TRAPPC9

Summary

TRAPPC9 (trafficking protein particle complex subunit 9, HGNC:30832) is a protein-coding gene on chromosome 8q24.3, encoding Trafficking protein particle complex subunit 9 (Q96Q05). Functions as an activator of NF-kappa-B through increased phosphorylation of the IKK complex.

This gene encodes a protein that likely plays a role in NF-kappa-B signaling. Mutations in this gene have been associated with autosomal-recessive cognitive disability. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 83696 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability-obesity-brain malformations-facial dysmorphism syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 21
• Clinical variants (ClinVar): 1,048 total — 56 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 50
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001160372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30832
Approved symbol	TRAPPC9
Name	trafficking protein particle complex subunit 9
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	IKBKBBP, NIBP, KIAA1882, T1, TRS120, MRT13
Ensembl gene	ENSG00000167632
Ensembl biotype	protein_coding
OMIM	611966
Entrez	83696

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 22 protein_coding, 9 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000438773, ENST00000517667, ENST00000518723, ENST00000518839, ENST00000519482, ENST00000520532, ENST00000520857, ENST00000521167, ENST00000521667, ENST00000521700, ENST00000521944, ENST00000522504, ENST00000523777, ENST00000524162, ENST00000634178, ENST00000648948, ENST00000889101, ENST00000889102, ENST00000889103, ENST00000889104, ENST00000889105, ENST00000889106, ENST00000889107, ENST00000889108, ENST00000889109, ENST00000920031, ENST00000920032, ENST00000920033, ENST00000920034, ENST00000920035, ENST00000920036, ENST00000967712, ENST00000967713, ENST00000967714

RefSeq mRNA: 6 — MANE Select: NM_001160372 NM_001160372, NM_001321646, NM_001374682, NM_001374683, NM_001374684, NM_031466

CCDS: CCDS55278

Canonical transcript exons

ENST00000438773 — 23 exons

Exon	Start	End
ENSE00001115091	140435112	140435240
ENSE00001115095	140397620	140397745
ENSE00001115099	140370964	140371180
ENSE00001115107	140405577	140405698
ENSE00001115109	140426615	140426641
ENSE00001170285	140311248	140311374
ENSE00001170289	140360050	140360193
ENSE00001656124	140439052	140439197
ENSE00003475274	140283889	140284021
ENSE00003477512	140290993	140291078
ENSE00003507606	140023937	140024079
ENSE00003512733	140252777	140252929
ENSE00003516158	140275658	140275821
ENSE00003537181	140300469	140300614
ENSE00003551412	139988726	139988836
ENSE00003556505	139885879	139885969
ENSE00003610885	140450790	140451383
ENSE00003616391	139910147	139910300
ENSE00003630090	139731979	139732202
ENSE00003665914	140287608	140287734
ENSE00003680769	140221459	140221583
ENSE00003838303	140457639	140457744
ENSE00003901581	139727725	139731228

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 92.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5174 / max 348.3474, expressed in 1796 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95324	16.7526	1789
95323	0.7533	427
95325	0.7169	354
95312	0.1094	19
95314	0.1084	20
95318	0.0431	7
95313	0.0298	6
95317	0.0039	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	92.53	gold quality
gastrocnemius	UBERON:0001388	90.01	gold quality
apex of heart	UBERON:0002098	89.95	gold quality
muscle of leg	UBERON:0001383	89.92	gold quality
pancreatic ductal cell	CL:0002079	89.73	silver quality
ganglionic eminence	UBERON:0004023	89.22	gold quality
cortical plate	UBERON:0005343	88.57	gold quality
right uterine tube	UBERON:0001302	88.34	gold quality
prefrontal cortex	UBERON:0000451	87.74	gold quality
adenohypophysis	UBERON:0002196	87.48	gold quality
pituitary gland	UBERON:0000007	87.40	gold quality
islet of Langerhans	UBERON:0000006	87.16	gold quality
muscle organ	UBERON:0001630	86.90	gold quality
tendon of biceps brachii	UBERON:0008188	86.82	silver quality
right frontal lobe	UBERON:0002810	86.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.66	gold quality
granulocyte	CL:0000094	86.21	gold quality
cerebellar hemisphere	UBERON:0002245	85.92	gold quality
cerebellar cortex	UBERON:0002129	85.84	gold quality
right atrium auricular region	UBERON:0006631	85.63	gold quality
ventricular zone	UBERON:0003053	85.42	gold quality
mucosa of transverse colon	UBERON:0004991	85.25	gold quality
lower esophagus mucosa	UBERON:0035834	85.24	gold quality
frontal cortex	UBERON:0001870	85.13	gold quality
adrenal tissue	UBERON:0018303	85.07	gold quality
heart left ventricle	UBERON:0002084	85.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.00	gold quality
cerebellum	UBERON:0002037	84.84	gold quality
neocortex	UBERON:0001950	84.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.71	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	162.39
E-ANND-3	yes	6.37
E-MTAB-6379	no	765.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting TRAPPC9, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6779-5P	99.70	65.76	2363

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 24)

• NIBP is a NIK and IKK(beta)-binding protein that enhances NF-(kappa)B activation (PMID:15951441)
• TRAPPC9 has a role in brain development, possibly through its effect on NF-kappaB activation and protein trafficking in the postmitotic neurons of the cerebral cortex (PMID:20004763)
• TRAPPC9, encodes the NIK- and IKK-beta-binding protein, has a role in nonsyndromic autosomal-recessive mental retardation (PMID:20004765)
• Studies indicate that a truncation of TRAPPC9 leads to mental retardation. (PMID:20966969)
• Data show that a disease-causing mutation of TRAPPC2, D47Y, failed to interact with either TRAPPC9 or TRAPPC8, suggesting that aspartate 47 in TRAPPC2 is at or near the site of interaction with TRAPPC9 or TRAPPC8. (PMID:21858081)
• Data suggest that TRAPPC9 serves to uncouple p150(Glued) from the COPII coat, and to relay the vesicle-dynactin interaction at the target membrane. (PMID:22279557)
• By detailed phenotypic analysis of our patients, and by critical literature review, we found that homozygous TRAPPC9 loss-of-function mutations cause a distinctive phenotype, characterized by peculiar facial appearance, obesity, hypotonia (PMID:22549410)
• A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly. (PMID:22989526)
• Identification and construction of a 3D protein model of trafficking protein particle complex 9 (TRAPPC9), a potetnially interesting molecular target for the development of drug therapy against non syndromic mental retardation (PMID:24040793)
• Data identified important roles of NIBP in promoting tumorigenesis via NFkappaBeta signaling. (PMID:25704885)
• NIBP reflects a higher metastatic potential of CRC tumors, and its mechanism of action may be through regulation of the classical NF-kappaB pathway and increased MMP-2 and MMP-9 expression (PMID:26596835)
• In this study, we report that WES analysis allowed identification of the causal molecular lesion in both patients. In the first family of Egyptian origin, a homozygous nonsense mutation (c.1423C>T; p.Arg377*) in TRAPPC9 was identified (PMID:27108886)
• NIBP impacts on the expression levels of Ecadherin, CD44 and vimentin via the NFkappaB classical and alternative pathways. (PMID:27109343)
• In conclusion, we demonstrated that NIBP knockdown reduces colorectal cancer metastasis through down-regulation of canonical NF-kappaBeta signaling and suppression of ERK and JNK signaling. (PMID:28125661)
• Homozygous TRAPPC9 gene nonsense mutation in OXTR gene is associated with intellectual disability, speech disorder, and secondary microcephaly. (PMID:29031008)
• CNVs significantly contribute to the mutational spectrum of TRAPPC9 gene associated with syndromic intellectual disability. (PMID:29187737)
• Data show that NIBP expression level is high in gastric cancer (GC) patients and indicate that the NIBPregulated NFkappaB signaling pathway plays a pivotal role in the chemoresistance of GC cells by promoting EMT. (PMID:29620292)
• TRAPPC9 is associated with ADHD risk. (PMID:32046534)
• Trappc9 deficiency causes parent-of-origin dependent microcephaly and obesity. (PMID:32877400)
• Identification of two novel homozygous nonsense mutations in TRAPPC9 in two unrelated consanguineous families with intellectual Disability from Iran. (PMID:33513295)
• Novel Compound Heterozygous Mutation in TRAPPC9 Gene: The Relevance of Whole Genome Sequencing. (PMID:33921338)
• Further insights into the spectrum phenotype of TRAPPC9 and CDK5RAP2 genes, segregating independently in a large Tunisian family with intellectual disability and microcephaly. (PMID:34737153)
• Neurodevelopmental Outcome and Epigenetic Changes at 2 Years Associated with the Oxygen Load Received upon Postnatal Stabilization: A Pilot Study. (PMID:35760056)
• Expanding the genetic and phenotypic spectrum of TRAPPC9 and MID2-related neurodevelopmental disabilities: report of two novel mutations, 3D-modelling, and molecular docking studies. (PMID:38467738)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	TRAPPC9	ENSDARG00000099118
danio_rerio	trappc9	ENSDARG00000103106
mus_musculus	Trappc9	ENSMUSG00000047921
rattus_norvegicus	Trappc9	ENSRNOG00000027569
drosophila_melanogaster	brun	FBGN0261787
caenorhabditis_elegans		WBGENE00007956

Protein

Protein identifiers

Trafficking protein particle complex subunit 9 — Q96Q05 (reviewed: Q96Q05)

Alternative names: NIK- and IKBKB-binding protein, Tularik gene 1 protein

All UniProt accessions (3): A0A0J9YWK7, Q96Q05, H0YBR0

UniProt curated annotations — full annotation on UniProt →

Function. Functions as an activator of NF-kappa-B through increased phosphorylation of the IKK complex. May function in neuronal cells differentiation. May play a role in vesicular transport from endoplasmic reticulum to Golgi.

Subunit / interactions. Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12. Directly interacts with IKBKB and MAP3K14.

Subcellular location. Golgi apparatus. cis-Golgi network. Endoplasmic reticulum. Cytoplasm.

Tissue specificity. Expressed at high levels in muscle and kidney and to a lower extent in brain, heart and placenta.

Disease relevance. Intellectual developmental disorder, autosomal recessive 13 (MRT13) [MIM:613192] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Brain magnetic resonance imaging of MRT13 patients indicates the presence of mild cerebral white matter hypoplasia. Microcephaly is present in some but not all affected individuals. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the NIBP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96Q05-1	1	yes
Q96Q05-2	2
Q96Q05-3	3

RefSeq proteins (6): NP_001153844, NP_001308575, NP_001361611, NP_001361612, NP_001361613, NP_113654 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013935	Trs120_TRAPPC9	Family
IPR058563	Trs120_TRAPPC9_N	Domain
IPR058564	TPR_TRAPPC9_Trs120	Domain
IPR058565	Ig_TRAPPC9_Trs120_1st	Domain
IPR058567	Ig_TRAPPC9_Trs120_3rd	Domain
IPR058568	Ig_TRAPPC9_Trs120_4th	Domain

Pfam: PF08626, PF26251, PF26254, PF26280, PF26282, PF26283

UniProt features (8 total): sequence conflict 3, modified residue 2, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96Q05-F1	82.98	0.54

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 (2): 566, 953

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 256 (showing top): GOBP_VESICLE_LOCALIZATION, GOBP_VESICLE_ORGANIZATION, GOBP_VESICLE_TARGETING, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_FOREBRAIN_DEVELOPMENT, GOCC_TRANS_GOLGI_NETWORK, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, BOYLAN_MULTIPLE_MYELOMA_D_CLUSTER_DN, GOBP_CEREBRAL_CORTEX_DEVELOPMENT, GOBP_PALLIUM_DEVELOPMENT, GOBP_HEAD_DEVELOPMENT, GOBP_MEMBRANE_ORGANIZATION, GOBP_ORGANELLE_LOCALIZATION

GO Biological Process (6): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), vesicle coat assembly (GO:0006901), cerebral cortex development (GO:0021987), neuron differentiation (GO:0030182), obsolete vesicle tethering (GO:0099022), cell differentiation (GO:0030154)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), trans-Golgi network (GO:0005802), cytosol (GO:0005829), TRAPP complex (GO:0030008), TRAPPII protein complex (GO:1990071), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	2
endomembrane system	2
intracellular membrane-bounded organelle	2
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
vesicle budding from membrane	1
vesicle organization	1
pallium development	1
anatomical structure development	1
cell differentiation	1
generation of neurons	1
cellular developmental process	1
binding	1
intracellular anatomical structure	1
Golgi apparatus subcompartment	1
vesicle tethering complex	1
intracellular protein-containing complex	1
endosome	1
Golgi apparatus	1
TRAPP complex	1

Protein interactions and networks

STRING

1726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAPPC9	TRAPPC10	P48553	997
TRAPPC9	TRAPPC5	Q8IUR0	938
TRAPPC9	TRAPPC8	Q9Y2L5	932
TRAPPC9	TRAPPC2	P0DI81	899
TRAPPC9	TRAPPC6A	O75865	898
TRAPPC9	TRAPPC3	O43617	898
TRAPPC9	TRAPPC1	Q9Y5R8	896
TRAPPC9	TRAPPC13	A5PLN9	881
TRAPPC9	TRAPPC4	Q9Y296	881
TRAPPC9	TRAPPC6B	Q86SZ2	837
TRAPPC9	TRAPPC2L	Q9UL33	813
TRAPPC9	UQCRFS1	P47985	794
TRAPPC9	TRAPPC12	Q8WVT3	777
TRAPPC9	TRAPPC11	Q7Z392	772
TRAPPC9	IKBKB	O14920	705

IntAct

105 interactions, top by confidence:

A	B	Type	Score
RUFY4	NDC80	psi-mi:“MI:0914”(association)	0.830
SART1	PRPF6	psi-mi:“MI:0914”(association)	0.750
SART1	PRPF3	psi-mi:“MI:0914”(association)	0.720
TRAPPC9	RAB3IP	psi-mi:“MI:0403”(colocalization)	0.720
RAB3IP	TRAPPC3	psi-mi:“MI:0914”(association)	0.700
RAB3IP	TRAPPC3	psi-mi:“MI:0915”(physical association)	0.700
KANK4	TRAPPC3	psi-mi:“MI:0914”(association)	0.640
PTGR3	DBT	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
APBA1	LIN7A	psi-mi:“MI:0914”(association)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
TRAPPC2L	TRAPPC13	psi-mi:“MI:0914”(association)	0.560
TRAPPC1	TRAPPC13	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
ACAA1	PEX7	psi-mi:“MI:0914”(association)	0.530
BCL2L14	CHEK1	psi-mi:“MI:0914”(association)	0.530
RAB30	UBB	psi-mi:“MI:0914”(association)	0.530
CABS1	TRAPPC10	psi-mi:“MI:0914”(association)	0.530
BTBD1	TRAPPC10	psi-mi:“MI:0914”(association)	0.530
TRAPPC9	TRAPPC3	psi-mi:“MI:0915”(physical association)	0.530
RUFY4	TRAPPC9	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (156): TRAPPC9 (Affinity Capture-RNA), TRAPPC9 (Affinity Capture-RNA), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Reconstituted Complex), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8F8I9, A0A2R8QPS5, A1A5P5, A7S2N8, B0BM28, B4FGS2, B8AXB6, B8B624, B8JKF4, B9FM64, F1QNV4, F4IQJ2, P49842, P97564, Q08CY4, Q08DB2, Q0P5W1, Q0VA04, Q14AI0, Q2KI89, Q32PH0, Q3SYG4, Q3U0M1, Q4R804, Q5R629, Q61586, Q66I84, Q68F70, Q6DHG8, Q6GL75, Q6GMB0, Q6GN08, Q6GPP1, Q6NU25, Q6PA97, Q7T006, Q7XAM0, Q7Z3E5, Q811G0, Q8CIM8

Diamond homologs: Q32PH0, Q3U0M1, Q6PA97, Q96Q05, Q9VIL0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TRAPPC9	“up-regulates activity”	MAP3K14	binding
TRAPPC9	“up-regulates activity”	IKBKB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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 GEFs exchange GTP for GDP on RABs	12	17.1×	3e-09
COPII-mediated vesicle transport	8	15.0×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle tethering	9	84.2×	1e-13
COPII vesicle coat assembly	7	46.4×	3e-08
endoplasmic reticulum to Golgi vesicle-mediated transport	11	14.1×	8e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

1048 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	56
Likely pathogenic	28
Uncertain significance	388
Likely benign	396
Benign	59

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
130637	NM_001160372.4(TRAPPC9):c.367G>T (p.Glu123Ter)	Pathogenic
1323708	NM_031466.8(TRAPPC9):c.-124dup	Pathogenic
1368892	NM_001160372.4(TRAPPC9):c.1929C>G (p.Tyr643Ter)	Pathogenic
1401233	NM_001160372.4(TRAPPC9):c.2749G>T (p.Glu917Ter)	Pathogenic
1452912	NM_001160372.4(TRAPPC9):c.2957G>A (p.Trp986Ter)	Pathogenic
1452925	NM_001160372.4(TRAPPC9):c.289G>T (p.Glu97Ter)	Pathogenic
1458449	NC_000008.10:g.(?141321327)(141321493_?)del	Pathogenic
1460058	NC_000008.10:g.(?141460869)(141461502_?)del	Pathogenic
1679936	NM_001160372.4(TRAPPC9):c.2699+1G>A	Pathogenic
1683498	NM_001160372.4(TRAPPC9):c.1994dup (p.Val666fs)	Pathogenic
1686272	NM_001160372.4(TRAPPC9):c.3279+1G>A	Pathogenic
1695239	NM_001160372.4(TRAPPC9):c.3036_3040dup (p.Ala1014fs)	Pathogenic
1709594	NM_001160372.4(TRAPPC9):c.1840C>T (p.Arg614Ter)	Pathogenic
1805300	NM_001160372.4(TRAPPC9):c.175del (p.His59fs)	Pathogenic
191233	NM_001160372.4(TRAPPC9):c.3034C>T (p.Gln1012Ter)	Pathogenic
1995486	NM_001160372.4(TRAPPC9):c.620_623dup (p.His208fs)	Pathogenic
2009537	NM_001160372.4(TRAPPC9):c.2954dup (p.Cys985fs)	Pathogenic
2014617	NM_001160372.4(TRAPPC9):c.3013C>T (p.Gln1005Ter)	Pathogenic
2015942	NM_001160372.4(TRAPPC9):c.1856_1857insACCAA (p.Leu620fs)	Pathogenic
2046948	NM_001160372.4(TRAPPC9):c.183C>G (p.Tyr61Ter)	Pathogenic
2092625	NM_001160372.4(TRAPPC9):c.1537A>T (p.Lys513Ter)	Pathogenic
2426975	NC_000008.10:g.(?141285737)(141285940_?)del	Pathogenic
2426976	NC_000008.10:g.(?141034014)(141034196_?)del	Pathogenic
2637918	NM_001160372.4(TRAPPC9):c.2186del (p.Gly729fs)	Pathogenic
2752127	NM_001160372.4(TRAPPC9):c.604del (p.Gln202fs)	Pathogenic
2759021	NM_001160372.4(TRAPPC9):c.2018del (p.Cys673fs)	Pathogenic
2778686	NM_001160372.4(TRAPPC9):c.2841dup (p.Glu948Ter)	Pathogenic
2849180	NM_031466.8(TRAPPC9):c.-110_-103dup	Pathogenic
2969288	NM_001160372.4(TRAPPC9):c.2194C>T (p.Gln732Ter)	Pathogenic
3063740	NM_001160372.4(TRAPPC9):c.203G>A (p.Trp68Ter)	Pathogenic

SpliceAI

8346 predictions. Top by Δscore:

Variant	Effect	Δscore
8:139731224:TGCAC:T	acceptor_gain	1.0000
8:139731226:CAC:C	acceptor_gain	1.0000
8:139731227:AC:A	acceptor_gain	1.0000
8:139731228:CC:C	acceptor_gain	1.0000
8:139731229:C:CC	acceptor_gain	1.0000
8:139731234:C:CT	acceptor_gain	1.0000
8:139731974:CGCA:C	donor_loss	1.0000
8:139731975:GCA:G	donor_loss	1.0000
8:139731976:CA:C	donor_loss	1.0000
8:139731977:A:AC	donor_gain	1.0000
8:139731978:C:CC	donor_gain	1.0000
8:139731978:C:CG	donor_loss	1.0000
8:139731978:CCG:C	donor_gain	1.0000
8:139731978:CCGCG:C	donor_gain	1.0000
8:139732199:ACAT:A	acceptor_gain	1.0000
8:139732200:CAT:C	acceptor_gain	1.0000
8:139732200:CATC:C	acceptor_gain	1.0000
8:139732202:TCTG:T	acceptor_loss	1.0000
8:139732203:C:A	acceptor_loss	1.0000
8:139732203:C:CC	acceptor_gain	1.0000
8:139910167:G:C	donor_gain	1.0000
8:139910296:CCATT:C	acceptor_gain	1.0000
8:139910297:CATTC:C	acceptor_gain	1.0000
8:139910299:TT:T	acceptor_gain	1.0000
8:139910301:C:CC	acceptor_gain	1.0000
8:139988719:CACTT:C	donor_loss	1.0000
8:139988720:ACTTA:A	donor_loss	1.0000
8:139988721:CTTAC:C	donor_loss	1.0000
8:139988722:TTA:T	donor_loss	1.0000
8:139988723:TACCG:T	donor_loss	1.0000

AlphaMissense

7523 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:140291026:G:C	N607K	1.000
8:140291026:G:T	N607K	1.000
8:140291070:A:G	W593R	1.000
8:140291070:A:T	W593R	1.000
8:140360179:A:G	W456R	1.000
8:140360179:A:T	W456R	1.000
8:140435229:C:G	G248R	1.000
8:140435229:C:T	G248R	1.000
8:140439061:A:G	W241R	1.000
8:140439061:A:T	W241R	1.000
8:140439141:A:G	L214P	1.000
8:140439147:A:G	L212P	1.000
8:140439153:C:T	G210E	1.000
8:140439154:C:A	G210W	1.000
8:140439154:C:G	G210R	1.000
8:140439154:C:T	G210R	1.000
8:140439165:C:G	R206P	1.000
8:140439171:C:G	R204P	1.000
8:140439172:G:T	R204S	1.000
8:140439174:C:T	G203D	1.000
8:140439175:C:G	G203R	1.000
8:140450887:G:T	R163S	1.000
8:140451138:C:T	G79D	1.000
8:140451139:C:G	G79R	1.000
8:140451150:C:G	R75P	1.000
8:140451151:G:T	R75S	1.000
8:140451172:A:G	W68R	1.000
8:140451172:A:T	W68R	1.000
8:140451315:A:T	V20D	1.000
8:140024015:C:A	R874M	0.999

dbSNP variants (sampled 300 via entrez): RS1000001473 (8:139932091 G>A), RS1000007366 (8:139741607 C>T), RS1000015227 (8:139990452 C>T), RS1000021268 (8:140302374 A>T), RS1000023746 (8:140143800 T>C), RS1000024626 (8:140029600 A>G), RS1000024658 (8:140035009 G>A), RS1000029227 (8:140331950 A>G), RS1000034982 (8:140189976 A>G), RS1000038983 (8:140449012 A>G), RS1000039135 (8:140005065 C>T), RS1000040036 (8:139741344 G>A), RS1000041109 (8:140230247 G>A), RS1000041832 (8:140269436 G>A), RS1000042945 (8:140029641 A>T)

Disease associations

OMIM: gene MIM:611966 | disease phenotypes: MIM:613192, MIM:249500, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal recessive 13	Definitive	Autosomal recessive
intellectual disability-obesity-brain malformations-facial dysmorphism syndrome	Supportive	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual disability-obesity-brain malformations-facial dysmorphism syndrome	Definitive	AR

Mondo (7): intellectual disability, autosomal recessive 13 (MONDO:0013173), congenital nervous system disorder (MONDO:0002320), intellectual disability (MONDO:0001071), intellectual disability-obesity-brain malformations-facial dysmorphism syndrome (MONDO:0018123), autosomal recessive non-syndromic intellectual disability (MONDO:0019502), autism spectrum disorder (MONDO:0005258), schizophrenia (MONDO:0005090)

Orphanet (5): Autosomal recessive non-syndromic intellectual disability (Orphanet:88616), Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome (Orphanet:352530), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000204	Cleft upper lip
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000341	Narrow forehead
HP:0000377	Abnormal pinna morphology
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000601	Hypotelorism
HP:0000664	Synophrys
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000851	Congenital hypothyroidism
HP:0001182	Tapered finger
HP:0001238	Slender finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001321	Cerebellar hypoplasia
HP:0001513	Obesity
HP:0001956	Truncal obesity
HP:0001999	Abnormal facial shape
HP:0002047	Malignant hyperthermia

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST001651_39	Response to amphetamines	7.000000e-06
GCST001762_609	Obesity-related traits	3.000000e-06
GCST002587_15	Blood pressure (smoking interaction)	3.000000e-07
GCST003761_7	Emphysema distribution in smoking	3.000000e-08
GCST004278_2	Pulse pressure	5.000000e-16
GCST004775_41	Pulse pressure	2.000000e-11
GCST004775_8	Pulse pressure	1.000000e-08
GCST004942_1	Pediatric non-alcoholic fatty liver disease activity score	9.000000e-07
GCST005231_7	Major depressive disorder	2.000000e-06
GCST005359_16	Disease progression in age-related macular degeneration	6.000000e-06
GCST007096_254	Pulse pressure	2.000000e-10
GCST007097_90	Pulse pressure	3.000000e-06
GCST007097_91	Pulse pressure	3.000000e-07
GCST007099_109	Systolic blood pressure	9.000000e-06
GCST007268_37	Diastolic blood pressure	2.000000e-08
GCST007269_227	Pulse pressure	1.000000e-13
GCST008156_138	Hip circumference adjusted for BMI	8.000000e-06
GCST009174_1	Response to (pegylated) interferon in chronic hepatitis B	6.000000e-07
GCST009193_8	Pars opercularis volume	4.000000e-06
GCST012138_3	Interleukin-6 levels in HIV infection	3.000000e-08
GCST012189_10	Systolic blood pressure and diastolic blood pressure (bivariate analysis)	8.000000e-06

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005190	urinary nitrogen measurement
EFO:0006335	systolic blood pressure
EFO:0006526	pack-years measurement
EFO:0005850	emphysema pattern measurement
EFO:0005763	pulse pressure measurement
EFO:0008421	non-alcoholic fatty liver disease severity measurement
EFO:0008336	disease progression measurement
EFO:0006336	diastolic blood pressure
EFO:0008039	BMI-adjusted hip circumference
EFO:0007859	response to interferon
EFO:0004810	interleukin-6 measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C567714	Mental Retardation, Autosomal Recessive 13 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	7
Aflatoxin B1	affects expression, affects methylation, decreases expression, increases methylation	6
bisphenol A	increases methylation, increases expression, affects methylation, affects cotreatment	3
sodium arsenite	decreases expression, increases expression, affects expression	3
Valproic Acid	affects expression, increases expression, increases methylation	3
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
methyleugenol	decreases expression	1
beta-lapachone	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
benzo(e)pyrene	affects methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	affects methylation	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
bisphenol S	increases methylation	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases reaction, 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_XU71	HAP1 TRAPPC9 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
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)