TTC8

Summary

TTC8 (tetratricopeptide repeat domain 8, HGNC:20087) is a protein-coding gene on chromosome 14q31.3, encoding Tetratricopeptide repeat protein 8 (Q8TAM2). The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.

This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is involved in the formation of cilia. A mutation in this gene has also been implicated in nonsyndromic retinitis pigmentosa. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 123016 — RefSeq curated summary.

At a glance

• Gene–disease (curated): TTC8-related ciliopathy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 621 total — 28 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 134
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_144596

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20087
Approved symbol	TTC8
Name	tetratricopeptide repeat domain 8
Location	14q31.3
Locus type	gene with protein product
Status	Approved
Aliases	BBS8, RP51
Ensembl gene	ENSG00000165533
Ensembl biotype	protein_coding
OMIM	608132
Entrez	123016

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 23 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000338104, ENST00000346301, ENST00000354441, ENST00000380656, ENST00000553718, ENST00000554686, ENST00000555057, ENST00000556077, ENST00000556133, ENST00000556567, ENST00000556651, ENST00000557580, ENST00000622513, ENST00000881353, ENST00000881354, ENST00000881355, ENST00000881356, ENST00000881357, ENST00000936984, ENST00000936985, ENST00000936986, ENST00000971771, ENST00000971772, ENST00000971773, ENST00000971774, ENST00000971775, ENST00000971776, ENST00000971777, ENST00000971778

RefSeq mRNA: 8 — MANE Select: NM_144596 NM_001288781, NM_001288782, NM_001288783, NM_001366535, NM_001366536, NM_144596, NM_198309, NM_198310

CCDS: CCDS32137, CCDS73674, CCDS9885, CCDS9886

Canonical transcript exons

ENST00000380656 — 15 exons

Exon	Start	End
ENSE00001485781	88833693	88833722
ENSE00002436755	88877294	88877988
ENSE00002438425	88824651	88824821
ENSE00003460286	88841425	88841514
ENSE00003513787	88875026	88875109
ENSE00003514537	88871549	88871723
ENSE00003527890	88841037	88841196
ENSE00003542187	88840865	88840928
ENSE00003567593	88843806	88843850
ENSE00003577425	88852971	88853056
ENSE00003586338	88861222	88861332
ENSE00003621275	88872330	88872452
ENSE00003642355	88870059	88870198
ENSE00003677259	88839452	88839572
ENSE00003715902	88857190	88857277

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 95.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.9794 / max 275.7995, expressed in 1801 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140973	24.4551	1799
140972	0.4952	247
140978	0.0114	1
140975	0.0075	1
140976	0.0056	1
140977	0.0045	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	95.60	gold quality
islet of Langerhans	UBERON:0000006	94.98	gold quality
adrenal tissue	UBERON:0018303	94.75	gold quality
right adrenal gland cortex	UBERON:0035827	94.71	gold quality
right uterine tube	UBERON:0001302	94.55	gold quality
right adrenal gland	UBERON:0001233	94.38	gold quality
pituitary gland	UBERON:0000007	94.37	gold quality
right ovary	UBERON:0002118	94.26	gold quality
adenohypophysis	UBERON:0002196	94.23	gold quality
left adrenal gland	UBERON:0001234	93.35	gold quality
left adrenal gland cortex	UBERON:0035825	93.15	gold quality
ovary	UBERON:0000992	92.95	gold quality
stromal cell of endometrium	CL:0002255	92.87	gold quality
adrenal gland	UBERON:0002369	92.87	gold quality
adrenal cortex	UBERON:0001235	92.64	gold quality
left lobe of thyroid gland	UBERON:0001120	91.56	gold quality
thyroid gland	UBERON:0002046	91.17	gold quality
right lobe of thyroid gland	UBERON:0001119	90.76	gold quality
right testis	UBERON:0004534	90.60	gold quality
left testis	UBERON:0004533	90.15	gold quality
testis	UBERON:0000473	89.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.27	gold quality
gall bladder	UBERON:0002110	88.91	gold quality
bronchial epithelial cell	CL:0002328	88.86	gold quality
smooth muscle tissue	UBERON:0001135	88.83	gold quality
calcaneal tendon	UBERON:0003701	88.71	gold quality
corpus epididymis	UBERON:0004359	88.21	gold quality
bronchus	UBERON:0002185	87.94	gold quality
metanephros	UBERON:0000081	87.88	gold quality
germinal epithelium of ovary	UBERON:0001304	87.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting TTC8, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-12135	98.99	70.26	1814

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 4)

• A homozygous null BBS8 mutation leads to Bardet-Biedl syndrome with randomization of left-right body axis symmetry, a known defect of the nodal cilium (PMID:14520415)
• small role of BBS7 and TTC8 in the overall mutational load of Bardet-Biedl syndrome patients (PMID:19402160)
• A splice-site mutation in a retina-specific exon of TTC8 causes nonsyndromic retinitis pigmentosa. (PMID:20451172)
• Two novel mutations and three previously reported variants, identified in the present study, further extend the body of evidence implicating BBS6, BBS7, BBS8, and BBS10 in causing Bardet-Biedl Syndrome. (PMID:28761321)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000099481
mus_musculus	Ttc8	ENSMUSG00000021013
rattus_norvegicus	Ttc8	ENSRNOG00000004542
drosophila_melanogaster	BBS8	FBGN0031255
caenorhabditis_elegans		WBGENE00000244

Paralogs (14): IFT88 (ENSG00000032742), TTC7A (ENSG00000068724), TMTC4 (ENSG00000125247), TMTC1 (ENSG00000133687), TMTC3 (ENSG00000139324), TTC6 (ENSG00000139865), BBS4 (ENSG00000140463), TTC13 (ENSG00000143643), OGT (ENSG00000147162), CFAP70 (ENSG00000156042), TTC7B (ENSG00000165914), TTC16 (ENSG00000167094), TMTC2 (ENSG00000179104), TTC34 (ENSG00000215912)

Protein

Protein identifiers

Tetratricopeptide repeat protein 8 — Q8TAM2 (reviewed: Q8TAM2)

Alternative names: Bardet-Biedl syndrome 8 protein

All UniProt accessions (11): A0A0C4DGH8, A0A0C4DGX9, A0A0C4DGY3, A0A0S2Z5V9, Q8TAM2, G3V2W6, G3V2Z9, G3V324, H0YJQ3, H0YJX0, Q86U25

UniProt curated annotations — full annotation on UniProt →

Function. The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization.

Subunit / interactions. Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with PCM1. Interacts with CCDC28B. Interacts with PKD1.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cell projection. Cilium membrane. Centriolar satellite. Cilium.

Tissue specificity. Widely expressed.

Disease relevance. Retinitis pigmentosa 51 (RP51) [MIM:613464] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry. Bardet-Biedl syndrome 8 (BBS8) [MIM:615985] A syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8TAM2-1	1	yes
Q8TAM2-2	2
Q8TAM2-3	3
Q8TAM2-4	4
Q8TAM2-6	5

RefSeq proteins (8): NP_001275710, NP_001275711, NP_001275712, NP_001353464, NP_001353465, NP_653197, NP_938051, NP_938052 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR028796	BBS8	Family

Pfam: PF13181, PF13432

UniProt features (18 total): repeat 8, splice variant 5, sequence variant 2, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAM2-F1	84.48	0.57

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620922	BBSome-mediated cargo-targeting to cilium

MSigDB gene sets: 442 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_COGNITION, GOBP_AXIS_SPECIFICATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (22): establishment of planar polarity (GO:0001736), axon guidance (GO:0007411), sensory perception of smell (GO:0007608), protein transport (GO:0015031), olfactory bulb development (GO:0021772), regulation of protein localization (GO:0032880), multicellular organism growth (GO:0035264), establishment of epithelial cell apical/basal polarity (GO:0045198), fat cell differentiation (GO:0045444), establishment of anatomical structure orientation (GO:0048560), sensory processing (GO:0050893), regulation of stress fiber assembly (GO:0051492), inner ear receptor cell stereocilium organization (GO:0060122), camera-type eye photoreceptor cell differentiation (GO:0060219), cilium assembly (GO:0060271), renal tubule development (GO:0061326), protein localization to plasma membrane (GO:0072659), multi-ciliated epithelial cell differentiation (GO:1903251), non-motile cilium assembly (GO:1905515), sensory perception (GO:0007600), anatomical structure morphogenesis (GO:0009653), cell projection organization (GO:0030030)

GO Molecular Function (2): RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515)

GO Cellular Component (18): fibrillar center (GO:0001650), mitochondrion (GO:0005739), centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), cilium (GO:0005929), photoreceptor connecting cilium (GO:0032391), perinuclear theca (GO:0033011), centriolar satellite (GO:0034451), BBSome (GO:0034464), ciliary basal body (GO:0036064), ciliary membrane (GO:0060170), non-motile cilium (GO:0097730), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cargo trafficking to the periciliary membrane	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cilium	4
microtubule organizing center	3
intracellular protein localization	2
cytoplasm	2
intracellular membraneless organelle	2
morphogenesis of a polarized epithelium	1
establishment of tissue polarity	1
axonogenesis	1
neuron projection guidance	1
sensory perception of chemical stimulus	1
transport	1
establishment of protein localization	1
olfactory lobe development	1
anatomical structure development	1
regulation of localization	1
multicellular organismal process	1
developmental growth	1
polarized epithelial cell differentiation	1
establishment of apical/basal cell polarity	1
establishment or maintenance of epithelial cell apical/basal polarity	1
establishment of epithelial cell polarity	1
cell differentiation	1
anatomical structure morphogenesis	1
axis specification	1
sensory perception	1
cognition	1
regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of actomyosin structure organization	1
neuron projection development	1
inner ear receptor cell development	1
eye photoreceptor cell differentiation	1
neural retina development	1
retina morphogenesis in camera-type eye	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1

Protein interactions and networks

STRING

1734 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC8	BBS2	Q9BXC9	996
TTC8	BBS1	Q8NFJ9	994
TTC8	BBS5	Q8N3I7	991
TTC8	BBS9	P78514	985
TTC8	BBS7	Q8IWZ6	983
TTC8	BBS4	Q96RK4	916
TTC8	BBS12	Q6ZW61	868
TTC8	BBS10	Q8TAM1	861
TTC8	CCDC28B	Q9BUN5	844
TTC8	WDPCP	O95876	819
TTC8	MKS1	Q9NXB0	807
TTC8	RAB3IP	Q96QF0	789
TTC8	CFAP418	Q96NL8	757
TTC8	TRIM32	Q13049	752
TTC8	PRCD	Q00LT1	750

IntAct

54 interactions, top by confidence:

A	B	Type	Score
IQCB1	CEP290	psi-mi:“MI:0914”(association)	0.950
BBS1	BBS9	psi-mi:“MI:0914”(association)	0.940
BBS2	BBS9	psi-mi:“MI:0914”(association)	0.920
BBS2	BBS9	psi-mi:“MI:0403”(colocalization)	0.920
BBS4	PCM1	psi-mi:“MI:0914”(association)	0.910
BBS5	BBS9	psi-mi:“MI:0914”(association)	0.890
BBS7	BBS9	psi-mi:“MI:0914”(association)	0.860
LZTFL1	BBS9	psi-mi:“MI:0914”(association)	0.850
BBS4	BBIP1	psi-mi:“MI:0914”(association)	0.810
TTC8	BBS7	psi-mi:“MI:0914”(association)	0.730
NME3	NME4	psi-mi:“MI:0914”(association)	0.640
TTC8	IQCB1	psi-mi:“MI:0915”(physical association)	0.570
IQCB1	TTC8	psi-mi:“MI:2364”(proximity)	0.570
TTC8	IQCB1	psi-mi:“MI:0403”(colocalization)	0.570
BBS1	PCM1	psi-mi:“MI:0915”(physical association)	0.570
TTC8	BBS9	psi-mi:“MI:0915”(physical association)	0.530
BBS9	TTC8	psi-mi:“MI:0915”(physical association)	0.530
BBS1	RAB8A	psi-mi:“MI:0914”(association)	0.510
BBS4	TRAFD1	psi-mi:“MI:0914”(association)	0.510
BBS5	BBIP1	psi-mi:“MI:0914”(association)	0.510
BBS7	TCP1	psi-mi:“MI:0914”(association)	0.460
TTC8	C2CD3	psi-mi:“MI:0915”(physical association)	0.400
CCDC28B	TTC8	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (34): TTC8 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), BBS5 (Affinity Capture-MS), BBS9 (Affinity Capture-MS), BBS4 (Affinity Capture-MS), BBS1 (Affinity Capture-MS), TTC8 (Affinity Capture-MS), BBS7 (Affinity Capture-MS), BBS2 (Affinity Capture-MS), LZTFL1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4R8, B0BNG0, B3DNN5, E7F590, F8VPK0, O89079, P45432, P49754, P62944, P63009, P63010, Q12996, Q15006, Q28G25, Q2KJ25, Q4QR29, Q5E993, Q5F3K0, Q5KU39, Q5M7J9, Q5R4J9, Q5R882, Q5RBI3, Q5RDW9, Q60445, Q62018, Q6DEU9, Q6DFB8, Q6INS3, Q6N069, Q6PD62, Q6PGP7, Q6TGY8, Q80UM3, Q8AVU9, Q8BGZ4, Q8TAM2, Q8VD72, Q8VY89, Q8VZM1

Diamond homologs: Q8TAM2, Q8VD72, Q23049

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TTC8	“form complex”	“BBsome complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 37 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
BBSome-mediated cargo-targeting to cilium	10	198.6×	4e-20
Cargo trafficking to the periciliary membrane	9	89.4×	9e-15
Cilium Assembly	12	52.2×	5e-17
Organelle biogenesis and maintenance	12	31.7×	1e-14
Anchoring of the basal body to the plasma membrane	5	22.6×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
melanosome transport	5	109.4×	4e-08
protein localization to cilium	6	68.8×	2e-08
non-motile cilium assembly	7	58.1×	3e-09
fat cell differentiation	7	36.2×	4e-08
cilium assembly	16	33.6×	6e-19
visual perception	7	15.9×	9e-06
protein transport	7	8.8×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	39
Uncertain significance	322
Likely benign	170
Benign	8

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075390	NM_144596.4(TTC8):c.1021C>T (p.Gln341Ter)	Pathogenic
1076679	NM_144596.4(TTC8):c.674G>A (p.Trp225Ter)	Pathogenic
1213931	NM_144596.4(TTC8):c.1343_1347+17del	Pathogenic
1431284	NM_144596.4(TTC8):c.106dup (p.Tyr36fs)	Pathogenic
1458440	NM_144596.4(TTC8):c.266-2A>G	Pathogenic
2098849	NM_144596.4(TTC8):c.1029_1032dup (p.Ala345fs)	Pathogenic
2227695	NM_144596.4(TTC8):c.1228del (p.Gly409_Ile410insTer)	Pathogenic
235131	NM_144596.4(TTC8):c.1347G>C (p.Gln449His)	Pathogenic
2427649	NC_000014.8:g.(?89319295)(89319420_?)del	Pathogenic
2428023	NM_144596.4(TTC8):c.256C>T (p.Gln86Ter)	Pathogenic
2498294	NM_144596.4(TTC8):c.572del (p.Leu191fs)	Pathogenic
2498313	NM_144596.4(TTC8):c.699del (p.Lys233fs)	Pathogenic
2528	NM_144596.4(TTC8):c.589_594del (p.Glu197_Tyr198del)	Pathogenic
2529	NM_144596.4(TTC8):c.1049+2_1049+4del	Pathogenic
2531	NM_144596.4(TTC8):c.624+1G>A	Pathogenic
2577456	NM_144596.4(TTC8):c.114+1G>T	Pathogenic
2724823	NM_144596.4(TTC8):c.112C>T (p.Gln38Ter)	Pathogenic
3075693	NM_144596.4(TTC8):c.1252C>T (p.Gln418Ter)	Pathogenic
3236396	NM_144596.4(TTC8):c.462_465del (p.Ser155fs)	Pathogenic
3243967	NC_000014.8:g.(?89291052)(89291185_?)del	Pathogenic
3250252	NM_144596.4(TTC8):c.826_829dup (p.Ala277fs)	Pathogenic
3544447	NM_144596.4(TTC8):c.798+2T>C	Pathogenic
3686329	NM_144596.4(TTC8):c.153G>A (p.Trp51Ter)	Pathogenic
3723406	NM_144596.4(TTC8):c.588dup (p.Glu197Ter)	Pathogenic
3726697	NM_144596.4(TTC8):c.680G>A (p.Trp227Ter)	Pathogenic
4718066	NM_144596.4(TTC8):c.211C>T (p.Gln71Ter)	Pathogenic
4808130	NM_144596.4(TTC8):c.327dup (p.Arg110Ter)	Pathogenic
974557	NM_198309.3:c.(768+1_769-1)_(879+1_880-1)del	Pathogenic
1066143	NM_144596.4(TTC8):c.579+5G>A	Likely pathogenic
1066311	NM_144596.4(TTC8):c.910-1G>A	Likely pathogenic

SpliceAI

2088 predictions. Top by Δscore:

Variant	Effect	Δscore
14:88824761:G:GT	donor_gain	1.0000
14:88824819:CAGGT:C	donor_loss	1.0000
14:88824820:AGGTA:A	donor_loss	1.0000
14:88824821:GGTA:G	donor_loss	1.0000
14:88824822:G:GA	donor_loss	1.0000
14:88839441:A:AG	acceptor_gain	1.0000
14:88839441:AT:A	acceptor_gain	1.0000
14:88839441:ATG:A	acceptor_gain	1.0000
14:88839441:ATGG:A	acceptor_gain	1.0000
14:88839442:T:G	acceptor_gain	1.0000
14:88839442:T:TA	acceptor_gain	1.0000
14:88839443:G:A	acceptor_gain	1.0000
14:88839447:TTTA:T	acceptor_loss	1.0000
14:88839448:TTA:T	acceptor_loss	1.0000
14:88839450:A:AG	acceptor_gain	1.0000
14:88839450:A:AT	acceptor_loss	1.0000
14:88839451:G:GG	acceptor_gain	1.0000
14:88839451:GGCA:G	acceptor_gain	1.0000
14:88839568:TCCAC:T	donor_gain	1.0000
14:88839569:CCACG:C	donor_loss	1.0000
14:88839570:CAC:C	donor_gain	1.0000
14:88839570:CACGT:C	donor_loss	1.0000
14:88839571:AC:A	donor_gain	1.0000
14:88839573:G:GC	donor_loss	1.0000
14:88839573:G:GG	donor_gain	1.0000
14:88839574:TAAG:T	donor_loss	1.0000
14:88839575:AA:A	donor_loss	1.0000
14:88841032:CACA:C	acceptor_loss	1.0000
14:88841034:CAGGC:C	acceptor_loss	1.0000
14:88841035:A:AG	acceptor_gain	1.0000

AlphaMissense

3385 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000095671 (14:88876455 C>G,T), RS1000212876 (14:88842523 G>A), RS1000289982 (14:88854803 C>T), RS1000365770 (14:88835313 A>G), RS1000423651 (14:88876898 A>C,G), RS1000454180 (14:88862789 T>C), RS1000508209 (14:88874183 A>G), RS1000529325 (14:88828273 G>C), RS1000534984 (14:88833992 A>G,T), RS1000564218 (14:88847417 G>A), RS1000635273 (14:88867517 C>CA), RS1000702394 (14:88840921 G>A), RS1000777635 (14:88835759 T>A), RS1000847440 (14:88862209 T>G), RS1000851956 (14:88861009 G>A)

Disease associations

OMIM: gene MIM:608132 | disease phenotypes: MIM:209900, MIM:613464, MIM:615985, MIM:268000, MIM:204000, MIM:604232

GenCC curated gene-disease

Disease	Classification	Inheritance
Bardet-Biedl syndrome 8	Definitive	Autosomal recessive
retinitis pigmentosa 51	Definitive	Autosomal recessive
Bardet-Biedl syndrome	Supportive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
TTC8-related ciliopathy	Definitive	AR

Mondo (7): Bardet-Biedl syndrome (MONDO:0015229), retinitis pigmentosa 51 (MONDO:0013274), Bardet-Biedl syndrome 8 (MONDO:0014436), retinitis pigmentosa (MONDO:0019200), inherited retinal dystrophy (MONDO:0019118), Leber congenital amaurosis (MONDO:0018998), Leber congenital amaurosis 3 (MONDO:0011415)

Orphanet (4): Bardet-Biedl syndrome (Orphanet:110), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Leber congenital amaurosis (Orphanet:65)

HPO phenotypes

134 total (30 of 134 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000077	Abnormality of the kidney
HP:0000085	Horseshoe kidney
HP:0000100	Nephrotic syndrome
HP:0000110	Renal dysplasia
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000147	Polycystic ovaries
HP:0000163	Abnormal oral cavity morphology
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001762_31	Obesity-related traits	9.000000e-06
GCST002938_34	Copper levels	7.000000e-06
GCST005555_6	Limited cutaneous systemic scleroderma	7.000000e-06
GCST006291_74	Spherical equivalent or myopia (age of diagnosis)	5.000000e-10
GCST006622_23	Neonatal cytokine/chemokine levels (fetal genetic effect)	9.000000e-07
GCST010002_157	Refractive error	3.000000e-19

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:1001017	limited scleroderma
EFO:0004847	age at onset
EFO:0004747	protein measurement
EFO:0007959	fetal genotype effect measurement
EFO:0008191	obsolete_interleukin 8 measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C565917	Bardet-Biedl Syndrome 8 (supp.)
C565814	Leber Congenital Amaurosis 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Valproic Acid	affects expression, decreases methylation, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
TAK-243	increases sumoylation	1
pirinixic acid	affects binding, increases activity, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
clothianidin	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	decreases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT03746522	PHASE3	COMPLETED	Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
NCT04966741	PHASE3	COMPLETED	Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
NCT05194124	PHASE3	COMPLETED	Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)