IFT81

Summary

IFT81 (intraflagellar transport 81, HGNC:14313) is a protein-coding gene on chromosome 12q24.11, encoding Intraflagellar transport protein 81 homolog (Q8WYA0). Component of the intraflagellar transport (IFT) complex B: together with IFT74, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium.

The protein encoded by this gene, together with IFT74, forms a tubulin-binding module of intraflagellar transport complex B. This module is involved in transport of tubulin within the cilium, and the encoded protein is required for ciliogenesis. Mutations in this gene are a cause of short-rib polydactyly syndromes.

Source: NCBI Gene 28981 — RefSeq curated summary.

At a glance

• Gene–disease (curated): short-rib thoracic dysplasia 19 with or without polydactyly (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 16
• Clinical variants (ClinVar): 529 total — 35 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 28
• MANE Select transcript: NM_014055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14313
Approved symbol	IFT81
Name	intraflagellar transport 81
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	CDV-1R, MGC4027
Ensembl gene	ENSG00000122970
Ensembl biotype	protein_coding
OMIM	605489
Entrez	28981

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000242591, ENST00000361948, ENST00000546374, ENST00000549009, ENST00000550156, ENST00000550748, ENST00000551055, ENST00000551273, ENST00000552912, ENST00000854250, ENST00000854251, ENST00000854252, ENST00000854253, ENST00000911823, ENST00000911824, ENST00000911825, ENST00000911826, ENST00000911827, ENST00000969903, ENST00000969904, ENST00000969905, ENST00000969906

RefSeq mRNA: 6 — MANE Select: NM_014055 NM_001143779, NM_001347946, NM_001347947, NM_001347948, NM_014055, NM_031473

CCDS: CCDS41831, CCDS9142

Canonical transcript exons

ENST00000242591 — 19 exons

Exon	Start	End
ENSE00001131619	110205443	110205514
ENSE00001131625	110203864	110203950
ENSE00001195377	110192617	110192706
ENSE00001195384	110190920	110191048
ENSE00001294709	110127360	110127524
ENSE00001296270	110128950	110129130
ENSE00001307991	110136776	110136860
ENSE00001315653	110132547	110132636
ENSE00001316095	110134948	110135013
ENSE00001319708	110128046	110128149
ENSE00001330009	110135327	110135437
ENSE00002377980	110124357	110124861
ENSE00002390970	110218044	110218793
ENSE00003514394	110146953	110147048
ENSE00003523331	110205595	110205680
ENSE00003648926	110143382	110143545
ENSE00003670254	110209171	110209216
ENSE00003683477	110180422	110180571
ENSE00003786977	110162919	110163065

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 94.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.5345 / max 237.4867, expressed in 1622 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127964	7.0962	1530
127965	1.9031	995
127966	0.5352	334

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	94.80	gold quality
ventricular zone	UBERON:0003053	94.49	gold quality
right uterine tube	UBERON:0001302	94.48	gold quality
epithelium of bronchus	UBERON:0002031	92.16	gold quality
bronchus	UBERON:0002185	91.34	gold quality
ganglionic eminence	UBERON:0004023	91.33	gold quality
calcaneal tendon	UBERON:0003701	90.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.80	gold quality
cortical plate	UBERON:0005343	88.65	gold quality
choroid plexus epithelium	UBERON:0003911	88.29	gold quality
left testis	UBERON:0004533	88.21	gold quality
right testis	UBERON:0004534	88.19	gold quality
caput epididymis	UBERON:0004358	88.05	gold quality
testis	UBERON:0000473	87.64	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.43	gold quality
tibial artery	UBERON:0007610	87.43	gold quality
popliteal artery	UBERON:0002250	87.42	gold quality
embryo	UBERON:0000922	87.27	gold quality
adenohypophysis	UBERON:0002196	86.77	gold quality
endocervix	UBERON:0000458	86.72	gold quality
right ovary	UBERON:0002118	86.30	gold quality
left ovary	UBERON:0002119	86.16	gold quality
stromal cell of endometrium	CL:0002255	86.11	gold quality
endometrium	UBERON:0001295	86.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.04	gold quality
body of uterus	UBERON:0009853	86.03	gold quality
pituitary gland	UBERON:0000007	85.98	gold quality
aorta	UBERON:0000947	85.79	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.62	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting IFT81, 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-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
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-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-7159-3P	99.51	70.17	1920

Literature-anchored findings (GeneRIF, showing 6)

• inconsistent expression levels of human CDV-1 and mouse Cdv-1 in heart implied that cardiac hypertrophy in human SCD might not be associated with the abnormal expression of CDV-1 (PMID:12549821)
• this study found that the two core intraflagellar transport proteins IFT74 and IFT81 form a tubulin-binding module and mapped the interaction to a calponin homology domain of IFT81 and a highly basic domain in IFT74. (PMID:23990561)
• This represents the first report of mutations in IFT81 as a candidate gene for nonsyndromic retinal dystrophy, hence expanding the phenotype spectrum of IFT-B components. (PMID:28460050)
• Our data highlights the importance of detection and careful characterization of intragenic duplication CNVs, presenting them as a novel and very rare genetic mechanism in IFT81-related Jeune syndrome and MATN3-related MED. (PMID:30080953)
• Expanding the phenotypic spectrum of IFT81: Associated ciliopathy syndrome. (PMID:32783357)
• Impaired cooperation between IFT74/BBS22-IFT81 and IFT25-IFT27/BBS19 causes Bardet-Biedl syndrome. (PMID:34888642)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ift81	ENSDARG00000007444
mus_musculus	Ift81	ENSMUSG00000029469
rattus_norvegicus	Ift81	ENSRNOG00000001294
caenorhabditis_elegans		WBGENE00017973

Protein

Protein identifiers

Intraflagellar transport protein 81 homolog — Q8WYA0 (reviewed: Q8WYA0)

Alternative names: Carnitine deficiency-associated protein expressed in ventricle 1

All UniProt accessions (4): F8W1J4, Q8WYA0, H0YHE2, H0YIR4

UniProt curated annotations — full annotation on UniProt →

Function. Component of the intraflagellar transport (IFT) complex B: together with IFT74, forms a tubulin-binding module that specifically mediates transport of tubulin within the cilium. Binds tubulin via its CH (calponin-homology)-like region. Required for ciliogenesis. Required for proper regulation of SHH signaling. Plays an important role during spermatogenesis by modulating the assembly and elongation of the sperm flagella.

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 IFT74; the interaction is direct: within the IFT complex B, IFT74 and IFT81 mediate the transport of tubulin within the cilium. Interacts with tubulin; the interaction is direct. Interacts with IFT57 and IFT70B. Interacts with RABL2/RABL2A; binding is equal in the presence of GTP or GDP. Interacts with IFT88. Interacts (via the IFT74/IFT81 heterodimer) with RABL2B. Interacts with CFAP61.

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

Tissue specificity. Highly expressed in testis, moderately in ovary, heart, liver, skeletal muscle, kidney and pancreas, low in prostate, brain, placenta and lung and not detected in spleen, thymus, small intestine and colon. Isoform CDV-1R is abundantly expressed in testis.

Disease relevance. Short-rib thoracic dysplasia 19 with or without polydactyly (SRTD19) [MIM:617895] 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.

Domain organisation. The CH (calponin-homology)-like region shows high similarity to a CH (calponin-homology) domain and mediates binding to the globular domain of tubulin.

Miscellaneous. Produced by alternative initiation at Met-570 of isoform CDV-1R.

Similarity. Belongs to the IFT81 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8WYA0-1	CDV-1R	yes
Q8WYA0-3	2
Q8WYA0-4	CDV-1

RefSeq proteins (6): NP_001137251, NP_001334875, NP_001334876, NP_001334877, NP_054774, NP_113661 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029600	IFT81	Family
IPR041146	IFT81_CH	Domain
IPR043016	IFT81_N_sf	Homologous_superfamily

Pfam: PF18383

UniProt features (19 total): sequence variant 4, coiled-coil region 4, splice variant 3, mutagenesis site 2, modified residue 2, initiator methionine 1, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WYA0-F1	83.45	0.28

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, 61

Mutagenesis-validated functional residues (2):

Position	Phenotype
73–75	abolishes tubulin-binding and impaired ciliogenesis; when associated with 113-e-e-114.
113–114	abolishes tubulin-binding and impaired ciliogenesis; when associated with 73-e–e-75.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 255 (showing top): GOBP_MALE_GAMETE_GENERATION, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, MODULE_205, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOCC_CENTROSOME, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOBP_SMOOTHENED_SIGNALING_PATHWAY, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY, ZHANG_BREAST_CANCER_PROGENITORS_UP

GO Biological Process (9): spermatogenesis (GO:0007283), regulation of smoothened signaling pathway (GO:0008589), intraciliary anterograde transport (GO:0035720), intraciliary transport involved in cilium assembly (GO:0035735), intraciliary transport (GO:0042073), cilium assembly (GO:0060271), sperm flagellum assembly (GO:0120316), cell projection organization (GO:0030030), cell differentiation (GO:0030154)

GO Molecular Function (2): tubulin binding (GO:0015631), protein binding (GO:0005515)

GO Cellular Component (14): cytoplasm (GO:0005737), centrosome (GO:0005813), centriole (GO:0005814), cilium (GO:0005929), intraciliary transport particle A (GO:0030991), intraciliary transport particle B (GO:0030992), motile cilium (GO:0031514), ciliary basal body (GO:0036064), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), ciliary tip (GO:0097542), microtubule organizing center (GO:0005815), 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	6
cilium	4
microtubule organizing center	3
intraciliary transport particle	3
developmental process involved in reproduction	2
intraciliary transport	2
cilium organization	2
intracellular membraneless organelle	2
protein-containing complex	2
sperm flagellum	2
male gamete generation	1
smoothened signaling pathway	1
regulation of signal transduction	1
cilium assembly	1
transport along microtubule	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	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
spermatid development	1
flagellated sperm motility	1
motile cilium assembly	1
cellular component organization	1
cellular developmental process	1
cytoskeletal protein binding	1
binding	1
intracellular anatomical structure	1
centriole	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule cytoskeleton	1

Protein interactions and networks

STRING

1880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFT81	IFT74	Q96LB3	998
IFT81	IFT46	Q9NQC8	996
IFT81	IFT27	Q9BW83	995
IFT81	IFT52	Q9Y366	993
IFT81	IFT88	Q13099	991
IFT81	IFT22	Q9H7X7	990
IFT81	IFT70B	Q8N4P2	986
IFT81	IFT25	Q9Y547	980
IFT81	IFT57	Q9NWB7	979
IFT81	IFT80	Q9P2H3	964
IFT81	IFT172	Q9UG01	953
IFT81	IFT54	Q8TDR0	943
IFT81	IFT20	Q8IY31	884
IFT81	IFT140	Q96RY7	881
IFT81	IFT56	A0AVF1	874

IntAct

117 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
IFT56	IFT70A	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
PRPF19	PLRG1	psi-mi:“MI:0914”(association)	0.770
IFT25	IFT56	psi-mi:“MI:0914”(association)	0.690
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.690
POLR1E	POLR1C	psi-mi:“MI:0914”(association)	0.670
IFT22	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT46	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT88	IFT56	psi-mi:“MI:0914”(association)	0.640

BioGRID (128): IFT81 (Affinity Capture-MS), IFT81 (Affinity Capture-MS), IFT81 (Affinity Capture-MS), IFT46 (Affinity Capture-MS), PRAME (Affinity Capture-MS), IFT74 (Affinity Capture-MS), SPATA5L1 (Affinity Capture-MS), NDC80 (Affinity Capture-MS), CEP44 (Affinity Capture-MS), PCM1 (Affinity Capture-MS), IFT81 (Affinity Capture-MS), IFT81 (Affinity Capture-MS), IFT81 (Proximity Label-MS), IFT81 (Affinity Capture-MS), IFT81 (Affinity Capture-MS)

ESM2 similar proteins: A1A5Q4, A4IH82, A6H782, A7S8T5, F7F3Q2, G5E8A8, O35594, O46469, Q0E908, Q149S1, Q26648, Q29RL1, Q2T9Q6, Q2TA16, Q2TA38, Q2YDI7, Q32KZ9, Q3SYS9, Q4R353, Q4R5V1, Q4R7G7, Q4V8G8, Q5PPV2, Q5RHQ8, Q5U584, Q5XIJ8, Q6AXV2, Q6AYM2, Q6DFJ6, Q6DGZ3, Q6PE87, Q6X6Z7, Q8CI04, Q8IXS2, Q8IYR0, Q8VHI7, Q8WW24, Q8WYA0, Q922G7, Q95JU3

Diamond homologs: O35594, P83829, Q8WYA0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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	49.2×	2e-18
Hedgehog ‘off’ state	6	18.8×	5e-05
Loss of Nlp from mitotic centrosomes	6	16.7×	7e-05
Loss of proteins required for interphase microtubule organization from the centrosome	6	16.7×	7e-05
AURKA Activation by TPX2	6	16.0×	8e-05
Regulation of PLK1 Activity at G2/M Transition	7	15.6×	4e-05
Recruitment of mitotic centrosome proteins and complexes	6	14.3×	1e-04
Anchoring of the basal body to the plasma membrane	7	13.9×	5e-05

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary anterograde transport	13	147.8×	2e-24
intraciliary transport	10	72.0×	1e-14
negative regulation of keratinocyte proliferation	5	45.0×	7e-06
keratinocyte proliferation	5	37.2×	2e-05
non-motile cilium assembly	9	33.5×	6e-10
dorsal/ventral pattern formation	5	27.0×	7e-05
smoothened signaling pathway	11	25.6×	6e-11
cilium assembly	19	17.9×	1e-16

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	35
Likely pathogenic	15
Uncertain significance	243
Likely benign	185
Benign	26

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071114	NM_014055.4(IFT81):c.637C>T (p.Arg213Ter)	Pathogenic
1299657	NC_000012.11:g.110593351_110576466dup	Pathogenic
1323109	NM_014055.4(IFT81):c.190C>T (p.Arg64Ter)	Pathogenic
1397159	NM_014055.4(IFT81):c.1102A>T (p.Lys368Ter)	Pathogenic
1425432	NM_014055.4(IFT81):c.1208_1220del (p.Lys403fs)	Pathogenic
1434360	NM_014055.4(IFT81):c.1195C>T (p.Arg399Ter)	Pathogenic
1457611	NM_014055.4(IFT81):c.1764dup (p.Ile589fs)	Pathogenic
1895856	NM_014055.4(IFT81):c.653_656del (p.Arg218fs)	Pathogenic
1946619	NM_014055.4(IFT81):c.1024_1025del (p.Ser342fs)	Pathogenic
1962677	NM_014055.4(IFT81):c.347del (p.Ala116fs)	Pathogenic
2020725	NM_014055.4(IFT81):c.1537C>T (p.Gln513Ter)	Pathogenic
2034068	NM_014055.4(IFT81):c.1147del (p.Thr383fs)	Pathogenic
2090156	NM_014055.4(IFT81):c.365del (p.Phe121_Leu122insTer)	Pathogenic
2425889	NC_000012.11:g.(?110581167)(110581370_?)del	Pathogenic
2691451	NM_014055.4(IFT81):c.1066G>T (p.Glu356Ter)	Pathogenic
2829996	NM_014055.4(IFT81):c.850G>T (p.Glu284Ter)	Pathogenic
2842011	NM_014055.4(IFT81):c.216_217insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCGGGCTTGGCCTGGCCGCGCCCCGCCCCCTCCCCGCCGAGCCGCCCGCCCATTGTCCCCCGCGGCCGCCCGAGCCTTCTTGGTATTCTT (p.Lys73fs)	Pathogenic
2866384	NM_014055.4(IFT81):c.952_956del (p.Glu318fs)	Pathogenic
2956595	NM_014055.4(IFT81):c.886C>T (p.Gln296Ter)	Pathogenic
2957720	NM_014055.4(IFT81):c.655_656del (p.Glu219fs)	Pathogenic
2981085	NM_014055.4(IFT81):c.174del (p.Glu59fs)	Pathogenic
3012449	NM_014055.4(IFT81):c.1087C>T (p.Gln363Ter)	Pathogenic
3249597	NM_014055.4(IFT81):c.457del (p.Thr153fs)	Pathogenic
4715657	NM_014055.4(IFT81):c.630del (p.Arg210fs)	Pathogenic
4726405	NM_014055.4(IFT81):c.1730_1737dup (p.Arg580fs)	Pathogenic
4766347	NM_014055.4(IFT81):c.1205dup (p.Asn402fs)	Pathogenic
4770678	NM_014055.4(IFT81):c.863del (p.Lys288fs)	Pathogenic
4780661	NM_014055.4(IFT81):c.899_900insT (p.Glu301fs)	Pathogenic
560182	Single allele	Pathogenic
834402	NM_014055.4(IFT81):c.723_724del (p.Arg242fs)	Pathogenic

SpliceAI

2914 predictions. Top by Δscore:

Variant	Effect	Δscore
12:110127358:A:AG	acceptor_gain	1.0000
12:110127359:G:GG	acceptor_gain	1.0000
12:110127359:GTT:G	acceptor_gain	1.0000
12:110127359:GTTA:G	acceptor_gain	1.0000
12:110127359:GTTAA:G	acceptor_gain	1.0000
12:110127406:T:TA	acceptor_gain	1.0000
12:110128116:T:TG	donor_gain	1.0000
12:110128145:GATAT:G	donor_gain	1.0000
12:110128146:A:G	donor_gain	1.0000
12:110128150:G:GG	donor_gain	1.0000
12:110129291:A:G	donor_gain	1.0000
12:110132541:TTCTA:T	acceptor_loss	1.0000
12:110132542:TCTA:T	acceptor_loss	1.0000
12:110132543:CTAG:C	acceptor_loss	1.0000
12:110132544:TAGT:T	acceptor_loss	1.0000
12:110132545:A:AG	acceptor_gain	1.0000
12:110132545:AG:A	acceptor_loss	1.0000
12:110132546:G:GA	acceptor_gain	1.0000
12:110132546:G:GT	acceptor_loss	1.0000
12:110132546:GT:G	acceptor_gain	1.0000
12:110132546:GTAT:G	acceptor_gain	1.0000
12:110132644:A:T	donor_gain	1.0000
12:110135012:GG:G	donor_gain	1.0000
12:110135013:GG:G	donor_gain	1.0000
12:110135013:GGTAA:G	donor_loss	1.0000
12:110135014:G:GC	donor_loss	1.0000
12:110135015:T:A	donor_loss	1.0000
12:110135325:A:T	acceptor_loss	1.0000
12:110135435:CAGG:C	donor_loss	1.0000
12:110135436:AGG:A	donor_loss	1.0000

AlphaMissense

4520 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:110129006:T:C	L102P	0.991
12:110162962:T:C	L362P	0.989
12:110129062:T:C	F121L	0.988
12:110129064:T:A	F121L	0.988
12:110129064:T:G	F121L	0.988
12:110127493:T:C	L38P	0.987
12:110129015:T:C	L105P	0.987
12:110162952:G:C	A359P	0.987
12:110162919:G:C	A348P	0.986
12:110162935:G:C	R353P	0.986
12:110127415:T:C	L12P	0.984
12:110132568:T:C	F151L	0.982
12:110132570:T:A	F151L	0.982
12:110132570:T:G	F151L	0.982
12:110180444:T:C	L404P	0.980
12:110135376:T:C	L212P	0.978
12:110135379:G:C	R213P	0.978
12:110128092:G:C	R64P	0.977
12:110128979:G:A	G93E	0.977
12:110129056:G:C	A119P	0.977
12:110127481:T:C	L34P	0.976
12:110180447:G:C	R405P	0.976
12:110180537:T:C	L435P	0.975
12:110218110:T:A	W639R	0.975
12:110218110:T:C	W639R	0.975
12:110127502:T:A	V41D	0.974
12:110128116:T:C	L72P	0.974
12:110127505:T:C	L42P	0.971
12:110129006:T:G	L102R	0.971
12:110136819:T:C	L247P	0.969

dbSNP variants (sampled 300 via entrez): RS1000013486 (12:110198695 G>C), RS1000022705 (12:110187611 G>A), RS1000111446 (12:110143281 C>T), RS1000113776 (12:110132954 C>T), RS1000138535 (12:110142643 C>A,G), RS1000189813 (12:110154933 T>G), RS1000194377 (12:110132538 T>C), RS1000215937 (12:110210877 G>T), RS1000248687 (12:110210568 A>G), RS1000256014 (12:110162825 T>C), RS1000264544 (12:110136698 G>A,C,T), RS1000288684 (12:110196584 A>G), RS1000289467 (12:110156925 A>G), RS1000331510 (12:110147635 A>G), RS1000419507 (12:110129745 G>T)

Disease associations

OMIM: gene MIM:605489 | disease phenotypes: MIM:617895, MIM:120970, MIM:268000, MIM:208500

GenCC curated gene-disease

Disease	Classification	Inheritance
short-rib thoracic dysplasia 19 with or without polydactyly	Strong	Autosomal recessive
ciliopathy	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
short-rib thoracic dysplasia 19 with or without polydactyly	Moderate	AR

Mondo (7): inherited retinal dystrophy (MONDO:0019118), short-rib thoracic dysplasia 19 with or without polydactyly (MONDO:0033485), ciliopathy (MONDO:0005308), cone-rod dystrophy (MONDO:0015993), retinitis pigmentosa (MONDO:0019200), Jeune syndrome (MONDO:0018770), short rib-polydactyly syndrome (MONDO:0015461)

Orphanet (6): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Ciliopathy (Orphanet:363250), Cone rod dystrophy (Orphanet:1872), Retinitis pigmentosa (Orphanet:791), Jeune syndrome (Orphanet:474), Short rib-polydactyly syndrome (Orphanet:1505)

HPO phenotypes

28 total (29 of 28 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000062	Ambiguous genitalia
HP:0000268	Dolichocephaly
HP:0000269	Prominent occiput
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000520	Proptosis
HP:0000773	Short ribs
HP:0000774	Narrow chest
HP:0000888	Horizontal ribs
HP:0000895	Lateral clavicle hook
HP:0000946	Hypoplastic ilia
HP:0001156	Brachydactyly
HP:0001159	Syndactyly
HP:0001290	Generalized hypotonia
HP:0001539	Omphalocele
HP:0001629	Ventricular septal defect
HP:0002089	Pulmonary hypoplasia
HP:0002098	Respiratory distress
HP:0002878	Respiratory failure
HP:0002983	Micromelia
HP:0002984	Hypoplasia of the radius
HP:0004482	Relative macrocephaly
HP:0005257	Thoracic hypoplasia
HP:0005280	Depressed nasal bridge
HP:0011220	Prominent forehead
HP:0011800	Midface retrusion
HP:0100259	Postaxial polydactyly
HP:0000556	Retinal dystrophy

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST005316_375	Intelligence (MTAG)	8.000000e-09
GCST005316_376	Intelligence (MTAG)	2.000000e-09
GCST005337_22	Headache	9.000000e-09
GCST008103_145	Bipolar disorder	3.000000e-06
GCST009204_13	Total intracranial volume	5.000000e-06
GCST009600_34	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	5.000000e-08
GCST010796_5301	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-17
GCST010796_5302	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-24
GCST010796_5303	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-21
GCST010796_5304	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-22
GCST010796_5305	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-23
GCST010796_5306	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-23
GCST010796_5307	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST010796_5308	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_5309	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_5350	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-24

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004886	intracranial volume measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
D012779	Short Rib-Polydactyly Syndrome	C05.116.099.708.857; C05.660.585.600.750; C16.131.077.850; C16.131.621.585.600.750
C537571	Jeune syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
bisphenol S	decreases methylation	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Air Pollutants	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dimethyl Sulfoxide	affects expression	1
Estradiol	affects expression	1
Manganese	increases abundance, increases expression	1
Selenium	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Vitamin E	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

267 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
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
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
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
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
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
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
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)
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration