TBC1D23

Summary

TBC1D23 (TBC1 domain family member 23, HGNC:25622) is a protein-coding gene on chromosome 3q12.1-q12.2, encoding TBC1 domain family member 23 (Q9NUY8). Putative Rab GTPase-activating protein which plays a role in vesicular trafficking.

Involved in brain development; retrograde transport, endosome to Golgi; and vesicle tethering to Golgi. Located in WASH complex; cytoplasmic vesicle; and trans-Golgi network. Implicated in pontocerebellar hypoplasia type 11.

Source: NCBI Gene 55773 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pontocerebellar hypoplasia, type 11 (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 161 total — 9 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 42
• MANE Select transcript: NM_001199198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25622
Approved symbol	TBC1D23
Name	TBC1 domain family member 23
Location	3q12.1-q12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11046
Ensembl gene	ENSG00000036054
Ensembl biotype	protein_coding
OMIM	617687
Entrez	55773

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 20 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000344949, ENST00000394144, ENST00000471098, ENST00000471273, ENST00000475134, ENST00000484231, ENST00000485687, ENST00000486274, ENST00000496167, ENST00000860078, ENST00000860079, ENST00000860080, ENST00000860081, ENST00000860082, ENST00000860083, ENST00000935604, ENST00000935605, ENST00000935606, ENST00000963829, ENST00000963830, ENST00000963831, ENST00000963832, ENST00000963833, ENST00000963834

RefSeq mRNA: 2 — MANE Select: NM_001199198 NM_001199198, NM_018309

CCDS: CCDS2936, CCDS56265

Canonical transcript exons

ENST00000394144 — 19 exons

Exon	Start	End
ENSE00001517605	100311833	100311877
ENSE00001843704	100260992	100261071
ENSE00003470240	100302067	100302237
ENSE00003480286	100295302	100295348
ENSE00003498540	100296172	100296275
ENSE00003516166	100316099	100316187
ENSE00003523635	100319069	100319204
ENSE00003531125	100297923	100298045
ENSE00003534558	100281742	100281847
ENSE00003538232	100310403	100310542
ENSE00003562772	100279649	100279760
ENSE00003575924	100290578	100290701
ENSE00003587887	100299239	100299331
ENSE00003609550	100295087	100295211
ENSE00003636290	100320777	100320971
ENSE00003642532	100323587	100325238
ENSE00003642714	100304846	100304888
ENSE00003653540	100306437	100306543
ENSE00003689957	100283607	100283811

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 97.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.3951 / max 769.5700, expressed in 1808 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37598	28.6424	1805
37596	0.3810	156
37597	0.1899	60
37599	0.0933	30
37600	0.0748	21
37604	0.0137	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	97.37	silver quality
left ventricle myocardium	UBERON:0006566	97.16	silver quality
ileal mucosa	UBERON:0000331	96.44	gold quality
secondary oocyte	CL:0000655	95.56	gold quality
myocardium	UBERON:0002349	95.24	silver quality
upper arm skin	UBERON:0004263	95.03	gold quality
oocyte	CL:0000023	94.97	gold quality
bone marrow cell	CL:0002092	94.85	gold quality
deltoid	UBERON:0001476	94.56	gold quality
calcaneal tendon	UBERON:0003701	94.47	gold quality
jejunal mucosa	UBERON:0000399	94.36	gold quality
oviduct epithelium	UBERON:0004804	93.45	gold quality
tibialis anterior	UBERON:0001385	93.37	gold quality
vastus lateralis	UBERON:0001379	93.16	gold quality
epithelial cell of pancreas	CL:0000083	93.14	gold quality
quadriceps femoris	UBERON:0001377	93.07	gold quality
kidney epithelium	UBERON:0004819	92.96	silver quality
colonic epithelium	UBERON:0000397	92.74	gold quality
heart right ventricle	UBERON:0002080	92.57	gold quality
trabecular bone tissue	UBERON:0002483	92.57	gold quality
muscle tissue	UBERON:0002385	92.36	gold quality
skeletal muscle tissue	UBERON:0001134	92.31	gold quality
bone marrow	UBERON:0002371	92.12	gold quality
cartilage tissue	UBERON:0002418	92.04	gold quality
decidua	UBERON:0002450	91.52	gold quality
colonic mucosa	UBERON:0000317	91.28	gold quality
biceps brachii	UBERON:0001507	91.27	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.25	gold quality
jejunum	UBERON:0002115	91.23	gold quality
adrenal tissue	UBERON:0018303	91.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	783.11
E-ANND-3	yes	5.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting TBC1D23, 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-340-5P	100.00	72.50	4437
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942

Literature-anchored findings (GeneRIF, showing 7)

• Homozygous Mutations in TBC1D23 gene are associated with Non-degenerative Form of Pontocerebellar Hypoplasia. (PMID:28823706)
• Homozygous Truncating Variants in TBC1D23 gene are associated with Pontocerebellar Hypoplasia and Alter Cortical Development. (PMID:28823707)
• The Rab GAP domain of TBC1D23 binds to a conserved motif at the tip of golgin-245 and golgin-97 at the trans-Golgi, while the C terminus binds to the WASH complex on endosome-derived vesicles. Thus, TBC1D23 is a specificity determinant that links the vesicle to the target membrane during endosome-to-Golgi trafficking. (PMID:29084197)
• Mutation of key residues of TBC1D23 or FAM21 selectively disrupts the endosomal vesicular trafficking toward the Trans-Golgi Network. (PMID:31624125)
• rhodanese domain packs against the TBC domain and forms part of the platform to interact with golgin-97/245 (PMID:32453802)
• TBC1 domain family member 23 interacts with Ras-related protein Rab-11A to promote poor prognosis of non-small-cell lung cancer via beta1-integrin. (PMID:34363324)
• FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH. (PMID:37903274)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d23	ENSDARG00000044357
mus_musculus	Tbc1d23	ENSMUSG00000022749
rattus_norvegicus	Tbc1d23	ENSRNOG00000001642
drosophila_melanogaster	TBC1D23	FBGN0031304
caenorhabditis_elegans		WBGENE00008974

Protein

Protein identifiers

TBC1 domain family member 23 — Q9NUY8 (reviewed: Q9NUY8)

Alternative names: HCV non-structural protein 4A-transactivated protein 1

All UniProt accessions (4): C9IZ32, C9JAM5, E9PGE5, Q9NUY8

UniProt curated annotations — full annotation on UniProt →

Function. Putative Rab GTPase-activating protein which plays a role in vesicular trafficking. Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, including GOLGA1 and GOLGA4, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles. Together with WDR11 complex facilitates the golgin-mediated capture of vesicles generated using AP-1. Plays a role in brain development, including in cortical neuron positioning. May also be important for neurite outgrowth, possibly through its involvement in membrane trafficking and cargo delivery, 2 processes that are essential for axonal and dendritic growth. May act as a general inhibitor of innate immunity signaling, strongly inhibiting multiple TLR and dectin/CLEC7A-signaling pathways. Does not alter initial activation events, but instead affects maintenance of inflammatory gene expression several hours after bacterial lipopolysaccharide (LPS) challenge.

Subunit / interactions. Directly interacts with GOLGA1 and GOLGA4. Interacts with FAM91A1, C17ORF75 and WDR11; the interaction recruits TBC1D23 to AP-1-derived vesicles. Directly interacts with WASHC1 and WASHC2A/FAM21A. Interacts with FKBP15.

Subcellular location. Golgi apparatus. trans-Golgi network. Cytoplasmic vesicle.

Tissue specificity. Isoform 1: Widely expressed, including in fetal adult brain (corpus callosum, pons, cerebellum), spinal cord, heart, skeletal muscle, thymus and bone marrow, and at lower levels in spleen. Hardly detected in liver, kidney, colon and testis. Isoform 2: Expressed at high levels in liver, kidney, colon and testis. Hardly detected in tissues expressing high levels of isoform 1. Expressed at low levels in spleen.

Disease relevance. Pontocerebellar hypoplasia 11 (PCH11) [MIM:617695] A non-degenerative form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH11 features include severely delayed psychomotor development with intellectual disability and poor speech, microcephaly, dysmorphic features, and pontocerebellar hypoplasia. PCH11 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NUY8-1	1	yes
Q9NUY8-2	2

RefSeq proteins (2): NP_001186127, NP_060779 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR001763	Rhodanese-like_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR036873	Rhodanese-like_dom_sf	Homologous_superfamily
IPR039755	TBC1D23	Family
IPR045799	TBC1D23_C	Domain

Pfam: PF00566, PF00581, PF19430

UniProt features (74 total): helix 31, strand 19, modified residue 7, turn 4, region of interest 4, sequence conflict 3, domain 2, chain 1, splice variant 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6JM5	X-RAY DIFFRACTION	1.6
8QQF	X-RAY DIFFRACTION	2.19
6JL7	X-RAY DIFFRACTION	2.5
8JJ9	X-RAY DIFFRACTION	2.51

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUY8-F1	80.69	0.56

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): 474, 507, 514, 520, 571, 300, 469

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 213 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_VESICLE_LOCALIZATION, GOBP_VESICLE_TARGETING, GOBP_NEUROGENESIS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_TRANS_GOLGI_NETWORK, ATF1_Q6, E4F1_Q6, GOBP_HEAD_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_RETROGRADE_TRANSPORT_ENDOSOME_TO_GOLGI, MARIADASON_RESPONSE_TO_BUTYRATE_CURCUMIN_SULINDAC_TSA_8, GOBP_ORGANELLE_LOCALIZATION, GOBP_EMBRYONIC_ORGAN_DEVELOPMENT

GO Biological Process (8): brain development (GO:0007420), vesicle-mediated transport (GO:0016192), neuron projection development (GO:0031175), retrograde transport, endosome to Golgi (GO:0042147), obsolete vesicle tethering to Golgi (GO:0099041), embryonic brain development (GO:1990403), nervous system development (GO:0007399), animal organ development (GO:0048513)

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

GO Cellular Component (5): Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), cytosol (GO:0005829), cytoplasmic vesicle (GO:0031410), WASH complex (GO:0071203)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
central nervous system development	1
animal organ development	1
head development	1
transport	1
cellular process	1
neuron development	1
plasma membrane bounded cell projection organization	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
embryonic organ development	1
system development	1
anatomical structure development	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
cellular anatomical structure	1
intracellular vesicle	1
protein-containing complex	1

Protein interactions and networks

STRING

886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D23	C17orf75	Q9HAS0	830
TBC1D23	FAM91A1	Q658Y4	792
TBC1D23	TBC1D20	Q96BZ9	708
TBC1D23	GOLGA4	Q13439	704
TBC1D23	GOLGA1	Q92805	703
TBC1D23	CDC16	Q13042	646
TBC1D23	WASHC2A	Q641Q2	634
TBC1D23	TBC1D25	Q3MII6	544
TBC1D23	GCC1	Q96CN9	543
TBC1D23	TBC1D14	Q9P2M4	540
TBC1D23	TBC1D16	Q8TBP0	535
TBC1D23	FKBP15	Q5T1M5	534
TBC1D23	RAB11A	P24410	531
TBC1D23	TBCK	Q8TEA7	522
TBC1D23	TBC1D12	O60347	509

IntAct

61 interactions, top by confidence:

A	B	Type	Score
HS2ST1	SLC7A1	psi-mi:“MI:0914”(association)	0.730
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
ARRDC1	NEDD4	psi-mi:“MI:0914”(association)	0.640
FAM174A	GAK	psi-mi:“MI:0914”(association)	0.640
TBC1D23	WDR62	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560
TBC1D23	CAGE1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP4-12	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560
TBC1D23	SSBP3	psi-mi:“MI:0915”(physical association)	0.560
	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560
WDR62	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560
TBC1D23	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
TBC1D23	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
CAGE1	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560
SSBP3	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560
ATOSB	TBC1D23	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (76): TBC1D23 (Two-hybrid), KRTAP4-12 (Two-hybrid), WDR62 (Two-hybrid), CAGE1 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), TBC1D23 (Affinity Capture-MS), TBC1D23 (Affinity Capture-MS), TBC1D23 (Affinity Capture-MS), TBC1D23 (Affinity Capture-MS), GLRX3 (Co-fractionation), OSGEP (Co-fractionation), TBC1D23 (Co-fractionation), STK11 (Two-hybrid)

ESM2 similar proteins: A0A0G2JTR4, A1A4S6, A2AWA9, A4FUD6, A4II46, A6H6A9, A6QNS3, A6QQZ7, O60890, P09851, P0CAX5, P20936, P23727, P26450, P27986, P50904, Q08DP6, Q12979, Q5R372, Q5R5M3, Q5R685, Q5R6F2, Q5R8I6, Q5RCC1, Q5RCW6, Q5SSL4, Q5T2T1, Q5U2Y3, Q5ZJ17, Q5ZLX4, Q5ZMW5, Q62696, Q63787, Q6Y5D8, Q6ZQ82, Q7YQL5, Q7YQL6, Q8AVG0, Q8BPU7, Q8K0F1

Diamond homologs: Q5F415, Q5R8I6, Q6NRC7, Q7SXV1, Q8K0F1, Q9NUY8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
Golgi Associated Vesicle Biogenesis	5	29.5×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	6	14.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	4
Uncertain significance	98
Likely benign	11
Benign	18

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1323676	NM_001199198.3(TBC1D23):c.1092+2T>A	Pathogenic
2503049	NM_001199198.3(TBC1D23):c.1018del (p.Val340fs)	Pathogenic
397553	NM_001199198.3(TBC1D23):c.1475_1476del (p.Val492fs)	Pathogenic
397554	NM_001199198.3(TBC1D23):c.1526delinsAA (p.Ile509fs)	Pathogenic
397555	NM_001199198.3(TBC1D23):c.1687+2T>G	Pathogenic
4293118	NM_001199198.3(TBC1D23):c.743_744del (p.Gln248fs)	Pathogenic
440764	NM_001199198.3(TBC1D23):c.1687+1G>A	Pathogenic
4845334	NM_001199198.3(TBC1D23):c.667C>T (p.Gln223Ter)	Pathogenic
930943	NM_001199198.3(TBC1D23):c.1687+1G>C	Pathogenic
1323675	NM_001199198.3(TBC1D23):c.630del (p.Thr211fs)	Likely pathogenic
3901557	NM_001199198.3(TBC1D23):c.603dup (p.Gly202fs)	Likely pathogenic
4057202	NM_001199198.3(TBC1D23):c.1250del (p.Ala417fs)	Likely pathogenic
440763	NM_001199198.3(TBC1D23):c.1687+2T>A	Likely pathogenic

SpliceAI

2913 predictions. Top by Δscore:

Variant	Effect	Δscore
3:100261067:GGCTG:G	donor_gain	1.0000
3:100261068:GCTG:G	donor_gain	1.0000
3:100261068:GCTGG:G	donor_gain	1.0000
3:100261070:TG:T	donor_gain	1.0000
3:100261071:GG:G	donor_gain	1.0000
3:100261072:G:GG	donor_gain	1.0000
3:100261072:GTGA:G	donor_loss	1.0000
3:100261073:T:A	donor_loss	1.0000
3:100279647:A:AG	acceptor_gain	1.0000
3:100279648:G:GG	acceptor_gain	1.0000
3:100281741:GATT:G	acceptor_gain	1.0000
3:100283605:A:AG	acceptor_gain	1.0000
3:100283606:G:GG	acceptor_gain	1.0000
3:100283794:GAA:G	donor_gain	1.0000
3:100283796:A:AG	donor_gain	1.0000
3:100283796:A:G	donor_gain	1.0000
3:100290711:TGA:T	donor_gain	1.0000
3:100290712:GAA:G	donor_gain	1.0000
3:100290713:A:T	donor_gain	1.0000
3:100290713:AAA:A	donor_gain	1.0000
3:100290716:G:GG	donor_gain	1.0000
3:100295300:A:AG	acceptor_gain	1.0000
3:100295301:G:GG	acceptor_gain	1.0000
3:100295301:GA:G	acceptor_gain	1.0000
3:100295301:GAGA:G	acceptor_gain	1.0000
3:100295301:GAGAA:G	acceptor_gain	1.0000
3:100295349:G:A	donor_loss	1.0000
3:100295349:G:GG	donor_gain	1.0000
3:100295350:TA:T	donor_loss	1.0000
3:100295351:AAG:A	donor_loss	1.0000

AlphaMissense

4642 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:100290630:T:G	Y177D	1.000
3:100297997:T:G	C317W	1.000
3:100299261:T:A	V341E	1.000
3:100299263:G:C	D342H	1.000
3:100299263:G:T	D342Y	1.000
3:100299264:A:C	D342A	1.000
3:100299264:A:G	D342G	1.000
3:100299264:A:T	D342V	1.000
3:100299265:T:A	D342E	1.000
3:100299265:T:G	D342E	1.000
3:100299266:T:C	C343R	1.000
3:100299267:G:A	C343Y	1.000
3:100299268:C:G	C343W	1.000
3:100299269:C:A	R344S	1.000
3:100299269:C:G	R344G	1.000
3:100299270:G:C	R344P	1.000
3:100299284:T:G	Y349D	1.000
3:100299296:C:G	H353D	1.000
3:100299308:G:C	A357P	1.000
3:100299309:C:A	A357D	1.000
3:100299311:T:C	F358L	1.000
3:100299313:C:A	F358L	1.000
3:100299313:C:G	F358L	1.000
3:100299314:C:G	H359D	1.000
3:100299318:T:C	L360S	1.000
3:100299330:T:C	L364P	1.000
3:100302068:T:C	M365T	1.000
3:100302071:T:C	L366P	1.000
3:100302088:T:C	F372L	1.000
3:100302089:T:C	F372S	1.000

dbSNP variants (sampled 300 via entrez): RS1000019694 (3:100306423 T>A), RS1000020430 (3:100262506 C>T), RS1000033394 (3:100299850 A>G), RS1000085353 (3:100300200 C>T), RS1000094761 (3:100318141 T>G), RS1000140859 (3:100323349 C>G,T), RS1000162792 (3:100280849 C>G,T), RS1000215514 (3:100268948 T>C,G), RS1000300597 (3:100293428 T>A), RS1000342596 (3:100286959 C>A,T), RS1000393476 (3:100303701 T>A), RS1000435652 (3:100287104 C>T), RS1000474369 (3:100321957 A>C,T), RS1000496589 (3:100277504 A>G), RS1000497723 (3:100311122 C>G,T)

Disease associations

OMIM: gene MIM:617687 | disease phenotypes: MIM:617695, MIM:607596

GenCC curated gene-disease

Disease	Classification	Inheritance
pontocerebellar hypoplasia, type 11	Definitive	Autosomal recessive

Mondo (2): pontocerebellar hypoplasia, type 11 (MONDO:0054669), pontocerebellar hypoplasia (MONDO:0020135)

Orphanet (2): Pontocerebellar hypoplasia type 11 (Orphanet:611247), Non-syndromic pontocerebellar hypoplasia (Orphanet:98523)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000486	Strabismus
HP:0000540	Hypermetropia
HP:0000565	Esotropia
HP:0000589	Coloboma
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0000817	Reduced eye contact
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001274	Agenesis of corpus callosum
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001321	Cerebellar hypoplasia
HP:0001762	Talipes equinovarus
HP:0001763	Pes planus
HP:0002015	Dysphagia
HP:0002023	Anal atresia
HP:0002070	Limb ataxia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002136	Broad-based gait
HP:0002205	Recurrent respiratory infections

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001524_6	Visceral adipose tissue/subcutaneous adipose tissue ratio	7.000000e-06
GCST002115_7	Axial length	5.000000e-11
GCST010002_434	Refractive error	5.000000e-25

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0005318	axial length measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C580383	Pontocerebellar Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Tunicamycin	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, increases methylation	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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