IFT54

Summary

IFT54 (intraflagellar transport 54, HGNC:17861) is a protein-coding gene on chromosome 2q37.3, encoding TRAF3-interacting protein 1 (Q8TDR0). Plays an inhibitory role on IL13 signaling by binding to IL13RA1.

The protein encoded by this gene interacts with TNF receptor-associated factor 3, tethering it to cytoskeletal microtubules. The encoded protein is also an inhibitor of the innate type I IFN response. Defects in this gene are a cause of Senior-Loken syndrome 9.

Source: NCBI Gene 26146 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 17
• Clinical variants (ClinVar): 696 total — 26 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_015650

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17861
Approved symbol	IFT54
Name	intraflagellar transport 54
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	MIP-T3, DKFZP434F124, MIPT3, FAP116, CFAP116
Ensembl gene	ENSG00000204104
Ensembl biotype	protein_coding
OMIM	607380
Entrez	26146

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000373327, ENST00000391993, ENST00000409739, ENST00000462122, ENST00000483951, ENST00000876684, ENST00000935943, ENST00000935944, ENST00000935945, ENST00000968966, ENST00000968967, ENST00000968968, ENST00000968969, ENST00000968970, ENST00000968971, ENST00000968972, ENST00000968973, ENST00000968974, ENST00000968975, ENST00000968976, ENST00000968977, ENST00000968978

RefSeq mRNA: 2 — MANE Select: NM_015650 NM_001139490, NM_015650

CCDS: CCDS33415, CCDS46557

Canonical transcript exons

ENST00000373327 — 17 exons

Exon	Start	End
ENSE00001460244	238397459	238397679
ENSE00001460251	238347455	238347475
ENSE00001460252	238344497	238344598
ENSE00001460253	238338362	238338457
ENSE00001460255	238333960	238334035
ENSE00001460256	238332824	238332895
ENSE00001956209	238398754	238400897
ENSE00003492370	238348764	238348848
ENSE00003497336	238328686	238328829
ENSE00003510233	238353173	238353209
ENSE00003526433	238325306	238325374
ENSE00003569192	238328926	238329342
ENSE00003571929	238325809	238325970
ENSE00003620325	238356004	238356080
ENSE00003638845	238349325	238349408
ENSE00003656008	238352827	238352950
ENSE00003844091	238320518	238320785

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 96.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6764 / max 444.9620, expressed in 1734 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26340	10.3731	1732
26339	0.3033	117

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.71	gold quality
bronchial epithelial cell	CL:0002328	96.28	gold quality
sural nerve	UBERON:0015488	96.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.72	gold quality
epithelium of nasopharynx	UBERON:0001951	93.06	gold quality
secondary oocyte	CL:0000655	92.21	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.82	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.44	gold quality
germinal epithelium of ovary	UBERON:0001304	90.38	gold quality
left testis	UBERON:0004533	90.11	gold quality
right testis	UBERON:0004534	89.69	gold quality
caput epididymis	UBERON:0004358	89.27	gold quality
testis	UBERON:0000473	89.24	gold quality
medial globus pallidus	UBERON:0002477	89.13	gold quality
right uterine tube	UBERON:0001302	89.09	gold quality
gingival epithelium	UBERON:0001949	88.48	gold quality
globus pallidus	UBERON:0001875	87.73	gold quality
saphenous vein	UBERON:0007318	87.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.32	gold quality
superior vestibular nucleus	UBERON:0007227	87.32	gold quality
bronchus	UBERON:0002185	87.24	gold quality
epithelium of bronchus	UBERON:0002031	87.21	gold quality
middle temporal gyrus	UBERON:0002771	86.99	gold quality
endothelial cell	CL:0000115	86.55	silver quality
corpus epididymis	UBERON:0004359	86.55	gold quality
calcaneal tendon	UBERON:0003701	86.05	gold quality
mammary duct	UBERON:0001765	86.01	gold quality
biceps brachii	UBERON:0001507	85.34	gold quality
tendon	UBERON:0000043	85.31	gold quality
pons	UBERON:0000988	84.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting IFT54, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-5003-3P	99.85	69.29	2517

Literature-anchored findings (GeneRIF, showing 6)

• These results suggest that MIP-T3 is a novel inhibitor of IL-13 signaling and may be a useful molecule in ameliorating various conditions in which IL-13 plays a central role. (PMID:12935900)
• The interaction of MIP-T3 with both actin filaments and microtubule suggested that MIP-T3 may play an important role in regulation of cytoskeleton dynamics in cells. (PMID:20391533)
• Data show that MIP-T3 protein level is highly regulated; mainly mediated by the ubiquitin-proteasome system. (PMID:21510943)
• MIP-T3 functions as a negative regulator of the innate type I interferon response by preventing TRAF3 from forming protein complexes with critical downstream transducers and effectors of antiviral response. (PMID:22079989)
• Mutations in TRAF3IP1 are identified in patients with nephronophthisis and retinal degeneration. The identified mutations result in mild ciliary defects in patients and reveal a role of IFT54 as a negative regulator of microtubule stability via MAP4. (PMID:26487268)
• [1]H, [13]C, and [15]N resonance assignments and solution structure of the N-terminal divergent calponin homology (NN-CH) domain of human intraflagellar transport protein 54. (PMID:38551798)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	traf3ip1	ENSDARG00000010300
mus_musculus	Traf3ip1	ENSMUSG00000034292
rattus_norvegicus	Traf3ip1	ENSRNOG00000024468
drosophila_melanogaster	IFT54	FBGN0038221
caenorhabditis_elegans		WBGENE00001127

Protein

Protein identifiers

TRAF3-interacting protein 1 — Q8TDR0 (reviewed: Q8TDR0)

Alternative names: Interleukin-13 receptor alpha 1-binding protein 1, Intraflagellar transport protein 54 homolog, Microtubule-interacting protein associated with TRAF3

All UniProt accessions (2): Q8TDR0, H7BZ10

UniProt curated annotations — full annotation on UniProt →

Function. Plays an inhibitory role on IL13 signaling by binding to IL13RA1. Involved in suppression of IL13-induced STAT6 phosphorylation, transcriptional activity and DNA-binding. Recruits TRAF3 and DISC1 to the microtubules. Involved in kidney development and epithelial morphogenesis. Involved in the regulation of microtubule cytoskeleton organization. Is a negative regulator of microtubule stability, acting through the control of MAP4 levels. Involved in ciliogenesis.

Subunit / interactions. Component of the IFT complex B, at least composed of IFT20, IFT22, IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT57, IFT74, IFT80, IFT81, and IFT88. Interacts with IFT88. Interacts with IL13RA1. Binds to microtubules, TRAF3 and DISC1. Interacts with MAP4.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Cilium. Cilium axoneme. Cilium basal body.

Tissue specificity. Ubiquitous.

Disease relevance. Senior-Loken syndrome 9 (SLSN9) [MIM:616629] A renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TRAF3IP1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TDR0-1	1	yes
Q8TDR0-2	2

RefSeq proteins (2): NP_001132962, NP_056465* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018799	TRAF3IP1	Family
IPR040468	TRAF3IP1_N	Domain
IPR041476	TRAF3IP1_C	Domain
IPR042576	TRAF3IP1_N_sf	Homologous_superfamily

Pfam: PF10243, PF17749

UniProt features (34 total): sequence variant 9, helix 8, compositionally biased region 6, region of interest 3, turn 3, modified residue 2, chain 1, splice variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2EQO	SOLUTION NMR
8KCQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDR0-F1	61.95	0.32

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): 317, 476

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-5617833	Cilium Assembly

MSigDB gene sets: 253 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_EMBRYONIC_DIGIT_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, BROWNE_HCMV_INFECTION_24HR_UP

GO Biological Process (22): morphogenesis of a polarized epithelium (GO:0001738), kidney development (GO:0001822), negative regulation of protein phosphorylation (GO:0001933), dorsal/ventral neural tube patterning (GO:0021904), embryonic camera-type eye development (GO:0031076), negative regulation of protein-containing complex assembly (GO:0031333), negative regulation of type I interferon production (GO:0032480), negative regulation of interferon-beta production (GO:0032688), embryonic heart tube development (GO:0035050), intraciliary anterograde transport (GO:0035720), post-anal tail morphogenesis (GO:0036342), intraciliary transport (GO:0042073), embryonic digit morphogenesis (GO:0042733), negative regulation of smoothened signaling pathway (GO:0045879), negative regulation of defense response to virus (GO:0050687), defense response to virus (GO:0051607), cilium assembly (GO:0060271), regulation of microtubule cytoskeleton organization (GO:0070507), neural tube patterning (GO:0021532), cell projection organization (GO:0030030), animal organ development (GO:0048513), system development (GO:0048731)

GO Molecular Function (2): microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (15): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), centrosome (GO:0005813), cilium (GO:0005929), axoneme (GO:0005930), nuclear body (GO:0016604), intraciliary transport particle A (GO:0030991), intraciliary transport particle B (GO:0030992), ciliary transition zone (GO:0035869), ciliary basal body (GO:0036064), ciliary tip (GO:0097542), ciliary base (GO:0097546), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

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
cellular anatomical structure	8
cilium	5
intraciliary transport particle	3
embryonic organ development	2
cilium organization	2
microtubule organizing center	2
intracellular membraneless organelle	2
protein-containing complex	2
morphogenesis of an epithelium	1
animal organ development	1
renal system development	1
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
dorsal/ventral pattern formation	1
neural tube patterning	1
camera-type eye development	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
protein-containing complex assembly	1
negative regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
negative regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	1
heart development	1
tube development	1
epithelium development	1
intraciliary transport	1
anatomical structure morphogenesis	1
transport along microtubule	1
embryonic limb morphogenesis	1
embryonic morphogenesis	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
negative regulation of signal transduction	1
negative regulation of response to biotic stimulus	1
negative regulation of defense response	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFT54	IFT57	Q9NWB7	995
IFT54	IFT20	Q8IY31	995
IFT54	IFT80	Q9P2H3	987
IFT54	IFT38	Q96AJ1	986
IFT54	IFT172	Q9UG01	984
IFT54	IFT46	Q9NQC8	977
IFT54	IFT27	Q9BW83	977
IFT54	IFT22	Q9H7X7	976
IFT54	IFT25	Q9Y547	974
IFT54	IFT74	Q96LB3	973
IFT54	IFT52	Q9Y366	962
IFT54	IFT70B	Q8N4P2	961
IFT54	RABEP1	Q15276	948
IFT54	IFT81	Q8WYA0	943
IFT54	TRAF3	Q13114	939

IntAct

99 interactions, top by confidence:

A	B	Type	Score
IFT57	CORO1A	psi-mi:“MI:0914”(association)	0.790
IFT70A	IFT56	psi-mi:“MI:0914”(association)	0.790
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
TRAF3IP1	DISC1	psi-mi:“MI:0915”(physical association)	0.740
DISC1	TRAF3IP1	psi-mi:“MI:0915”(physical association)	0.740
DISC1	TRAF3IP1	psi-mi:“MI:0403”(colocalization)	0.740
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
IFT25	IFT56	psi-mi:“MI:0914”(association)	0.690
TRAF3IP1	HSPA8	psi-mi:“MI:0915”(physical association)	0.660
TRAF3IP1	HSPA8	psi-mi:“MI:0403”(colocalization)	0.660
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640
TRAF3	TRAF3IP1	psi-mi:“MI:0915”(physical association)	0.640
TRAF3IP1	TRAF3	psi-mi:“MI:0915”(physical association)	0.640
TRAF3IP1	TRAF3	psi-mi:“MI:0403”(colocalization)	0.640

BioGRID (128): TRAF3IP1 (Affinity Capture-MS), TRAF3IP1 (Reconstituted Complex), TRAF3IP1 (Affinity Capture-MS), TRAF3IP1 (Proximity Label-MS), TRAF3IP1 (Affinity Capture-MS), TRAF3IP1 (Affinity Capture-MS), UBXN10 (Reconstituted Complex), TRAF3IP1 (Affinity Capture-MS), TRAF3IP1 (Affinity Capture-MS), TRAF3IP1 (Affinity Capture-MS), TRAF3IP1 (Affinity Capture-MS), TRAF3IP1 (Affinity Capture-MS), IFT20 (Affinity Capture-MS), DTNBP1 (Affinity Capture-MS), TRAF3IP1 (Affinity Capture-MS)

ESM2 similar proteins: A2AJT4, A2CG63, B0S733, F1QNX7, G3V8T1, O75376, O94988, P29536, Q02040, Q14241, Q149C2, Q15695, Q15696, Q28G87, Q2KIC0, Q4FZU3, Q4G0J3, Q4KKX4, Q4LE39, Q4R627, Q53F19, Q561R3, Q5NCR9, Q5R4U2, Q5RL73, Q5U2T3, Q5XIN3, Q5ZM19, Q60974, Q62377, Q63187, Q64707, Q6PFK1, Q6PGZ3, Q8BZR9, Q8C761, Q8CB77, Q8K2X2, Q8QG78, Q8TDR0

Diamond homologs: A8B976, Q149C2, Q5XIN3, Q6PGZ3, Q8TDR0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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
Intraflagellar transport	13	59.2×	4e-18

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary anterograde transport	12	186.7×	1e-23
intraciliary transport	10	98.5×	3e-16
microtubule nucleation	5	54.8×	2e-06
non-motile cilium assembly	7	35.7×	8e-08
smoothened signaling pathway	9	28.6×	2e-09
cilium assembly	18	23.2×	5e-18
kidney development	5	12.3×	2e-03
microtubule cytoskeleton organization	5	10.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	26
Likely pathogenic	12
Uncertain significance	314
Likely benign	259
Benign	38

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1002602	NM_015650.4(TRAF3IP1):c.1490del (p.Glu497fs)	Pathogenic
1006456	NM_015650.4(TRAF3IP1):c.926del (p.Ser308_Ser309insTer)	Pathogenic
1025887	NM_015650.4(TRAF3IP1):c.1693C>T (p.Arg565Ter)	Pathogenic
1352748	NM_015650.4(TRAF3IP1):c.522del (p.Glu175fs)	Pathogenic
1399586	NM_015650.4(TRAF3IP1):c.796del (p.Asp266fs)	Pathogenic
1418058	NM_015650.4(TRAF3IP1):c.750_753del (p.Lys252fs)	Pathogenic
1498494	NM_015650.4(TRAF3IP1):c.768dup (p.Lys257fs)	Pathogenic
2105958	NM_015650.4(TRAF3IP1):c.688C>T (p.Arg230Ter)	Pathogenic
2119349	NM_015650.4(TRAF3IP1):c.802G>T (p.Glu268Ter)	Pathogenic
2164282	NM_015650.4(TRAF3IP1):c.699del (p.Asp233fs)	Pathogenic
2164957	NM_015650.4(TRAF3IP1):c.369dup (p.Ala124fs)	Pathogenic
2426204	NC_000002.11:g.(?239229304)(239238003_?)del	Pathogenic
254146	NM_015650.4(TRAF3IP1):c.463C>T (p.Arg155Ter)	Pathogenic
254148	NM_015650.4(TRAF3IP1):c.1575+6T>G	Pathogenic
254149	NM_015650.4(TRAF3IP1):c.373G>A (p.Val125Met)	Pathogenic
254150	NM_015650.4(TRAF3IP1):c.51T>G (p.Ile17Met)	Pathogenic
2734434	NM_015650.4(TRAF3IP1):c.771del (p.Glu258fs)	Pathogenic
2734435	NM_015650.4(TRAF3IP1):c.774_775del (p.Lys259fs)	Pathogenic
2840830	NM_015650.4(TRAF3IP1):c.559G>T (p.Glu187Ter)	Pathogenic
3706261	NM_015650.4(TRAF3IP1):c.799C>T (p.Arg267Ter)	Pathogenic
4691621	NM_015650.4(TRAF3IP1):c.345del (p.Leu116fs)	Pathogenic
4717736	NM_015650.4(TRAF3IP1):c.1388_1395dup (p.Pro466fs)	Pathogenic
4771345	NM_015650.4(TRAF3IP1):c.1716G>A (p.Trp572Ter)	Pathogenic
852433	NM_015650.4(TRAF3IP1):c.1159G>T (p.Gly387Ter)	Pathogenic
855002	NM_015650.4(TRAF3IP1):c.702_703del (p.Gly235fs)	Pathogenic
947977	NM_015650.4(TRAF3IP1):c.1081_1082del (p.Ile361fs)	Pathogenic
1035683	NM_015650.4(TRAF3IP1):c.192+1G>C	Likely pathogenic
1423607	NM_015650.4(TRAF3IP1):c.987+1G>A	Likely pathogenic
1489914	NM_015650.4(TRAF3IP1):c.1159+1G>C	Likely pathogenic
1519642	NM_015650.4(TRAF3IP1):c.915+1G>A	Likely pathogenic

SpliceAI

4081 predictions. Top by Δscore:

Variant	Effect	Δscore
2:238320783:G:GT	donor_gain	1.0000
2:238325793:A:AG	acceptor_gain	1.0000
2:238325793:AAT:A	acceptor_gain	1.0000
2:238325793:AATG:A	acceptor_gain	1.0000
2:238325795:T:TA	acceptor_gain	1.0000
2:238325796:G:A	acceptor_gain	1.0000
2:238325967:CAAG:C	donor_loss	1.0000
2:238325968:AAGGT:A	donor_loss	1.0000
2:238325969:AGGTA:A	donor_loss	1.0000
2:238325970:GG:G	donor_loss	1.0000
2:238325972:T:A	donor_loss	1.0000
2:238328672:A:AG	acceptor_gain	1.0000
2:238328672:ATTT:A	acceptor_gain	1.0000
2:238328672:ATTTG:A	acceptor_gain	1.0000
2:238328673:T:G	acceptor_gain	1.0000
2:238328675:T:A	acceptor_gain	1.0000
2:238328676:G:A	acceptor_gain	1.0000
2:238333958:A:G	acceptor_gain	1.0000
2:238348762:A:AG	acceptor_gain	1.0000
2:238348763:G:GG	acceptor_gain	1.0000
2:238348763:GAA:G	acceptor_gain	1.0000
2:238349301:T:A	acceptor_gain	1.0000
2:238349310:A:AG	acceptor_gain	1.0000
2:238349311:A:G	acceptor_gain	1.0000
2:238349313:ATTT:A	acceptor_gain	1.0000
2:238349313:ATTTG:A	acceptor_gain	1.0000
2:238349316:T:TA	acceptor_gain	1.0000
2:238349317:G:A	acceptor_gain	1.0000
2:238352823:TTAG:T	acceptor_loss	1.0000
2:238352825:A:T	acceptor_loss	1.0000

AlphaMissense

4559 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:238320742:T:C	L27P	0.999
2:238320766:T:C	L35P	0.999
2:238325823:A:C	K69N	0.999
2:238325823:A:T	K69N	0.999
2:238325834:T:C	L73P	0.999
2:238325909:G:A	G98E	0.999
2:238325939:T:C	L108P	0.999
2:238320751:C:A	P30H	0.998
2:238320756:T:C	F32L	0.998
2:238320758:C:A	F32L	0.998
2:238320758:C:G	F32L	0.998
2:238320762:T:G	Y34D	0.998
2:238320768:C:G	H36D	0.998
2:238325822:A:T	K69I	0.998
2:238325906:C:A	A97E	0.998
2:238325936:T:C	L107P	0.998
2:238349357:C:A	A467D	0.998
2:238356022:T:C	I544T	0.998
2:238320739:T:C	L26P	0.997
2:238320742:T:A	L27Q	0.997
2:238320747:A:G	K29E	0.997
2:238320749:G:C	K29N	0.997
2:238320749:G:T	K29N	0.997
2:238320759:C:A	R33S	0.997
2:238320762:T:C	Y34H	0.997
2:238320771:G:C	D37H	0.997
2:238325814:A:C	K66N	0.997
2:238325814:A:T	K66N	0.997
2:238325821:A:G	K69E	0.997
2:238325831:T:C	F72S	0.997

dbSNP variants (sampled 300 via entrez): RS1000057097 (2:238337751 G>A), RS1000094366 (2:238335670 G>C), RS1000105027 (2:238374309 A>G), RS1000220776 (2:238375700 C>A,G), RS1000283684 (2:238352354 G>A), RS1000313471 (2:238380046 T>C), RS1000327734 (2:238334750 C>T), RS1000450147 (2:238370752 A>G), RS1000463537 (2:238346536 G>A), RS1000489640 (2:238381514 G>T), RS1000501779 (2:238370483 G>A), RS1000528969 (2:238385140 C>G,T), RS1000621034 (2:238351441 G>A,C,T), RS1000622306 (2:238339636 G>A), RS1000648146 (2:238376985 G>A)

Disease associations

OMIM: gene MIM:607380 | disease phenotypes: MIM:616629, MIM:263520, MIM:208500, MIM:225500

GenCC curated gene-disease

Disease	Classification	Inheritance
Senior-Loken syndrome 9	Definitive	Autosomal recessive
Senior-Loken syndrome	Supportive	Autosomal recessive
short rib-polydactyly syndrome, Majewski type	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliopathy	Definitive	AR

Mondo (6): Senior-Loken syndrome 9 (MONDO:0014712), short-rib thoracic dysplasia 6 with or without polydactyly (MONDO:0009894), Jeune syndrome (MONDO:0018770), Ellis-van Creveld syndrome (MONDO:0009162), Senior-Loken syndrome (MONDO:0017842), short rib-polydactyly syndrome, Majewski type (MONDO:0019662)

Orphanet (3): Senior-Loken syndrome (Orphanet:3156), Jeune syndrome (Orphanet:474), Ellis Van Creveld syndrome (Orphanet:289)

HPO phenotypes

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

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000090	Nephronophthisis
HP:0000135	Hypogonadism
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000529	Progressive visual loss
HP:0000556	Retinal dystrophy
HP:0000608	Macular degeneration
HP:0000639	Nystagmus
HP:0000822	Hypertension
HP:0000938	Osteopenia
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001513	Obesity
HP:0001970	Tubulointerstitial nephritis
HP:0002612	Congenital hepatic fibrosis
HP:0003774	Stage 5 chronic kidney disease
HP:0004322	Short stature
HP:0004348	Abnormality of bone mineral density
HP:0004469	Chronic bronchitis
HP:0007703	Abnormal retinal pigmentation
HP:0008209	Premature ovarian insufficiency
HP:0008802	Hypoplasia of the femoral head
HP:0010442	Polydactyly
HP:0010579	Cone-shaped epiphysis
HP:0012622	Chronic kidney disease

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001199_2	Iris characteristics	6.000000e-06
GCST001199_6	Iris characteristics	2.000000e-12
GCST004185_18	Lung function (FEV1/FVC)	3.000000e-10
GCST005580_164	Intraocular pressure	1.000000e-08
GCST005580_248	Intraocular pressure	1.000000e-10
GCST006394_65	Intraocular pressure	7.000000e-09
GCST006412_31	Intraocular pressure	6.000000e-09
GCST007160_7	Refractive astigmatism	5.000000e-07
GCST007431_80	Lung function (FEV1/FVC)	3.000000e-11
GCST007432_118	FEV1	9.000000e-13
GCST007565_147	Morning person	4.000000e-43
GCST007576_2	Chronotype	4.000000e-43
GCST007576_375	Chronotype	9.000000e-14
GCST009391_1639	Metabolite levels	5.000000e-06
GCST009723_95	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2.000000e-06
GCST009724_27	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-08
GCST010002_412	Refractive error	6.000000e-16

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004731	eye measurement
EFO:0004713	FEV/FVC ratio
EFO:0004695	intraocular pressure measurement
EFO:0004314	forced expiratory volume
EFO:0008328	chronotype measurement
EFO:0007787	plasma betaine measurement
EFO:0006939	cup-to-disc ratio measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004613	Ellis-Van Creveld Syndrome	C05.116.099.708.327; C16.131.077.350.398; C16.131.831.350.398; C16.320.850.250.398; C17.800.804.350.398; C17.800.827.250.398
C537571	Jeune syndrome (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

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, affects methylation, increases methylation	1
2-butenal	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
aflatoxin B2	increases methylation	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
Fulvestrant	affects cotreatment, affects methylation	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, increases expression	1
Arsenicals	increases methylation	1
Ethyl Methanesulfonate	increases expression	1
Manganese	increases expression, increases abundance	1
Menthol	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Vitamin E	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT00948376	Not specified	COMPLETED	Natural History of Asphyxiating Thoracic Dystrophy (DTJ)
NCT04143841	Not specified	TERMINATED	Viveye Ocular Magnetic Neurostimulation System (OMNS) for the Management of Severe Dry Eye Disease