SCFD1

Summary

SCFD1 (sec1 family domain containing 1, HGNC:20726) is a protein-coding gene on chromosome 14q12, encoding Sec1 family domain-containing protein 1 (Q8WVM8). Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with COG4. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

Predicted to enable syntaxin binding activity. Involved in negative regulation of autophagosome assembly; regulation of protein transport; and response to toxic substance. Located in cis-Golgi network.

Source: NCBI Gene 23256 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 106 total
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_016106

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20726
Approved symbol	SCFD1
Name	sec1 family domain containing 1
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	RA410, KIAA0917, STXBP1L2, SLY1
Ensembl gene	ENSG00000092108
Ensembl biotype	protein_coding
OMIM	618207
Entrez	23256

Gene structure

Transcript identifiers

Ensembl transcripts: 76 — 26 nonsense_mediated_decay, 24 protein_coding, 24 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000311943, ENST00000396629, ENST00000458591, ENST00000463622, ENST00000469043, ENST00000484733, ENST00000544052, ENST00000553278, ENST00000553280, ENST00000553693, ENST00000554437, ENST00000554486, ENST00000554776, ENST00000554819, ENST00000555259, ENST00000555550, ENST00000556256, ENST00000556413, ENST00000556486, ENST00000556534, ENST00000556768, ENST00000557076, ENST00000557713, ENST00000676465, ENST00000676473, ENST00000676509, ENST00000676520, ENST00000676658, ENST00000676674, ENST00000676750, ENST00000676812, ENST00000676817, ENST00000676834, ENST00000676876, ENST00000676914, ENST00000676954, ENST00000677027, ENST00000677176, ENST00000677334, ENST00000677340, ENST00000677413, ENST00000677445, ENST00000677456, ENST00000677576, ENST00000677617, ENST00000677637, ENST00000677690, ENST00000677833, ENST00000677974, ENST00000678006, ENST00000678104, ENST00000678124, ENST00000678185, ENST00000678396, ENST00000678399, ENST00000678402, ENST00000678475, ENST00000678516, ENST00000678579, ENST00000678637, ENST00000678669, ENST00000678716, ENST00000678735, ENST00000678760, ENST00000678802, ENST00000678858, ENST00000679075, ENST00000679096, ENST00000679102, ENST00000679153, ENST00000679165, ENST00000679342, ENST00000865391, ENST00000865392, ENST00000913286, ENST00000971240

RefSeq mRNA: 6 — MANE Select: NM_016106 NM_001257376, NM_001283031, NM_001283032, NM_001283033, NM_016106, NM_182835

CCDS: CCDS45092, CCDS58308, CCDS91858, CCDS9639

Canonical transcript exons

ENST00000458591 — 25 exons

Exon	Start	End
ENSE00001786319	30735586	30735850
ENSE00003465559	30670256	30670395
ENSE00003466337	30673924	30673997
ENSE00003469858	30674984	30675065
ENSE00003476277	30633947	30634037
ENSE00003479242	30630477	30630565
ENSE00003481418	30653489	30653588
ENSE00003491745	30650565	30650650
ENSE00003493079	30694773	30694869
ENSE00003497297	30700188	30700258
ENSE00003498795	30707990	30708065
ENSE00003513100	30638125	30638247
ENSE00003518690	30715924	30715977
ENSE00003536639	30719325	30719377
ENSE00003537425	30673257	30673347
ENSE00003548659	30643316	30643405
ENSE00003557644	30639777	30639864
ENSE00003579175	30734790	30734858
ENSE00003585747	30721884	30721917
ENSE00003612380	30702296	30702375
ENSE00003641302	30722494	30722559
ENSE00003652065	30628209	30628279
ENSE00003656282	30705823	30705885
ENSE00003684893	30622319	30622399
ENSE00003790295	30649528	30649583

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 97.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.0128 / max 421.0361, expressed in 1815 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139094	36.0128	1815

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.06	gold quality
body of pancreas	UBERON:0001150	96.12	gold quality
adenohypophysis	UBERON:0002196	96.10	gold quality
pituitary gland	UBERON:0000007	96.06	gold quality
adrenal tissue	UBERON:0018303	96.05	gold quality
parotid gland	UBERON:0001831	95.90	gold quality
corpus epididymis	UBERON:0004359	95.64	gold quality
oral cavity	UBERON:0000167	95.23	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.05	gold quality
islet of Langerhans	UBERON:0000006	95.03	gold quality
biceps brachii	UBERON:0001507	94.85	gold quality
bone marrow cell	CL:0002092	94.83	gold quality
cortical plate	UBERON:0005343	94.76	gold quality
ventricular zone	UBERON:0003053	94.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.53	gold quality
pancreas	UBERON:0001264	94.48	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.36	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.35	gold quality
colonic epithelium	UBERON:0000397	94.32	gold quality
rectum	UBERON:0001052	94.28	gold quality
colonic mucosa	UBERON:0000317	94.10	gold quality
bronchial epithelial cell	CL:0002328	94.03	gold quality
ganglionic eminence	UBERON:0004023	93.95	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.86	gold quality
lower esophagus mucosa	UBERON:0035834	93.83	gold quality
caput epididymis	UBERON:0004358	93.74	gold quality
ectocervix	UBERON:0012249	93.68	gold quality
cardia of stomach	UBERON:0001162	93.65	gold quality
endocervix	UBERON:0000458	93.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting SCFD1, 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-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-361-5P	98.95	70.16	1340
HSA-MIR-376A-2-5P	96.43	68.06	715
HSA-MIR-1258	96.08	67.74	700

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• Study shows that the SM protein, Sly1, interacts directly with the conserved oligomeric Golgi (COG) tethering complex; Sly1-COG interaction is mediated by the Cog4 subunit, which also interacts with Syntaxin 5 through a different binding site. (PMID:19536132)
• Mutation in SCFD1 gene is associated with amyotrophic lateral sclerosis. (PMID:27455348)
• The found of this study confirmed the lack of association of SCFD1 rs10139154 with the risk for ALS in a large Chinese population. (PMID:29260601)
• SCFD1 rs10139154 is associated with a decreased risk of developing Alzheimer disease. (PMID:31267315)
• mTOR-mediated phosphorylation of VAMP8 and SCFD1 regulates autophagosome maturation. (PMID:34785650)
• Lack of an association between SCFD1 rs10139154 polymorphism and amyotrophic lateral sclerosis. (PMID:35234271)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	scfd1	ENSDARG00000000779
mus_musculus	Scfd1	ENSMUSG00000020952
rattus_norvegicus	Scfd1	ENSRNOG00000031203
drosophila_melanogaster	Slh	FBGN0264978
caenorhabditis_elegans		WBGENE00009654

Paralogs (7): STXBP2 (ENSG00000076944), STXBP3 (ENSG00000116266), VPS45 (ENSG00000136631), STXBP1 (ENSG00000136854), VPS33A (ENSG00000139719), VPS33B (ENSG00000184056), SCFD2 (ENSG00000184178)

Protein

Protein identifiers

Sec1 family domain-containing protein 1 — Q8WVM8 (reviewed: Q8WVM8)

Alternative names: SLY1 homolog, Syntaxin-binding protein 1-like 2

All UniProt accessions (38): Q8WVM8, A0A7I2V2U5, A0A7I2V320, A0A7I2V321, A0A7I2V362, A0A7I2V3B4, A0A7I2V3C9, A0A7I2V3G4, A0A7I2V3Y3, A0A7I2V414, A0A7I2V448, A0A7I2V4B8, A0A7I2V4B9, A0A7I2V4J1, A0A7I2V4R0, A0A7I2V4U2, A0A7I2V534, A0A7I2V590, A0A7I2V5H5, A0A7I2V5I2, A0A7I2V5L2, A0A7I2V5R9, A0A7I2V5Z4, A0A7I2YQG3, A0A7I2YQQ1, A0A7I2YQR2, B7Z5N7, G3V2M8, G3V363, G3V3K9, G3V4I1, G3V551, G3V5E2, G3V5F3, H0YIZ7, H0YJS6, H0YJY1, J3KNG4

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with COG4. Involved in vesicular transport between the endoplasmic reticulum and the Golgi.

Subunit / interactions. Interacts with STX17. Interacts with STX5A. Interacts with the COG complex via COG4.

Subcellular location. Cytoplasm. Endoplasmic reticulum membrane. Golgi apparatus. Golgi stack membrane.

Similarity. Belongs to the STXBP/unc-18/SEC1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WVM8-1	1	yes
Q8WVM8-2	2
Q8WVM8-3	3

RefSeq proteins (6): NP_001244305, NP_001269960, NP_001269961, NP_001269962, NP_057190, NP_878255 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001619	Sec1-like	Family
IPR027482	Sec1-like_dom2	Homologous_superfamily
IPR036045	Sec1-like_sf	Homologous_superfamily
IPR043127	Sec-1-like_dom3a	Homologous_superfamily
IPR043154	Sec-1-like_dom1	Homologous_superfamily

Pfam: PF00995

UniProt features (18 total): sequence conflict 9, modified residue 4, splice variant 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVM8-F1	85.70	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 2, 37, 303, 528

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-8980692	RHOA GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-9012999	RHO GTPase cycle
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 161 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GCANCTGNY_MYOD_Q6, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, chr14q12, GOBP_MACROAUTOPHAGY, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY

GO Biological Process (10): intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), post-Golgi vesicle-mediated transport (GO:0006892), response to toxic substance (GO:0009636), regulation of protein transport (GO:0051223), regulation of ER to Golgi vesicle-mediated transport (GO:0060628), negative regulation of autophagosome assembly (GO:1902902), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): syntaxin binding (GO:0019905), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (10): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), Golgi-associated vesicle (GO:0005798), cis-Golgi network (GO:0005801), cytosol (GO:0005829), Golgi cisterna membrane (GO:0032580), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism of proteins	1
Signaling by Rho GTPases	1
Asparagine N-linked glycosylation	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
Golgi vesicle transport	3
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
intracellular protein localization	2
protein transport	2
intracellular transport	2
transport	2
binding	2
Golgi apparatus	2
organelle membrane	2
endomembrane system	2
intercellular transport	1
response to chemical	1
regulation of transport	1
regulation of establishment of protein localization	1
endoplasmic reticulum to Golgi vesicle-mediated transport	1
regulation of intracellular transport	1
regulation of vesicle-mediated transport	1
autophagosome assembly	1
negative regulation of macroautophagy	1
negative regulation of organelle assembly	1
regulation of autophagosome assembly	1
establishment of protein localization	1
cellular process	1
SNARE binding	1
bounding membrane of organelle	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasmic vesicle	1
Golgi cisterna	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1740 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCFD1	STX5	Q13190	998
SCFD1	BET1	O15155	981
SCFD1	STX18	Q9P2W9	980
SCFD1	GOSR2	O14653	957
SCFD1	SEC22B	O75396	948
SCFD1	GOSR1	O95249	936
SCFD1	COG4	Q9H9E3	930
SCFD1	VTI1B	Q9UEU0	844
SCFD1	RAB1A	P11476	827
SCFD1	USO1	O60763	822
SCFD1	ZW10	O43264	767
SCFD1	RINT1	Q6NUQ1	726
SCFD1	MIA3	Q5JRA6	718
SCFD1	YKT6	O15498	712
SCFD1	VPS45	Q9NRW7	707

IntAct

216 interactions, top by confidence:

A	B	Type	Score
RINT1	NBAS	psi-mi:“MI:0914”(association)	0.830
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
GOSR2	BET1	psi-mi:“MI:0914”(association)	0.810
NAPA	SNAP23	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
STX5	GOSR2	psi-mi:“MI:0914”(association)	0.670
STX6	GOSR2	psi-mi:“MI:0914”(association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
BNIP1	NBAS	psi-mi:“MI:0914”(association)	0.640
SEC22B	ZW10	psi-mi:“MI:0914”(association)	0.640
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
Zw10	NBAS	psi-mi:“MI:0914”(association)	0.560
HTT	SCFD1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (376): SCFD1 (Affinity Capture-RNA), SCFD1 (Affinity Capture-RNA), SCFD1 (Affinity Capture-MS), SCFD1 (Affinity Capture-MS), SCFD1 (Affinity Capture-MS), SCFD1 (Affinity Capture-MS), SCFD1 (Affinity Capture-MS), MRPL9 (Co-fractionation), SCFD1 (Co-fractionation), SCFD1 (Co-fractionation), SCFD1 (Affinity Capture-MS), SCFD1 (Proximity Label-MS), SCFD1 (Proximity Label-MS), SCFD1 (Proximity Label-MS), SCFD1 (Proximity Label-MS)

ESM2 similar proteins: A7RG82, A8X9U4, B4GGT6, B4JVN0, B4KML2, B4MCL6, B4MRZ9, O08599, O08700, O18637, O74534, O94590, P22012, P34815, P36617, P38932, P52874, P61763, P61764, P61765, P97390, Q07327, Q09805, Q15833, Q22307, Q24179, Q28288, Q28ZT4, Q54GE3, Q54QC8, Q58EM4, Q5R6D2, Q60770, Q62753, Q62991, Q64324, Q6R748, Q851W1, Q8BRF7, Q8SS97

Diamond homologs: O18637, O74534, P22213, Q24179, Q54IJ1, Q62991, Q851W1, Q8BRF7, Q8SS97, Q8WVM8, Q9SL48, Q29268, O00186, O08599, P34815, P61763, P61764, P61765, Q07327, Q15833, Q28288, Q54QC8, Q5R6D2, Q5VNU3, Q60770, Q62753, Q64324, Q6R748, Q7XWP3, Q9C5P7, Q9C5X3, Q9SZ77

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 212 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
Intra-Golgi traffic	12	21.3×	5e-11
Retrograde transport at the Trans-Golgi-Network	9	13.5×	1e-06
COPII-mediated vesicle transport	12	13.4×	1e-08
COPI-dependent Golgi-to-ER retrograde traffic	17	12.9×	7e-12
COPI-mediated anterograde transport	16	12.0×	5e-11
Cargo concentration in the ER	5	11.5×	3e-03
trans-Golgi Network Vesicle Budding	6	10.4×	1e-03
Amino acid transport across the plasma membrane	5	10.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
vesicle fusion	10	32.2×	8e-11
obsolete vesicle docking	7	28.7×	5e-07
intra-Golgi vesicle-mediated transport	10	28.2×	3e-10
zinc ion transmembrane transport	7	26.3×	9e-07
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	14	25.2×	1e-13
membrane fusion	7	23.4×	2e-06
intracellular zinc ion homeostasis	7	18.0×	1e-05
regulation of protein localization to plasma membrane	5	17.3×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3785 predictions. Top by Δscore:

Variant	Effect	Δscore
14:30628207:A:AG	acceptor_gain	1.0000
14:30628207:AGT:A	acceptor_gain	1.0000
14:30628208:G:GG	acceptor_gain	1.0000
14:30628208:GT:G	acceptor_gain	1.0000
14:30628208:GTG:G	acceptor_gain	1.0000
14:30630474:TA:T	acceptor_loss	1.0000
14:30630475:A:AT	acceptor_loss	1.0000
14:30630534:GAGC:G	donor_gain	1.0000
14:30630537:C:G	donor_gain	1.0000
14:30630561:CATCT:C	donor_gain	1.0000
14:30630562:ATCTG:A	donor_loss	1.0000
14:30630563:TCT:T	donor_gain	1.0000
14:30630564:CTG:C	donor_loss	1.0000
14:30630565:TGT:T	donor_loss	1.0000
14:30630566:G:GA	donor_loss	1.0000
14:30630566:G:GG	donor_gain	1.0000
14:30630567:T:A	donor_loss	1.0000
14:30630568:GAG:G	donor_loss	1.0000
14:30638172:T:TA	acceptor_gain	1.0000
14:30638182:A:G	acceptor_gain	1.0000
14:30649581:GTG:G	donor_gain	1.0000
14:30650560:TTCA:T	acceptor_loss	1.0000
14:30650562:CA:C	acceptor_loss	1.0000
14:30650563:A:AC	acceptor_loss	1.0000
14:30650563:A:AG	acceptor_gain	1.0000
14:30650564:G:A	acceptor_loss	1.0000
14:30650564:G:GA	acceptor_gain	1.0000
14:30650564:GA:G	acceptor_gain	1.0000
14:30650564:GAA:G	acceptor_gain	1.0000
14:30650564:GAAA:G	acceptor_gain	1.0000

AlphaMissense

4235 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:30628274:T:A	W43R	1.000
14:30628274:T:C	W43R	1.000
14:30628276:G:C	W43C	1.000
14:30628276:G:T	W43C	1.000
14:30630481:T:A	L46H	1.000
14:30630481:T:C	L46P	1.000
14:30630490:A:T	D49V	1.000
14:30630498:G:C	G52R	1.000
14:30630499:G:A	G52D	1.000
14:30630538:T:C	L65P	1.000
14:30630559:T:C	L72P	1.000
14:30638192:T:C	L127P	1.000
14:30638204:C:A	A131E	1.000
14:30649534:T:A	V207D	1.000
14:30649537:C:A	P208H	1.000
14:30649537:C:G	P208R	1.000
14:30649578:G:C	A222P	1.000
14:30650569:T:C	L225P	1.000
14:30650581:T:C	L229P	1.000
14:30650584:G:C	R230P	1.000
14:30653497:G:T	R255M	1.000
14:30653550:C:G	H273D	1.000
14:30653556:T:A	W275R	1.000
14:30653556:T:C	W275R	1.000
14:30653562:T:C	Y277H	1.000
14:30670376:T:A	W326R	1.000
14:30670376:T:C	W326R	1.000
14:30673261:T:C	F334L	1.000
14:30673262:T:G	F334C	1.000
14:30673263:C:A	F334L	1.000

dbSNP variants (sampled 300 via entrez): RS1000002913 (14:30652118 A>C), RS1000018690 (14:30712977 G>A), RS1000070975 (14:30713356 TA>T,TAA), RS1000072306 (14:30734472 G>T), RS1000123477 (14:30637476 G>A,T), RS1000143696 (14:30736226 G>A), RS1000172092 (14:30669061 A>C,T), RS1000175065 (14:30656343 G>A), RS1000206139 (14:30656569 C>T), RS1000258388 (14:30707114 T>C), RS1000291208 (14:30669381 C>A), RS1000297098 (14:30719705 A>G), RS1000312499 (14:30698956 A>G), RS1000317976 (14:30714077 G>A), RS1000320660 (14:30699293 T>C)

Disease associations

OMIM: gene MIM:618207 | disease phenotypes:

GenCC curated gene-disease

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

6 associations (top):

Study	Trait	p-value
GCST003542_117	Night sleep phenotypes	3.000000e-06
GCST003901_18	Cognitive decline (age-related)	5.000000e-06
GCST004692_3	Amyotrophic lateral sclerosis	3.000000e-08
GCST005647_8	Amyotrophic lateral sclerosis	1.000000e-07
GCST009391_1345	Metabolite levels	8.000000e-06
GCST90002397_71	Mean spheric corpuscular volume	6.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010362	lysophosphatidylcholine 20:3 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: yes

ChEMBL targets (1): CHEMBL6067340 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.77	Kd	171.1	nM	CHEMBL3752910
6.77	ED50	171.1	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149351: Binding affinity to human SCFD1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1711	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	4
Cyclosporine	increases expression	3
sodium arsenite	decreases expression, increases expression	2
Caffeine	decreases expression, decreases phosphorylation	2
Particulate Matter	increases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
deoxynivalenol	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
ochratoxin A	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Diethylstilbestrol	decreases expression	1
Ivermectin	decreases expression	1
Thioacetamide	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Thapsigargin	decreases expression	1
Genistein	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652393	Binding	Binding affinity to human SCFD1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

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