TRAPPC12

Summary

TRAPPC12 (trafficking protein particle complex subunit 12, HGNC:24284) is a protein-coding gene on chromosome 2p25.3, encoding Trafficking protein particle complex subunit 12 (Q8WVT3). Component of the TRAPP complex, which is involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.

Involved in several processes, including endoplasmic reticulum to Golgi vesicle-mediated transport; positive regulation of protein localization to kinetochore; and regulation of kinetochore assembly. Located in several cellular components, including endoplasmic reticulum-Golgi intermediate compartment; kinetochore; and perinuclear region of cytoplasm. Part of TRAPP complex.

Source: NCBI Gene 51112 — RefSeq curated summary.

At a glance

• Gene–disease (curated): early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 376 total — 12 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 43
• MANE Select transcript: NM_016030

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24284
Approved symbol	TRAPPC12
Name	trafficking protein particle complex subunit 12
Location	2p25.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-87, TTC-15
Ensembl gene	ENSG00000171853
Ensembl biotype	protein_coding
OMIM	614139
Entrez	51112

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 20 protein_coding, 7 retained_intron, 5 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000324266, ENST00000382110, ENST00000411973, ENST00000415624, ENST00000416918, ENST00000417243, ENST00000433382, ENST00000437733, ENST00000441099, ENST00000441983, ENST00000452495, ENST00000457845, ENST00000461577, ENST00000462983, ENST00000469147, ENST00000469400, ENST00000473348, ENST00000479897, ENST00000479955, ENST00000482645, ENST00000489032, ENST00000493792, ENST00000497597, ENST00000858082, ENST00000858083, ENST00000858084, ENST00000858085, ENST00000858086, ENST00000858087, ENST00000858088, ENST00000858089, ENST00000935225, ENST00000935226, ENST00000935227, ENST00000964174, ENST00000964175

RefSeq mRNA: 2 — MANE Select: NM_016030 NM_001321102, NM_016030

CCDS: CCDS1652

Canonical transcript exons

ENST00000324266 — 12 exons

Exon	Start	End
ENSE00001145941	3401777	3401893
ENSE00001328043	3387620	3388670
ENSE00001919066	3379694	3379876
ENSE00003467928	3460263	3460336
ENSE00003553124	3443779	3443891
ENSE00003566391	3457621	3457693
ENSE00003594462	3421881	3421994
ENSE00003610095	3424525	3424663
ENSE00003626211	3477695	3477795
ENSE00003661640	3479219	3479565
ENSE00003669324	3478846	3478933
ENSE00003684906	3465597	3465695

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 99.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.5168 / max 288.7617, expressed in 1819 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18614	23.3587	1816
18615	4.6048	1736
18616	3.5694	1674
18617	0.4874	232
18619	0.2880	122
18622	0.0676	12
18627	0.0550	24
18623	0.0265	4
18620	0.0193	4
18625	0.0156	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.22	gold quality
right testis	UBERON:0004534	99.20	gold quality
testis	UBERON:0000473	98.07	gold quality
pituitary gland	UBERON:0000007	98.03	gold quality
right lobe of thyroid gland	UBERON:0001119	97.95	gold quality
adenohypophysis	UBERON:0002196	97.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.89	gold quality
tibial nerve	UBERON:0001323	97.88	gold quality
thyroid gland	UBERON:0002046	97.86	gold quality
left lobe of thyroid gland	UBERON:0001120	97.85	gold quality
apex of heart	UBERON:0002098	97.79	gold quality
cerebellar hemisphere	UBERON:0002245	97.77	gold quality
skin of abdomen	UBERON:0001416	97.70	gold quality
cerebellar cortex	UBERON:0002129	97.62	gold quality
right uterine tube	UBERON:0001302	97.60	gold quality
cerebellum	UBERON:0002037	97.60	gold quality
zone of skin	UBERON:0000014	97.59	gold quality
skin of leg	UBERON:0001511	97.53	gold quality
right ovary	UBERON:0002118	97.52	gold quality
left ovary	UBERON:0002119	97.43	gold quality
endocervix	UBERON:0000458	97.41	gold quality
lower esophagus mucosa	UBERON:0035834	97.37	gold quality
body of uterus	UBERON:0009853	97.24	gold quality
right frontal lobe	UBERON:0002810	97.22	gold quality
hypothalamus	UBERON:0001898	97.16	gold quality
ovary	UBERON:0000992	97.15	gold quality
right atrium auricular region	UBERON:0006631	97.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.04	gold quality
putamen	UBERON:0001874	97.00	gold quality
primary visual cortex	UBERON:0002436	96.99	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.43
E-MTAB-6075	no	287.17
E-CURD-112	no	2.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting TRAPPC12, 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-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4433A-3P	97.75	62.82	1435

Literature-anchored findings (GeneRIF, showing 2)

• TRAPPC12, but not TRAPPC8, bound to Sec13/Sec31A tetramer but each Sec protein alone could not interact with TRAPPC12. (PMID:28240221)
• The authors report that variants in TRAPPC12 result in progressive childhood encephalopathy. Fibroblasts derived from three affected individuals showed a fragmented Golgi that could be rescued by expression of wild-type TRAPPC12. (PMID:28777934)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	trappc12	ENSDARG00000060101
mus_musculus	Trappc12	ENSMUSG00000020628
rattus_norvegicus	Trappc12	ENSRNOG00000009039
drosophila_melanogaster	CG11396	FBGN0037022
caenorhabditis_elegans		WBGENE00016614

Protein

Protein identifiers

Trafficking protein particle complex subunit 12 — Q8WVT3 (reviewed: Q8WVT3)

Alternative names: Tetratricopeptide repeat protein 15, Trafficking of membranes and mitosis

All UniProt accessions (10): Q8WVT3, F8WCB4, H0Y550, H7C0K3, H7C0T3, H7C185, H7C1E5, H7C1M4, H7C2F7, H7C373

UniProt curated annotations — full annotation on UniProt →

Function. Component of the TRAPP complex, which is involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage. Also plays a role in chromosome congression, kinetochore assembly and stability and controls the recruitment of CENPE to the kinetochores.

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 CENPE.

Subcellular location. Endoplasmic reticulum-Golgi intermediate compartment. Nucleus.

Post-translational modifications. Phosphorylated as the cells enter mitosis but is dephosphorylated at or before the onset of anaphase. The phosphorylated form recruits CENPE to kinetochores more efficiently than the non-phosphorylated form.

Disease relevance. Encephalopathy, progressive, early-onset, with brain atrophy and spasticity (PEBAS) [MIM:617669] An autosomal recessive, progressive encephalopathy characterized by central nervous system atrophy and dysfunction, spasticity, microcephaly, global developmental delay, and hearing loss. The disease is caused by variants affecting the gene represented in this entry. Cells display a fragmented Golgi apparatus.

RefSeq proteins (2): NP_001308031, NP_057114* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat

Pfam: PF13174, PF14559

UniProt features (17 total): repeat 4, sequence variant 3, sequence conflict 3, modified residue 2, region of interest 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVT3-F1	68.52	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 (2): 184, 109

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 265 (showing top): GOBP_CHROMOSOME_ORGANIZATION, chr2p25, TGCGCANK_UNKNOWN, GOBP_VESICLE_LOCALIZATION, GOBP_VESICLE_ORGANIZATION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_VESICLE_TARGETING, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME_CENTROMERIC_REGION, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY

GO Biological Process (8): endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi organization (GO:0007030), COPII vesicle coat assembly (GO:0048208), metaphase chromosome alignment (GO:0051310), regulation of kinetochore assembly (GO:0090234), obsolete vesicle tethering (GO:0099022), positive regulation of protein localization to kinetochore (GO:1905342), vesicle-mediated transport (GO:0016192)

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

GO Cellular Component (10): kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum-Golgi intermediate compartment (GO:0005793), Golgi apparatus (GO:0005794), cytosol (GO:0005829), TRAPP complex (GO:0030008), TRAPPIII protein complex (GO:1990072), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
cellular anatomical structure	4
intracellular membrane-bounded organelle	3
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
organelle organization	1
endomembrane system organization	1
vesicle coat assembly	1
protein-containing complex assembly	1
COPII-coated vesicle budding	1
chromosome localization	1
nuclear chromosome segregation	1
regulation of chromosome organization	1
regulation of protein-containing complex assembly	1
kinetochore assembly	1
regulation of organelle assembly	1
protein localization to kinetochore	1
positive regulation of protein localization	1
regulation of protein localization to kinetochore	1
transport	1
cellular process	1
binding	1
condensed chromosome, centromeric region	1
intracellular membraneless organelle	1
supramolecular complex	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
vesicle tethering complex	1
intracellular protein-containing complex	1
Golgi apparatus	1
TRAPP complex	1

Protein interactions and networks

STRING

672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRAPPC12	TRAPPC11	Q7Z392	984
TRAPPC12	TRAPPC8	Q9Y2L5	970
TRAPPC12	TRAPPC13	A5PLN9	955
TRAPPC12	TRAPPC4	Q9Y296	868
TRAPPC12	TRAPPC2	P0DI81	866
TRAPPC12	TRAPPC2L	Q9UL33	859
TRAPPC12	TRAPPC3	O43617	832
TRAPPC12	TRAPPC10	P48553	824
TRAPPC12	TRAPPC6B	Q86SZ2	809
TRAPPC12	TRAPPC9	Q96Q05	777
TRAPPC12	TRAPPC1	Q9Y5R8	768
TRAPPC12	TRAPPC5	Q8IUR0	766
TRAPPC12	TRAPPC6A	O75865	727
TRAPPC12	TRAPPC3L	Q5T215	719
TRAPPC12	EIPR1	Q53HC9	612

IntAct

55 interactions, top by confidence:

A	B	Type	Score
RSKR	TRAPPC12	psi-mi:“MI:0915”(physical association)	0.560
BMAL1	TRAPPC12	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC12	LIN7B	psi-mi:“MI:0915”(physical association)	0.560
HNRNPA2B1	TRAPPC12	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC12	RSKR	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC2L	TRAPPC13	psi-mi:“MI:0914”(association)	0.560
TRAPPC12	TRAPPC3	psi-mi:“MI:0914”(association)	0.530
TRAPPC1	TRAPPC13	psi-mi:“MI:0914”(association)	0.530
BET1L	TRAPPC12	psi-mi:“MI:0915”(physical association)	0.400
Trappc11	TRAPPC3	psi-mi:“MI:0914”(association)	0.350
Trappc8	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TRAPPC5	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TBC1D14		psi-mi:“MI:0914”(association)	0.350
TRAPPC1	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TRAPPC13	UBB	psi-mi:“MI:0914”(association)	0.350
TECPR1	PLOD3	psi-mi:“MI:0914”(association)	0.350
TRAPPC11	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
TRAPPC2	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
trappc2_trappc2b_human	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
CMBL	TRAPPC13	psi-mi:“MI:0914”(association)	0.350

BioGRID (154): TRAPPC12 (Two-hybrid), TRAPPC12 (Affinity Capture-MS), TRAPPC12 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS), CEP55 (Affinity Capture-MS), TRAPPC11 (Affinity Capture-MS), TRAPPC8 (Affinity Capture-MS), TRAPPC6B (Affinity Capture-MS), TRAPPC1 (Affinity Capture-MS), TRAPPC6A (Affinity Capture-MS), AMY1C (Affinity Capture-MS), TRAPPC3 (Affinity Capture-MS), TRAPPC5 (Affinity Capture-MS), EDRF1 (Affinity Capture-MS), TRAPPC2L (Affinity Capture-MS)

ESM2 similar proteins: A0A5F9C6I2, A0JPN6, A4IIZ9, A5WUL3, D3ZUQ0, D3ZXK7, F1R7R1, O43513, O57595, O75916, P51593, P53349, P68943, P85299, Q08DY8, Q13233, Q15528, Q17QG3, Q2F7Z4, Q2TBN4, Q2YDF2, Q3B8I4, Q3T123, Q5BJ48, Q5E9K2, Q5EBL4, Q5FVG6, Q5RKN3, Q5XIX8, Q5XPI3, Q5XPI4, Q62276, Q62739, Q6GQ95, Q6QB00, Q6ZUS6, Q7TMY8, Q7ZV35, Q800L3, Q80U62

Diamond homologs: Q8K2L8, Q8WVT3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TRAPPC12	“form complex”	“TRAPP III complex, TRAPPC2 variant”	binding
TRAPPC12	“form complex”	“TRAPP III complex, TRAPPC2B variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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	7	36.2×	2e-07
COPII-mediated vesicle transport	5	34.0×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle tethering	7	257.0×	4e-14
COPII vesicle coat assembly	6	156.0×	7e-11
endoplasmic reticulum to Golgi vesicle-mediated transport	8	40.3×	6e-10

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	14
Uncertain significance	203
Likely benign	84
Benign	29

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1679937	NM_016030.6(TRAPPC12):c.1776+16C>A	Pathogenic
1710180	NM_016030.6(TRAPPC12):c.1677+5G>A	Pathogenic
2008693	NM_016030.6(TRAPPC12):c.1127C>G (p.Ser376Ter)	Pathogenic
2340793	NM_016030.6(TRAPPC12):c.678dup (p.Phe227fs)	Pathogenic
2424126	NC_000002.11:g.(?3391395)(3428454_?)del	Pathogenic
2467995	NM_016030.6(TRAPPC12):c.445C>T (p.Gln149Ter)	Pathogenic
3069113	NM_016030.6(TRAPPC12):c.979C>T (p.Gln327Ter)	Pathogenic
3254923	NM_016030.6(TRAPPC12):c.1822A>T (p.Lys608Ter)	Pathogenic
3254924	NM_016030.6(TRAPPC12):c.94del (p.Gln32fs)	Pathogenic
4278095	NM_016030.6(TRAPPC12):c.1966-1G>A	Pathogenic
430822	NM_016030.6(TRAPPC12):c.360dup (p.Glu121fs)	Pathogenic
688945	GRCh37/hg19 2p25.3(chr2:3385474-3418641)x1	Pathogenic
1027666	NM_016030.6(TRAPPC12):c.361G>T (p.Glu121Ter)	Likely pathogenic
1029569	NM_016030.6(TRAPPC12):c.1604-1G>T	Likely pathogenic
2584443	NM_016030.6(TRAPPC12):c.56del (p.Pro19fs)	Likely pathogenic
2585067	NM_016030.6(TRAPPC12):c.1678-2A>G	Likely pathogenic
2585068	NM_016030.6(TRAPPC12):c.195_196del (p.Met66fs)	Likely pathogenic
2636361	NM_016030.6(TRAPPC12):c.850C>T (p.Gln284Ter)	Likely pathogenic
2692483	NM_016030.6(TRAPPC12):c.1164+1G>T	Likely pathogenic
3065808	NM_016030.6(TRAPPC12):c.249_268del (p.Asp84fs)	Likely pathogenic
3255601	NM_016030.6(TRAPPC12):c.722del (p.Gly241fs)	Likely pathogenic
4291807	NM_016030.6(TRAPPC12):c.1966-2A>G	Likely pathogenic
438738	NM_016030.6(TRAPPC12):c.145del (p.Glu49fs)	Likely pathogenic
4823032	NM_016030.6(TRAPPC12):c.1847_1854del (p.Leu616fs)	Likely pathogenic
808661	NM_016030.6(TRAPPC12):c.1965+4A>G	Likely pathogenic
985642	NM_016030.6(TRAPPC12):c.1530+1G>A	Likely pathogenic

SpliceAI

3747 predictions. Top by Δscore:

Variant	Effect	Δscore
2:3387618:AG:A	acceptor_gain	1.0000
2:3387619:GG:G	acceptor_gain	1.0000
2:3401766:A:AG	acceptor_gain	1.0000
2:3401767:T:G	acceptor_gain	1.0000
2:3401772:CCCA:C	acceptor_loss	1.0000
2:3401773:CCAG:C	acceptor_loss	1.0000
2:3401774:CAGGG:C	acceptor_gain	1.0000
2:3401775:A:AG	acceptor_gain	1.0000
2:3401775:AG:A	acceptor_gain	1.0000
2:3401775:AGG:A	acceptor_gain	1.0000
2:3401775:AGGGA:A	acceptor_gain	1.0000
2:3401776:G:GG	acceptor_gain	1.0000
2:3401776:GG:G	acceptor_gain	1.0000
2:3401776:GGG:G	acceptor_gain	1.0000
2:3401776:GGGA:G	acceptor_gain	1.0000
2:3401776:GGGAG:G	acceptor_gain	1.0000
2:3401889:TAATC:T	donor_gain	1.0000
2:3401890:AATC:A	donor_gain	1.0000
2:3401891:ATC:A	donor_gain	1.0000
2:3401892:TC:T	donor_gain	1.0000
2:3401892:TCGTA:T	donor_loss	1.0000
2:3401894:G:GG	donor_gain	1.0000
2:3401894:G:T	donor_loss	1.0000
2:3401895:T:G	donor_loss	1.0000
2:3421686:A:AG	acceptor_gain	1.0000
2:3421693:C:G	acceptor_gain	1.0000
2:3421877:GCA:G	acceptor_loss	1.0000
2:3421878:CAG:C	acceptor_gain	1.0000
2:3421879:A:AC	acceptor_loss	1.0000
2:3421879:A:AG	acceptor_gain	1.0000

AlphaMissense

4828 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:3424547:T:C	L434P	1.000
2:3465691:T:C	L591P	1.000
2:3479343:T:C	L697P	1.000
2:3479361:T:C	L703P	1.000
2:3388551:T:A	W310R	0.999
2:3388551:T:C	W310R	0.999
2:3401787:T:A	V353D	0.999
2:3401836:A:C	R369S	0.999
2:3401836:A:T	R369S	0.999
2:3401889:T:C	L387P	0.999
2:3421912:T:C	L399P	0.999
2:3421924:T:C	L403P	0.999
2:3424528:T:A	W428R	0.999
2:3424528:T:C	W428R	0.999
2:3424538:G:C	R431T	0.999
2:3424538:G:T	R431M	0.999
2:3424547:T:G	L434R	0.999
2:3443863:T:C	L501P	0.999
2:3460277:T:A	W540R	0.999
2:3460277:T:C	W540R	0.999
2:3465610:C:A	A564D	0.999
2:3465679:G:A	G587D	0.999
2:3465682:G:C	R588P	0.999
2:3477699:G:A	G594E	0.999
2:3477699:G:T	G594V	0.999
2:3477714:C:A	A599D	0.999
2:3478848:C:A	A627E	0.999
2:3478860:T:C	L631P	0.999
2:3479227:C:A	N658K	0.999
2:3479227:C:G	N658K	0.999

dbSNP variants (sampled 300 via entrez): RS1000000388 (2:3408563 G>T), RS1000032831 (2:3447623 C>T), RS1000065401 (2:3433288 G>A), RS1000074793 (2:3457179 C>A,G,T), RS1000081205 (2:3402453 G>A,T), RS1000107869 (2:3382519 A>G), RS1000116741 (2:3396703 C>T), RS1000172997 (2:3422519 T>G), RS1000237311 (2:3440509 G>A), RS1000286288 (2:3461151 A>G), RS1000319072 (2:3407344 C>CA), RS1000329876 (2:3446545 C>T), RS1000336670 (2:3390975 A>C,G), RS1000375921 (2:3464285 G>T), RS1000408979 (2:3428130 G>A,T)

Disease associations

OMIM: gene MIM:614139 | disease phenotypes: MIM:617669

GenCC curated gene-disease

Disease	Classification	Inheritance
early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome	Strong	Autosomal recessive

Mondo (1): early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome (MONDO:0044696)

Orphanet (1): Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome (Orphanet:500144)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000648	Optic atrophy
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001274	Agenesis of corpus callosum
HP:0001298	Encephalopathy
HP:0001321	Cerebellar hypoplasia
HP:0001332	Dystonia
HP:0001336	Myoclonus
HP:0001338	Partial agenesis of the corpus callosum
HP:0001561	Polyhydramnios
HP:0001605	Vocal cord paralysis
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002119	Ventriculomegaly
HP:0002120	Cerebral cortical atrophy
HP:0002376	Developmental regression
HP:0002490	Increased CSF lactate
HP:0002521	Hypsarrhythmia
HP:0002650	Scoliosis
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003676	Progressive
HP:0005484	Secondary microcephaly
HP:0007096	Hypoplasia of the optic tract
HP:0008936	Axial hypotonia
HP:0009879	Simplified gyral pattern

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002337_63	Amyotrophic lateral sclerosis (sporadic)	3.000000e-07
GCST002594_20	Neurofibrillary tangles	2.000000e-07
GCST002594_5	Neurofibrillary tangles	3.000000e-06
GCST005514_3	Neuritic plaques or neurofibrillary tangles or cerebral amyloid angiopathy (pleiotropy)	6.000000e-07
GCST010146_20	Serum immune biomarker levels	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006797	neurofibrillary tangles measurement
EFO:0006798	neuritic plaque measurement
EFO:0004872	inflammatory biomarker measurement
EFO:0010596	monocyte chemotactic protein 1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
FR900359	decreases phosphorylation	1
bisphenol F	decreases methylation	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases methylation, affects cotreatment, increases methylation	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
1-hydroxypyrene	affects cotreatment, decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	decreases methylation, increases abundance	1
Caffeine	affects phosphorylation	1
Ivermectin	decreases expression	1
Lead	affects expression, affects splicing	1
Methapyrilene	increases methylation	1
Nickel	decreases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Valproic Acid	increases methylation	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Metals, Heavy	affects cotreatment, decreases methylation, increases abundance	1
Copper Sulfate	affects expression	1

Clinical trials (associated diseases)

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