TBC1D20

Summary

TBC1D20 (TBC1 domain family member 20, HGNC:16133) is a protein-coding gene on chromosome 20p13, encoding TBC1 domain family member 20 (Q96BZ9). GTPase-activating protein (GAP) specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude.

This gene encodes a protein that belongs to a family of GTPase activator proteins of Rab-like small GTPases. The encoded protein and its cognate GTPase, Rab1, bind the nonstructural protein 5A (NS5A) of the hepatitis C virus (HCV) to mediate viral replication. Depletion of this protein inhibits replication of the virus and HCV infection. Mutations in this gene are associated with Warburg micro syndrome 4. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 128637 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Warburg micro syndrome 4 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 167 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 76
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_144628

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16133
Approved symbol	TBC1D20
Name	TBC1 domain family member 20
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	dJ852M4.2
Ensembl gene	ENSG00000125875
Ensembl biotype	protein_coding
OMIM	611663
Entrez	128637

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 15 protein_coding, 14 nonsense_mediated_decay, 9 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000354200, ENST00000461188, ENST00000461304, ENST00000494633, ENST00000679451, ENST00000679741, ENST00000679895, ENST00000679944, ENST00000679953, ENST00000679973, ENST00000680050, ENST00000680088, ENST00000680106, ENST00000680284, ENST00000680491, ENST00000680515, ENST00000680521, ENST00000680792, ENST00000680815, ENST00000680911, ENST00000680990, ENST00000681129, ENST00000681193, ENST00000681389, ENST00000681414, ENST00000681441, ENST00000681539, ENST00000681551, ENST00000681636, ENST00000681742, ENST00000681777, ENST00000893231, ENST00000893232, ENST00000893233, ENST00000932929, ENST00000951241, ENST00000951242, ENST00000951243, ENST00000951244

RefSeq mRNA: 1 — MANE Select: NM_144628 NM_144628

CCDS: CCDS13002

Canonical transcript exons

ENST00000354200 — 8 exons

Exon	Start	End
ENSE00000858546	441857	442043
ENSE00001211770	441588	441689
ENSE00001884816	462336	462533
ENSE00003469273	439108	439295
ENSE00003512823	440248	440389
ENSE00003526255	447889	448074
ENSE00003569323	445050	445130
ENSE00003585358	435480	438841

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 93.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.1567 / max 163.6229, expressed in 1818 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185969	25.1567	1818

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	93.51	gold quality
medial globus pallidus	UBERON:0002477	91.97	gold quality
parotid gland	UBERON:0001831	91.96	gold quality
stromal cell of endometrium	CL:0002255	91.75	gold quality
lower esophagus mucosa	UBERON:0035834	91.38	gold quality
upper arm skin	UBERON:0004263	91.03	gold quality
right lung	UBERON:0002167	90.39	gold quality
smooth muscle tissue	UBERON:0001135	90.38	gold quality
endothelial cell	CL:0000115	90.32	gold quality
left adrenal gland	UBERON:0001234	90.04	gold quality
oviduct epithelium	UBERON:0004804	89.97	gold quality
right adrenal gland cortex	UBERON:0035827	89.97	gold quality
globus pallidus	UBERON:0001875	89.96	gold quality
right adrenal gland	UBERON:0001233	89.81	gold quality
cerebellar hemisphere	UBERON:0002245	89.79	gold quality
islet of Langerhans	UBERON:0000006	89.76	gold quality
cerebellar cortex	UBERON:0002129	89.72	gold quality
left adrenal gland cortex	UBERON:0035825	89.71	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.68	gold quality
cerebellum	UBERON:0002037	89.53	gold quality
adrenal cortex	UBERON:0001235	89.43	gold quality
tibialis anterior	UBERON:0001385	89.37	gold quality
cartilage tissue	UBERON:0002418	89.36	gold quality
skin of leg	UBERON:0001511	89.29	gold quality
lower esophagus	UBERON:0013473	89.28	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.27	gold quality
adrenal gland	UBERON:0002369	89.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.00	gold quality
endocervix	UBERON:0000458	88.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting TBC1D20, 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-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-545-3P	99.95	70.74	2783
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-7978	99.86	66.90	856

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 8)

• TBC1D20 was found to be the first known GAP for Rab1, which is implicated in the regulation of anterograde traffic between the endoplasmic reticulum and the Golgi complex (PMID:17901050)
• These findings add TBC1D20 to the network of host factors regulating HIV replication cycle. (PMID:22260459)
• The NS5A interaction with TBC1D20 and Rab1 is essential for the viral life cycle. (PMID:22491470)
• The detailed molecular reaction mechanism of a complex between human Rab and RabGAP at the highest possible spatiotemporal resolution and in atomic detail, is described. (PMID:23236136)
• Loss-of-function mutations in TBC1D20 cause cataracts and male infertility in blind sterile mice and Warburg micro syndrome in humans. (PMID:24239381)
• Warburg Micro syndrome is caused by TBC1D20 deficiency. (PMID:26063829)
• Martsolf syndrome with novel mutation in the TBC1D20 gene in a family from Iran. (PMID:32162791)
• Micro and Martsolf syndromes in 34 new patients: Refining the phenotypic spectrum and further molecular insights. (PMID:32740904)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tbc1d20	ENSDARG00000032298
mus_musculus	Tbc1d20	ENSMUSG00000027465
rattus_norvegicus	Tbc1d20	ENSRNOG00000005766
drosophila_melanogaster	CG17883	FBGN0040005
caenorhabditis_elegans		WBGENE00013196

Protein

Protein identifiers

TBC1 domain family member 20 — Q96BZ9 (reviewed: Q96BZ9)

All UniProt accessions (9): Q96BZ9, A0A7P0T865, A0A7P0T876, A0A7P0T8Q3, A0A7P0T991, A0A7P0T9R2, A0A7P0TAF7, A0A7P0TBA8, A0A7P0TBI8

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein (GAP) specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude. Also shows GAP activity for RAB18 GTPase. Promotes RAB18 dissociation from the endoplasmic reticulum (ER) membrane into the cytosol, probably through stimulating RAB18 GTP-hydrolysis. Involved in maintaining endoplasmic reticulum structure.

Subunit / interactions. (Microbial infection) Directly interacts with the N-terminal amphipathic helix of hepatitis C virus (HCV) NS5A.

Subcellular location. Membrane.

Disease relevance. Warburg micro syndrome 4 (WARBM4) [MIM:615663] A form of Warburg micro syndrome, a rare syndrome characterized by microcephaly, microphthalmia, microcornia, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab’s ‘switch 2’ glutamine and insert in Rab’s active site.

Miscellaneous. May be due to intron retention.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96BZ9-1	1	yes
Q96BZ9-2	2
Q96BZ9-3	3

RefSeq proteins (1): NP_653229* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR045913	TBC20/Gyp8-like	Family

Pfam: PF00566

UniProt features (42 total): helix 20, splice variant 4, turn 4, strand 3, transmembrane region 2, mutagenesis site 2, site 2, chain 1, sequence variant 1, sequence conflict 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4HL4	X-RAY DIFFRACTION	2.2
4HLQ	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BZ9-F1	82.15	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 105 (arginine finger); 144 (glutamine finger)

Mutagenesis-validated functional residues (2):

Position	Phenotype
105	1000-fold decrease in gap activity.
144	1000-fold decrease in gap activity.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-8854214	TBC/RABGAPs
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-5653656	Vesicle-mediated transport
R-HSA-597592	Post-translational protein modification
R-HSA-9007101	Rab regulation of trafficking
R-HSA-948021	Transport to the Golgi and subsequent modification

MSigDB gene sets: 343 (showing top): GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_VESICLE_ORGANIZATION, GOBP_REGULATION_BY_VIRUS_OF_VIRAL_PROTEIN_LEVELS_IN_HOST_CELL, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, CHX10_01, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (18): acrosome assembly (GO:0001675), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi organization (GO:0007030), virion assembly (GO:0019068), lipid droplet organization (GO:0034389), positive regulation of GTPase activity (GO:0043547), host-mediated activation of viral genome replication (GO:0044829), positive regulation by virus of viral protein levels in host cell (GO:0046726), lens fiber cell morphogenesis (GO:0070309), seminiferous tubule development (GO:0072520), COPII-coated vesicle cargo loading (GO:0090110), positive regulation of ER to Golgi vesicle-mediated transport (GO:1902953), lens development in camera-type eye (GO:0002088), spermatogenesis (GO:0007283), male gonad development (GO:0008584), vesicle organization (GO:0016050), vesicle-mediated transport (GO:0016192), camera-type eye development (GO:0043010)

GO Molecular Function (3): GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (6): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), nuclear membrane (GO:0031965), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Membrane Trafficking	2
ER to Golgi Anterograde Transport	1
Rab regulation of trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism of proteins	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
organelle organization	3
developmental process involved in reproduction	2
cytoplasm	2
intracellular transport	2
GTPase activity	2
bounding membrane of organelle	2
organelle membrane	2
spermatid development	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
intercellular transport	1
Golgi vesicle transport	1
endomembrane system organization	1
viral process	1
viral life cycle	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
host-mediated activation of viral process	1
host-mediated perturbation of viral genome replication	1
regulation by virus of viral protein levels in host cell	1
positive regulation of viral process	1
cell morphogenesis	1
lens morphogenesis in camera-type eye	1
lens fiber cell development	1
male gonad development	1
tube development	1
reproductive structure development	1
vesicle cargo loading	1
COPII-coated vesicle budding	1
endoplasmic reticulum to Golgi vesicle-mediated transport	1
positive regulation of intracellular transport	1
regulation of ER to Golgi vesicle-mediated transport	1
camera-type eye development	1
anatomical structure development	1
male gamete generation	1
gonad development	1
development of primary male sexual characteristics	1
transport	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TBC1D20	RAB1B	Q9H0U4	916
TBC1D20	USP6	P35125	896
TBC1D20	CDC16	Q13042	876
TBC1D20	RAB3GAP2	Q9H2M9	815
TBC1D20	RAB18	Q9NP72	791
TBC1D20	RAB3GAP1	Q15042	766
TBC1D20	TBC1D23	Q9NUY8	708
TBC1D20	CANX	P27824	642
TBC1D20	TBC1D5	Q92609	615
TBC1D20	RAB1A	P11476	597
TBC1D20	TBC1D21	Q8IYX1	594
TBC1D20	TBC1D9B	Q66K14	594
TBC1D20	RAB2A	P08886	591
TBC1D20	TBC1D8B	Q0IIM8	591
TBC1D20	TBC1D22A	Q8WUA7	586

IntAct

36 interactions, top by confidence:

A	B	Type	Score
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
TBC1D20		psi-mi:“MI:0403”(colocalization)	0.700
TBC1D20		psi-mi:“MI:0915”(physical association)	0.700
	TBC1D20	psi-mi:“MI:0915”(physical association)	0.700
	TBC1D20	psi-mi:“MI:0403”(colocalization)	0.700
	RAB8A	psi-mi:“MI:0915”(physical association)	0.680
AQP6	TBC1D20	psi-mi:“MI:0915”(physical association)	0.560
EBP	TBC1D20	psi-mi:“MI:0915”(physical association)	0.560
APOC4	TBC1D20	psi-mi:“MI:0915”(physical association)	0.560
TBC1D20	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
	TBC1D20	psi-mi:“MI:0915”(physical association)	0.400
HLCS	TBC1D20	psi-mi:“MI:0915”(physical association)	0.400
TBC1D20	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
	NBAS	psi-mi:“MI:0914”(association)	0.350
TPST2	NDC80	psi-mi:“MI:0914”(association)	0.350
MTCH2	IPO5	psi-mi:“MI:0914”(association)	0.350
CD40	IPO5	psi-mi:“MI:0914”(association)	0.350
SLC30A4	ESYT2	psi-mi:“MI:0914”(association)	0.350
TBC1D20	AQP6	psi-mi:“MI:0915”(physical association)	0.000
TBC1D20	EBP	psi-mi:“MI:0915”(physical association)	0.000
TBC1D20	APOC4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): TBC1D20 (Affinity Capture-MS), TBC1D20 (Affinity Capture-MS), TBC1D20 (Affinity Capture-MS), TBC1D20 (Proximity Label-MS), TBC1D20 (Two-hybrid), TMEM14B (Two-hybrid), EBP (Two-hybrid), APOC2 (Two-hybrid), APOC4 (Two-hybrid), TBC1D20 (Proximity Label-MS), TBC1D20 (Proximity Label-MS), TBC1D20 (Proximity Label-MS), TBC1D20 (Proximity Label-MS), TBC1D20 (Proximity Label-MS), TBC1D20 (Proximity Label-MS)

ESM2 similar proteins: A2WY50, A2XV81, A2YFN7, B8AJT9, B9N1F9, E0CSI1, F1N9S8, O00178, O76031, O81770, O82730, P11497, P37271, P37272, P49085, Q0DWQ1, Q0J035, Q0JBZ6, Q10D38, Q13085, Q28559, Q2QLV9, Q2T9Q1, Q304A0, Q4R4M1, Q5NCE8, Q5R7N3, Q5SWU9, Q5Z5B7, Q61143, Q653T6, Q67UQ7, Q69QJ7, Q6EI12, Q8L4S2, Q8L5Y9, Q8N4J0, Q93ZD7, Q96BZ9, Q9D9I4

Diamond homologs: O94661, Q2T9Q1, Q96BZ9, Q9D9I4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	68
Likely benign	68
Benign	17

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
100774	NM_144628.4(TBC1D20):c.199C>T (p.Arg67Ter)	Pathogenic
100775	NM_144628.4(TBC1D20):c.292C>T (p.Gln98Ter)	Pathogenic
100776	NM_144628.4(TBC1D20):c.352_353del (p.Gln118fs)	Pathogenic
100777	NM_144628.4(TBC1D20):c.672G>A (p.Trp224Ter)	Pathogenic
100778	NM_144628.4(TBC1D20):c.(70+1_71-1)(*3107+1?)del	Pathogenic
3906950	NM_144628.4(TBC1D20):c.474C>T (p.Gly158=)	Pathogenic
2241578	NM_144628.4(TBC1D20):c.627-1G>C	Likely pathogenic

SpliceAI

2547 predictions. Top by Δscore:

Variant	Effect	Δscore
20:428490:GGCC:G	acceptor_gain	1.0000
20:428587:AAGGT:A	donor_loss	1.0000
20:428588:AGGTG:A	donor_loss	1.0000
20:428589:GGT:G	donor_loss	1.0000
20:428591:T:G	donor_loss	1.0000
20:438837:CCGTC:C	acceptor_gain	1.0000
20:438838:CGTC:C	acceptor_gain	1.0000
20:438838:CGTCC:C	acceptor_gain	1.0000
20:438839:GTC:G	acceptor_gain	1.0000
20:438840:TC:T	acceptor_gain	1.0000
20:438841:CC:C	acceptor_gain	1.0000
20:438842:C:CC	acceptor_gain	1.0000
20:438843:T:C	acceptor_loss	1.0000
20:439103:CTCA:C	donor_loss	1.0000
20:439104:TCA:T	donor_loss	1.0000
20:439105:CACC:C	donor_loss	1.0000
20:439106:A:C	donor_loss	1.0000
20:439107:CCT:C	donor_gain	1.0000
20:439292:CAAT:C	acceptor_gain	1.0000
20:439294:ATCT:A	acceptor_loss	1.0000
20:439295:TCTG:T	acceptor_loss	1.0000
20:439296:C:CC	acceptor_gain	1.0000
20:440247:CCA:C	donor_gain	1.0000
20:440385:CAGCA:C	acceptor_gain	1.0000
20:440388:CA:C	acceptor_gain	1.0000
20:440390:C:CC	acceptor_gain	1.0000
20:441587:CCT:C	donor_gain	1.0000
20:441930:C:CT	donor_gain	1.0000
20:442044:C:CA	acceptor_loss	1.0000
20:442045:T:A	acceptor_loss	1.0000

AlphaMissense

2641 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:440297:T:A	D240V	1.000
20:440358:A:G	W220R	1.000
20:440358:A:T	W220R	1.000
20:447937:A:G	W70R	1.000
20:447937:A:T	W70R	1.000
20:439181:C:G	A295P	0.999
20:439228:A:G	L279S	0.999
20:439238:G:C	H276D	0.999
20:440285:G:T	A244D	0.999
20:440297:T:G	D240A	0.999
20:440298:C:G	D240H	0.999
20:440335:A:C	H227Q	0.999
20:440335:A:T	H227Q	0.999
20:440340:C:A	G226W	0.999
20:440346:A:G	W224R	0.999
20:440346:A:T	W224R	0.999
20:440359:G:C	S219R	0.999
20:440359:G:T	S219R	0.999
20:440361:T:G	S219R	0.999
20:440366:G:T	A217D	0.999
20:440368:A:C	F216L	0.999
20:440368:A:T	F216L	0.999
20:440370:A:G	F216L	0.999
20:441948:C:G	G145R	0.999
20:441949:C:A	Q144H	0.999
20:441949:C:G	Q144H	0.999
20:441957:A:G	Y142H	0.999
20:442004:A:G	L126P	0.999
20:445073:C:G	R105P	0.999
20:445081:G:C	D102E	0.999

dbSNP variants (sampled 300 via entrez): RS1000018898 (20:435649 G>A), RS1000146797 (20:440509 C>T), RS1000159155 (20:458873 A>G,T), RS1000273323 (20:458493 A>G), RS1000434245 (20:461565 T>C), RS1000637485 (20:449735 T>C), RS1000759338 (20:459671 G>A), RS1000769549 (20:464362 A>T), RS1000866642 (20:443664 G>A,C), RS1000946730 (20:455864 G>A), RS1000963658 (20:437337 G>T), RS1000990509 (20:447544 G>A), RS1001194294 (20:443382 C>A), RS1001272742 (20:441745 G>C), RS1001330451 (20:449452 A>C,G)

Disease associations

OMIM: gene MIM:611663 | disease phenotypes: MIM:615663

GenCC curated gene-disease

Disease	Classification	Inheritance
Warburg micro syndrome 4	Definitive	Autosomal recessive
Warburg micro syndrome	Supportive	Autosomal recessive

Mondo (2): Warburg micro syndrome 4 (MONDO:0014296), Warburg micro syndrome (MONDO:0016649)

Orphanet (1): Micro syndrome (Orphanet:2510)

HPO phenotypes

76 total (30 of 76 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000046	Small scrotum
HP:0000054	Micropenis
HP:0000060	Clitoral hypoplasia
HP:0000064	Hypoplastic labia minora
HP:0000126	Hydronephrosis
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000294	Low anterior hairline
HP:0000322	Short philtrum
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000400	Macrotia
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000480	Retinal coloboma
HP:0000482	Microcornea
HP:0000490	Deeply set eye
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000568	Microphthalmia
HP:0000648	Optic atrophy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003542_11	Night sleep phenotypes	8.000000e-08
GCST003542_24	Night sleep phenotypes	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Caffeine	increases phosphorylation	1
Formaldehyde	decreases expression	1
Thiram	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford