IFT80

Summary

IFT80 (intraflagellar transport 80, HGNC:29262) is a protein-coding gene on chromosome 3q25.33, encoding Intraflagellar transport protein 80 homolog (Q9P2H3). Component of the intraflagellar transport (IFT) complex B, which is essential for the development and maintenance of motile and sensory cilia.

The protein encoded by this gene is part of the intraflagellar transport complex B and is necessary for the function of motile and sensory cilia. Defects in this gene are a cause of asphyxiating thoracic dystrophy 2 (ATD2). Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 57560 — RefSeq curated summary.

At a glance

• Gene–disease (curated): asphyxiating thoracic dystrophy 2 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 480 total — 24 pathogenic, 17 likely-pathogenic
• Phenotypes (HPO): 69
• MANE Select transcript: NM_020800

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29262
Approved symbol	IFT80
Name	intraflagellar transport 80
Location	3q25.33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1374, FAP167, CFAP167
Ensembl gene	ENSG00000068885
Ensembl biotype	protein_coding
OMIM	611177
Entrez	57560

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 17 protein_coding, 8 protein_coding_CDS_not_defined, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000326448, ENST00000461213, ENST00000463240, ENST00000465537, ENST00000465972, ENST00000466326, ENST00000467254, ENST00000468218, ENST00000468327, ENST00000472555, ENST00000472773, ENST00000475677, ENST00000477495, ENST00000478278, ENST00000478370, ENST00000478460, ENST00000478536, ENST00000482317, ENST00000483325, ENST00000483465, ENST00000484963, ENST00000486856, ENST00000487943, ENST00000489004, ENST00000496589, ENST00000498145, ENST00000498409, ENST00000866736, ENST00000866737, ENST00000866738, ENST00000915648, ENST00000967444

RefSeq mRNA: 3 — MANE Select: NM_020800 NM_001190241, NM_001190242, NM_020800

CCDS: CCDS3188, CCDS54668

Canonical transcript exons

ENST00000326448 — 20 exons

Exon	Start	End
ENSE00001430097	160399146	160399225
ENSE00001826122	160256986	160258635
ENSE00003486065	160384564	160384646
ENSE00003507563	160279193	160279364
ENSE00003509058	160268413	160268536
ENSE00003535577	160303915	160303989
ENSE00003535597	160277306	160277478
ENSE00003541522	160381503	160381724
ENSE00003554049	160357489	160357578
ENSE00003608822	160285804	160285868
ENSE00003620006	160300883	160301046
ENSE00003625071	160277581	160277670
ENSE00003630135	160282478	160282613
ENSE00003636437	160319760	160319939
ENSE00003664249	160377430	160377540
ENSE00003668387	160307663	160307781
ENSE00003670165	160280667	160280814
ENSE00003685657	160375812	160375880
ENSE00003688291	160366043	160366152
ENSE00003788325	160356013	160356150

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.2960 / max 459.3157, expressed in 1655 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45351	10.5265	1607
45353	1.4559	732
45352	0.4694	245
45350	0.3944	200
45348	0.3875	98
45349	0.0622	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	99.36	gold quality
oviduct epithelium	UBERON:0004804	99.00	gold quality
endothelial cell	CL:0000115	98.38	gold quality
bronchial epithelial cell	CL:0002328	98.21	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.98	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.87	gold quality
bronchus	UBERON:0002185	97.73	gold quality
corpus callosum	UBERON:0002336	97.53	gold quality
germinal epithelium of ovary	UBERON:0001304	97.32	gold quality
lateral globus pallidus	UBERON:0002476	97.11	gold quality
visceral pleura	UBERON:0002401	96.46	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.42	gold quality
inferior vagus X ganglion	UBERON:0005363	96.37	gold quality
bone marrow cell	CL:0002092	96.22	gold quality
pigmented layer of retina	UBERON:0001782	96.22	gold quality
thymus	UBERON:0002370	96.11	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.09	gold quality
subthalamic nucleus	UBERON:0001906	96.03	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.03	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.84	gold quality
epithelium of nasopharynx	UBERON:0001951	95.72	gold quality
parietal pleura	UBERON:0002400	95.72	gold quality
renal medulla	UBERON:0000362	95.45	gold quality
substantia nigra pars compacta	UBERON:0001965	95.14	gold quality
superior vestibular nucleus	UBERON:0007227	94.90	gold quality
caput epididymis	UBERON:0004358	94.78	gold quality
medulla oblongata	UBERON:0001896	94.66	gold quality
occipital lobe	UBERON:0002021	94.57	gold quality
primary visual cortex	UBERON:0002436	94.40	gold quality
palpebral conjunctiva	UBERON:0001812	94.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	11.00
E-ANND-3	yes	6.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

96 targeting IFT80, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-9-3P	99.96	70.88	2068
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3143	99.93	71.96	3104

Literature-anchored findings (GeneRIF, showing 5)

• Mutations in IFT80 is associated with Jeune asphyxiating thoracic dystrophy (PMID:17468754)
• Identification and characterization of a human IFT80 long isoform (namely IFT80-L), the carboxyl terminus of which shares the protein sequence of IFT80, is reported. (PMID:18601909)
• Mutations in IFT80 can be responsible for a lethal form of short-rib polydactyly and provide the molecular basis for the Jeune-Verma-Naumoff dysplasia spectrum. (PMID:19648123)
• IFT80 plays an important role in invasion of gastric cancer. (PMID:30453504)
• Mutations in IFT80 cause Short rib-polydactyly syndrome, Beemer type. (PMID:30767363)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ift80	ENSDARG00000038879
mus_musculus	Ift80	ENSMUSG00000027778
rattus_norvegicus	Ift80	ENSRNOG00000009808
drosophila_melanogaster	Oseg5	FBGN0032891
caenorhabditis_elegans		WBGENE00000484

Paralogs (1): TRIM59 (ENSG00000213186)

Protein

Protein identifiers

Intraflagellar transport protein 80 homolog — Q9P2H3 (reviewed: Q9P2H3)

Alternative names: WD repeat-containing protein 56

All UniProt accessions (12): Q9P2H3, C9IZR2, C9J627, C9J6G8, C9J6I5, C9JSB1, C9JUI1, C9JUJ1, F8WCB0, H7C4K6, H7C5M3, H7C5P3

UniProt curated annotations — full annotation on UniProt →

Function. Component of the intraflagellar transport (IFT) complex B, which is essential for the development and maintenance of motile and sensory cilia.

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 IFT57 and IFT70B.

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

Tissue specificity. Isoform IFT80-L is widely expressed.

Disease relevance. Short-rib thoracic dysplasia 2 with or without polydactyly (SRTD2) [MIM:611263] A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a ’trident’ appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Based on a naturally occurring readthrough transcript which produces a TRIM59-IFT80 fusion protein.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9P2H3-1	1	yes
Q9P2H3-2	2
Q9P2H3-3	IFT80-L

RefSeq proteins (3): NP_001177170, NP_001177171, NP_065851* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR056157	TPR_IFT80_172_dom	Domain
IPR056456	Beta-prop_IFT80_2nd	Domain

Pfam: PF00400, PF23335, PF23387

UniProt features (18 total): repeat 7, sequence variant 4, splice variant 2, sequence conflict 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2H3-F1	92.50	0.83

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 489 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL

GO Biological Process (45): osteoblast differentiation (GO:0001649), endochondral ossification (GO:0001958), growth plate cartilage chondrocyte differentiation (GO:0003418), apoptotic process (GO:0006915), establishment or maintenance of cell polarity (GO:0007163), smoothened signaling pathway (GO:0007224), canonical NF-kappaB signal transduction (GO:0007249), fibroblast growth factor receptor signaling pathway (GO:0008543), gene expression (GO:0010467), proteasomal protein catabolic process (GO:0010498), negative regulation of keratinocyte proliferation (GO:0010839), protein ubiquitination (GO:0016567), spinal cord development (GO:0021510), osteoclast differentiation (GO:0030316), osteoblast proliferation (GO:0033687), multicellular organism growth (GO:0035264), non-canonical Wnt signaling pathway (GO:0035567), bone mineralization involved in bone maturation (GO:0035630), intraciliary anterograde transport (GO:0035720), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), keratinocyte proliferation (GO:0043616), tooth eruption (GO:0044691), stem cell differentiation (GO:0048863), protein stabilization (GO:0050821), limb development (GO:0060173), cilium assembly (GO:0060271), articular cartilage development (GO:0061975), odontoblast differentiation (GO:0071895), stem cell proliferation (GO:0072089), receptor localization to non-motile cilium (GO:0097500), response to inositol (GO:1902140), non-motile cilium assembly (GO:1905515), cartilage homeostasis (GO:1990079), negative regulation of non-canonical Wnt signaling pathway (GO:2000051), skeletal system development (GO:0001501), ossification (GO:0001503), chondrocyte differentiation (GO:0002062), growth plate cartilage development (GO:0003417), cell population proliferation (GO:0008283), tissue development (GO:0009888)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (11): centrosome (GO:0005813), cilium (GO:0005929), axoneme (GO:0005930), intraciliary transport particle A (GO:0030991), intraciliary transport particle B (GO:0030992), ciliary basal body (GO:0036064), ciliary tip (GO:0097542), 9+0 non-motile cilium (GO:0097731), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intraciliary transport particle	3
intracellular signaling cassette	2
microtubule organizing center	2
protein-containing complex	2
cilium	2
ossification	1
cell differentiation	1
replacement ossification	1
endochondral bone morphogenesis	1
chondrocyte differentiation involved in endochondral bone morphogenesis	1
growth plate cartilage development	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
cell surface receptor signaling pathway	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
macromolecule biosynthetic process	1
protein catabolic process	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
negative regulation of epithelial cell proliferation	1
protein modification by small protein conjugation	1
central nervous system development	1
anatomical structure development	1
myeloid leukocyte differentiation	1
cell population proliferation	1
multicellular organismal process	1
developmental growth	1
Wnt signaling pathway	1
bone mineralization	1
ossification involved in bone maturation	1
intraciliary transport	1
binding	1
centriole	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1

Protein interactions and networks

STRING

2460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFT80	IFT57	Q9NWB7	995
IFT80	IFT20	Q8IY31	990
IFT80	IFT54	Q8TDR0	987
IFT80	IFT172	Q9UG01	986
IFT80	IFT52	Q9Y366	982
IFT80	IFT88	Q13099	978
IFT80	IFT38	Q96AJ1	977
IFT80	DYNC2H1	Q8NCM8	971
IFT80	IFT81	Q8WYA0	964
IFT80	IFT74	Q96LB3	964
IFT80	IFT46	Q9NQC8	963
IFT80	IFT70B	Q8N4P2	947
IFT80	IFT27	Q9BW83	917
IFT80	IFT140	Q96RY7	899
IFT80	IFT25	Q9Y547	854

IntAct

62 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
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
IFT25	IFT56	psi-mi:“MI:0914”(association)	0.690
IFT46	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT22	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT172	IFT56	psi-mi:“MI:0914”(association)	0.590
CORO1A	VARS1	psi-mi:“MI:0914”(association)	0.530
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (60): IFT80 (Affinity Capture-MS), IFT80 (Affinity Capture-MS), IFT52 (Co-fractionation), IFT80 (Co-fractionation), IFT80 (Affinity Capture-MS), UBXN10 (Reconstituted Complex), IFT80 (Affinity Capture-MS), IFT80 (Affinity Capture-MS), IFT80 (Affinity Capture-MS), IFT80 (Affinity Capture-MS), IFT80 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT88 (Affinity Capture-MS), IFT57 (Affinity Capture-MS), IFT20 (Affinity Capture-MS)

ESM2 similar proteins: A5DHD9, B6QC56, B8M0Q1, G0SA60, O00423, O15143, O62621, O64740, O80856, O88656, O93277, O94319, O95834, O96622, P53024, P55735, P78774, Q04491, Q05BC3, Q0UNA9, Q15269, Q1DZQ0, Q26613, Q2KJH4, Q38884, Q3ZCC9, Q4V8C3, Q54D08, Q58CQ2, Q5B8Y3, Q5EBD9, Q5IH81, Q5RFQ3, Q5XFW8, Q66HB3, Q6BZX5, Q6CSZ5, Q6GNU1, Q6P6T4, Q7K2X8

Diamond homologs: Q66HB3, Q6GPC6, Q7SZM9, Q8BHJ5, Q8K057, Q9BZK7, Q9P2H3, C4Q0P6, C4R6H3, D1ZEB4, O35828, O54927, O60907, O74845, O80990, P57737, Q0V8F1, Q17N69, Q2HBX6, Q4R8H1, Q5RBW3, Q6GPB9, Q75C26, Q7RY30, Q7T2F6, Q8C0J2, Q95RJ9, Q9BQ87, Q9C1X0, Q9D2V7, Q9FN19, Q9QXE7, Q9W351, Q9Y6I7, B0R0D7, Q6CGP9, Q6CMA2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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	14	127.5×	3e-26

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary anterograde transport	13	411.8×	2e-31
intraciliary transport	12	240.7×	3e-25
smoothened signaling pathway	9	58.2×	1e-12
non-motile cilium assembly	5	51.9×	2e-06
cilium assembly	13	34.2×	9e-16

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	17
Uncertain significance	237
Likely benign	132
Benign	30

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100665	NM_020800.3(IFT80):c.721G>A (p.Gly241Arg)	Pathogenic
1072907	NM_020800.3(IFT80):c.972_973insNNNNNNNNTTTTTTTT (p.Asn325delinsXaaXaaXaaPhePheTer)	Pathogenic
1075438	NM_020800.3(IFT80):c.639+1del	Pathogenic
1435198	NM_020800.3(IFT80):c.898_899del (p.Glu300fs)	Pathogenic
1442026	NM_020800.3(IFT80):c.225_226insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAGAAACAAACC (p.Gln76fs)	Pathogenic
1451633	NM_020800.3(IFT80):c.1388del (p.Ile463fs)	Pathogenic
1453983	NM_020800.3(IFT80):c.1066del (p.Tyr356fs)	Pathogenic
1942597	NM_020800.3(IFT80):c.951del (p.Met318fs)	Pathogenic
1957267	NM_020800.3(IFT80):c.28G>T (p.Glu10Ter)	Pathogenic
2075255	NM_020800.3(IFT80):c.120G>A (p.Trp40Ter)	Pathogenic
2098812	NM_020800.3(IFT80):c.2119A>T (p.Lys707Ter)	Pathogenic
2201153	NM_020800.3(IFT80):c.2124C>G (p.Tyr708Ter)	Pathogenic
2426597	NC_000003.11:g.(?160083811)(160099532_?)del	Pathogenic
2426598	NC_000003.11:g.(?160073781)(160099532_?)del	Pathogenic
2426599	NC_000003.11:g.(?160073781)(160083960_?)del	Pathogenic
2751676	NM_020800.3(IFT80):c.128T>G (p.Leu43Ter)	Pathogenic
2813217	NM_020800.3(IFT80):c.2094G>A (p.Trp698Ter)	Pathogenic
2888490	NM_020800.3(IFT80):c.1866dup (p.Met623fs)	Pathogenic
3246846	NC_000003.11:g.(?159986181)(160021797_?)del	Pathogenic
343976	NM_020800.3(IFT80):c.710G>A (p.Trp237Ter)	Pathogenic
3695083	NM_020800.3(IFT80):c.301del (p.Ser101fs)	Pathogenic
4531879	NM_020800.3(IFT80):c.1198G>T (p.Glu400Ter)	Pathogenic
4706112	NM_020800.3(IFT80):c.1769del (p.Ala590fs)	Pathogenic
830648	NC_000003.12:g.(?160299237)(160319939_?)del	Pathogenic
1066914	NM_020800.3(IFT80):c.1152-1G>C	Likely pathogenic
1522059	NM_020800.3(IFT80):c.1380+2del	Likely pathogenic
2008736	NM_020800.3(IFT80):c.1664+1G>A	Likely pathogenic
2169908	NM_020800.3(IFT80):c.957+1G>A	Likely pathogenic
2426602	NC_000003.11:g.(?159992649)(160000363_?)del	Likely pathogenic
3588718	NM_020800.3(IFT80):c.1994del (p.Ile665fs)	Likely pathogenic

SpliceAI

4003 predictions. Top by Δscore:

Variant	Effect	Δscore
3:160268405:ATACT:A	donor_loss	1.0000
3:160268406:TACTT:T	donor_loss	1.0000
3:160268407:ACTT:A	donor_loss	1.0000
3:160268408:CTTA:C	donor_loss	1.0000
3:160268408:CTTAC:C	donor_loss	1.0000
3:160268410:TACA:T	donor_loss	1.0000
3:160268411:A:AC	donor_gain	1.0000
3:160268411:A:C	donor_loss	1.0000
3:160268411:ACAC:A	donor_gain	1.0000
3:160268411:ACACC:A	donor_loss	1.0000
3:160268412:C:CA	donor_loss	1.0000
3:160268412:C:CC	donor_gain	1.0000
3:160268412:CA:C	donor_gain	1.0000
3:160268412:CACC:C	donor_gain	1.0000
3:160268412:CACCT:C	donor_gain	1.0000
3:160277300:TATTA:T	donor_loss	1.0000
3:160277302:TTA:T	donor_loss	1.0000
3:160277303:TAC:T	donor_loss	1.0000
3:160277303:TACC:T	donor_loss	1.0000
3:160277304:ACCTT:A	donor_loss	1.0000
3:160277305:C:CA	donor_loss	1.0000
3:160277474:TCAAT:T	acceptor_gain	1.0000
3:160277475:CAAT:C	acceptor_gain	1.0000
3:160277475:CAATC:C	acceptor_gain	1.0000
3:160277476:AAT:A	acceptor_gain	1.0000
3:160277477:AT:A	acceptor_gain	1.0000
3:160277479:C:CC	acceptor_gain	1.0000
3:160277576:CTT:C	donor_loss	1.0000
3:160277576:CTTA:C	donor_gain	1.0000
3:160277577:TTAC:T	donor_loss	1.0000

AlphaMissense

5118 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:160268480:C:G	R719P	0.999
3:160319888:A:G	W277R	0.999
3:160319888:A:T	W277R	0.999
3:160366129:A:G	W155R	0.999
3:160366129:A:T	W155R	0.999
3:160375854:A:G	W133R	0.999
3:160375854:A:T	W133R	0.999
3:160377460:A:G	W114R	0.999
3:160377460:A:T	W114R	0.999
3:160268492:A:T	V715D	0.998
3:160268523:C:G	A705P	0.998
3:160280791:A:G	W514R	0.998
3:160280791:A:T	W514R	0.998
3:160356081:A:G	W237R	0.998
3:160356081:A:T	W237R	0.998
3:160356147:A:G	W215R	0.998
3:160356147:A:T	W215R	0.998
3:160375831:T:A	R140S	0.998
3:160375831:T:G	R140S	0.998
3:160375832:C:G	R140T	0.998
3:160377432:G:T	T123K	0.998
3:160381698:A:G	W22R	0.998
3:160381698:A:T	W22R	0.998
3:160268481:G:T	R719S	0.997
3:160268522:G:T	A705D	0.997
3:160277313:A:G	W698R	0.997
3:160277313:A:T	W698R	0.997
3:160277600:G:T	A636D	0.997
3:160277637:C:G	A624P	0.997
3:160307693:A:T	V349D	0.997

dbSNP variants (sampled 300 via entrez): RS1000017155 (3:160351431 A>G), RS1000026255 (3:160375707 A>C), RS1000038332 (3:160291477 T>C), RS1000063488 (3:160392597 T>C), RS1000132899 (3:160383454 C>A,G,T), RS1000164213 (3:160324826 G>A), RS1000184637 (3:160322041 T>A,C), RS1000184864 (3:160383081 C>T), RS1000200870 (3:160281796 TG>T), RS1000223508 (3:160285220 T>C), RS1000237844 (3:160285209 A>C), RS1000238925 (3:160334386 C>T), RS1000258129 (3:160258286 G>A), RS1000273089 (3:160263046 C>T), RS1000286445 (3:160377893 A>G)

Disease associations

OMIM: gene MIM:611177 | disease phenotypes: MIM:208500, MIM:611263, MIM:263520, MIM:269860, MIM:615630

GenCC curated gene-disease

Disease	Classification	Inheritance
asphyxiating thoracic dystrophy 2	Definitive	Autosomal recessive
Jeune syndrome	Supportive	Autosomal recessive
Beemer-Langer syndrome	Supportive	Autosomal recessive
short rib-polydactyly syndrome, Verma-Naumoff type	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
asphyxiating thoracic dystrophy 2	Definitive	AR

Mondo (7): Jeune syndrome (MONDO:0018770), asphyxiating thoracic dystrophy 2 (MONDO:0012644), connective tissue disorder (MONDO:0003900), short-rib thoracic dysplasia 6 with or without polydactyly (MONDO:0009894), Beemer-Langer syndrome (MONDO:0010024), short-rib thoracic dysplasia 10 with or without polydactyly (MONDO:0014284), (MONDO:0019664)

Orphanet (2): Jeune syndrome (Orphanet:474), Short rib-polydactyly syndrome, Beemer-Langer type (Orphanet:93268)

HPO phenotypes

69 total (30 of 69 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000062	Ambiguous genitalia
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000090	Nephronophthisis
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000126	Hydronephrosis
HP:0000204	Cleft upper lip
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000445	Wide nose
HP:0000518	Cataract
HP:0000766	Abnormal sternum morphology
HP:0000772	Abnormal rib morphology
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0000889	Abnormal clavicle morphology
HP:0000944	Abnormal metaphysis morphology
HP:0001156	Brachydactyly
HP:0001162	Postaxial hand polydactyly
HP:0001169	Broad palm
HP:0001177	Preaxial hand polydactyly
HP:0001274	Agenesis of corpus callosum
HP:0001305	Dandy-Walker malformation
HP:0001321	Cerebellar hypoplasia
HP:0001392	Abnormality of the liver

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST006612_4	LDL cholesterol	1.000000e-10
GCST008103_105	Bipolar disorder	4.000000e-06
GCST010725_1	Malaria	3.000000e-09
GCST010725_57	Malaria	2.000000e-08
GCST010725_87	Malaria	3.000000e-09
GCST90013405_49	Liver enzyme levels (alanine transaminase)	7.000000e-22
GCST90013407_102	Liver enzyme levels (gamma-glutamyl transferase)	3.000000e-35
GCST90013663_13	Alanine aminotransferase levels	3.000000e-17
GCST90013664_39	Aspartate aminotransferase levels	2.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004532	serum gamma-glutamyl transferase measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
C566982	Asphyxiating Thoracic Dystrophy 2 (supp.)
C537571	Jeune syndrome (supp.)
C537599	Short rib-polydactyly syndrome, Beemer type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	3
Arsenic	affects methylation, decreases expression, increases abundance	2
Valproic Acid	decreases methylation, affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
trichostatin A	affects expression	1
sodium arsenite	decreases expression, increases abundance	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Clorgyline	increases expression	1
Coal	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Lead	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	PHASE1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	PHASE1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	PHASE1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	PHASE1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
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
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT01424033	PHASE2/PHASE3	TERMINATED	A Clinical Trial for CTD-ILD Treatment
NCT04915482	PHASE2/PHASE3	UNKNOWN	TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT06574581	PHASE1/PHASE2	RECRUITING	ADSCs Therapy in Patients With CTD-ILD
NCT00001330	Not specified	COMPLETED	Study of Silicone-Associated Connective Tissue Diseases
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00001978	Not specified	TERMINATED	Determination of Kidney Function
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease