SMCR8

Summary

SMCR8 (SMCR8-C9orf72 complex subunit, HGNC:17921) is a protein-coding gene on chromosome 17p11.2, encoding Guanine nucleotide exchange protein SMCR8 (Q8TEV9). Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy.

Enables GTPase activator activity; protein kinase binding activity; and protein kinase inhibitor activity. Contributes to guanyl-nucleotide exchange factor activity. Involved in negative regulation of gene expression; regulation of TOR signaling; and regulation of macroautophagy. Located in Atg1/ULK1 kinase complex; chromatin; and nucleoplasm. Part of guanyl-nucleotide exchange factor complex.

Source: NCBI Gene 140775 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 154 total
• MANE Select transcript: NM_144775

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17921
Approved symbol	SMCR8
Name	SMCR8-C9orf72 complex subunit
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34716, DENND8A
Ensembl gene	ENSG00000176994
Ensembl biotype	protein_coding
OMIM	617074
Entrez	140775

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000406438, ENST00000926351

RefSeq mRNA: 1 — MANE Select: NM_144775 NM_144775

CCDS: CCDS11195

Canonical transcript exons

ENST00000406438 — 2 exons

Exon	Start	End
ENSE00001562487	18315293	18318149
ENSE00003756152	18322617	18328056

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 86.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6176 / max 298.5511, expressed in 1811 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159808	22.6176	1811

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	86.97	gold quality
leukocyte	CL:0000738	86.96	gold quality
bone marrow	UBERON:0002371	84.44	gold quality
granulocyte	CL:0000094	82.93	gold quality
blood	UBERON:0000178	82.92	gold quality
bone marrow cell	CL:0002092	82.55	gold quality
lymph node	UBERON:0000029	81.68	gold quality
islet of Langerhans	UBERON:0000006	81.39	gold quality
stromal cell of endometrium	CL:0002255	80.77	gold quality
vermiform appendix	UBERON:0001154	80.66	gold quality
skeletal muscle tissue	UBERON:0001134	79.50	gold quality
tonsil	UBERON:0002372	78.64	gold quality
muscle of leg	UBERON:0001383	77.90	gold quality
gastrocnemius	UBERON:0001388	77.76	gold quality
muscle tissue	UBERON:0002385	77.72	gold quality
rectum	UBERON:0001052	77.71	gold quality
smooth muscle tissue	UBERON:0001135	77.41	gold quality
spleen	UBERON:0002106	77.37	gold quality
placenta	UBERON:0001987	76.96	gold quality
ventricular zone	UBERON:0003053	76.88	gold quality
duodenum	UBERON:0002114	76.66	gold quality
urinary bladder	UBERON:0001255	76.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.32	gold quality
adrenal tissue	UBERON:0018303	76.22	gold quality
ganglionic eminence	UBERON:0004023	76.16	gold quality
body of stomach	UBERON:0001161	76.03	gold quality
prefrontal cortex	UBERON:0000451	75.80	gold quality
gall bladder	UBERON:0002110	75.61	gold quality
pancreas	UBERON:0001264	75.58	gold quality
stomach	UBERON:0000945	75.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.69

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
ULK1	Repression
WIPI2	Activation

miRNA regulators (miRDB)

171 targeting SMCR8, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650

Literature-anchored findings (GeneRIF, showing 6)

• Study describes the identification of two binding partners for C9orf72: SMCR8 and WDR41 and demonstrated that C9orf72/SMCR8/WDR41 interacts with the FIP200/Ulk1/ATG13/ATG101 complex. (PMID:27193190)
• While focusing on the role of SMCR8 during autophagy initiation, we found that kinase activity and gene expression of ULK1 are increased upon SMCR8 depletion. The latter phenotype involved association of SMCR8 with the ULK1 gene locus. (PMID:28195531)
• Our study not only illustrates the basis of C9ORF72-SMCR8-WDR41 complex assembly but also reveals the GAP activity of the C9ORF72-SMCR8 complex (PMID:32303654)
• C9orf72-associated SMCR8 protein binds in the ubiquitin pathway and with proteins linked with neurological disease. (PMID:32678027)
• Structure of the C9orf72 ARF GAP complex that is haploinsufficient in ALS and FTD. (PMID:32848248)
• ALS-linked C9orf72-SMCR8 complex is a negative regulator of primary ciliogenesis. (PMID:38064514)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	smcr8a	ENSDARG00000052818
mus_musculus	Smcr8	ENSMUSG00000049323
rattus_norvegicus	Smcr8	ENSRNOG00000005165
caenorhabditis_elegans		WBGENE00020095

Protein

Protein identifiers

Guanine nucleotide exchange protein SMCR8 — Q8TEV9 (reviewed: Q8TEV9)

Alternative names: Smith-Magenis syndrome chromosomal region candidate gene 8 protein

All UniProt accessions (1): Q8TEV9

UniProt curated annotations — full annotation on UniProt →

Function. Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy. In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation. The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ULK1/ATG1 kinase complex and inhibiting its protein kinase activity. As part of the C9orf72-SMCR8 complex, stimulates RAB8A and RAB11A GTPase activity in vitro. Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates. In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes.

Subunit / interactions. Component of the C9orf72-SMCR8 complex, at least composed of C9orf72, SMCR8 and WDR41. The complex is formed of two protomers, each individually consisting of one molecule each of C9orf72, SMCR8 and WDR41. The protomers homodimerize via an interaction between C9orf72 (via C-terminus) and SMCR8 (via N-terminus). Within each protomer SMCR8 (via DENN domain) acts as a bridging protein between WDR41 (via C-terminus and N-terminus) and C9orf72 (via C-terminus). The C9orf72-SMCR8 complex associates with the ULK1/ATG1 kinase complex. Interacts with C9orf72; the interaction is direct. Interacts with DLG4/PSD-95.

Subcellular location. Cytoplasm. Nucleus. Presynapse. Postsynapse.

Tissue specificity. Expressed in all tissues tested.

Post-translational modifications. Phosphorylation by TBK1 is required to promote autophagosome maturation. Phosphorylated by ULK1.

Similarity. Belongs to the SMCR8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TEV9-1	1	yes
Q8TEV9-2	2

RefSeq proteins (1): NP_658988* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037520	Folliculin/SMCR8_longin	Domain
IPR037521	FLCN/SMCR8_DENN	Domain

Pfam: PF11704

UniProt features (64 total): helix 19, strand 13, modified residue 9, mutagenesis site 5, region of interest 5, domain 3, compositionally biased region 3, sequence variant 3, turn 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7EL6	X-RAY DIFFRACTION	2.8
6LT0	ELECTRON MICROSCOPY	3.2
6V4U	ELECTRON MICROSCOPY	3.8
7O2W	ELECTRON MICROSCOPY	3.8
7MGE	ELECTRON MICROSCOPY	3.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TEV9-F1	63.06	0.24

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 (9): 402, 417, 468, 471, 489, 492, 498, 790, 796

Mutagenesis-validated functional residues (5):

Position	Phenotype
147	loss of c9orf72-smcr8 complex-mediated stimulation of rab8a and rab11a gtpase activity.
402	impaired autophagosome maturation; when associated with a-796.
402	phosphomimetic mutant; able to promote autophagosome maturation; when associated with d-796.
796	impaired autophagosome maturation; when associated with a-402.
796	phosphomimetic mutant; able to promote autophagosome maturation; when associated with d-402.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 178 (showing top): RRAGTTGT_UNKNOWN, GOBP_REGULATION_OF_AUTOPHAGY, ACTACCT_MIR196A_MIR196B, GOBP_VACUOLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_EXOCYTOSIS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, YY1_Q6, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY

GO Biological Process (10): autophagy (GO:0006914), regulation of autophagy (GO:0010506), negative regulation of gene expression (GO:0010629), negative regulation of macroautophagy (GO:0016242), positive regulation of TOR signaling (GO:0032008), negative regulation of exocytosis (GO:0045920), negative regulation of immune response (GO:0050777), positive regulation of autophagosome maturation (GO:1901098), negative regulation of autophagosome assembly (GO:1902902), regulation of TORC1 signaling (GO:1903432)

GO Molecular Function (5): protein kinase inhibitor activity (GO:0004860), guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (10): chromatin (GO:0000785), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), guanyl-nucleotide exchange factor complex (GO:0032045), presynapse (GO:0098793), postsynapse (GO:0098794), Atg1/ULK1 kinase complex (GO:1990316), nucleus (GO:0005634), cell projection (GO:0042995), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
regulation of TOR signaling	2
GTPase regulator activity	2
synapse	2
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
autophagy	1
regulation of catabolic process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
TOR signaling	1
positive regulation of intracellular signal transduction	1
exocytosis	1
regulation of exocytosis	1
negative regulation of secretion by cell	1
negative regulation of immune system process	1
immune response	1
negative regulation of response to stimulus	1
regulation of immune response	1
positive regulation of organelle organization	1
positive regulation of macroautophagy	1
positive regulation of protein-containing complex disassembly	1
autophagosome maturation	1
regulation of autophagosome maturation	1
autophagosome assembly	1
negative regulation of macroautophagy	1
negative regulation of organelle assembly	1
regulation of autophagosome assembly	1
TORC1 signaling	1
protein kinase activity	1
kinase inhibitor activity	1
protein kinase regulator activity	1
GTP binding	1
GDP binding	1
GTPase activity	1

Protein interactions and networks

STRING

768 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMCR8	WDR41	Q9HAD4	998
SMCR8	C9orf72	Q96LT7	996
SMCR8	ATG101	Q9BSB4	783
SMCR8	RAB1A	P11476	753
SMCR8	RAB39B	Q96DA2	729
SMCR8	MADD	Q8WXG6	728
SMCR8	RAB29	O14966	727
SMCR8	FLCN	Q8NFG4	667
SMCR8	WDR1	O75083	651
SMCR8	RAB8A	P24407	633
SMCR8	FNIP1	Q8TF40	626
SMCR8	RAB5A	P20339	604
SMCR8	RAB33A	Q14088	568
SMCR8	RRAGC	Q9HB90	565
SMCR8	SLC66A1	Q6ZP29	544

IntAct

70 interactions, top by confidence:

A	B	Type	Score
C9orf72	SMCR8	psi-mi:“MI:0915”(physical association)	0.850
SMCR8	C9orf72	psi-mi:“MI:0915”(physical association)	0.850
C9orf72	SMCR8	psi-mi:“MI:2252”(guanine nucleotide exchange factor reaction)	0.850
C9orf72	SMCR8	psi-mi:“MI:0217”(phosphorylation reaction)	0.850
C9orf72	SMCR8	psi-mi:“MI:0914”(association)	0.850
RB1CC1	ATG13	psi-mi:“MI:0914”(association)	0.820
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
C9orf72	ATG13	psi-mi:“MI:0914”(association)	0.690
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
C9orf72	SMCR8	psi-mi:“MI:0914”(association)	0.620
C9orf72	SMCR8	psi-mi:“MI:0915”(physical association)	0.620
C9orf72	ULK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.570
CRYAB	CCDC85C	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
IMPDH2	IMPDH1	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
C9orf72	RAB8A	psi-mi:“MI:2252”(guanine nucleotide exchange factor reaction)	0.440
RAB8A	SMCR8	psi-mi:“MI:0915”(physical association)	0.400
RAB39B	SMCR8	psi-mi:“MI:0915”(physical association)	0.400
RAB24	SMCR8	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (169): SMCR8 (Affinity Capture-MS), SMCR8 (Affinity Capture-MS), SMCR8 (Affinity Capture-MS), SMCR8 (Proximity Label-MS), SMCR8 (Affinity Capture-MS), SMCR8 (Affinity Capture-MS), SMCR8 (Affinity Capture-MS), SMCR8 (Affinity Capture-MS), SMCR8 (Affinity Capture-MS), FANCA (Affinity Capture-Luminescence), SMCR8 (Affinity Capture-Western), SMCR8 (Reconstituted Complex), SMCR8 (Biochemical Activity), SMCR8 (Two-hybrid), SMCR8 (Proximity Label-MS)

ESM2 similar proteins: A0JP43, A2AHC3, A2RRS8, A2VCV0, A4FU69, A4IG55, A5WUN7, A8T6P4, D3Z6S9, D3Z8E6, D4AEC2, E7F7X0, F7EC58, G3UZ78, Q06190, Q08AD1, Q2MJV9, Q3KQW7, Q3UH68, Q3UMB5, Q3V036, Q5SUV2, Q5T5Y3, Q5ZM60, Q640L3, Q640U0, Q66H73, Q69CM7, Q6AYC8, Q6IRN6, Q6PG04, Q6Q759, Q76LL6, Q76N89, Q7L0X2, Q80VH0, Q8C1B1, Q8C627, Q8CCG4, Q8CDN1

Diamond homologs: E7FA21, Q3UMB5, Q6PUR7, Q8TEV9, Q09346

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SMCR8	“up-regulates quantity”	WIPI2	“transcriptional regulation”
SMCR8	“down-regulates activity”	ULK1	binding
SMCR8	“down-regulates quantity”	ULK1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 63 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
RAB geranylgeranylation	6	23.1×	6e-05
RAB GEFs exchange GTP for GDP on RABs	5	13.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
autophagy	7	14.0×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	141
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

379 predictions. Top by Δscore:

Variant	Effect	Δscore
17:18317817:C:G	donor_gain	0.9900
17:18322909:A:G	donor_gain	0.9900
17:18322959:GGTCC:G	donor_gain	0.9900
17:18323002:G:GT	donor_gain	0.9900
17:18323013:G:T	donor_gain	0.9900
17:18317816:GCTAC:G	donor_gain	0.9800
17:18322616:GA:G	acceptor_gain	0.9800
17:18322615:A:AG	acceptor_gain	0.9700
17:18322616:G:GG	acceptor_gain	0.9700
17:18323003:A:T	donor_gain	0.9700
17:18322615:AGAGT:A	acceptor_gain	0.9600
17:18322616:GAGTG:G	acceptor_gain	0.9600
17:18322895:T:TA	donor_gain	0.9600
17:18322896:A:AA	donor_gain	0.9600
17:18318147:GAG:G	donor_gain	0.9500
17:18324489:A:AG	acceptor_gain	0.9500
17:18324490:A:G	acceptor_gain	0.9500
17:18322616:G:C	acceptor_gain	0.9400
17:18322616:GAGT:G	acceptor_gain	0.9300
17:18327708:T:G	acceptor_gain	0.9200
17:18318166:G:GA	donor_gain	0.9100
17:18323029:CTCAG:C	donor_loss	0.9100
17:18323031:CAGG:C	donor_loss	0.9100
17:18323032:AGGTT:A	donor_loss	0.9100
17:18323033:G:C	donor_loss	0.9100
17:18323034:GTTT:G	donor_loss	0.9100
17:18322943:A:G	donor_gain	0.9000
17:18324488:C:G	acceptor_gain	0.9000
17:18317821:G:GG	donor_gain	0.8900
17:18322614:CAG:C	acceptor_gain	0.8900

AlphaMissense

6228 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:18315965:T:C	L59P	1.000
17:18315976:T:C	F63L	1.000
17:18315977:T:C	F63S	1.000
17:18315977:T:G	F63C	1.000
17:18315978:C:A	F63L	1.000
17:18315978:C:G	F63L	1.000
17:18315983:A:T	E65V	1.000
17:18315984:G:C	E65D	1.000
17:18315984:G:T	E65D	1.000
17:18315991:G:A	G68R	1.000
17:18315991:G:C	G68R	1.000
17:18315992:G:A	G68E	1.000
17:18315995:C:A	P69H	1.000
17:18316147:G:C	D120H	1.000
17:18316201:C:G	H138D	1.000
17:18316205:T:C	L139P	1.000
17:18316211:T:C	L141P	1.000
17:18316231:G:C	G148R	1.000
17:18316232:G:A	G148D	1.000
17:18316241:G:C	R151T	1.000
17:18316241:G:T	R151M	1.000
17:18316242:G:C	R151S	1.000
17:18316242:G:T	R151S	1.000
17:18316244:C:A	P152Q	1.000
17:18316250:G:A	C154Y	1.000
17:18316251:C:G	C154W	1.000
17:18316360:T:C	F191L	1.000
17:18316361:T:C	F191S	1.000
17:18316362:T:A	F191L	1.000
17:18316362:T:G	F191L	1.000

dbSNP variants (sampled 300 via entrez): RS1000087819 (17:18327062 G>A,C), RS1000110566 (17:18322248 C>T), RS1000176296 (17:18315742 G>A), RS1000183037 (17:18323299 T>G), RS1000399078 (17:18322023 GT>G,GTT), RS1000605820 (17:18322412 C>T), RS1000839618 (17:18316872 T>A,C), RS1001067533 (17:18317002 G>A), RS1001217752 (17:18327410 G>C), RS1001245448 (17:18327720 G>A), RS1001401806 (17:18327142 C>G), RS1001432904 (17:18327451 G>A,C), RS1001445484 (17:18321562 C>G,T), RS1001937736 (17:18317603 A>G), RS1002476580 (17:18322988 T>A,C)

Disease associations

OMIM: gene MIM:617074 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007267_30	Systolic blood pressure	5.000000e-18
GCST007268_74	Diastolic blood pressure	7.000000e-15
GCST008497_5	Change in neurofilament light levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1979277	SHMT1, SMCR8	3	4.00	2	bevacizumab;fluorouracil;irinotecan;leucovorin;methotrexate

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression, increases expression, affects cotreatment	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cadmium	decreases expression, increases expression	2
Cyclosporine	increases expression, increases methylation	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
lead acetate	affects cotreatment, decreases expression	1
methylparaben	increases expression	1
zinc protoporphyrin	affects cotreatment, decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Caffeine	affects phosphorylation	1
Dexamethasone	affects cotreatment, increases expression, decreases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression, decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_DX29	HAP1 C9orf72 (-) SMCR8 (-) 1	Cancer cell line	Male
CVCL_DX30	HAP1 C9orf72 (-) SMCR8 (-) 2	Cancer cell line	Male
CVCL_DX31	HAP1 C9orf72 (-) SMCR8 (-) 3	Cancer cell line	Male
CVCL_DX32	HAP1 C9orf72 (-) SMCR8 (-) 4	Cancer cell line	Male
CVCL_TP64	HAP1 SMCR8 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice