TRAPPC4

Summary

TRAPPC4 (trafficking protein particle complex subunit 4, HGNC:19943) is a protein-coding gene on chromosome 11q23.3, encoding Trafficking protein particle complex subunit 4 (Q9Y296). Core component of the TRAPP complexes which has a function of guanine nucleotide exchange factor activity for Rab1 GTPase. It is a common-essential gene (DepMap: required in 97.2% of cancer cell lines).

Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex.

Source: NCBI Gene 51399 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 83 total — 3 likely-pathogenic
• Phenotypes (HPO): 14
• Cancer dependency (DepMap): dependent in 97.2% of screened cell lines (common-essential)
• MANE Select transcript: NM_016146

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19943
Approved symbol	TRAPPC4
Name	trafficking protein particle complex subunit 4
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	TRS23, SBDN, PTD009
Ensembl gene	ENSG00000196655
Ensembl biotype	protein_coding
OMIM	610971
Entrez	51399

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000359005, ENST00000434101, ENST00000447216, ENST00000524797, ENST00000525079, ENST00000525303, ENST00000526141, ENST00000527680, ENST00000528230, ENST00000531290, ENST00000533012, ENST00000533058, ENST00000533149, ENST00000533632, ENST00000868253, ENST00000925890

RefSeq mRNA: 7 — MANE Select: NM_016146 NM_001318486, NM_001318488, NM_001318489, NM_001318490, NM_001318492, NM_001318494, NM_016146

CCDS: CCDS81632, CCDS81633, CCDS81634, CCDS81635, CCDS8407

Canonical transcript exons

ENST00000533632 — 5 exons

Exon	Start	End
ENSE00002163805	119023321	119024134
ENSE00003521241	119021760	119021886
ENSE00003540388	119019143	119019317
ENSE00003545520	119018766	119018970
ENSE00003684212	119020150	119020253

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.2610 / max 354.5567, expressed in 1816 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117083	38.2610	1816

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.23	gold quality
islet of Langerhans	UBERON:0000006	97.03	gold quality
adenohypophysis	UBERON:0002196	96.71	gold quality
pituitary gland	UBERON:0000007	96.62	gold quality
right testis	UBERON:0004534	96.42	gold quality
left testis	UBERON:0004533	96.27	gold quality
stromal cell of endometrium	CL:0002255	96.21	gold quality
testis	UBERON:0000473	95.94	gold quality
ganglionic eminence	UBERON:0004023	95.92	gold quality
right adrenal gland	UBERON:0001233	95.84	gold quality
metanephros cortex	UBERON:0010533	95.74	gold quality
left adrenal gland	UBERON:0001234	95.67	gold quality
left adrenal gland cortex	UBERON:0035825	95.63	gold quality
adult mammalian kidney	UBERON:0000082	95.59	gold quality
cortex of kidney	UBERON:0001225	95.55	gold quality
mucosa of transverse colon	UBERON:0004991	95.47	gold quality
adrenal gland	UBERON:0002369	95.38	gold quality
right adrenal gland cortex	UBERON:0035827	95.36	gold quality
pancreas	UBERON:0001264	95.30	gold quality
ventricular zone	UBERON:0003053	94.93	gold quality
left coronary artery	UBERON:0001626	94.88	gold quality
rectum	UBERON:0001052	94.86	gold quality
duodenum	UBERON:0002114	94.86	gold quality
prostate gland	UBERON:0002367	94.84	gold quality
hypothalamus	UBERON:0001898	94.76	gold quality
right lobe of thyroid gland	UBERON:0001119	94.73	gold quality
body of pancreas	UBERON:0001150	94.70	gold quality
cerebellum	UBERON:0002037	94.59	gold quality
cerebellar cortex	UBERON:0002129	94.57	gold quality
cerebellar hemisphere	UBERON:0002245	94.56	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-109979	no	126.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting TRAPPC4, 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-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-571	95.38	66.54	671

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.2% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• The three-dimensional structure of human synbindin, which contains a longin domain and an atypical PDZ domain is presented. (PMID:18466758)
• Data demonstrate that TRAPPC4 may regulate cell proliferation and apoptosis in CRC by interaction with ERK2 and phosphorylating ERK1/2 as well as modulating the subcellular location of pERK1/2 to activate the relevant signaling pathway. (PMID:21826244)
• Overexpression of TRAPPC4 increased colorectal carcinogenesis. (PMID:23625650)
• Synbindin contributes to malignant phenotypes of GC by activating ERK on the Golgi, and synbindin is a potential biomarker and therapeutic target for GC. (PMID:24104608)
• Findings identify a critical role of Synbindin in gut microbiome composition and Wnt signaling activation in colorectal carcinogenesis, and highlight Synbindin as an adaptor protein with multifaceted roles. (PMID:30561033)
• Deficiencies in vesicular transport mediated by TRAPPC4 are associated with severe syndromic intellectual disability. (PMID:31794024)
• A relatively common homozygous TRAPPC4 splicing variant is associated with an early-infantile neurodegenerative syndrome. (PMID:32901138)
• TRAPPC4 regulates the intracellular trafficking of PD-L1 and antitumor immunity. (PMID:34518538)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trappc4	ENSDARG00000027418
mus_musculus	Trappc4	ENSMUSG00000032112
rattus_norvegicus	Trappc4	ENSRNOG00000011904
drosophila_melanogaster	Trs23	FBGN0260861
caenorhabditis_elegans		WBGENE00018088

Paralogs (1): TRAPPC1 (ENSG00000170043)

Protein

Protein identifiers

Trafficking protein particle complex subunit 4 — Q9Y296 (reviewed: Q9Y296)

Alternative names: Hematopoietic stem/progenitor cell protein 172, Synbindin, TRS23 homolog

All UniProt accessions (7): E9PKS9, E9PN70, E9PQE8, Q9Y296, G3V1A0, G5EA23, J3KP27

UniProt curated annotations — full annotation on UniProt →

Function. Core component of the TRAPP complexes which has a function of guanine nucleotide exchange factor activity for Rab1 GTPase. Plays a role in vesicular transport from endoplasmic reticulum to Golgi and autophagy. May play a role in dendrite postsynaptic membrane trafficking.

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. Interacts with SDC2.

Subcellular location. Postsynaptic cell membrane. Golgi apparatus membrane. Endoplasmic reticulum. Vesicle.

Disease relevance. Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (NEDESBA) [MIM:618741] An autosomal recessive disorder characterized by severely impaired global development apparent soon after birth, early-onset seizures, lack of psychomotor development, spastic quadriparesis, progressive cortical and cerebellar atrophy, and dysmorphic features, including microcephaly. Death in childhood may occur. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRAPP small subunits family. TRAPPC4 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y296-1	1	yes
Q9Y296-2	2

RefSeq proteins (7): NP_001305415, NP_001305417, NP_001305418, NP_001305419, NP_001305421, NP_001305423, NP_057230* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007233	TRAPPC	Family
IPR011012	Longin-like_dom_sf	Homologous_superfamily

Pfam: PF04099

UniProt features (22 total): strand 13, helix 5, chain 1, splice variant 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2J3T	X-RAY DIFFRACTION	2.4
2ZMV	X-RAY DIFFRACTION	2.8
2JSN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y296-F1	91.02	0.78

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-3000170	Syndecan interactions
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 179 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_VESICLE_LOCALIZATION, GOBP_VESICLE_ORGANIZATION, GOBP_VESICLE_TARGETING, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, LIAO_METASTASIS, GARY_CD5_TARGETS_DN, TIEN_INTESTINE_PROBIOTICS_24HR_UP, GOCC_NEURON_PROJECTION, GOBP_MEMBRANE_ORGANIZATION, GOBP_CELL_PROJECTION_ORGANIZATION, ACEVEDO_LIVER_CANCER_UP

GO Biological Process (7): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), vesicle coat assembly (GO:0006901), autophagy (GO:0006914), dendrite development (GO:0016358), COPII vesicle coat assembly (GO:0048208), obsolete vesicle tethering (GO:0099022), vesicle-mediated transport (GO:0016192)

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

GO Cellular Component (18): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi stack (GO:0005795), cytosol (GO:0005829), synaptic vesicle (GO:0008021), TRAPP complex (GO:0030008), dendrite (GO:0030425), synapse (GO:0045202), presynaptic active zone (GO:0048786), postsynaptic density membrane (GO:0098839), TRAPPII protein complex (GO:1990071), TRAPPIII protein complex (GO:1990072), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), vesicle (GO:0031982), postsynaptic membrane (GO:0045211)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	1
Non-integrin membrane-ECM interactions	1
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	4
Golgi apparatus	3
endomembrane system	2
intracellular membrane-bounded organelle	2
presynapse	2
TRAPP complex	2
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
vesicle budding from membrane	1
vesicle organization	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
neuron projection development	1
anatomical structure development	1
vesicle coat assembly	1
protein-containing complex assembly	1
COPII-coated vesicle budding	1
transport	1
cellular process	1
binding	1
bounding membrane of organelle	1
intracellular anatomical structure	1
Golgi apparatus subcompartment	1
exocytic vesicle	1
vesicle tethering complex	1
intracellular protein-containing complex	1
neuron projection	1
dendritic tree	1
cell junction	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
endosome	1
membrane	1
cell periphery	1
membrane-bounded organelle	1
synaptic membrane	1

Protein interactions and networks

STRING

938 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAPPC4	TRAPPC6A	O75865	998
TRAPPC4	TRAPPC2	P0DI81	998
TRAPPC4	TRAPPC3	O43617	998
TRAPPC4	TRAPPC5	Q8IUR0	998
TRAPPC4	TRAPPC1	Q9Y5R8	991
TRAPPC4	TRAPPC8	Q9Y2L5	989
TRAPPC4	TRAPPC10	P48553	913
TRAPPC4	SDC2	P34741	912
TRAPPC4	RAB1A	P11476	900
TRAPPC4	TRAPPC9	Q96Q05	881
TRAPPC4	TRAPPC12	Q8WVT3	868
TRAPPC4	SDC4	P31431	828
TRAPPC4	TRAPPC6B	Q86SZ2	827
TRAPPC4	TRAPPC11	Q7Z392	771
TRAPPC4	TRAPPC13	A5PLN9	768

IntAct

112 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
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
MAPK1	TRAPPC4	psi-mi:“MI:0915”(physical association)	0.580
TRAPPC2L	TRAPPC13	psi-mi:“MI:0914”(association)	0.560
RAB3IP	TRAPPC2	psi-mi:“MI:0914”(association)	0.560
TRAPPC6A	Trappc3	psi-mi:“MI:0915”(physical association)	0.540
TRAPPC6A	Trappc3	psi-mi:“MI:0407”(direct interaction)	0.540
TRAPPC12	TRAPPC3	psi-mi:“MI:0914”(association)	0.530
CNN2	ATE1	psi-mi:“MI:0914”(association)	0.530
RAB30	UBB	psi-mi:“MI:0914”(association)	0.530
BTBD1	TRAPPC10	psi-mi:“MI:0914”(association)	0.530
MIS12	SPC24	psi-mi:“MI:0914”(association)	0.530
TRAPPC1	TRAPPC13	psi-mi:“MI:0914”(association)	0.530
BCL2L14	CHEK1	psi-mi:“MI:0914”(association)	0.530
CABS1	TRAPPC10	psi-mi:“MI:0914”(association)	0.530

BioGRID (123): TRAPPC4 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS), TRAPPC3 (Co-fractionation), TRAPPC4 (Co-fractionation), TRAPPC4 (Co-fractionation), TRAPPC4 (Co-fractionation), TRAPPC4 (Co-fractionation), TRAPPC4 (Co-fractionation), TRAPPC6B (Co-fractionation), TRAPPC4 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS)

ESM2 similar proteins: A0JN27, A6H7F7, B2RYU6, B5FXJ6, B5FYY5, B5X7X4, B5XGE7, O43504, P55168, P61201, P61202, P61203, P79101, Q05048, Q13888, Q28F72, Q2TBL9, Q2TBV5, Q2YDH6, Q3T132, Q4KLA0, Q4R9A8, Q4VC33, Q5BJQ6, Q5F398, Q5M8X5, Q5R532, Q5R8K2, Q5R9J9, Q5RKJ1, Q63ZJ2, Q6DEG4, Q6DF40, Q6GR10, Q6IQT4, Q6IR75, Q6P1K8, Q7L5Y9, Q7SXR3, Q7ZXB7

Diamond homologs: O43041, Q2TBL9, Q54UU1, Q5R9J9, Q69BT7, Q9ES56, Q9Y296, Q03630, Q17QI1, Q2KMM2, Q557G3, Q5NCF2, Q9UT70, Q9Y5R8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TRAPPC4	“form complex”	“TRAPP III complex, TRAPPC2 variant”	binding
TRAPPC4	“form complex”	“TRAPP III complex, TRAPPC2B variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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
Negative regulation of FGFR1 signaling	5	25.2×	1e-04
Intrinsic Pathway for Apoptosis	6	24.1×	2e-05
RAB GEFs exchange GTP for GDP on RABs	14	23.8×	3e-13
Parasite infection	5	23.7×	1e-04
Leishmania phagocytosis	5	23.7×	1e-04
Negative regulation of MAPK pathway	6	21.8×	2e-05
RHO GTPases Activate WASPs and WAVEs	5	21.7×	1e-04
Signaling by high-kinase activity BRAF mutants	5	21.7×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle tethering	11	122.5×	4e-19
COPII vesicle coat assembly	8	63.1×	7e-11
endoplasmic reticulum to Golgi vesicle-mediated transport	12	18.3×	4e-10
MAPK cascade	6	10.3×	3e-03
chromosome segregation	5	9.8×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	42
Likely benign	4
Benign	25

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2580934	NM_016146.6(TRAPPC4):c.374T>C (p.Leu125Pro)	Likely pathogenic
3378415	NM_016146.6(TRAPPC4):c.23_24del (p.Val8fs)	Likely pathogenic
916549	NM_016146.6(TRAPPC4):c.638_*4del (p.Gly213_Ter220delinsXaa)	Likely pathogenic

SpliceAI

881 predictions. Top by Δscore:

Variant	Effect	Δscore
11:119019141:A:AG	acceptor_gain	1.0000
11:119019141:AGT:A	acceptor_gain	1.0000
11:119019141:AGTG:A	acceptor_gain	1.0000
11:119019142:G:GG	acceptor_gain	1.0000
11:119019142:GTG:G	acceptor_gain	1.0000
11:119019142:GTGG:G	acceptor_gain	1.0000
11:119019315:CTC:C	donor_gain	1.0000
11:119019318:G:GG	donor_gain	1.0000
11:119021757:CA:C	acceptor_loss	1.0000
11:119021758:A:AG	acceptor_gain	1.0000
11:119021758:A:AT	acceptor_loss	1.0000
11:119021758:AG:A	acceptor_gain	1.0000
11:119021758:AGG:A	acceptor_gain	1.0000
11:119021759:G:GG	acceptor_gain	1.0000
11:119021759:GG:G	acceptor_gain	1.0000
11:119021759:GGG:G	acceptor_gain	1.0000
11:119021886:GGT:G	donor_loss	1.0000
11:119021887:GTAA:G	donor_loss	1.0000
11:119021888:T:A	donor_loss	1.0000
11:119025073:CCCA:C	acceptor_gain	1.0000
11:119025074:CCA:C	acceptor_gain	1.0000
11:119025074:CCAC:C	acceptor_gain	1.0000
11:119025075:CA:C	acceptor_gain	1.0000
11:119025075:CAC:C	acceptor_gain	1.0000
11:119025077:C:CC	acceptor_gain	1.0000
11:119025186:CTTA:C	donor_loss	1.0000
11:119025187:TTAC:T	donor_loss	1.0000
11:119025188:TACC:T	donor_loss	1.0000
11:119025189:A:AC	donor_gain	1.0000
11:119025189:AC:A	donor_gain	1.0000

AlphaMissense

1414 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:119018832:G:C	G13R	1.000
11:119018832:G:T	G13C	1.000
11:119018833:G:A	G13D	1.000
11:119018833:G:T	G13V	1.000
11:119019293:T:A	L109H	1.000
11:119019293:T:C	L109P	1.000
11:119019299:T:C	L111P	1.000
11:119019302:C:A	A112D	1.000
11:119019305:C:A	S113Y	1.000
11:119019305:C:T	S113F	1.000
11:119019313:C:G	H116D	1.000
11:119020161:T:A	I121N	1.000
11:119020163:G:C	G122R	1.000
11:119020164:G:A	G122D	1.000
11:119020173:T:C	L125P	1.000
11:119020196:G:C	G133R	1.000
11:119020197:G:A	G133D	1.000
11:119020209:T:C	L137P	1.000
11:119020237:C:G	C146W	1.000
11:119020253:G:T	G152W	1.000
11:119021760:G:T	G152V	1.000
11:119021769:T:C	F155S	1.000
11:119021775:T:A	V157D	1.000
11:119021834:T:G	Y177D	1.000
11:119021847:C:A	A181D	1.000
11:119021850:T:A	L182H	1.000
11:119021850:T:C	L182P	1.000
11:119021852:A:G	K183E	1.000
11:119021854:G:C	K183N	1.000
11:119021854:G:T	K183N	1.000

dbSNP variants (sampled 300 via entrez): RS1000178354 (11:119021545 C>T), RS1000250463 (11:119021935 C>T), RS1000708180 (11:119019907 A>G), RS1000730956 (11:119017219 G>A,C,T), RS1000893817 (11:119024149 A>C,G), RS1001022384 (11:119018706 G>A,C,T), RS1001128485 (11:119024503 A>C), RS1001474460 (11:119018506 A>G), RS1001527529 (11:119017265 T>A,C), RS1001558402 (11:119017693 A>G), RS1002903568 (11:119021215 C>A,T), RS1003027653 (11:119016902 G>A,C), RS1003273212 (11:119018458 A>C,T), RS1004734559 (11:119021476 C>G), RS1004842040 (11:119017305 T>C)

Disease associations

OMIM: gene MIM:610971 | disease phenotypes: MIM:618741, MIM:617527

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy	Definitive	Autosomal recessive
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy	Definitive	AR

Mondo (3): neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (MONDO:0032894), neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (MONDO:0060502), syndromic intellectual disability (MONDO:0000508)

Orphanet (1): PLAA-associated neurodevelopmental disorder (Orphanet:521426)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000407	Sensorineural hearing impairment
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001285	Spastic tetraparesis
HP:0002187	Profound intellectual disability
HP:0002650	Scoliosis
HP:0003623	Neonatal onset
HP:0008872	Feeding difficulties in infancy
HP:0012444	Brain atrophy

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
clothianidin	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ketoconazole	decreases expression	1
Manganese	decreases expression, increases abundance	1
Phthalic Acids	increases methylation	1
Piroxicam	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Testosterone	decreases expression	1
Dronabinol	decreases expression	1
Thiram	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1

Cellosaurus cell lines

9 cell lines: 9 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_E6WR	MCRIi035-A	Induced pluripotent stem cell	Female
CVCL_E6WS	MCRIi035-B	Induced pluripotent stem cell	Female
CVCL_E6WT	MCRIi035-C	Induced pluripotent stem cell	Female
CVCL_E6WU	MCRIi036-A	Induced pluripotent stem cell	Male
CVCL_E6WV	MCRIi036-B	Induced pluripotent stem cell	Male
CVCL_E6WW	MCRIi036-C	Induced pluripotent stem cell	Male
CVCL_E6WX	MCRIi036-B-1	Induced pluripotent stem cell	Male
CVCL_E6WY	MCRIi035-B-1	Induced pluripotent stem cell	Female
CVCL_E6WZ	MCRIi035-B-2	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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