORN repeat	Repeat
  PF02493	MORN	1100 → 1122	MORN repeat	Repeat
  PF02493	MORN	1123 → 1142	MORN repeat	Repeat
  PF02493	MORN	1151 → 1168	MORN repeat	Repeat
  PF02493	MORN	1175 → 1191	MORN repeat	Repeat
  PF02493	MORN	1198 → 1220	MORN repeat	Repeat
  PF02493	MORN	1221 → 1244	MORN repeat	Repeat
  PF02204	VPS9	1552 → 1656	Vacuolar sorting protein 9 (VPS9) domain	Family

• Sequence:

  MDSKKRSSTEAEGSKERGLVHIWQAGSFPITPERLPGWGGKTVLQAALGVKHGVLLTEDG
  EVYSFGTLPWRSGPVEICPSSPILENALVGQYVITVATGSFHSGAVTDNGVAYMWGENSA
  GQCAVANQQYVPEPNPVSIADSEASPLLAVRILQLACGEEHTLALSISREIWAWGTGCQL
  GLITTAFPVTKPQKVEHLAGRVVLQVACGAFHSLALVQCLPSQDLKPVPERCNQCSQLLI
  TMTDKEDHVIISDSHCCPLGVTLTESQAENHASTALSPSTETLDRQEEVFENTLVANDQS
  VATELNAVSAQITSSDAMSSQQNVMGTTEISSARNIPSYPDTQAVNEYLRKLSDHSVRED
  SEHGEKPVPSQPLLEEAIPNLHSPPTTSTSALNSLVVSCASAVGVRVAATYEAGALSLKK
  VMNFYSTTPCETGAQAGSSAIGPEGLKDSREEQVKQESMQGKKSSSLVDIREEETEGGSR
  RLSLPGLLSQVSPRLLRKAARVKTRTVVLTPTYSGEADALLPSLRTEVWTWGKGKEGQLG
  HGDVLPRLQPLCVKCLDGKEVIHLEAGGYHSLALTAKSQVYSWGSNTFGQLGHSDFPTTV
  PRLAKISSENGVWSIAAGRDYSLFLVDTEDFQPGLYYSGRQDPTEGDNLPENHSGSKTPV
  LLSCSKLGYISRVTAGKDSYLALVDKNIMGYIASLHELATTERRFYSKLSDIKSQILRPL
  LSLENLGTTTTVQLLQEVASRFSKLCYLIGQHGASLSSFLHGVKEARSLVILKHSSLFLD
  SYTEYCTSITNFLVMGGFQLLAKPAIDFLNKNQELLQDLSEVNDENTQLMEILNTLFFLP
  IRRLHNYAKVLLKLATCFEVASPEYQKLQDSSSCYECLALHLGRKRKEAEYTLGFWKTFP
  GKMTDSLRKPERRLLCESSNRALSLQHAGRFSVNWFILFNDALVHAQFSTHHVFPLATLW
  AEPLSEEAGGVNGLKITTPEEQFTLISSTPQEKTKWLRAISQAVDQALRGMSDLPPYGSG
  SSVQRQEPPISRSAKYTFYKDPRLKDATYDGRWLSGKPHGRGVLKWPDGKMYSGMFRNGL
  EDGYGEYRIPNKAMNKEDHYVGHWKEGKMCGQGVYSYASGEVFEGCFQDNMRHGHGLLRS
  GKLTSSSPSMFIGQWVMDKKAGYGVFDDITRGEKYMGMWQDDVCQGNGVVVTQFGLYYEG
  NFHLNKMMGNGVLLSEDDTIYEGEFSDDWTLSGKGTLTMPNGDYIEGYFSGEWGSGIKIT
  GTYFKPSLYESDKDRPKVFRKLGNLAVPADEKWKAVFDECWRQLGCEGPGQGEVWKAWDN
  IAVALTTSRRQHRDSPEILSRSQTQTLESLEFIPQHVGAFSVEKYDDIRKYLIKACDTPL
  HPLGRLVETLVAVYRMTYVGVGANRRLLQEAVKEIKSYLKRIFQLVRFLFPELPEEGSTI
  PLSAPLPTERKSFCTGKSDSRSESPEPGYVVTSSGLLLPVLLPRLYPPLFMLYALDNDRE
  EDIYWECVLRLNKQPDIALLGFLGVQRKFWPATLSILGESKKVLPTTKDACFASAVECLQ
  QISTTFTPSDKLKVIQQTFEEISQSVLASLHEDFLWSMDDLFPVFLYVVLRARIRNLGSE
  VHLIEDLMDPYLQHGEQGIMFTTLKACYYQIQREKLN

• Sequence length: 1657

Pathways

KEGG:

Amyotrophic lateral sclerosis
Pathways of neurodegeneration - multiple diseases

Reactome:

RAB GEFs exchange GTP for GDP on RABs

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormal central motor function	Likely pathogenic; Pathogenic	rs2106074229, rs1340248169	RCV001814407 RCV001814425	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
ALS2-related disorder	Likely pathogenic	rs767762611	RCV004584274	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
ALS2-related motor neuron disease	Likely pathogenic	rs538311710	RCV003994564	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Amyotrophic lateral sclerosis	Likely pathogenic; Pathogenic	rs2105998730, rs2106102324, rs759408917	RCV003106223 RCV003107983 RCV003106160	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Amyotrophic lateral sclerosis type 2, juvenile	Pathogenic; Likely pathogenic	rs587777132, rs1234882220, rs2106071765, rs2105972075, rs2106012637, rs2106023727, rs730882255, rs730882256, rs386134173, rs386134174, rs2469899610, rs863225293, rs770096661, rs2469724450, rs2469852909, rs767350733, rs1064797281, rs369577952, rs757972700, rs763455928, rs1574748038, rs1574787779, rs1689580631, rs374047961, rs1689584119	RCV001095478 RCV003128270 RCV001824228 RCV002223744 RCV002223745 RCV003225989 RCV000162071 RCV000162072 RCV000004655 RCV000004664 RCV002512482 RCV002500830 RCV003147910 RCV003152844 RCV003153174 RCV000735438 RCV002512105 RCV000763471 RCV001375960 RCV001095477 RCV000991370 RCV000991371 RCV001095480 RCV001095479 RCV001250151	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Infantile-onset ascending hereditary spastic paralysis	Likely pathogenic; Pathogenic	rs1690335308, rs2105998730, rs2106001462, rs2106005949, rs2106009582, rs587777132, rs2106074229, rs2106080813, rs2106074302, rs1391892163, rs1690532210, rs2105969251, rs2106088185, rs1689931402, rs2106089689, rs2106023727, rs1275973309, rs2106011709, rs2106102271, rs1317051984, rs730882256, rs1690523978, rs2469900041, rs2469758488, rs2469784078, rs745657866, rs386134181, rs386134187, rs387906316, rs386134183, rs386134175, rs386134188, rs121908137, rs121908138, rs121908139, rs2469899610, rs2469913984, rs863225293, rs863225294, rs2469774653, rs878855058, rs770096661, rs2469758597, rs1263013448, rs2469943073, rs2469917312, rs767032589, rs2469734144, rs2469780591, rs1014953504, rs1213175712, rs2469768159, rs767350733, rs1060503672, rs1064793583, rs1064797281, rs746255868, rs386134182, rs369577952, rs1553511680, rs757972700, rs1691183538, rs763455928, rs1693726956, rs1693462968, rs1574786170, rs1574748038, rs1574787779, rs1574786641, rs374047961, rs1692492382, rs1167814155, rs1337097412, rs759408917, rs2105999102, rs2106005994, rs2106089798	RCV001379780 RCV001377565 RCV001379989 RCV001379324 RCV001379573 RCV000087053 RCV002471117 RCV002014253 RCV001955652 RCV001992862 RCV001995649 RCV001960666 RCV001942307 RCV002259411 RCV002259428 RCV002259429 RCV002259430 RCV002259431 RCV002259432 RCV002259433 RCV001089474 RCV002471488 RCV002508855 RCV002508856 RCV003072341 RCV002603393 RCV000995486 RCV000004658 RCV000004659 RCV000004660 RCV000004661 RCV000004662 RCV000004663 RCV000004665 RCV000004667 RCV002512482 RCV002842277 RCV000986979 RCV000986980 RCV003046500 RCV000232793 RCV003147912 RCV003229781 RCV003340930 RCV003503887 RCV003611929 RCV003612611 RCV003612818 RCV003612761 RCV003613437 RCV003611088 RCV003611022 RCV003833902 RCV004515775 RCV001851103 RCV000457236 RCV001386854 RCV002512105 RCV001868005 RCV000034887 RCV000640988 RCV000640989 RCV000800103 RCV001089473 RCV001089471 RCV001089472 RCV001089476 RCV000984509 RCV000991370 RCV000991371 RCV000995487 RCV001391373 RCV001217451 RCV001218439 RCV001232129 RCV001234628 RCV001391372 RCV001391371 RCV001391369	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Juvenile amyotrophic lateral sclerosis	Pathogenic	rs1689931402	RCV002227850	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Juvenile primary lateral sclerosis	Pathogenic; Likely pathogenic	rs386134181, rs386134176, rs386134174, rs386134184, rs2469899610, rs863225293, rs770096661, rs767350733, rs1064797281, rs386134178, rs369577952, rs1693780539, rs1574748038, rs1574787779, rs1574698048	RCV000004656 RCV000004657 RCV000995489 RCV000004666 RCV002512482 RCV002500830 RCV003147911 RCV002481351 RCV002512105 RCV000034964 RCV000763471 RCV001089475 RCV000991370 RCV000991371 RCV000995485	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Tip-toe gait	Likely pathogenic; Pathogenic	rs2469683799, rs1064797281	RCV003319275 RCV003318583	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AMYOTROPHIC LATERAL SCLEROSIS 2, JUVENILE	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Amyotrophic Lateral Sclerosis, Recessive	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLOBAL DEVELOPMENTAL DELAY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hereditary spastic paraplegia	Conflicting classifications of pathogenicity; Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTYROSINEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MOTOR NEURON DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Peripheral axonal neuropathy	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARALYSIS, INFANTILE-ONSET ASCENDING	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Likely benign; Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	31405128	Associate	★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	11586298, 12507415, 12866199, 14676054, 14970233, 16670179, 16802286, 16909018, 17093100, 17566607, 17955197, 18026741, 18160256, 18422522, 18714162, 18759352, 20728492, 21937428, 22727276, 27439389, 28891518, 29469808, 31702469		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	LHGDN	12138710, 15388334, 17955197		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Amyotrophic Lateral Sclerosis	Amyotrophic lateral sclerosis	Pubtator	12145748, 18422522, 23755159, 23881933, 25474699, 29469808, 31405128, 36549973, 40316175	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Amyotrophic Lateral Sclerosis	Amyotrophic Lateral Sclerosis	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Amyotrophic Lateral Sclerosis 2 Juvenile	Amyotrophic lateral sclerosis	Pubtator	18422522, 24562058, 25474699, 30128655, 30224357, 33409823, 37055917	Associate	★☆☆☆☆ Found in Text Mining only
AMYOTROPHIC LATERAL SCLEROSIS 2, JUVENILE (disorder)	Amyotrophic lateral sclerosis	GENOMICS_ENGLAND_DG	11586297, 11586298, 20018642, 23881933, 27601211		★☆☆☆☆ Found in Text Mining only
AMYOTROPHIC LATERAL SCLEROSIS 2, JUVENILE (disorder)	Amyotrophic lateral sclerosis	BEFREE	11586298, 12866199, 16240357, 17855450, 17955197, 20339559, 22438926, 24315819, 26751646, 9889004		★☆☆☆☆ Found in Text Mining only
AMYOTROPHIC LATERAL SCLEROSIS 2, JUVENILE (disorder)	Amyotrophic lateral sclerosis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
AMYOTROPHIC LATERAL SCLEROSIS 2, JUVENILE (disorder)	Amyotrophic lateral sclerosis	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis, Familial	Amyotrophic lateral sclerosis	BEFREE	14676054, 18160256, 9933298		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis, Sporadic	Lateral Sclerosis	BEFREE	15050437		★☆☆☆☆ Found in Text Mining only
Anarthria speech disorder	Anarthria Speech Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	BEFREE	30009132		★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	24562058	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral cortical atrophy	Cerebral cortical atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Complicated hereditary spastic paraplegia	Spastic paraplegia	BEFREE	16670179		★☆☆☆☆ Found in Text Mining only
Deglutition Disorders	Dysphagia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Distal amyotrophy	Distal amyotrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dystonia	Dystonia	Pubtator	24562058, 25474699, 30128655	Associate	★☆☆☆☆ Found in Text Mining only
Dystonia Disorders	Dystonia	BEFREE	24562058, 24978640, 30128655		★☆☆☆☆ Found in Text Mining only
Frontotemporal Dementia	Frontotemporal dementia	Pubtator	31405128	Associate	★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	12145748	Associate	★☆☆☆☆ Found in Text Mining only
Henoch-Schoenlein Purpura	Henoch-Schonlein Nephritis	BEFREE	27601211		★☆☆☆☆ Found in Text Mining only
Hereditary spastic paralysis, infantile onset ascending	Spastic paralysis	GENOMICS_ENGLAND_DG	11586298, 12145748, 23881933, 27601211		★☆☆☆☆ Found in Text Mining only
Hereditary spastic paralysis, infantile onset ascending	Spastic paralysis	BEFREE	12145748, 12601111, 12919135, 16670179, 16718699, 17566607, 17855450, 18523452, 18810511, 22248478, 24144828, 24704789, 30128655		★☆☆☆☆ Found in Text Mining only
Hereditary spastic paralysis, infantile onset ascending	Spastic paralysis	CLINVAR_DG	12145748		★☆☆☆☆ Found in Text Mining only
Hereditary spastic paralysis, infantile onset ascending	Spastic paralysis	ORPHANET_DG	24315819		★☆☆☆☆ Found in Text Mining only
Hereditary spastic paralysis, infantile onset ascending	Spastic paralysis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Infantile-onset ascending hereditary spastic paralysis	Spastic paralysis	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Juvenile amyotrophic lateral sclerosis	Amyotrophic Lateral Sclerosis	BEFREE	12145748, 16085057, 16240357, 16718699, 17855450, 22982304, 24315819, 25474699, 30128655		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Juvenile amyotrophic lateral sclerosis	Amyotrophic Lateral Sclerosis	ORPHANET_DG	23282280		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Juvenile amyotrophic lateral sclerosis	Amyotrophic Lateral Sclerosis	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Juvenile primary lateral sclerosis	Lateral Sclerosis	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Lateral Sclerosis	Lateral Sclerosis	BEFREE	18523452, 19122027		★☆☆☆☆ Found in Text Mining only
Lewy Body Disease	Lewy body disease	Pubtator	31405128	Associate	★☆☆☆☆ Found in Text Mining only
Motor neuron atrophy	Motor neuron atrophy	BEFREE	16973244, 17093100, 19279216		★☆☆☆☆ Found in Text Mining only
Motor Neuron Disease	Motor neuron disease	Pubtator	12145748, 21300063	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Motor Neuron Disease	Motor Neuron Disease	BEFREE	12919135, 14668431, 14970233, 16718699, 16802286, 16973244, 17566607, 17955197, 18714162, 19023603, 19304783, 20339559, 24144828, 24315819, 30224357		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Motor Neuron Disease	Motor Neuron Disease	LHGDN	14668431		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Motor Neuron Disease, Upper	Motor Neuron Disease	BEFREE	16802286		★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	BEFREE	18714162		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	31405128	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	17566607, 18422522		★☆☆☆☆ Found in Text Mining only
Papillon-Lefevre Disease	Papillon-Lefevre Disease	BEFREE	31117107		★☆☆☆☆ Found in Text Mining only
Paraplegia	Paraplegia	LHGDN	12919135		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	Pubtator	31405128, 35289213	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral axonal neuropathy	Peripheral axonal neuropathy	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary lateral sclerosis juvenile	Lateral Sclerosis	BEFREE	11586297, 17855450, 22248478, 22982304, 24315819, 30128655		★☆☆☆☆ Found in Text Mining only
Primary lateral sclerosis juvenile	Lateral Sclerosis	GENOMICS_ENGLAND_DG	11586298, 23881933, 27601211		★☆☆☆☆ Found in Text Mining only
Primary lateral sclerosis juvenile	Lateral Sclerosis	ORPHANET_DG	19122027		★☆☆☆☆ Found in Text Mining only
Primary lateral sclerosis juvenile	Lateral Sclerosis	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Primary lateral sclerosis juvenile	Lateral Sclerosis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Quadriplegia	Quadriplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sarcoma	Sarcoma	Pubtator	36232302	Associate	★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensory neuropathy	Sensory neuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia	Spastic Paraplegia	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia	Spastic Paraplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia Hereditary	Hereditary spastic paraplegia	Pubtator	35039335	Associate	★☆☆☆☆ Found in Text Mining only
Spastic Paraplegia, Hereditary	Spastic paraplegia	BEFREE	17955197, 18714162, 24704789		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Spastic Quadriplegia	Spastic Quadriplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spastic tetraparesis	Spastic tetraparesis	HPO_DG			★☆☆☆☆ Found in Text Mining only