TUBGCP6

Summary

TUBGCP6 (tubulin gamma complex component 6, HGNC:18127) is a protein-coding gene on chromosome 22q13.33, encoding Gamma-tubulin complex component 6 (Q96RT7). Component of the gamma-tubulin ring complex (gTuRC) which mediates microtubule nucleation. It is a common-essential gene (DepMap: required in 90.9% of cancer cell lines).

The protein encoded by this gene is part of a large multisubunit complex required for microtubule nucleation at the centrosome.

Source: NCBI Gene 85378 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly and chorioretinopathy 1 (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 2,318 total — 94 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 37
• Cancer dependency (DepMap): dependent in 90.9% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_020461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18127
Approved symbol	TUBGCP6
Name	tubulin gamma complex component 6
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	GCP6, KIAA1669, DJ402G11.6
Ensembl gene	ENSG00000128159
Ensembl biotype	protein_coding
OMIM	610053
Entrez	85378

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000248846, ENST00000425018, ENST00000434349, ENST00000439308, ENST00000473946, ENST00000489511, ENST00000491449, ENST00000498611, ENST00000883330, ENST00000949023, ENST00000949024, ENST00000949025, ENST00000949026, ENST00000949027, ENST00000949028

RefSeq mRNA: 1 — MANE Select: NM_020461 NM_020461

CCDS: CCDS14087

Canonical transcript exons

ENST00000248846 — 25 exons

Exon	Start	End
ENSE00001032668	50220251	50221874
ENSE00001892806	50243719	50245023
ENSE00003458501	50219288	50219456
ENSE00003465578	50217918	50218117
ENSE00003483482	50233316	50233526
ENSE00003511675	50222454	50222592
ENSE00003533380	50218488	50218620
ENSE00003534249	50227907	50228028
ENSE00003539630	50226287	50226378
ENSE00003543579	50219068	50219209
ENSE00003555041	50225794	50225943
ENSE00003613060	50218703	50218897
ENSE00003623580	50229404	50229577
ENSE00003625248	50217694	50217827
ENSE00003627964	50219957	50220015
ENSE00003632863	50224141	50224256
ENSE00003649182	50224332	50224420
ENSE00003651228	50224511	50224592
ENSE00003660023	50222028	50222102
ENSE00003662673	50218189	50218402
ENSE00003663253	50226733	50226842
ENSE00003663885	50219644	50219791
ENSE00003666447	50226050	50226189
ENSE00003676978	50240204	50240367
ENSE00003689280	50226999	50227077

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 96.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9822 / max 229.1759, expressed in 1807 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194708	9.6969	1776
194709	3.4971	1424
194710	0.7882	499

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.74	gold quality
cerebellar hemisphere	UBERON:0002245	96.28	gold quality
cerebellar cortex	UBERON:0002129	96.06	gold quality
adenohypophysis	UBERON:0002196	95.47	gold quality
right lobe of thyroid gland	UBERON:0001119	94.76	gold quality
left lobe of thyroid gland	UBERON:0001120	94.26	gold quality
body of pancreas	UBERON:0001150	94.16	gold quality
granulocyte	CL:0000094	94.00	gold quality
cerebellum	UBERON:0002037	93.87	gold quality
sural nerve	UBERON:0015488	93.81	gold quality
right frontal lobe	UBERON:0002810	93.73	gold quality
right ovary	UBERON:0002118	93.35	gold quality
apex of heart	UBERON:0002098	93.26	gold quality
left ovary	UBERON:0002119	93.17	gold quality
right uterine tube	UBERON:0001302	93.10	gold quality
pituitary gland	UBERON:0000007	93.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.89	gold quality
endocervix	UBERON:0000458	92.81	gold quality
metanephros cortex	UBERON:0010533	92.76	gold quality
body of stomach	UBERON:0001161	92.58	gold quality
thyroid gland	UBERON:0002046	92.51	gold quality
body of uterus	UBERON:0009853	92.45	gold quality
spleen	UBERON:0002106	92.41	gold quality
right adrenal gland	UBERON:0001233	92.17	gold quality
left adrenal gland cortex	UBERON:0035825	92.04	gold quality
right adrenal gland cortex	UBERON:0035827	91.97	gold quality
minor salivary gland	UBERON:0001830	91.91	gold quality
left uterine tube	UBERON:0001303	91.82	gold quality
left adrenal gland	UBERON:0001234	91.76	gold quality
upper lobe of left lung	UBERON:0008952	91.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.51

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 90.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• GCP6 participates in the attachment of microtubule-organizing centers to intermediate filaments in epithelial cells and is among the factors that determine the peculiar architecture of microtubules in polarized epithelia. (PMID:17182859)
• Study identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS. (PMID:22279524)
• The data suggest that GCP6 is a target of Plk4 in centriole biogenesis. (PMID:22302995)
• a family of 2 children with learning difficulties, abnormal peripheral retinal vasculogenesis, and rod-cone dystrophy were investigated. They were found to have bi-allelic splicing variants in TUBGCP6. (PMID:31077665)
• Genotype Phenotype Correlation and Variability in Microcephaly Associated With Chorioretinopathy or Familial Exudative Vitreoretinopathy. (PMID:33137195)
• SF3B14 is involved in the centrosome regulation through splicing of TUBGCP6 pre-mRNA. (PMID:34954520)
• Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review. (PMID:37031378)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	appl2	ENSDARG00000100151
mus_musculus	Tubgcp6	ENSMUSG00000051786
rattus_norvegicus	Tubgcp6	ENSRNOG00000006028
drosophila_melanogaster	Grip163	FBGN0026432

Paralogs (4): TUBGCP3 (ENSG00000126216), TUBGCP2 (ENSG00000130640), TUBGCP4 (ENSG00000137822), TUBGCP5 (ENSG00000275835)

Protein

Protein identifiers

Gamma-tubulin complex component 6 — Q96RT7 (reviewed: Q96RT7)

All UniProt accessions (4): Q96RT7, E7EQL8, H7C2H5, H7C358

UniProt curated annotations — full annotation on UniProt →

Function. Component of the gamma-tubulin ring complex (gTuRC) which mediates microtubule nucleation. The gTuRC regulates the minus-end nucleation of alpha-beta tubulin heterodimers that grow into microtubule protafilaments, a critical step in centrosome duplication and spindle formation.

Subunit / interactions. Component of the gamma-tubulin ring complex (gTuRC) consisting of TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6 and gamma-tubulin TUBG1 or TUBG2. TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6 assemble in a 5:5:2:1:1 stoichiometry; each is associated with a gamma-tubulin, thereby arranging 14 gamma-tubulins in a helical manner. Gamma-tubulin at the first position is blocked by TUBGCP3 at the last position, allowing 13 protafilaments to grow into a microtubule. The gTuRC (via TUBGCP3 and TUBGCP6) interacts with ACTB and MZT1; the interactions form a luminal bridge that stabilizes the initial structure during complex assembly. The gTuRC (via TUBGCP2) interacts with MZT2A/MZT2B and CDK5RAP2 (via CM1 motif); the interactions play a role in gTuRC activation.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Disease relevance. Microcephaly and chorioretinopathy, autosomal recessive, 1 (MCCRP1) [MIM:251270] A syndrome characterized by microcephaly, cognitive impairment, underdeveloped retina and choroid, and epilepsy in some patients. The more anterior parts of the retina, near the periphery and pars plana, have a grayish hue and diminutive vasculature similar to retinopathy of prematurity. Visual impairment becomes evident during the first year of life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TUBGCP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96RT7-1	1	yes
Q96RT7-2	2
Q96RT7-3	3

RefSeq proteins (1): NP_065194* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007259	GCP	Family
IPR040457	GCP_C	Domain
IPR041470	GCP_N	Domain
IPR042241	GCP_C_sf	Homologous_superfamily
IPR045818	GCP6_N	Domain

Pfam: PF04130, PF17681, PF19340

UniProt features (34 total): repeat 9, sequence variant 8, region of interest 5, helix 5, compositionally biased region 3, splice variant 3, chain 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
6M33	X-RAY DIFFRACTION	3.29
8RX1	ELECTRON MICROSCOPY	3.57
6X0U	ELECTRON MICROSCOPY	3.6
8Q62	ELECTRON MICROSCOPY	3.72
7AS4	ELECTRON MICROSCOPY	4.13
6V6S	ELECTRON MICROSCOPY	4.3
6V6C	ELECTRON MICROSCOPY	4.5
9H9P	ELECTRON MICROSCOPY	4.5
9QVN	ELECTRON MICROSCOPY	4.7
7QJ0	ELECTRON MICROSCOPY	5.32
9QVM	ELECTRON MICROSCOPY	6.8
7QJ1	ELECTRON MICROSCOPY	7
8VRD	ELECTRON MICROSCOPY	7
7QJD	ELECTRON MICROSCOPY	7.1
7QJ3	ELECTRON MICROSCOPY	7.6
8VRJ	ELECTRON MICROSCOPY	7.7
7QJ6	ELECTRON MICROSCOPY	7.8
7QJE	ELECTRON MICROSCOPY	7.8
7QJ9	ELECTRON MICROSCOPY	8.1
8VRK	ELECTRON MICROSCOPY	8.5
7QJ2	ELECTRON MICROSCOPY	8.6
7QJ5	ELECTRON MICROSCOPY	8.7
7QJ7	ELECTRON MICROSCOPY	8.7
7QJ8	ELECTRON MICROSCOPY	8.7
7QJ4	ELECTRON MICROSCOPY	9
7QJA	ELECTRON MICROSCOPY	9.2
7QJB	ELECTRON MICROSCOPY	9.2
7QJC	ELECTRON MICROSCOPY	16.1
9I8G	ELECTRON MICROSCOPY	22.4
9I8H	ELECTRON MICROSCOPY	23.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RT7-F1	60.53	0.12

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes

MSigDB gene sets: 163 (showing top): GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_MICROTUBULE_NUCLEATION, GGGTGGRR_PAX4_03, GOCC_MICROTUBULE_ORGANIZING_CENTER, NIKOLSKY_BREAST_CANCER_22Q13_AMPLICON, GOCC_CENTROSOME, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE, GOBP_SPINDLE_ASSEMBLY, GOBP_MICROTUBULE_POLYMERIZATION, GOCC_SPINDLE, GOBP_MEIOTIC_CELL_CYCLE, chr22q13, GOCC_GAMMA_TUBULIN_COMPLEX, GOBP_CELL_CYCLE_PROCESS

GO Biological Process (6): mitotic cell cycle (GO:0000278), microtubule nucleation (GO:0007020), cytoplasmic microtubule organization (GO:0031122), spindle assembly (GO:0051225), meiotic cell cycle (GO:0051321), microtubule cytoskeleton organization (GO:0000226)

GO Molecular Function (3): microtubule binding (GO:0008017), gamma-tubulin binding (GO:0043015), microtubule minus-end binding (GO:0051011)

GO Cellular Component (11): spindle pole (GO:0000922), gamma-tubulin complex (GO:0000930), gamma-tubulin ring complex (GO:0000931), centrosome (GO:0005813), cytosol (GO:0005829), microtubule (GO:0005874), membrane (GO:0016020), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), microtubule cytoskeleton (GO:0015630)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Centrosome maturation	1
Mitotic Prometaphase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell cycle	2
microtubule cytoskeleton organization	2
tubulin binding	2
microtubule organizing center	2
microtubule cytoskeleton	2
mitotic nuclear division	1
microtubule polymerization	1
supramolecular fiber organization	1
spindle organization	1
chromosome segregation	1
membraneless organelle assembly	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
cytoskeleton organization	1
microtubule-based process	1
microtubule binding	1
spindle	1
protein-containing complex	1
gamma-tubulin complex	1
gamma-tubulin small complex	1
centriole	1
cytoplasm	1
polymeric cytoskeletal fiber	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cytoskeleton	1

Protein interactions and networks

STRING

1690 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUBGCP6	TUBGCP4	Q9UGJ1	991
TUBGCP6	TUBGCP5	Q96RT8	987
TUBGCP6	TUBGCP3	Q96CW5	966
TUBGCP6	TUBG1	P23258	946
TUBGCP6	MZT1	Q08AG7	869
TUBGCP6	TUBGCP2	Q9BSJ2	866
TUBGCP6	NEDD1	Q8NHV4	853
TUBGCP6	TUBG2	Q9NRH3	683
TUBGCP6	NME7	Q9Y5B8	639
TUBGCP6	PLK4	O00444	610
TUBGCP6	MZT2A	Q6P582	608
TUBGCP6	CDK5RAP2	Q96SN8	598
TUBGCP6	CKAP5	Q14008	543
TUBGCP6	GRIP2	Q9C0E4	542
TUBGCP6	SDR39U1	Q9NRG7	538

IntAct

77 interactions, top by confidence:

A	B	Type	Score
TUBGCP5	TUBG1	psi-mi:“MI:0914”(association)	0.840
MZT2B	TUBG1	psi-mi:“MI:0914”(association)	0.770
Mzt2	TUBG1	psi-mi:“MI:0914”(association)	0.560
KCTD14	ACSF3	psi-mi:“MI:0914”(association)	0.560
PRICKLE3	SIAH2	psi-mi:“MI:0914”(association)	0.530
MZT1	PCNT	psi-mi:“MI:0914”(association)	0.530
TUBG2	TCP1	psi-mi:“MI:0914”(association)	0.530
TXNDC12	TUBG1	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	TUBG1	psi-mi:“MI:0914”(association)	0.530
TUBG2	TXNDC9	psi-mi:“MI:0914”(association)	0.530
NEDD1	CEP290	psi-mi:“MI:0914”(association)	0.480
Tubgcp3		psi-mi:“MI:0915”(physical association)	0.400
Mzt2		psi-mi:“MI:0915”(physical association)	0.400
Mzt1		psi-mi:“MI:0915”(physical association)	0.400
Tubg1		psi-mi:“MI:0915”(physical association)	0.400
Tubgcp6		psi-mi:“MI:0915”(physical association)	0.400
Tubg1	BDP1	psi-mi:“MI:0914”(association)	0.350
Fam83d	SEC16A	psi-mi:“MI:0914”(association)	0.350
Tubg1	RTL8C	psi-mi:“MI:0914”(association)	0.350
SCAF11	MRPL3	psi-mi:“MI:0914”(association)	0.350
Tubgcp4	CEP128	psi-mi:“MI:0914”(association)	0.350
Tubgcp5	TUBG1	psi-mi:“MI:0914”(association)	0.350
TUBGCP2	WWP2	psi-mi:“MI:0914”(association)	0.350
TUBGCP4	PZP	psi-mi:“MI:0914”(association)	0.350
TUBG1	DPM1	psi-mi:“MI:0914”(association)	0.350
Lgals3bp	CS	psi-mi:“MI:0914”(association)	0.350

BioGRID (108): TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-RNA), TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-MS), TUBG1 (Co-fractionation), TUBGCP6 (Co-fractionation), TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-MS), TUBGCP6 (Affinity Capture-MS)

ESM2 similar proteins: A1A4V9, A2A8U2, A4IFI1, A8E4X8, B0BMZ6, F1R7R1, G5E8P0, O75161, P12755, P59017, P59240, P85299, P97432, Q14DQ1, Q2HJA5, Q3B7M3, Q3U0L2, Q3ZBK7, Q3ZK22, Q53GS7, Q569K6, Q58DT5, Q5FVG6, Q5RAS2, Q5SNT2, Q5T7N3, Q5XI52, Q60698, Q6NZQ0, Q80U62, Q812A5, Q8C0R7, Q8C190, Q8CC12, Q8IWY9, Q8IYY4, Q8N9B5, Q8NFW9, Q8R1F1, Q8R322

Diamond homologs: G5E8P0, Q96RT7

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
TUBGCP6	“form complex”	“g-TuRC complex”	binding
PLK4	“up-regulates activity”	TUBGCP6	phosphorylation

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
Centrosome maturation	6	29.3×	4e-06
Recruitment of mitotic centrosome proteins and complexes	11	28.8×	2e-11
Recruitment of NuMA to mitotic centrosomes	11	24.6×	6e-11
Regulation of PLK1 Activity at G2/M Transition	7	17.1×	9e-06
Loss of Nlp from mitotic centrosomes	5	15.2×	4e-04
Loss of proteins required for interphase microtubule organization from the centrosome	5	15.2×	4e-04
Mitotic G2-G2/M phases	6	14.6×	1e-04
G2/M Transition	6	14.6×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
microtubule nucleation	7	52.0×	2e-08
cytoplasmic microtubule organization	5	20.5×	9e-04
mitotic cell cycle	6	9.6×	4e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	9	5.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2318 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	94
Likely pathogenic	37
Uncertain significance	1040
Likely benign	942
Benign	73

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070463	NM_020461.4(TUBGCP6):c.4067G>A (p.Trp1356Ter)	Pathogenic
1071616	NM_020461.4(TUBGCP6):c.3090_3091del (p.Gly1032fs)	Pathogenic
1071641	NM_020461.4(TUBGCP6):c.3784_3802del (p.Thr1262fs)	Pathogenic
1072414	NM_020461.4(TUBGCP6):c.4234C>T (p.Gln1412Ter)	Pathogenic
1072458	NM_020461.4(TUBGCP6):c.4175_4176del (p.Thr1392fs)	Pathogenic
1073518	NM_020461.4(TUBGCP6):c.3841dup (p.Ala1281fs)	Pathogenic
1073667	NM_020461.4(TUBGCP6):c.1900A>T (p.Lys634Ter)	Pathogenic
1074757	NM_020461.4(TUBGCP6):c.996dup (p.Leu333fs)	Pathogenic
1075129	NM_020461.4(TUBGCP6):c.1869del (p.Ile624fs)	Pathogenic
1075852	NM_020461.4(TUBGCP6):c.3392G>A (p.Trp1131Ter)	Pathogenic
1076117	NM_020461.4(TUBGCP6):c.3082C>T (p.Gln1028Ter)	Pathogenic
1361421	NM_020461.4(TUBGCP6):c.3525_3526del (p.Ser1176fs)	Pathogenic
1367488	NM_020461.4(TUBGCP6):c.3847_3848del (p.Ser1283fs)	Pathogenic
1374572	NM_020461.4(TUBGCP6):c.1314dup (p.Tyr439fs)	Pathogenic
1382361	NM_020461.4(TUBGCP6):c.2078C>G (p.Ser693Ter)	Pathogenic
1402469	NM_020461.4(TUBGCP6):c.1894del (p.Glu632fs)	Pathogenic
1424910	NM_020461.4(TUBGCP6):c.2503G>T (p.Glu835Ter)	Pathogenic
1427538	NM_020461.4(TUBGCP6):c.2382dup (p.Leu795fs)	Pathogenic
1428766	NM_020461.4(TUBGCP6):c.1320dup (p.Gln441fs)	Pathogenic
1433326	NM_020461.4(TUBGCP6):c.2484+1del	Pathogenic
1451832	NM_020461.4(TUBGCP6):c.4090_4091del (p.Ser1364fs)	Pathogenic
1452125	NM_020461.4(TUBGCP6):c.4165_4166del (p.Gln1389fs)	Pathogenic
1454258	NM_020461.4(TUBGCP6):c.4639C>T (p.Gln1547Ter)	Pathogenic
1454395	NM_020461.4(TUBGCP6):c.766G>T (p.Glu256Ter)	Pathogenic
1454771	NM_020461.4(TUBGCP6):c.112A>T (p.Lys38Ter)	Pathogenic
1456178	NM_020461.4(TUBGCP6):c.2939C>G (p.Ser980Ter)	Pathogenic
1456835	NM_020461.4(TUBGCP6):c.1690C>T (p.Arg564Ter)	Pathogenic
1457375	NM_020461.4(TUBGCP6):c.2064del (p.Ser688fs)	Pathogenic
1458600	NM_020461.4(TUBGCP6):c.2793del (p.Ser932fs)	Pathogenic
1458627	NM_020461.4(TUBGCP6):c.3887del (p.Ser1296fs)	Pathogenic

SpliceAI

4887 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50217823:CACCA:C	acceptor_gain	1.0000
22:50217825:CCA:C	acceptor_gain	1.0000
22:50217826:CA:C	acceptor_gain	1.0000
22:50217826:CAC:C	acceptor_gain	1.0000
22:50217828:C:CC	acceptor_gain	1.0000
22:50217914:TCAC:T	donor_loss	1.0000
22:50217915:CACCT:C	donor_loss	1.0000
22:50217916:A:C	donor_loss	1.0000
22:50218398:CAGGG:C	acceptor_gain	1.0000
22:50218399:AGGG:A	acceptor_gain	1.0000
22:50218400:GGG:G	acceptor_gain	1.0000
22:50218400:GGGC:G	acceptor_loss	1.0000
22:50218403:C:CA	acceptor_loss	1.0000
22:50218403:C:CC	acceptor_gain	1.0000
22:50218404:T:A	acceptor_loss	1.0000
22:50218407:C:CT	acceptor_gain	1.0000
22:50218408:G:T	acceptor_gain	1.0000
22:50218414:C:CT	acceptor_gain	1.0000
22:50218482:CCTCA:C	donor_loss	1.0000
22:50218483:CTCAC:C	donor_loss	1.0000
22:50218484:TCA:T	donor_loss	1.0000
22:50218485:CAC:C	donor_loss	1.0000
22:50218486:ACCTG:A	donor_loss	1.0000
22:50218487:C:CT	donor_loss	1.0000
22:50218514:T:TA	donor_gain	1.0000
22:50218619:ACCT:A	acceptor_loss	1.0000
22:50218621:C:G	acceptor_loss	1.0000
22:50218622:T:G	acceptor_loss	1.0000
22:50219070:T:A	donor_gain	1.0000
22:50219111:T:TA	donor_gain	1.0000

AlphaMissense

11834 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50217815:A:G	L1794P	0.999
22:50226365:A:G	W539R	0.999
22:50226365:A:T	W539R	0.999
22:50217776:A:G	L1807P	0.998
22:50217926:A:G	L1787P	0.998
22:50219090:A:G	L1535P	0.998
22:50226760:A:G	L525P	0.998
22:50217779:A:G	F1806S	0.997
22:50217788:A:G	L1803P	0.997
22:50218034:A:G	L1751P	0.997
22:50218339:A:C	M1673R	0.997
22:50224550:C:G	A676P	0.997
22:50226072:A:G	L604P	0.997
22:50226178:A:G	W569R	0.997
22:50226178:A:T	W569R	0.997
22:50226763:A:G	L524P	0.997
22:50217928:A:C	F1786L	0.996
22:50217928:A:T	F1786L	0.996
22:50217930:A:G	F1786L	0.996
22:50218310:A:C	Y1683D	0.996
22:50218614:A:G	W1610R	0.996
22:50218614:A:T	W1610R	0.996
22:50218839:A:G	L1562P	0.996
22:50219132:C:G	R1521P	0.996
22:50226324:G:C	F552L	0.996
22:50226324:G:T	F552L	0.996
22:50226325:A:G	F552S	0.996
22:50226326:A:G	F552L	0.996
22:50226363:C:A	W539C	0.996
22:50226363:C:G	W539C	0.996

dbSNP variants (sampled 300 via entrez): RS1000113726 (22:50218106 G>A), RS1000223681 (22:50244804 G>A), RS1000254492 (22:50217994 AC>A,ACC), RS1000302030 (22:50229146 T>C,G), RS1000471692 (22:50221320 A>G), RS1000556465 (22:50217487 C>G,T), RS1000596321 (22:50230354 C>A,G), RS1000713318 (22:50240937 C>A), RS1000764326 (22:50241099 T>C), RS1000780072 (22:50225510 G>A), RS1000806701 (22:50220302 T>A,C,G), RS1000824317 (22:50235890 A>C), RS1000881911 (22:50234972 C>A,T), RS1000889404 (22:50229206 T>A), RS1000943141 (22:50236113 A>G)

Disease associations

OMIM: gene MIM:610053 | disease phenotypes: MIM:251270

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly and chorioretinopathy 1	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
microcephaly and chorioretinopathy 1	Definitive	AR

Mondo (5): microcephaly and chorioretinopathy 1 (MONDO:0009624), inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149)

Orphanet (3): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Autosomal recessive chorioretinopathy-microcephaly syndrome (Orphanet:2518), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000307	Pointed chin
HP:0000340	Sloping forehead
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000499	Abnormal eyelash morphology
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000541	Retinal detachment
HP:0000543	Optic disc pallor
HP:0000556	Retinal dystrophy
HP:0000568	Microphthalmia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0001000	Abnormality of skin pigmentation
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001302	Pachygyria
HP:0001321	Cerebellar hypoplasia
HP:0001511	Intrauterine growth retardation
HP:0002059	Cerebral atrophy
HP:0002120	Cerebral cortical atrophy
HP:0002269	Abnormality of neuronal migration
HP:0002650	Scoliosis
HP:0003577	Congenital onset

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_608	Obesity-related traits	1.000000e-06
GCST002481_12	Acne (severe)	4.000000e-06
GCST006041_47	Major depressive disorder	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005190	urinary nitrogen measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Valproic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
mono(2-ethyl-5-oxohexyl)phthalate	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Catechin	affects cotreatment, decreases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	increases expression	1
Sodium Selenite	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

4 cell lines: 3 finite cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_CX92	GM25504	Finite cell line	Male
CVCL_GZ54	GM25502	Finite cell line	Female
CVCL_GZ60	GM25503	Finite cell line	Male
CVCL_HL68	GM25288	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies