SCLT1

Summary

SCLT1 (sodium channel and clathrin linker 1, HGNC:26406) is a protein-coding gene on chromosome 4q28.2, encoding Sodium channel and clathrin linker 1 (Q96NL6). Adapter protein that links SCN10A to clathrin.

This gene encodes an adaptor protein. Studies of a related gene in rat suggest that the encoded protein functions to link clathrin to the sodium channel protein type 10 subunit alpha protein. The encoded protein has also been identified as a component of distal appendages of centrioles that is necessary for ciliogenesis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 132320 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 586 total — 38 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 95
• MANE Select transcript: NM_144643

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26406
Approved symbol	SCLT1
Name	sodium channel and clathrin linker 1
Location	4q28.2
Locus type	gene with protein product
Status	Approved
Aliases	hCAP-1A, FLJ30655
Ensembl gene	ENSG00000151466
Ensembl biotype	protein_coding
OMIM	611399
Entrez	132320

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000281142, ENST00000439369, ENST00000502495, ENST00000503215, ENST00000503401, ENST00000503565, ENST00000506233, ENST00000506368, ENST00000511426, ENST00000651532, ENST00000893004, ENST00000893005, ENST00000893006, ENST00000893007, ENST00000919933, ENST00000919934, ENST00000919935, ENST00000947716, ENST00000947717

RefSeq mRNA: 4 — MANE Select: NM_144643 NM_001300897, NM_001300898, NM_001410807, NM_144643

CCDS: CCDS3740, CCDS77957, CCDS77958, CCDS93634

Canonical transcript exons

ENST00000281142 — 21 exons

Exon	Start	End
ENSE00001080744	129039041	129039096
ENSE00001080748	128999672	128999794
ENSE00001080749	129043993	129044051
ENSE00001080757	128997874	128997939
ENSE00001080759	129003741	129003876
ENSE00001080760	129043395	129043467
ENSE00001847444	128883993	128884539
ENSE00003485252	128948496	128948570
ENSE00003502367	128952769	128952840
ENSE00003522573	128992167	128992237
ENSE00003558531	128942996	128943188
ENSE00003569928	128946007	128946152
ENSE00003570045	128891059	128891137
ENSE00003575146	128936655	128936851
ENSE00003579762	128959600	128959777
ENSE00003595982	128888679	128888774
ENSE00003597375	128970378	128970468
ENSE00003604309	129082306	129082373
ENSE00003622944	128957026	128957124
ENSE00003651787	128965227	128965318
ENSE00003845722	129093070	129093539

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 97.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.9349 / max 575.4136, expressed in 1765 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53924	10.0314	1675
53926	2.5039	930
53925	1.9582	1047
53923	0.3313	121
53921	0.1101	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.73	gold quality
monocyte	CL:0000576	91.28	gold quality
leukocyte	CL:0000738	90.84	gold quality
ventricular zone	UBERON:0003053	90.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.04	gold quality
bone marrow cell	CL:0002092	88.81	gold quality
calcaneal tendon	UBERON:0003701	88.49	gold quality
granulocyte	CL:0000094	85.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.37	gold quality
sural nerve	UBERON:0015488	85.28	gold quality
blood	UBERON:0000178	84.85	gold quality
ganglionic eminence	UBERON:0004023	84.49	gold quality
adrenal tissue	UBERON:0018303	83.43	gold quality
secondary oocyte	CL:0000655	82.99	gold quality
colonic epithelium	UBERON:0000397	82.93	gold quality
cortical plate	UBERON:0005343	82.46	gold quality
epithelial cell of pancreas	CL:0000083	80.87	silver quality
oocyte	CL:0000023	80.38	gold quality
spleen	UBERON:0002106	79.63	gold quality
bone marrow	UBERON:0002371	79.30	gold quality
stromal cell of endometrium	CL:0002255	78.52	gold quality
vermiform appendix	UBERON:0001154	78.41	gold quality
epithelium of nasopharynx	UBERON:0001951	78.35	gold quality
nasopharynx	UBERON:0001728	78.33	gold quality
body of pancreas	UBERON:0001150	78.22	gold quality
tendon	UBERON:0000043	77.70	gold quality
cerebellar hemisphere	UBERON:0002245	77.15	gold quality
cerebellar cortex	UBERON:0002129	77.01	gold quality
pancreas	UBERON:0001264	76.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.83	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting SCLT1, 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-12118	100.00	65.88	1270
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-7158-5P	99.25	67.95	796

Literature-anchored findings (GeneRIF, showing 5)

• Functional study in rat suggests that CAP-1A links clathrin and a sodium channel. (PMID:15797711)
• study identified 2 cases with a severe ciliopathy phenotype consistent with oro-facio-digital syndrome type IX; the autozygome of each index harbored a single truncating variant and the affected genes (SCLT1 and TBC1D32/C6orf170) have roles in centrosomal biology and ciliogenesis; findings suggest a role of SCLT1 and TBC1D32 in ciliopathy pathogenesis (PMID:24285566)
• Study results indicate a genome-wide significant association between total alcohol use disorders identification test score in a trauma-exposed cohort and rs1433375, an intergenic single-nucleotide polymorphism located 323 kb upstream of the sodium channel and clathrin linker 1 at 4q28. (PMID:29082582)
• Bardet-Biedl syndrome in two unrelated patients with identical compound heterozygous SCLT1 mutations. (PMID:32253632)
• Reduced cone photoreceptor function and subtle systemic manifestations in two siblings with loss of SCLT1. (PMID:37246745)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sclt1	ENSDARG00000057248
mus_musculus	Sclt1	ENSMUSG00000059834
rattus_norvegicus	Sclt1	ENSRNOG00000014139

Protein

Protein identifiers

Sodium channel and clathrin linker 1 — Q96NL6 (reviewed: Q96NL6)

Alternative names: Sodium channel-associated protein 1

All UniProt accessions (5): A0A494C0G8, D6RBA6, D6RBP0, D6RDM2, Q96NL6

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that links SCN10A to clathrin. Regulates SCN10A channel activity, possibly by promoting channel internalization.

Subunit / interactions. Interacts with SCN10A and clathrin. Identified in a complex containing SCN10A, clathrin and SCLT1.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q96NL6-1	1	yes
Q96NL6-2	2
Q96NL6-3	3
Q96NL6-4	4

RefSeq proteins (4): NP_001287826, NP_001287827, NP_001397736, NP_653244* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038911	SCLT1	Family

UniProt features (10 total): splice variant 4, modified residue 2, initiator methionine 1, chain 1, coiled-coil region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NL6-F1	82.44	0.55

Functional residue map

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

Post-translational modifications (2): 2, 681

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-5617833	Cilium Assembly

MSigDB gene sets: 318 (showing top): GOBP_NEURON_MATURATION, GOBP_NEUROGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_ANATOMICAL_STRUCTURE_MATURATION, NF1_Q6_01, GOBP_CELL_MATURATION, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, GOBP_NEURONAL_ION_CHANNEL_CLUSTERING, GOBP_ORGANELLE_ASSEMBLY, CREB_Q3, FISCHER_DREAM_TARGETS, GOBP_MEMBRANE_ORGANIZATION, GOBP_CELL_PROJECTION_ORGANIZATION, GOCC_CENTRIOLE

GO Biological Process (2): clustering of voltage-gated sodium channels (GO:0045162), cilium assembly (GO:0060271)

GO Molecular Function (3): sodium channel regulator activity (GO:0017080), clathrin binding (GO:0030276), protein binding (GO:0005515)

GO Cellular Component (9): centrosome (GO:0005813), centriole (GO:0005814), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), ciliary basal body (GO:0036064), clathrin complex (GO:0071439), ciliary transition fiber (GO:0097539), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1
Organelle biogenesis and maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
microtubule organizing center	3
intracellular membraneless organelle	2
cellular anatomical structure	2
cilium	2
neuronal ion channel clustering	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
sodium channel activity	1
ion channel regulator activity	1
protein binding	1
binding	1
centriole	1
cytoplasm	1
cytoskeleton	1
clathrin coat	1
membrane protein complex	1
intracellular protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCLT1	CEP83	Q9Y592	994
SCLT1	CEP89	Q96ST8	988
SCLT1	FBF1	Q8TES7	974
SCLT1	CEP164	Q9UPV0	970
SCLT1	SCN10A	Q9Y5Y9	829
SCLT1	C2CD3	Q4AC94	727
SCLT1	TBC1D32	Q96NH3	715
SCLT1	CEP128	Q6ZU80	698
SCLT1	TTBK2	Q6IQ55	690
SCLT1	OFD1	O75665	671
SCLT1	LRRC45	Q96CN5	665
SCLT1	CLTC	Q00610	658
SCLT1	CCP110	O43303	654
SCLT1	CEP170	Q5SW79	641
SCLT1	CCDC120	Q96HB5	636

IntAct

46 interactions, top by confidence:

A	B	Type	Score
EXOC3	EXOC5	psi-mi:“MI:0914”(association)	0.790
BORCS6	HSBP1	psi-mi:“MI:0914”(association)	0.530
SYCE3	RER1	psi-mi:“MI:0914”(association)	0.530
SCLT1	CCDC22	psi-mi:“MI:0914”(association)	0.420
SCLT1		psi-mi:“MI:0915”(physical association)	0.370
Cep135		psi-mi:“MI:0914”(association)	0.350
CEP43	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Kif13b	TCF3	psi-mi:“MI:0914”(association)	0.350
TMEM132A	WWP2	psi-mi:“MI:0914”(association)	0.350
Cep43	TBC1D31	psi-mi:“MI:0914”(association)	0.350
Gpkow	BDP1	psi-mi:“MI:0914”(association)	0.350
Brca1	SMCHD1	psi-mi:“MI:0914”(association)	0.350
Osgep	RPSA	psi-mi:“MI:0914”(association)	0.350
CCDC14	TBC1D31	psi-mi:“MI:0914”(association)	0.350
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
SSX2IP	IPO7	psi-mi:“MI:0914”(association)	0.350
KIZ	BMX	psi-mi:“MI:0914”(association)	0.350
SYCE3	TRIM24	psi-mi:“MI:0914”(association)	0.350
TPM1	SPAG9	psi-mi:“MI:0914”(association)	0.350
AMOT	LIN7A	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
BFSP1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
BORCS6	UQCRQ	psi-mi:“MI:0914”(association)	0.350
ING1	TNRC18	psi-mi:“MI:0914”(association)	0.350

BioGRID (198): SCLT1 (Affinity Capture-MS), SCLT1 (Affinity Capture-MS), SCLT1 (Two-hybrid), SSBP1 (Affinity Capture-MS), CCDC22 (Affinity Capture-MS), COMMD2 (Affinity Capture-MS), DNAJC7 (Affinity Capture-MS), HSBP1 (Affinity Capture-MS), HSPA4L (Affinity Capture-MS), KIF23 (Affinity Capture-MS), LRRC45 (Affinity Capture-MS), KIZ (Affinity Capture-MS), TBK1 (Affinity Capture-MS), TPP2 (Affinity Capture-MS), LUZP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QCI3, A0JMK8, A3KGV1, A7YH32, A9X1A5, B0KWC9, B6MFW3, B8JK76, G5E861, G9G127, O35550, O35551, P59242, P85120, Q15276, Q3V6T2, Q502I3, Q5BJF6, Q5RG45, Q5SNZ0, Q5TZ80, Q5ZJ27, Q5ZKK5, Q66GS9, Q66KE8, Q6AYX5, Q6DIX6, Q6NRB0, Q6P402, Q6P5D4, Q6PGZ0, Q6VGS5, Q6ZU80, Q7TMK6, Q80UF4, Q80YF0, Q80YT7, Q86SQ7, Q8BIL5, Q8CJ99

Diamond homologs: G5E861, Q8CJ99, Q96NL6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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.

GO biological processes:

GO term	Partners	Fold	FDR
cilium assembly	7	11.0×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	38
Likely pathogenic	17
Uncertain significance	246
Likely benign	218
Benign	31

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1358401	NM_144643.4(SCLT1):c.660_661insT (p.Ile221fs)	Pathogenic
1359248	NM_144643.4(SCLT1):c.1620dup (p.Ala541fs)	Pathogenic
1387937	NC_000004.11:g.(?129960176)(129965226_?)del	Pathogenic
139612	NM_144643.4(SCLT1):c.290+2T>C	Pathogenic
1441458	NM_144643.4(SCLT1):c.20_23del (p.Asp6_Phe7insTer)	Pathogenic
1443499	NM_144643.4(SCLT1):c.538C>T (p.Gln180Ter)	Pathogenic
1451934	NC_000004.11:g.(?129857790)(129869745_?)del	Pathogenic
1453033	NM_144643.4(SCLT1):c.412C>T (p.Gln138Ter)	Pathogenic
1454868	NM_144643.4(SCLT1):c.1486C>T (p.Gln496Ter)	Pathogenic
1455584	NM_144643.4(SCLT1):c.1753_1754del (p.Gln585fs)	Pathogenic
1456730	NM_144643.4(SCLT1):c.37C>T (p.Arg13Ter)	Pathogenic
1457156	NM_144643.4(SCLT1):c.664del (p.Glu222fs)	Pathogenic
1459205	NM_144643.4(SCLT1):c.1261del (p.Glu421fs)	Pathogenic
1459224	NC_000004.11:g.(?129960176)(130014258_?)del	Pathogenic
1804042	NM_144643.4(SCLT1):c.1043del (p.Ser348fs)	Pathogenic
1921374	NM_144643.4(SCLT1):c.478del (p.Arg160fs)	Pathogenic
1950972	NM_144643.4(SCLT1):c.1876C>T (p.Gln626Ter)	Pathogenic
1998636	NM_144643.4(SCLT1):c.839T>A (p.Leu280Ter)	Pathogenic
2007684	NM_144643.4(SCLT1):c.681del (p.Lys227fs)	Pathogenic
2040063	NM_144643.4(SCLT1):c.957C>A (p.Cys319Ter)	Pathogenic
2060332	NM_144643.4(SCLT1):c.1512_1513del (p.Asn505fs)	Pathogenic
2062235	NM_144643.4(SCLT1):c.327del (p.Lys109fs)	Pathogenic
2129277	NM_144643.4(SCLT1):c.364dup (p.Asp122fs)	Pathogenic
2130017	NM_144643.4(SCLT1):c.935_939del (p.Thr312fs)	Pathogenic
2177974	NM_144643.4(SCLT1):c.1249C>T (p.Arg417Ter)	Pathogenic
2427300	NC_000004.11:g.(?130003441)(130003548_?)del	Pathogenic
2740008	NM_144643.4(SCLT1):c.1177C>T (p.Gln393Ter)	Pathogenic
2749755	NM_144643.4(SCLT1):c.1684C>T (p.Gln562Ter)	Pathogenic
2791352	NM_144643.4(SCLT1):c.389_392del (p.Val130fs)	Pathogenic
2895009	NM_144643.4(SCLT1):c.1912G>T (p.Glu638Ter)	Pathogenic

SpliceAI

4395 predictions. Top by Δscore:

Variant	Effect	Δscore
4:128867850:TTCTA:T	acceptor_loss	1.0000
4:128867851:TCTA:T	acceptor_loss	1.0000
4:128867852:CTA:C	acceptor_loss	1.0000
4:128867853:TA:T	acceptor_loss	1.0000
4:128867854:A:AT	acceptor_loss	1.0000
4:128888673:CCCTA:C	donor_loss	1.0000
4:128888674:CCTA:C	donor_loss	1.0000
4:128888675:CTAC:C	donor_loss	1.0000
4:128888676:TAC:T	donor_loss	1.0000
4:128888677:A:AG	donor_loss	1.0000
4:128888678:CC:C	donor_loss	1.0000
4:128888678:CCTG:C	donor_gain	1.0000
4:128888770:TCATT:T	acceptor_gain	1.0000
4:128888771:CATT:C	acceptor_gain	1.0000
4:128888771:CATTC:C	acceptor_gain	1.0000
4:128888772:ATT:A	acceptor_gain	1.0000
4:128888773:TT:T	acceptor_gain	1.0000
4:128888774:TC:T	acceptor_loss	1.0000
4:128888775:C:CC	acceptor_gain	1.0000
4:128888776:T:A	acceptor_loss	1.0000
4:128888778:T:TC	acceptor_gain	1.0000
4:128891133:CACTC:C	acceptor_gain	1.0000
4:128891135:CTC:C	acceptor_gain	1.0000
4:128891135:CTCCT:C	acceptor_loss	1.0000
4:128891137:CCTAT:C	acceptor_loss	1.0000
4:128891138:C:CC	acceptor_gain	1.0000
4:128936653:A:AC	donor_gain	1.0000
4:128936654:C:CC	donor_gain	1.0000
4:128936685:T:A	donor_gain	1.0000
4:128943193:T:TC	acceptor_gain	1.0000

AlphaMissense

4569 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:128888711:C:G	A658P	0.987
4:128888719:A:G	L655P	0.983
4:128888731:A:G	L651P	0.982
4:128959620:C:G	A343P	0.981
4:128888699:C:G	A662P	0.974
4:128936658:A:G	L609P	0.969
4:128936745:A:G	L580P	0.969
4:128891099:A:G	L623P	0.967
4:128888722:C:G	R654P	0.966
4:128936754:A:G	L577P	0.960
4:128891129:A:G	L613P	0.956
4:129003769:A:G	L133P	0.954
4:128891087:A:G	L627P	0.951
4:128999782:C:G	A147P	0.943
4:128891079:C:G	A630P	0.933
4:128943081:A:G	L516P	0.933
4:128999772:A:G	L150P	0.930
4:128936713:A:G	W591R	0.928
4:128936713:A:T	W591R	0.928
4:128943007:C:G	A541P	0.925
4:128992182:A:G	L224P	0.925
4:128888741:C:G	A648P	0.919
4:128946058:A:G	L463P	0.917
4:128999739:A:G	L161P	0.917
4:128946038:C:G	A470P	0.914
4:128888690:C:G	A665P	0.912
4:128959662:C:G	A329P	0.912
4:128943019:C:G	A537P	0.911
4:128959613:A:G	L345P	0.910
4:128884538:A:G	L669P	0.909

dbSNP variants (sampled 300 via entrez): RS1000000480 (4:128959728 G>A), RS1000038428 (4:128883867 G>T), RS1000038978 (4:128940217 T>C), RS1000042181 (4:129079121 C>T), RS1000089582 (4:129084852 A>G), RS1000107272 (4:128914141 G>A), RS1000115288 (4:129022387 T>C), RS1000124673 (4:129081455 C>G), RS1000125698 (4:128994897 T>A,C), RS10001286 (4:128973511 A>G), RS10001360 (4:128973537 A>G), RS1000149994 (4:128932703 T>C), RS1000157198 (4:129081228 T>C,G), RS1000168372 (4:129034627 A>T), RS1000169448 (4:128890929 A>T)

Disease associations

OMIM: gene MIM:611399 | disease phenotypes: MIM:189960, MIM:241800, MIM:603047, MIM:209900, MIM:120970, MIM:258865

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliopathy	Strong	Autosomal recessive
Senior-Loken syndrome	Limited	Autosomal recessive
retinitis pigmentosa	Limited	Autosomal recessive
Bardet-Biedl syndrome	Limited	Autosomal recessive

Mondo (13): inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), esophageal atresia/tracheoesophageal fistula (MONDO:0008586), pathologic nystagmus (MONDO:0004843), hyperopia (MONDO:0004891), congenital hypothalamic hamartoma syndrome (MONDO:0009436), astigmatism (MONDO:0011284), Bardet-Biedl syndrome (MONDO:0015229), cone-rod dystrophy (MONDO:0015993), orofaciodigital syndrome IX (MONDO:0009795), Senior-Loken syndrome (MONDO:0017842), ciliopathy (MONDO:0005308), retinitis pigmentosa (MONDO:0019200)

Orphanet (6): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Esophageal atresia (Orphanet:1199), Bardet-Biedl syndrome (Orphanet:110), Cone rod dystrophy (Orphanet:1872), Orofaciodigital syndrome type 9 (Orphanet:141007), Congenital hypothalamic hamartoma syndrome (Orphanet:2113)

HPO phenotypes

95 total (30 of 95 shown, HPO-id order):

HPO	Term
HP:0000011	Neurogenic bladder
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000100	Nephrotic syndrome
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: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:0000426	Prominent nasal bridge
HP:0000470	Short neck
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000548	Cone/cone-rod dystrophy
HP:0000551	Color vision defect
HP:0000556	Retinal dystrophy
HP:0000613	Photophobia
HP:0000618	Blindness

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002351_8	Chronic obstructive pulmonary disease (moderate to severe)	7.000000e-07
GCST005236_1	Problematic alcohol use in trauma-exposed individuals	3.000000e-08
GCST009391_1499	Metabolite levels	6.000000e-06
GCST009615_6	Triglyceride levels x loop diuretics use interaction	6.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008483	response to trauma exposure
EFO:0009458	alcohol use disorder measurement
EFO:0010416	triacylglycerol 52:4 measurement
EFO:0004530	triglyceride measurement

MeSH disease descriptors (12)

Descriptor	Name	Tree numbers
D001251	Astigmatism	C11.744.212
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D006956	Hyperopia	C11.744.479
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C531835	Esophageal atresia with or without tracheoesophageal fistula (supp.)
C537158	Hypothalamic hamartomas (supp.)
C557818	Orofaciodigital syndrome 9 (supp.)
C537580	Senior Loken Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	4
Valproic Acid	affects cotreatment, increases expression	3
bisphenol A	decreases expression, increases methylation	2
trichostatin A	increases expression	2
Air Pollutants	affects methylation, increases abundance, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
belinostat	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Acetaminophen	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	affects cotreatment, decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	decreases expression	1
Nitrogen Oxides	increases abundance, affects methylation	1

Clinical trials (associated diseases)

516 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
NCT00347204	PHASE4	COMPLETED	Comparison of Acular LS Versus Nevanac for Pain Control in Eyes Undergoing PRK
NCT00455455	PHASE4	COMPLETED	Corneal and Conjunctival Sensitivity and Staining Study
NCT00937105	PHASE4	COMPLETED	Daily Wear Corneal Infiltrative Event Study
NCT01387360	PHASE4	COMPLETED	Presbyopic Supracor Treatment for Near Myopic/Hyperopic Pseudophakic Eyes
NCT01977807	PHASE4	UNKNOWN	A Prospective Safety and Effectiveness Study of the 500 Hz Technolas Perfect Vision Excimer Laser in Asian Eyes Using LASIK
NCT02071576	PHASE4	UNKNOWN	A Prospective Safety and Effectiveness Study of the 500 Hz Technolas Perfect Vision Excimer Laser Using LASIK
NCT02112968	PHASE4	UNKNOWN	A Prospective Safety and Effectiveness Study of a New High Repetition Rate Excimer Laser Using LASIK for the Correction of Ammetropia and Presbyopia
NCT03881670	PHASE4	COMPLETED	On-Eye Optical Quality of Lotrafilcon B Lenses Over 12 Hours
NCT04208750	PHASE4	COMPLETED	Clinical Investigation of the Vision-R800 Device.
NCT04283331	PHASE4	UNKNOWN	Anesthetic Impregnated Bandage Soft Contact Lens (BSCL) in Pain Management After Photorefractive Keratectomy (PRK)
NCT00770094	PHASE4	UNKNOWN	Multi Laser Platform Comparison Study for LASIK
NCT00821236	PHASE4	COMPLETED	Contralateral Comparison of Three Excimer Laser Systems in Performing LASIK
NCT00825513	PHASE4	COMPLETED	Safety and Effectiveness of the Akreos Toric Intraocular Lens.
NCT01018797	PHASE4	COMPLETED	Intrastromal Corneal Ring for High Astigmatism on Postkeratoplasty
NCT01279031	PHASE4	COMPLETED	Randomized Comparison of the Abbott WHITESTAR Signature System With Ellips Tranversal Ultrasound vs. the Alcon Infiniti With the Ozil Torsional Handpiece in Phacoemulsification: A Contralaterally-Controlled Trial
NCT01396616	PHASE4	UNKNOWN	Clinical Evaluation of Toric Intraocular Lens Made by Aurolab
NCT01454843	PHASE4	COMPLETED	LASIK Using the Alcon Allegretto Wavefront-Guided Excimer Laser vs AMO Visx Wavefront-Guided Excimer Laser
NCT01554761	PHASE4	UNKNOWN	Effect of Posterior Corneal Toricity on Refractive Outcome of Pseudophakia
NCT01885780	PHASE4	COMPLETED	Prospective Evaluation of the Effectiveness of the Femtosecond Laser-assisted Refractive Astigmatic Keratotomy.
NCT04321226	PHASE4	UNKNOWN	Femtosecond Laser-assisted Astigmatism Treatment
NCT04418986	PHASE4	COMPLETED	Incisional Correction of Corneal Astigmatism During Phacoemulsification
NCT07140653	PHASE4	RECRUITING	Arcuate Incisions With Light Adjustable Lens for Astigmatism Correction in Lens Surgery
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
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
NCT00520689	PHASE3	COMPLETED	Multipurpose Disinfecting Solution Compatibility With a Silicone Hydrogel Contact Lens
NCT00910403	PHASE3	COMPLETED	Multicenter Evaluation of Safety and Effectiveness of Presbyopic LASIK for Hyperopes