SMG9

Summary

SMG9 (SMG9 nonsense mediated mRNA decay factor, HGNC:25763) is a protein-coding gene on chromosome 19q13.31, encoding Nonsense-mediated mRNA decay factor SMG9 (Q9H0W8). Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons.

This gene encodes a regulatory subunit of the SMG1 complex, which plays a critical role in nonsense-mediated mRNA decay (NMD). Binding of the encoded protein to the SMG1 complex kinase scaffold protein results in the inhibition of its kinase activity. Mutations in this gene cause a multiple congenital anomaly syndrome in human patients, characterized by brain malformation, congenital heart disease and other features.

Source: NCBI Gene 56006 — RefSeq curated summary.

At a glance

• Gene–disease (curated): heart and brain malformation syndrome (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 133 total — 8 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 64
• MANE Select transcript: NM_019108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25763
Approved symbol	SMG9
Name	SMG9 nonsense mediated mRNA decay factor
Location	19q13.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12886
Ensembl gene	ENSG00000105771
Ensembl biotype	protein_coding
OMIM	613176
Entrez	56006

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000270066, ENST00000594081, ENST00000595700, ENST00000596714, ENST00000597586, ENST00000597598, ENST00000598860, ENST00000598886, ENST00000599804, ENST00000600097, ENST00000601170, ENST00000601925, ENST00000602222, ENST00000892517, ENST00000892518, ENST00000892519, ENST00000892520, ENST00000936242, ENST00000936243, ENST00000963698, ENST00000963699

RefSeq mRNA: 1 — MANE Select: NM_019108 NM_019108

CCDS: CCDS33043

Canonical transcript exons

ENST00000270066 — 14 exons

Exon	Start	End
ENSE00000710885	43733324	43733452
ENSE00000847443	43727983	43731674
ENSE00000847447	43734389	43734495
ENSE00001193577	43732858	43733002
ENSE00003086370	43754654	43754962
ENSE00003458430	43733626	43733733
ENSE00003475972	43747442	43747539
ENSE00003477081	43747978	43748052
ENSE00003532646	43744772	43744884
ENSE00003534795	43747633	43747897
ENSE00003534826	43738122	43738217
ENSE00003548068	43740107	43740218
ENSE00003582392	43750592	43750747
ENSE00003611534	43737597	43737682

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 96.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.8076 / max 297.9161, expressed in 1817 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181345	29.1506	1815
181344	3.2140	1567
181346	1.6958	1006
181347	0.8421	517
181343	0.3743	157
181348	0.2938	113
181339	0.1161	50
181340	0.0702	19
181336	0.0222	7
181342	0.0144	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.34	gold quality
right testis	UBERON:0004534	96.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.10	gold quality
cerebellar hemisphere	UBERON:0002245	95.78	gold quality
cerebellar cortex	UBERON:0002129	95.68	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.39	gold quality
ventricular zone	UBERON:0003053	95.30	gold quality
right frontal lobe	UBERON:0002810	94.28	gold quality
endocervix	UBERON:0000458	94.01	gold quality
cerebellum	UBERON:0002037	93.99	gold quality
lower esophagus mucosa	UBERON:0035834	93.86	gold quality
adenohypophysis	UBERON:0002196	93.78	gold quality
granulocyte	CL:0000094	93.71	gold quality
mucosa of transverse colon	UBERON:0004991	93.62	gold quality
spinal cord	UBERON:0002240	93.61	gold quality
testis	UBERON:0000473	93.41	gold quality
ganglionic eminence	UBERON:0004023	93.35	gold quality
minor salivary gland	UBERON:0001830	93.16	gold quality
nerve	UBERON:0001021	93.11	gold quality
tibial nerve	UBERON:0001323	93.11	gold quality
anterior cingulate cortex	UBERON:0009835	92.78	gold quality
ectocervix	UBERON:0012249	92.78	gold quality
cingulate cortex	UBERON:0003027	92.76	gold quality
pituitary gland	UBERON:0000007	92.59	gold quality
nucleus accumbens	UBERON:0001882	92.36	gold quality
spleen	UBERON:0002106	92.22	gold quality
right adrenal gland	UBERON:0001233	92.09	gold quality
skin of leg	UBERON:0001511	92.05	gold quality
body of uterus	UBERON:0009853	92.03	gold quality
lymph node	UBERON:0000029	92.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting SMG9, 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-345-3P	99.89	70.23	1421
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-6797-3P	99.17	66.94	668
HSA-MIR-6076	98.61	65.69	637
HSA-MIR-3158-3P	98.45	64.25	560
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-7847-3P	96.63	64.58	952

Literature-anchored findings (GeneRIF, showing 11)

• IQGAP1 protein, an actin cytoskeleton modifier acts as a binding partner with SMG-9 and this binding is regulated by phosphorylation of SMG-9 at Tyr-41. (PMID:21640080)
• Mutations in SMG9 cause a multiple congenital anomaly syndrome in humans and mice (PMID:27018474)
• These results indicated that miR-4651 regulated Nonsense-mediated mRNA decay by targeting SMG9 mRNA. (PMID:30902786)
• Cryo-EM structure of SMG1-SMG8-SMG9 complex. (PMID:31729466)
• This study reports the 3.45-A resolution cryo-EM structure of human SMG1-SMG8-SMG9, a phosphatidylinositol-3-kinase (PI(3)K)-related protein kinase (PIKK) complex central to messenger RNA surveillance. (PMID:31792449)
• SMG9-deficiency syndrome caused by a homozygous missense variant: Expanding the genotypic and phenotypic spectrum of this developmental disorder. (PMID:32412169)
• Structure of substrate-bound SMG1-8-9 kinase complex reveals molecular basis for phosphorylation specificity. (PMID:32469312)
• SMG9 drives ferroptosis by directly inhibiting GPX4 degradation. (PMID:34146907)
• Expanding the phenotypic and allelic spectrum of SMG8: Clinical observations reveal overlap with SMG9-associated disease trait. (PMID:34761517)
• A novel variant in SMG9 causes intellectual disability, confirming a role for nonsense-mediated decay components in neurocognitive development. (PMID:35087184)
• Identification of a novel compound heterozygous SMG9 variants in a Chinese family with heart and brain malformation syndrome using whole exome sequencing. (PMID:35321723)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	smg9	ENSDARG00000076627
mus_musculus	Smg9	ENSMUSG00000002210
rattus_norvegicus	Smg9	ENSRNOG00000019596
drosophila_melanogaster	CG3857	FBGN0023520
caenorhabditis_elegans		WBGENE00013188

Protein

Protein identifiers

Nonsense-mediated mRNA decay factor SMG9 — Q9H0W8 (reviewed: Q9H0W8)

All UniProt accessions (7): Q9H0W8, M0QX70, M0QYR7, M0QZC7, M0QZH1, M0R0U0, M0R2N0

UniProt curated annotations — full annotation on UniProt →

Function. Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with SMG1 and SMG8 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required for the efficient association between SMG1 and SMG8. Plays a role in brain, heart, and eye development.

Subunit / interactions. Self-associates to form homodimers and forms heterodimers with SMG8; these assembly forms may represent SMG1C intermediate forms. Component of the SMG1C complex composed of SMG1, SMG8 and SMG9. Interacts with DHX34; the interaction is RNA-independent.

Post-translational modifications. Phosphorylated by SMG1.

Disease relevance. Heart and brain malformation syndrome (HBMS) [MIM:616920] An autosomal recessive syndrome characterized by multiple congenital anomalies such as cardiac defects, brain malformations, including cerebellar vermis hypoplasia, hypoplastic corpus callosum and Dandy-Walker malformation, profoundly delayed psychomotor development, microphthalmia, and facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry. Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies (NEDITPO) [MIM:619995] An autosomal recessive disorder characterized by characterized by mild to moderate intellectual disability, dysmorphic facial features, intention tremor, dyspraxia, and vertical strabismus. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SMG9 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H0W8-1	1	yes
Q9H0W8-2	2

RefSeq proteins (1): NP_061981* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR039177	SMG9	Family

UniProt features (48 total): strand 14, helix 14, modified residue 7, compositionally biased region 4, region of interest 3, turn 2, initiator methionine 1, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7PW8	ELECTRON MICROSCOPY	2.82
6Z3R	ELECTRON MICROSCOPY	2.97
8FE7	X-RAY DIFFRACTION	2.98
7PW9	ELECTRON MICROSCOPY	3.12
7PW4	ELECTRON MICROSCOPY	3.27
7PW5	ELECTRON MICROSCOPY	3.4
6L54	ELECTRON MICROSCOPY	3.43
6SYT	ELECTRON MICROSCOPY	3.45
7PW7	ELECTRON MICROSCOPY	3.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0W8-F1	71.75	0.39

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 (7): 2, 4, 7, 32, 53, 451, 2

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-8953854	Metabolism of RNA
R-HSA-927802	Nonsense-Mediated Decay (NMD)

MSigDB gene sets: 246 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_HEAD_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_NONSENSE_MEDIATED_DECAY, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, REACTOME_METABOLISM_OF_RNA, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, GOCC_TRANSFERASE_COMPLEX, GOCC_PROTEIN_KINASE_COMPLEX

GO Biological Process (6): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), eye development (GO:0001654), in utero embryonic development (GO:0001701), brain development (GO:0007420), heart development (GO:0007507), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Nonsense-Mediated Decay (NMD)	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	2
nuclear-transcribed mRNA catabolic process	1
sensory organ development	1
visual system development	1
chordate embryonic development	1
central nervous system development	1
head development	1
circulatory system development	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
protein binding	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

714 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMG9	SMG8	Q8ND04	999
SMG9	SMG1	Q96Q15	999
SMG9	UPF1	Q92900	992
SMG9	UPF2	Q9HAU5	979
SMG9	ETF1	P46055	958
SMG9	UPF3A	Q9H1J1	947
SMG9	SMG7	Q92540	895
SMG9	GSPT1	P15170	882
SMG9	SMG6	Q86US8	879
SMG9	DHX34	Q14147	856
SMG9	SMG5	Q9UPR3	847
SMG9	UPF3B	Q9BZI7	771
SMG9	EIF4A3	P38919	667
SMG9	PRKCI	P41743	666
SMG9	PNRC2	Q9NPJ4	664

IntAct

162 interactions, top by confidence:

A	B	Type	Score
RBM8A	EIF4A3	psi-mi:“MI:0914”(association)	0.950
TRIM23	SMG9	psi-mi:“MI:0915”(physical association)	0.720
SMG9	TRAF2	psi-mi:“MI:0915”(physical association)	0.720
KRT31	SMG9	psi-mi:“MI:0915”(physical association)	0.720
SMG9	TRIM23	psi-mi:“MI:0915”(physical association)	0.720
SMG9	KRT31	psi-mi:“MI:0915”(physical association)	0.720
TRAF2	SMG9	psi-mi:“MI:0915”(physical association)	0.720
SMG9	SMG8	psi-mi:“MI:0914”(association)	0.710
SMG8	SMG9	psi-mi:“MI:0915”(physical association)	0.710
SMG1	SMG8	psi-mi:“MI:0914”(association)	0.690
SMG9	SMG9	psi-mi:“MI:0915”(physical association)	0.620
SMG1	TTI1	psi-mi:“MI:0914”(association)	0.600
CTAG1A	SMG9	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	SMG9	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (90): SMG9 (Two-hybrid), SMG9 (Two-hybrid), SMG9 (Two-hybrid), SMG9 (Proximity Label-MS), SMG9 (Proximity Label-MS), DDX11 (Affinity Capture-MS), PRPSAP1 (Affinity Capture-MS), VPRBP (Affinity Capture-MS), SMG1 (Affinity Capture-MS), SMG8 (Affinity Capture-MS), SMG9 (Affinity Capture-MS), SMG9 (Affinity Capture-MS), SMG9 (Proximity Label-MS), SMG9 (Two-hybrid), SMG9 (Two-hybrid)

ESM2 similar proteins: A2RSY1, F1R7R1, O54972, O75069, O75151, O88873, P0CH95, P49140, P58929, Q02225, Q06455, Q13233, Q1LY51, Q24767, Q2VPU4, Q2YDD2, Q3KR73, Q499B3, Q4VGL6, Q5F3B1, Q5PQS6, Q5TC82, Q60416, Q60698, Q61909, Q62415, Q62739, Q66IV1, Q6F6B3, Q6NUC6, Q6NYU6, Q7Z3K3, Q80TJ7, Q80W04, Q8BZH4, Q8CHY6, Q8CID0, Q8K2L8, Q8NEM7, Q8TEK3

Diamond homologs: B5DDX6, B5X165, Q05AW9, Q2YDD2, Q5PQS6, Q9DB90, Q9H0W8, A8WX27, Q9XWJ1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	6	13.9×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	5	36.6×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	5
Uncertain significance	74
Likely benign	24
Benign	5

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1700631	NM_019108.4(SMG9):c.551T>C (p.Val184Ala)	Pathogenic
2228670	NM_019108.4(SMG9):c.787G>T (p.Glu263Ter)	Pathogenic
2691293	NC_000019.9:g.(?44232134)(44259115_?)del	Pathogenic
2920667	NM_019108.4(SMG9):c.1508G>C (p.Trp503Ser)	Pathogenic
3251378	NM_019108.4(SMG9):c.1426C>T (p.Gln476Ter)	Pathogenic
3339762	NM_019108.4(SMG9):c.195del (p.Ile66fs)	Pathogenic
4819706	NM_019108.4(SMG9):c.749dup (p.Asn251fs)	Pathogenic
984562	NM_019108.4(SMG9):c.1177C>T (p.Gln393Ter)	Pathogenic
224497	NM_019108.4(SMG9):c.520_521del (p.Pro174fs)	Likely pathogenic
2572731	NM_019108.4(SMG9):c.22C>T (p.Gln8Ter)	Likely pathogenic
3767626	NM_019108.4(SMG9):c.441C>A (p.Tyr147Ter)	Likely pathogenic
4538591	NM_019108.4(SMG9):c.909G>T (p.Gln303His)	Likely pathogenic
987257	NM_019108.4(SMG9):c.610dup (p.Val204fs)	Likely pathogenic

SpliceAI

2141 predictions. Top by Δscore:

Variant	Effect	Δscore
19:43732852:TCTTA:T	donor_loss	1.0000
19:43732853:CTTAC:C	donor_loss	1.0000
19:43732854:TTACC:T	donor_loss	1.0000
19:43732855:TA:T	donor_loss	1.0000
19:43732856:A:AC	donor_gain	1.0000
19:43732856:A:AG	donor_loss	1.0000
19:43732857:C:CA	donor_loss	1.0000
19:43732857:C:CC	donor_gain	1.0000
19:43733620:CCTTA:C	donor_loss	1.0000
19:43733621:CTTAC:C	donor_loss	1.0000
19:43733622:TTA:T	donor_loss	1.0000
19:43733623:TA:T	donor_loss	1.0000
19:43733624:A:AC	donor_gain	1.0000
19:43733624:AC:A	donor_gain	1.0000
19:43733624:ACC:A	donor_gain	1.0000
19:43733625:C:A	donor_loss	1.0000
19:43733625:C:CC	donor_gain	1.0000
19:43733625:CC:C	donor_gain	1.0000
19:43733625:CCC:C	donor_gain	1.0000
19:43733729:GAAGA:G	acceptor_gain	1.0000
19:43733730:AAGA:A	acceptor_gain	1.0000
19:43733731:AGA:A	acceptor_gain	1.0000
19:43733732:GA:G	acceptor_gain	1.0000
19:43733734:C:CC	acceptor_gain	1.0000
19:43738214:TGGG:T	acceptor_gain	1.0000
19:43738218:C:CC	acceptor_gain	1.0000
19:43738222:A:T	acceptor_gain	1.0000
19:43744885:C:CC	acceptor_gain	1.0000
19:43747537:CAG:C	acceptor_gain	1.0000
19:43747547:T:C	acceptor_gain	1.0000

AlphaMissense

3390 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:43731663:G:T	A499D	1.000
19:43731664:C:G	A499P	1.000
19:43732859:A:G	W495R	1.000
19:43732859:A:T	W495R	1.000
19:43737647:G:C	C315W	1.000
19:43737648:C:T	C315Y	1.000
19:43737649:A:G	C315R	1.000
19:43737651:A:T	V314D	1.000
19:43738186:A:G	L282P	1.000
19:43738195:A:G	L279P	1.000
19:43738206:G:C	S275R	1.000
19:43738206:G:T	S275R	1.000
19:43738208:T:G	S275R	1.000
19:43740117:A:G	L268P	1.000
19:43740206:G:C	F238L	1.000
19:43740206:G:T	F238L	1.000
19:43740207:A:G	F238S	1.000
19:43740208:A:G	F238L	1.000
19:43744820:G:A	S218F	1.000
19:43744842:C:G	G211R	1.000
19:43744851:C:G	G208R	1.000
19:43744853:A:T	V207D	1.000
19:43744880:A:G	L198P	1.000
19:43747462:A:G	W190R	1.000
19:43747462:A:T	W190R	1.000
19:43747482:A:G	L183S	1.000
19:43748000:A:T	L68H	1.000
19:43748003:A:C	I67S	1.000
19:43748003:A:G	I67T	1.000
19:43748003:A:T	I67N	1.000

dbSNP variants (sampled 300 via entrez): RS1000059131 (19:43738642 C>G), RS1000069713 (19:43754659 G>A), RS1000102087 (19:43754500 G>A,C), RS1000118181 (19:43732531 C>G), RS1000147386 (19:43742581 C>T), RS1000368275 (19:43742912 A>G), RS1000519261 (19:43731033 C>T), RS1000537148 (19:43730804 G>C), RS1000584289 (19:43737073 A>G), RS1000710113 (19:43748265 G>A), RS1000714311 (19:43754463 G>A,T), RS1000756185 (19:43736876 G>A), RS1000826622 (19:43748527 T>C), RS1000910834 (19:43731517 C>G,T), RS1000959530 (19:43742955 G>T)

Disease associations

OMIM: gene MIM:613176 | disease phenotypes: MIM:616920, MIM:619995

GenCC curated gene-disease

Disease	Classification	Inheritance
heart and brain malformation syndrome	Strong	Autosomal recessive

Mondo (3): heart and brain malformation syndrome (MONDO:0014833), neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies (MONDO:0859274), autism spectrum disorder (MONDO:0005258)

Orphanet (1): NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000179	Thick lower lip vermilion
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000269	Prominent occiput
HP:0000316	Hypertelorism
HP:0000341	Narrow forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000403	Recurrent otitis media
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000568	Microphthalmia
HP:0000750	Delayed speech and language development
HP:0000960	Sacral dimple
HP:0001156	Brachydactyly
HP:0001188	Hand clenching
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001305	Dandy-Walker malformation
HP:0001320	Cerebellar vermis hypoplasia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001937_27	Breast cancer	2.000000e-10
GCST004627_102	Lymphocyte count	1.000000e-12
GCST005992_38	Mean corpuscular hemoglobin concentration	5.000000e-12
GCST006011_59	Mean corpuscular volume	2.000000e-08
GCST90002388_371	Lymphocyte count	2.000000e-25

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Smoke	decreases expression, increases abundance	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
arsenite	decreases methylation	1
methylparaben	increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases methylation	1
jinfukang	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases expression	1
Urethane	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2KC	HAP1 SMG9 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder