IFT172

Summary

IFT172 (intraflagellar transport 172, HGNC:30391) is a protein-coding gene on chromosome 2p23.3, encoding Intraflagellar transport protein 172 homolog (Q9UG01). Required for the maintenance and formation of cilia.

This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10.

Source: NCBI Gene 26160 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,970 total — 74 pathogenic, 64 likely-pathogenic
• Phenotypes (HPO): 182
• MANE Select transcript: NM_015662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30391
Approved symbol	IFT172
Name	intraflagellar transport 172
Location	2p23.3
Locus type	gene with protein product
Status	Approved
Aliases	SLB, wim, osm-1, NPHP17, BBS20
Ensembl gene	ENSG00000138002
Ensembl biotype	protein_coding
OMIM	607386
Entrez	26160

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 18 retained_intron, 10 protein_coding, 10 nonsense_mediated_decay

ENST00000260570, ENST00000359466, ENST00000416524, ENST00000420854, ENST00000443889, ENST00000450564, ENST00000463613, ENST00000475476, ENST00000475909, ENST00000476264, ENST00000476693, ENST00000479419, ENST00000480892, ENST00000489492, ENST00000494163, ENST00000507184, ENST00000509128, ENST00000511842, ENST00000674594, ENST00000674701, ENST00000674824, ENST00000674932, ENST00000675410, ENST00000675618, ENST00000675690, ENST00000675728, ENST00000675729, ENST00000675757, ENST00000675826, ENST00000675925, ENST00000675963, ENST00000676101, ENST00000676119, ENST00000676300, ENST00000872012, ENST00000923256, ENST00000945697, ENST00000945698

RefSeq mRNA: 2 — MANE Select: NM_015662 NM_001410739, NM_015662

CCDS: CCDS1755, CCDS92725

Canonical transcript exons

ENST00000260570 — 48 exons

Exon	Start	End
ENSE00000733229	27444377	27444521
ENSE00000932415	27457841	27457976
ENSE00001899467	27489615	27489743
ENSE00003461586	27449691	27449800
ENSE00003464788	27485360	27485503
ENSE00003466071	27449294	27449380
ENSE00003468759	27472250	27472362
ENSE00003470756	27449499	27449562
ENSE00003476465	27456511	27456653
ENSE00003483684	27447515	27447634
ENSE00003484932	27463097	27463181
ENSE00003488780	27445296	27445449
ENSE00003492514	27445745	27445843
ENSE00003493261	27454354	27454418
ENSE00003513485	27448915	27449031
ENSE00003519780	27445014	27445105
ENSE00003528214	27462701	27462793
ENSE00003534373	27445929	27445988
ENSE00003538127	27477217	27477320
ENSE00003540021	27449998	27450096
ENSE00003543062	27477559	27477612
ENSE00003548754	27476641	27476726
ENSE00003553659	27453982	27454162
ENSE00003566530	27458126	27458223
ENSE00003567598	27458779	27458868
ENSE00003569379	27453630	27453739
ENSE00003585623	27461759	27461836
ENSE00003586067	27461269	27461517
ENSE00003588809	27465746	27465882
ENSE00003600894	27457639	27457755
ENSE00003611367	27485018	27485130
ENSE00003613209	27447812	27447922
ENSE00003614220	27470928	27471095
ENSE00003614324	27483289	27483376
ENSE00003621632	27483580	27483659
ENSE00003627790	27483872	27483937
ENSE00003628597	27481046	27481260
ENSE00003637180	27479509	27479604
ENSE00003640153	27484227	27484266
ENSE00003654823	27465411	27465518
ENSE00003655102	27459709	27459829
ENSE00003660679	27446260	27446355
ENSE00003665988	27453384	27453513
ENSE00003671593	27454567	27454660
ENSE00003673637	27477995	27478156
ENSE00003681247	27459378	27459522
ENSE00003682268	27461015	27461093
ENSE00003683524	27480026	27480149

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 98.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.8490 / max 545.1668, expressed in 1703 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27510	10.3143	1692
27509	1.1776	458
27503	0.1773	46
27511	0.1250	43
27508	0.0442	17
27504	0.0053	3
27505	0.0026	2
27507	0.0026	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.60	gold quality
bronchial epithelial cell	CL:0002328	97.57	gold quality
left testis	UBERON:0004533	97.34	gold quality
right testis	UBERON:0004534	97.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.13	gold quality
bronchus	UBERON:0002185	96.89	gold quality
adenohypophysis	UBERON:0002196	96.27	gold quality
pituitary gland	UBERON:0000007	96.08	gold quality
left ovary	UBERON:0002119	94.63	gold quality
testis	UBERON:0000473	94.57	gold quality
right ovary	UBERON:0002118	94.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.26	gold quality
rectum	UBERON:0001052	94.23	gold quality
cerebellar hemisphere	UBERON:0002245	94.00	gold quality
cerebellar cortex	UBERON:0002129	93.90	gold quality
right frontal lobe	UBERON:0002810	93.89	gold quality
transverse colon	UBERON:0001157	93.28	gold quality
mucosa of transverse colon	UBERON:0004991	93.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.98	gold quality
right lobe of thyroid gland	UBERON:0001119	92.94	gold quality
apex of heart	UBERON:0002098	92.59	gold quality
ileal mucosa	UBERON:0000331	92.58	gold quality
gall bladder	UBERON:0002110	92.52	gold quality
cerebellum	UBERON:0002037	92.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.43	gold quality
left lobe of thyroid gland	UBERON:0001120	92.21	gold quality
hypothalamus	UBERON:0001898	91.91	gold quality
anterior cingulate cortex	UBERON:0009835	91.91	gold quality
minor salivary gland	UBERON:0001830	91.70	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	23.50
E-ANND-3	yes	10.14
E-CURD-97	no	120.68
E-MTAB-6142	no	49.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): LHX4, RFX4

Literature-anchored findings (GeneRIF, showing 7)

• We have identified defects in IFT172 as a cause of complex asphyxiating thoracic dystrophy and Mainzer-Saldino syndrome. (PMID:24140113)
• Findings identified mutations in IFT172 that lead to a recessive form of non-syndromic retinitis pigmentosa and Bardet-Biedl syndrome and suggest that the primary IFT172 mutations alone are not sufficient to explain the wide range of phenotypes. (PMID:25168386)
• This is the second report of IFT172 mutations in BBS patients validating IFT172 as the twentieth BBS gene (BBS20). (PMID:26763875)
• We found that depletion of IFT172 in rod photoreceptors leads to a rapid degeneration of the retina, with severely reduced electroretinography (ERG) responses by 1 month and complete outer-nuclear layer (ONL) degeneration by 2 months (PMID:29659833)
• Multimodal imaging of retinitis pigmentosa associated with Mainzer-Saldino syndrome. (PMID:33393400)
• Novel alterations in IFT172 and KIFAP3 may induce basal cell carcinoma. (PMID:34674729)
• Exome sequencing reveals IFT172 variants in patients with non-syndromic cholestatic liver disease. (PMID:37471416)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ift172	ENSDARG00000041870
mus_musculus	Ift172	ENSMUSG00000038564
rattus_norvegicus	Ift172	ENSRNOG00000057813
drosophila_melanogaster	Oseg2	FBGN0035317
caenorhabditis_elegans		WBGENE00003883

Paralogs (1): IFT140 (ENSG00000187535)

Protein

Protein identifiers

Intraflagellar transport protein 172 homolog — Q9UG01 (reviewed: Q9UG01)

All UniProt accessions (13): Q9UG01, A0A6Q8PFB6, A0A6Q8PFK2, A0A6Q8PFU9, A0A6Q8PG03, A0A6Q8PGJ2, A0A6Q8PGK4, A0A6Q8PHF0, F5GZ56, H0YAI8, H7C161, H7C186, H7C252

UniProt curated annotations — full annotation on UniProt →

Function. Required for the maintenance and formation of cilia. Plays an indirect role in hedgehog (Hh) signaling, cilia being required for all activity of the hedgehog pathway.

Subunit / interactions. Interacts with IFT88. Interacts with IFT57. Interacts with RABL2/RABL2A; binds preferentially to GDP-bound RABL2.

Subcellular location. Cell projection. Cilium.

Disease relevance. Short-rib thoracic dysplasia 10 with or without polydactyly (SRTD10) [MIM:615630] 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. Retinitis pigmentosa 71 (RP71) [MIM:616394] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry. Bardet-Biedl syndrome 20 (BBS20) [MIM:619471] A form of Bardet-Biedl syndrome, a syndrome characterized by usually severe pigmentary retinopathy, early-onset obesity, polydactyly, hypogenitalism, renal malformation and intellectual disability. Secondary features include diabetes mellitus, hypertension and congenital heart disease. Bardet-Biedl syndrome inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for clinical manifestation of some forms of the disease. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the IFT172 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UG01-1	1	yes
Q9UG01-2	2
Q9UG01-3	3

RefSeq proteins (2): NP_001397668, NP_056477* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR056157	TPR_IFT80_172_dom	Domain
IPR056168	TPR_IF140/IFT172/WDR19	Domain

Pfam: PF00400, PF23387, PF24762

UniProt features (63 total): repeat 23, helix 13, sequence variant 12, splice variant 4, strand 4, modified residue 2, turn 2, chain 1, cross-link 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9H2D	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UG01-F1	83.98	0.25

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 (3): 1, 672, 4

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 550 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_AXIS_SPECIFICATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, GOCC_MICROTUBULE_ORGANIZING_CENTER

GO Biological Process (31): neural tube closure (GO:0001843), heart looping (GO:0001947), Notch signaling pathway (GO:0007219), smoothened signaling pathway (GO:0007224), brain development (GO:0007420), epidermis development (GO:0008544), dorsal/ventral pattern formation (GO:0009953), negative regulation of keratinocyte proliferation (GO:0010839), protein processing (GO:0016485), spinal cord motor neuron differentiation (GO:0021522), cytoplasmic microtubule organization (GO:0031122), intraciliary anterograde transport (GO:0035720), intraciliary transport (GO:0042073), keratinocyte proliferation (GO:0043616), negative regulation of smoothened signaling pathway (GO:0045879), positive regulation of smoothened signaling pathway (GO:0045880), embryonic camera-type eye morphogenesis (GO:0048596), roof of mouth development (GO:0060021), limb development (GO:0060173), cilium assembly (GO:0060271), bone development (GO:0060348), hindgut development (GO:0061525), left/right axis specification (GO:0070986), non-motile cilium assembly (GO:1905515), neural tube formation (GO:0001841), determination of left/right symmetry (GO:0007368), heart development (GO:0007507), regulation of smoothened signaling pathway (GO:0008589), neural tube development (GO:0021915), cilium organization (GO:0044782), negative regulation of epithelial cell proliferation (GO:0050680)

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

GO Cellular Component (12): cilium (GO:0005929), axoneme (GO:0005930), intraciliary transport particle A (GO:0030991), intraciliary transport particle B (GO:0030992), ciliary basal body (GO:0036064), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), ciliary tip (GO:0097542), sperm cytoplasmic droplet (GO:0097598), extracellular vesicle (GO:1903561), intraciliary transport particle (GO:0030990), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Hedgehog	1
Assembly of the 9+0 primary cilium	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cilium	3
intraciliary transport particle	3
protein-containing complex	3
cell surface receptor signaling pathway	2
cilium organization	2
smoothened signaling pathway	2
regulation of smoothened signaling pathway	2
sperm flagellum	2
primary neural tube formation	1
tube closure	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
central nervous system development	1
animal organ development	1
head development	1
tissue development	1
regionalization	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
negative regulation of epithelial cell proliferation	1
proteolysis	1
protein maturation	1
cell differentiation in spinal cord	1
ventral spinal cord development	1
central nervous system neuron differentiation	1
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
intraciliary transport	1
transport along microtubule	1
epithelial cell proliferation	1
negative regulation of signal transduction	1
positive regulation of signal transduction	1
embryonic camera-type eye development	1
embryonic eye morphogenesis	1
camera-type eye morphogenesis	1
anatomical structure development	1
appendage development	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1

Protein interactions and networks

STRING

1761 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFT172	IFT88	Q13099	988
IFT172	IFT57	Q9NWB7	988
IFT172	IFT80	Q9P2H3	986
IFT172	IFT54	Q8TDR0	984
IFT172	IFT20	Q8IY31	979
IFT172	IFT52	Q9Y366	971
IFT172	IFT38	Q96AJ1	969
IFT172	IFT81	Q8WYA0	953
IFT172	IFT27	Q9BW83	946
IFT172	IFT46	Q9NQC8	944
IFT172	IFT74	Q96LB3	940
IFT172	KIF3A	Q9Y496	900
IFT172	IFT22	Q9H7X7	888
IFT172	IFT70B	Q8N4P2	878
IFT172	DYNC2H1	Q8NCM8	877

IntAct

82 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
IFT22	IFT56	psi-mi:“MI:0914”(association)	0.640
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
IFT172	IFT56	psi-mi:“MI:0914”(association)	0.590
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
KRBA1	TRIM27	psi-mi:“MI:0914”(association)	0.530

BioGRID (79): IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS), IFT172 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IC37, A0JN52, A1A4K3, E9PY46, O49552, P0CR22, P0CR23, P0DKL4, P0DKL6, P33194, P59015, Q15269, Q15393, Q16531, Q1LVE8, Q21554, Q3U1J4, Q3V3N7, Q4PGM6, Q4WLI5, Q52E49, Q5B1X8, Q5R649, Q5RBI5, Q5RFQ3, Q6AX60, Q6E7D1, Q6L4S0, Q6P6Z0, Q6QNU4, Q7RYR4, Q805F9, Q811G0, Q8BU03, Q8NFJ9, Q8R2N2, Q921M3, Q93VQ0, Q969X6, Q96RY7

Diamond homologs: Q22830, Q5DM57, Q5RHH4, Q6VH22, Q9JKU3, Q9UG01, Q9W040

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RFX4	“up-regulates quantity by expression”	IFT172	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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	75.8×	1e-21

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary anterograde transport	14	243.5×	4e-30
intraciliary transport	12	132.2×	3e-21
keratinocyte proliferation	5	57.0×	1e-06
non-motile cilium assembly	8	45.6×	7e-10
smoothened signaling pathway	9	32.0×	7e-10
cilium assembly	18	26.0×	3e-19

Disease & clinical

Clinical variants and AI predictions

ClinVar

1970 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	74
Likely pathogenic	64
Uncertain significance	865
Likely benign	768
Benign	47

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069553	NM_015662.3(IFT172):c.4508G>A (p.Trp1503Ter)	Pathogenic
1070963	NM_015662.3(IFT172):c.4853del (p.Ser1618fs)	Pathogenic
1071120	NM_015662.3(IFT172):c.2567del (p.Leu856fs)	Pathogenic
1071329	NM_015662.3(IFT172):c.4680_4683del (p.Ser1561fs)	Pathogenic
1074967	NM_015662.3(IFT172):c.3944G>A (p.Trp1315Ter)	Pathogenic
1076916	NM_015662.3(IFT172):c.3949A>T (p.Lys1317Ter)	Pathogenic
1179103	NM_015662.3(IFT172):c.1342_1343del (p.Arg448fs)	Pathogenic
1189092	NM_015662.3(IFT172):c.4428+3A>G	Pathogenic
1362201	NM_015662.3(IFT172):c.2866C>T (p.Gln956Ter)	Pathogenic
1365957	NM_015662.3(IFT172):c.4597dup (p.Thr1533fs)	Pathogenic
1390470	NM_015662.3(IFT172):c.1209del (p.Phe403fs)	Pathogenic
1431370	NM_015662.3(IFT172):c.4194dup (p.Phe1399fs)	Pathogenic
1451190	NM_015662.3(IFT172):c.1115dup (p.His372fs)	Pathogenic
1452074	NM_015662.3(IFT172):c.2078del (p.Lys693fs)	Pathogenic
1457968	NM_015662.3(IFT172):c.2146C>T (p.Gln716Ter)	Pathogenic
191369	NM_015662.3(IFT172):c.770T>C (p.Leu257Pro)	Pathogenic
191370	NM_015662.3(IFT172):c.3112-5T>A	Pathogenic
1932760	NM_015662.3(IFT172):c.952C>T (p.Arg318Ter)	Pathogenic
2008662	NM_015662.3(IFT172):c.3648dup (p.Gln1217fs)	Pathogenic
2016015	NM_015662.3(IFT172):c.1555A>T (p.Lys519Ter)	Pathogenic
2017084	NM_015662.3(IFT172):c.2224_2236dup (p.Trp746Ter)	Pathogenic
2021031	NM_015662.3(IFT172):c.1315dup (p.His439fs)	Pathogenic
2023475	NM_015662.3(IFT172):c.1100_1103dup (p.Tyr368Ter)	Pathogenic
2028073	NM_015662.3(IFT172):c.1412-1G>C	Pathogenic
2033144	NM_015662.3(IFT172):c.4493_4494del (p.Glu1498fs)	Pathogenic
2035232	NM_015662.3(IFT172):c.2233C>T (p.Gln745Ter)	Pathogenic
2079183	NM_015662.3(IFT172):c.2760dup (p.His921fs)	Pathogenic
2107008	NM_015662.3(IFT172):c.1412-2A>G	Pathogenic
2115651	NM_015662.3(IFT172):c.189_192del (p.Lys65fs)	Pathogenic
2115892	NM_015662.3(IFT172):c.691del (p.Thr231fs)	Pathogenic

SpliceAI

6937 predictions. Top by Δscore:

Variant	Effect	Δscore
2:27445102:TATCC:T	acceptor_loss	1.0000
2:27445103:ATCC:A	acceptor_loss	1.0000
2:27445104:TC:T	acceptor_gain	1.0000
2:27445104:TCC:T	acceptor_loss	1.0000
2:27445105:CC:C	acceptor_gain	1.0000
2:27445105:CCTGT:C	acceptor_loss	1.0000
2:27445106:C:CC	acceptor_gain	1.0000
2:27445106:CT:C	acceptor_loss	1.0000
2:27445107:T:A	acceptor_loss	1.0000
2:27445293:TA:T	donor_loss	1.0000
2:27445445:GCCTC:G	acceptor_gain	1.0000
2:27445446:CCTCC:C	acceptor_gain	1.0000
2:27445447:CTC:C	acceptor_gain	1.0000
2:27445448:TC:T	acceptor_gain	1.0000
2:27445449:CC:C	acceptor_gain	1.0000
2:27445449:CCTGG:C	acceptor_loss	1.0000
2:27445450:C:CC	acceptor_gain	1.0000
2:27445450:C:T	acceptor_gain	1.0000
2:27445919:C:A	donor_gain	1.0000
2:27445923:A:AC	donor_gain	1.0000
2:27445923:ACT:A	donor_loss	1.0000
2:27445924:C:CC	donor_gain	1.0000
2:27445924:CTC:C	donor_loss	1.0000
2:27445925:TCA:T	donor_loss	1.0000
2:27445926:CA:C	donor_loss	1.0000
2:27445927:A:AC	donor_gain	1.0000
2:27445927:AC:A	donor_loss	1.0000
2:27445928:C:CC	donor_gain	1.0000
2:27447514:CCAG:C	donor_gain	1.0000
2:27447631:CACA:C	acceptor_gain	1.0000

AlphaMissense

11471 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:27483655:C:G	R136P	0.999
2:27483658:A:T	V135D	0.999
2:27483916:A:G	W120R	0.999
2:27483916:A:T	W120R	0.999
2:27484237:A:G	F109S	0.999
2:27485037:A:C	Y93D	0.999
2:27485039:A:T	V92D	0.999
2:27485055:C:G	D87H	0.999
2:27485069:G:T	A82D	0.999
2:27485385:A:G	F53S	0.999
2:27485424:A:T	V40D	0.999
2:27485448:G:T	A32D	0.999
2:27449731:A:G	W1374R	0.998
2:27449731:A:T	W1374R	0.998
2:27454121:G:T	A1191D	0.998
2:27454133:G:T	A1187D	0.998
2:27454360:A:T	V1175D	0.998
2:27454389:G:C	F1165L	0.998
2:27454389:G:T	F1165L	0.998
2:27454391:A:G	F1165L	0.998
2:27454586:G:T	A1149D	0.998
2:27458169:C:G	A978P	0.998
2:27478050:G:T	A371D	0.998
2:27478051:C:G	A371P	0.998
2:27480055:A:G	W294R	0.998
2:27480055:A:T	W294R	0.998
2:27483350:C:T	G170D	0.998
2:27483876:C:A	G133V	0.998
2:27483877:C:A	G133W	0.998
2:27483888:C:T	G129E	0.998

dbSNP variants (sampled 300 via entrez): RS1000030001 (2:27450640 G>A), RS1000172880 (2:27458847 T>C), RS1000214492 (2:27469897 C>A), RS1000268293 (2:27469714 C>T), RS1000276261 (2:27473084 C>T), RS1000322111 (2:27457773 A>G), RS1000435284 (2:27484746 G>A), RS1000536523 (2:27487471 A>G), RS1000608331 (2:27458491 G>A,C,T), RS1000610224 (2:27445518 G>A,C), RS1000614431 (2:27452114 T>G), RS1000685726 (2:27490293 A>G), RS1000728626 (2:27451785 T>C), RS1000882971 (2:27471394 C>T), RS1000903874 (2:27478945 A>G)

Disease associations

OMIM: gene MIM:607386 | disease phenotypes: MIM:615630, MIM:616394, MIM:619471, MIM:209900, MIM:268000, MIM:263520, MIM:608615, MIM:208500, MIM:617119, MIM:213300, MIM:256100

GenCC curated gene-disease

Disease	Classification	Inheritance
short-rib thoracic dysplasia 10 with or without polydactyly	Definitive	Autosomal recessive
ciliopathy	Definitive	Autosomal recessive
retinitis pigmentosa 71	Strong	Autosomal recessive
Bardet-Biedl syndrome 20	Strong	Autosomal recessive
Bardet-Biedl syndrome	Supportive	Autosomal recessive
short-rib thoracic dysplasia 9 with or without polydactyly	Supportive	Autosomal recessive
Jeune syndrome	Supportive	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ciliopathy	Definitive	AR

Mondo (20): short-rib thoracic dysplasia 10 with or without polydactyly (MONDO:0014284), retinitis pigmentosa 71 (MONDO:0014618), Bardet-Biedl syndrome 20 (MONDO:0023670), inherited retinal dystrophy (MONDO:0019118), Bardet-Biedl syndrome (MONDO:0015229), Bardet-Biedl syndrome 1 (MONDO:0008854), retinitis pigmentosa (MONDO:0019200), intellectual disability (MONDO:0001071), short-rib thoracic dysplasia 6 with or without polydactyly (MONDO:0009894), retinal disorder (MONDO:0005283), oligodontia-cancer predisposition syndrome (MONDO:0012075), optic atrophy (MONDO:0003608), neurodevelopmental disorder (MONDO:0700092), asphyxiating thoracic dystrophy 1 (MONDO:0008831), Bardet-Biedl syndrome 22 (MONDO:0014926)

Orphanet (9): Jeune syndrome (Orphanet:474), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Bardet-Biedl syndrome (Orphanet:110), Microphthalmia-anophthalmia-coloboma (Orphanet:98555), Oligodontia-cancer predisposition syndrome (Orphanet:300576), Isolated Joubert syndrome (Orphanet:475), Nephronophthisis (Orphanet:655), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

182 total (30 of 182 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000011	Neurogenic bladder
HP:0000026	Male hypogonadism
HP:0000028	Cryptorchidism
HP:0000054	Micropenis
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000085	Horseshoe kidney
HP:0000090	Nephronophthisis
HP:0000093	Proteinuria
HP:0000100	Nephrotic syndrome
HP:0000112	Nephropathy
HP:0000119	Abnormality of the genitourinary system
HP:0000126	Hydronephrosis
HP:0000135	Hypogonadism
HP:0000147	Polycystic ovaries
HP:0000163	Abnormal oral cavity morphology
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000649_21	Chronic kidney disease	3.000000e-14
GCST000769_3	Calcium levels	7.000000e-06
GCST001905_4	Hypertriglyceridemia	2.000000e-13
GCST004131_72	Inflammatory bowel disease	1.000000e-07
GCST004132_64	Crohn’s disease	6.000000e-11
GCST007441_6	Total cholesterol levels	8.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004838	calcium measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement

MeSH disease descriptors (10)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C537909	Bardet-Biedl syndrome 1 (supp.)
C537571	Jeune syndrome (supp.)
C563898	Oligodontia-Colorectal Cancer Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	decreases expression, affects methylation	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
glycidyl methacrylate	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
abrine	decreases expression	1
enzalutamide	affects expression	1
bisphenol S	decreases methylation	1
jinfukang	increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Atrazine	decreases expression	1
Vehicle Emissions	affects expression, increases abundance	1
Cisplatin	decreases expression	1
Doxorubicin	increases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Nickel	decreases expression	1
Quercetin	decreases expression	1
Aflatoxin B1	increases methylation	1
Particulate Matter	affects expression, increases abundance	1

Clinical trials (associated diseases)

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

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