SS18L1

Summary

SS18L1 (SS18L1 subunit of BAF chromatin remodeling complex, HGNC:15592) is a protein-coding gene on chromosome 20q13.33, encoding Calcium-responsive transactivator (O75177). Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons.

This gene encodes a calcium-responsive transactivator which is an essential subunit of a neuron-specific chromatin-remodeling complex. The structure of this gene is similar to that of the SS18 gene. Mutations in this gene are involved in amyotrophic lateral sclerosis (ALS). Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 26039 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis (Moderate, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 97 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_198935

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15592
Approved symbol	SS18L1
Name	SS18L1 subunit of BAF chromatin remodeling complex
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0693, CREST, SMARCL2
Ensembl gene	ENSG00000184402
Ensembl biotype	protein_coding
OMIM	606472
Entrez	26039

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000331758, ENST00000370848, ENST00000450482, ENST00000491916, ENST00000492466

RefSeq mRNA: 2 — MANE Select: NM_198935 NM_001301778, NM_198935

CCDS: CCDS13491

Canonical transcript exons

ENST00000331758 — 11 exons

Exon	Start	End
ENSE00000380268	62158672	62158748
ENSE00000380269	62159877	62159961
ENSE00001176410	62172682	62172801
ENSE00001284657	62174517	62174644
ENSE00001284673	62165422	62165514
ENSE00001328334	62179182	62182514
ENSE00001355581	62164145	62164246
ENSE00001355582	62163458	62163622
ENSE00001355583	62162752	62162931
ENSE00003570148	62143769	62143889
ENSE00003788519	62161436	62161580

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 95.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8336 / max 164.3969, expressed in 1803 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185704	21.4210	1803
185703	0.4126	240

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	95.18	gold quality
cortical plate	UBERON:0005343	94.65	gold quality
cerebellar vermis	UBERON:0004720	93.60	gold quality
cerebellar cortex	UBERON:0002129	92.56	gold quality
cerebellum	UBERON:0002037	92.55	gold quality
cerebellar hemisphere	UBERON:0002245	92.54	gold quality
postcentral gyrus	UBERON:0002581	92.44	gold quality
parietal lobe	UBERON:0001872	91.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.80	gold quality
upper leg skin	UBERON:0004262	91.60	gold quality
ganglionic eminence	UBERON:0004023	91.38	gold quality
pons	UBERON:0000988	91.34	gold quality
right lobe of liver	UBERON:0001114	91.24	gold quality
tibia	UBERON:0000979	90.96	gold quality
superior frontal gyrus	UBERON:0002661	90.60	gold quality
superior vestibular nucleus	UBERON:0007227	90.60	gold quality
choroid plexus epithelium	UBERON:0003911	90.17	gold quality
subthalamic nucleus	UBERON:0001906	89.47	gold quality
entorhinal cortex	UBERON:0002728	89.36	gold quality
liver	UBERON:0002107	89.28	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.23	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.91	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.69	gold quality
substantia nigra pars compacta	UBERON:0001965	88.42	gold quality
skin of hip	UBERON:0001554	88.27	gold quality
medulla oblongata	UBERON:0001896	88.24	gold quality
CA1 field of hippocampus	UBERON:0003881	87.95	gold quality
orbitofrontal cortex	UBERON:0004167	87.85	gold quality
inferior vagus X ganglion	UBERON:0005363	87.79	gold quality
biceps brachii	UBERON:0001507	87.78	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

166 targeting SS18L1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-185-3P	99.95	67.01	1743

Literature-anchored findings (GeneRIF, showing 9)

• A synovial sarcoma of classic morphology contained a novel t(20;X) SS18L1(strong homology to SS18 on Ch20)/SSX1 fusion transcript in which nucleotide 1216 (exon 10) of SS18L1 was fused in-frame with nucleotide 422 (exon 6) of SSX1. (PMID:12696068)
• analysis of the CREST domain that inhibits dendritic growth in cultured neurons (PMID:15866867)
• SS18 and SS18L1 genes map within co-linear DNA segments that may have evolved through a relatively recent genomic duplication event. (PMID:16484776)
• This study demonistrated that CREST mutations inhibited activity-dependent neurite outgrowth in primary neurons, and CREST associated with the ALS protein FUS. (PMID:23708140)
• Its mutation causes amyotrophic lateral sclerosis. (PMID:24360741)
• calcium-responsive transactivator and certain other amyotrophic lateral sclerosis-linked proteins share several features implicated in amyotrophic lateral sclerosis pathogenesis (PMID:25888396)
• Protein expression pattern of calcium-responsive transactivator in early postnatal and adult testes. (PMID:33398438)
• The SS18L1 gene rs2295207 polymorphisms in association with hepatocellular carcinoma. (PMID:35584997)
• Identification of a novel MEF2C::SS18L1 fusion in childhood acute B-lymphoblastic leukemia. (PMID:38907739)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ss18l1	ENSMUSG00000039086
rattus_norvegicus	Ss18l1	ENSRNOG00000060010
caenorhabditis_elegans	ZK973.9	WBGENE00022835

Paralogs (2): SS18L2 (ENSG00000008324), SS18 (ENSG00000141380)

Protein

Protein identifiers

Calcium-responsive transactivator — O75177 (reviewed: O75177)

Alternative names: SS18-like protein 1, SYT homolog 1

All UniProt accessions (3): O75177, H0YDW4, Q9BR54

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP.

Subunit / interactions. Homodimer. Dimerization may be necessary for its function in neuronal dendritic development. Interacts (via C-terminus) with CREBBP (via N-terminus), EP300 and SMARCA4/BRG1. Interacts with the nBAF complex. Association with CREBBP facilitates transcription while the association with SMARCA4/BRG1 suppresses CREST-mediated transcription in resting neurons.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Tissue specificity. Ubiquitous; with lowest levels in spleen.

Domain organisation. The MFD (multi-functional domain) domain is involved in transcription transactivation, nuclear body targeting and dimerization.

Similarity. Belongs to the SS18 family.

Isoforms (5)

UniProt ID	Names	Canonical?
O75177-1	1	yes
O75177-2	2
O75177-3	3
O75177-4	4
O75177-5	5

RefSeq proteins (2): NP_001288707, NP_945173* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007726	SS18_N	Domain

Pfam: PF05030

UniProt features (29 total): region of interest 8, compositionally biased region 7, short sequence motif 4, splice variant 4, sequence conflict 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75177-F1	51.33	0.12

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9933937	Formation of the canonical BAF (cBAF) complex
R-HSA-9933947	Formation of the non-canonical BAF (ncBAF) complex
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)

MSigDB gene sets: 174 (showing top): GOBP_DENDRITE_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GCM_GSPT1, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GCM_ZNF198, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GOBP_DENDRITE_MORPHOGENESIS, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, GCM_SUFU

GO Biological Process (5): chromatin organization (GO:0006325), dendrite development (GO:0016358), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of dendrite morphogenesis (GO:0050775)

GO Molecular Function (2): transcription coactivator activity (GO:0003713), protein binding (GO:0005515)

GO Cellular Component (8): kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nBAF complex (GO:0071565), chromosome, centromeric region (GO:0000775), condensed chromosome, centromeric region (GO:0000779), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
SWI/SNF chromatin remodelers	3
MITF-M-dependent gene expression	1
Regulation of endogenous retroelements	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	2
intracellular membraneless organelle	2
cellular anatomical structure	2
cellular component organization	1
neuron projection development	1
anatomical structure development	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of cell morphogenesis	1
positive regulation of cell projection organization	1
dendrite morphogenesis	1
regulation of dendrite morphogenesis	1
positive regulation of neurogenesis	1
transcription coregulator activity	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
SWI/SNF superfamily-type complex	1
chromosomal region	1
chromosome, centromeric region	1
condensed chromosome	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SS18L1	ACTL6B	O94805	890
SS18L1	SSX1	Q16384	878
SS18L1	DPF1	Q92782	859
SS18L1	RFX6	Q8HWS3	826
SS18L1	SSX4	O60224	817
SS18L1	DPF3	Q92784	768
SS18L1	DPF2	Q92785	751
SS18L1	DTX2	Q86UW9	746
SS18L1	BCL7B	Q9BQE9	720
SS18L1	CCNK	O75909	704
SS18L1	RFX3	P48380	690
SS18L1	SMARCD1	Q96GM5	667
SS18L1	BCL7A	Q4VC05	662
SS18L1	PHF10	Q8WUB8	644
SS18L1	RFX2	P48378	612

IntAct

87 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCC2	ARID1A	psi-mi:“MI:0914”(association)	0.790
DPF2	ARID1A	psi-mi:“MI:0914”(association)	0.730
SF3B4	SS18L1	psi-mi:“MI:0915”(physical association)	0.670
FAM168A	SS18L1	psi-mi:“MI:0915”(physical association)	0.670
SS18L1	SF3B4	psi-mi:“MI:0915”(physical association)	0.670
SS18L1	FAM168A	psi-mi:“MI:0915”(physical association)	0.670
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
MIA2	SS18L1	psi-mi:“MI:0915”(physical association)	0.560
LGALS3	SS18L1	psi-mi:“MI:0915”(physical association)	0.560
MAPK1IP1L	SS18L1	psi-mi:“MI:0915”(physical association)	0.560
SNRPB	SS18L1	psi-mi:“MI:0915”(physical association)	0.560
SS18L1	CSTF2	psi-mi:“MI:0915”(physical association)	0.560
SS18L1	SNRPC	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (142): SS18L1 (Two-hybrid), SS18L1 (Two-hybrid), SS18L1 (Two-hybrid), SS18L1 (Two-hybrid), SS18L1 (Two-hybrid), SS18L1 (Two-hybrid), SS18L1 (Two-hybrid), SS18L1 (Two-hybrid), MAPK1IP1L (Two-hybrid), SS18L1 (Affinity Capture-MS), SS18L1 (Affinity Capture-MS), SS18L1 (Affinity Capture-MS), SS18L1 (Affinity Capture-MS), SS18L1 (Affinity Capture-MS), SS18L1 (Two-hybrid)

ESM2 similar proteins: A2AJK6, A2BH40, A5HEH4, B2RWS6, B7SBD2, G5EEL0, O14497, O15405, O42569, O74345, O75177, P02833, P32315, P34622, P47792, P49750, P79007, Q06A37, Q08E31, Q09472, Q15532, Q20870, Q21955, Q24645, Q4V3C1, Q571K4, Q5RFQ1, Q5U303, Q61L47, Q62280, Q64201, Q6AVI1, Q6DDK1, Q6LD29, Q6NVN0, Q80W03, Q8AWH1, Q8BW22, Q8BXJ2, Q8L8A5

Diamond homologs: A5HEH4, O75177, Q08E31, Q15532, Q5RFQ1, Q62280, Q6AVI1, Q6DDK1, Q8BW22, Q8L8A5, Q91XJ0, Q93VH6, Q9D174, Q9MAL9, Q9UHA2, Q86HX9, Q54HX6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SS18L1	up-regulates	CREBBP	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the canonical BAF (cBAF) complex	11	126.9×	7e-20
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	12	99.7×	7e-20
Formation of the embryonic stem cell BAF (esBAF) complex	9	98.3×	6e-15
Formation of the polybromo-BAF (pBAF) complex	7	80.8×	6e-11
Formation of the non-canonical BAF (ncBAF) complex	5	61.1×	3e-07
Regulation of endogenous retroelements	9	60.3×	8e-13
Regulation of MITF-M-dependent genes involved in pigmentation	12	58.0×	8e-17
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	7	38.2×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	12	130.5×	7e-21
regulation of nucleotide-excision repair	12	116.5×	2e-20
regulation of mitotic metaphase/anaphase transition	12	95.9×	2e-19
nucleosome disassembly	6	77.7×	4e-09
positive regulation of double-strand break repair	12	66.6×	2e-17
regulation of G1/S transition of mitotic cell cycle	12	59.3×	7e-17
positive regulation of myoblast differentiation	9	53.2×	5e-12
positive regulation of T cell differentiation	7	51.4×	3e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

97 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	10
Benign	39

Top pathogenic / likely-pathogenic (0)

SpliceAI

2239 predictions. Top by Δscore:

Variant	Effect	Δscore
20:62158749:G:GG	donor_gain	1.0000
20:62159875:A:AG	acceptor_gain	1.0000
20:62159875:A:AT	acceptor_loss	1.0000
20:62159876:G:C	acceptor_loss	1.0000
20:62159876:G:GT	acceptor_gain	1.0000
20:62159876:GGT:G	acceptor_gain	1.0000
20:62159957:CTGCC:C	donor_gain	1.0000
20:62159958:TGCC:T	donor_gain	1.0000
20:62159958:TGCCG:T	donor_loss	1.0000
20:62159959:GCC:G	donor_gain	1.0000
20:62159959:GCCG:G	donor_gain	1.0000
20:62159960:CC:C	donor_gain	1.0000
20:62159961:CGTG:C	donor_loss	1.0000
20:62159962:G:GG	donor_gain	1.0000
20:62159962:GTGA:G	donor_loss	1.0000
20:62159963:T:TG	donor_loss	1.0000
20:62159964:GA:G	donor_loss	1.0000
20:62159965:AGT:A	donor_loss	1.0000
20:62162745:A:AG	acceptor_gain	1.0000
20:62162745:AT:A	acceptor_gain	1.0000
20:62162746:T:G	acceptor_gain	1.0000
20:62162746:T:TA	acceptor_gain	1.0000
20:62162747:GCCAG:G	acceptor_loss	1.0000
20:62162748:CCAGG:C	acceptor_loss	1.0000
20:62162750:A:AG	acceptor_gain	1.0000
20:62162750:AG:A	acceptor_gain	1.0000
20:62162751:G:A	acceptor_loss	1.0000
20:62162751:G:GG	acceptor_gain	1.0000
20:62162751:GG:G	acceptor_gain	1.0000
20:62162751:GGGC:G	acceptor_gain	1.0000

AlphaMissense

2592 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:62143882:T:A	I21N	1.000
20:62158676:T:A	L25Q	1.000
20:62158676:T:C	L25P	1.000
20:62158684:A:C	N28H	1.000
20:62158684:A:T	N28Y	1.000
20:62158685:A:T	N28I	1.000
20:62158686:C:A	N28K	1.000
20:62158686:C:G	N28K	1.000
20:62158694:T:C	L31P	1.000
20:62158697:T:A	I32N	1.000
20:62158697:T:G	I32S	1.000
20:62158706:T:A	I35N	1.000
20:62159891:T:A	L54Q	1.000
20:62159891:T:C	L54P	1.000
20:62159893:C:G	H55D	1.000
20:62159897:G:C	R56P	1.000
20:62159900:A:T	N57I	1.000
20:62159903:T:A	L58Q	1.000
20:62159903:T:C	L58P	1.000
20:62159903:T:G	L58R	1.000
20:62159912:T:A	L61Q	1.000
20:62159912:T:C	L61P	1.000
20:62159912:T:G	L61R	1.000
20:62159914:G:C	A62P	1.000
20:62159915:C:A	A62D	1.000
20:62159921:T:A	I64N	1.000
20:62159923:G:C	A65P	1.000
20:62143833:T:C	F5L	0.999
20:62143835:C:A	F5L	0.999
20:62143835:C:G	F5L	0.999

dbSNP variants (sampled 300 via entrez): RS1000160033 (20:62159221 G>T), RS1000243706 (20:62153098 G>A), RS1000301838 (20:62161507 T>C), RS1000372364 (20:62169452 T>C), RS1000388930 (20:62169195 C>T), RS1000459975 (20:62177911 A>G), RS1000478246 (20:62164896 A>G), RS1000478977 (20:62178740 C>G), RS1000518952 (20:62149577 A>C,G,T), RS1000549251 (20:62145803 A>G,T), RS1000589146 (20:62162331 G>A), RS1000652606 (20:62161278 C>A,G), RS1000695745 (20:62153922 T>G), RS1000758879 (20:62158045 G>A,C), RS1000815143 (20:62165857 T>C)

Disease associations

OMIM: gene MIM:606472 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	AD

Mondo (1): amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (1): Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0007354	Amyotrophic lateral sclerosis

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90013406_143	Liver enzyme levels (alkaline phosphatase)	3.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
GSK-J4	increases expression	1
bisphenol A	affects cotreatment, decreases expression	1
cobaltous chloride	increases expression	1
Sunitinib	increases expression	1
Amiodarone	increases expression	1
Atrazine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects splicing	1
Smoke	decreases expression	1
Thiram	increases expression	1
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	increases expression	1
tert-Butylhydroperoxide	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2KY	HAP1 SS18L1 (-) 1	Cancer cell line	Male
CVCL_E2KZ	HAP1 SS18L1 (-) 2	Cancer cell line	Male
CVCL_E2L0	HAP1 SS18L1 (-) 3	Cancer cell line	Male
CVCL_E2L1	HAP1 SS18L1 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS