IFT25

Summary

IFT25 (intraflagellar transport 25, HGNC:25019) is a protein-coding gene on chromosome 1p32.3, encoding Intraflagellar transport protein 25 homolog (Q9Y547). Component of the IFT complex B required for sonic hedgehog/SHH signaling.

Predicted to enable metal ion binding activity. Predicted to be involved in kidney development; smoothened signaling pathway; and spermatogenesis. Predicted to act upstream of or within several processes, including left/right axis specification; lung development; and skeletal system development. Part of intraciliary transport particle B.

Source: NCBI Gene 51668 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 39 total
• Phenotypes (HPO): 2
• MANE Select transcript: NM_016126

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25019
Approved symbol	IFT25
Name	intraflagellar transport 25
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	HSPCO34, PP25, FAP232, CFAP232
Ensembl gene	ENSG00000081870
Ensembl biotype	protein_coding
OMIM	620841
Entrez	51668

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 17 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000194214, ENST00000371376, ENST00000371377, ENST00000371378, ENST00000488884, ENST00000489675, ENST00000899897, ENST00000899898, ENST00000899899, ENST00000899900, ENST00000899901, ENST00000899902, ENST00000899903, ENST00000899904, ENST00000899905, ENST00000925679, ENST00000925680, ENST00000925681, ENST00000925682

RefSeq mRNA: 9 — MANE Select: NM_016126 NM_001316935, NM_001382249, NM_001382250, NM_001382251, NM_001382252, NM_001382253, NM_001382254, NM_001382261, NM_016126

CCDS: CCDS41341, CCDS90960

Canonical transcript exons

ENST00000194214 — 6 exons

Exon	Start	End
ENSE00000772733	53930039	53930145
ENSE00001242678	53928372	53928440
ENSE00001334213	53939985	53940097
ENSE00001455098	53921561	53921767
ENSE00001841796	53945555	53945699
ENSE00003618665	53923904	53923947

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.8575 / max 244.6738, expressed in 1811 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12441	14.2108	1757
12439	8.3409	1682
12442	3.1105	1477
12438	1.5369	831
12440	0.5825	326
12436	0.0698	22
12437	0.0060	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.58	gold quality
bronchial epithelial cell	CL:0002328	99.48	gold quality
epithelium of bronchus	UBERON:0002031	99.24	gold quality
bronchus	UBERON:0002185	99.19	gold quality
secondary oocyte	CL:0000655	99.03	gold quality
endothelial cell	CL:0000115	98.69	gold quality
epithelium of nasopharynx	UBERON:0001951	98.32	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.92	gold quality
right uterine tube	UBERON:0001302	97.79	gold quality
pancreatic ductal cell	CL:0002079	97.57	gold quality
choroid plexus epithelium	UBERON:0003911	97.37	gold quality
tongue squamous epithelium	UBERON:0006919	97.28	gold quality
right lobe of thyroid gland	UBERON:0001119	97.20	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.18	gold quality
left lobe of thyroid gland	UBERON:0001120	97.17	gold quality
thyroid gland	UBERON:0002046	97.06	gold quality
nasal cavity mucosa	UBERON:0001826	96.80	gold quality
nasal cavity epithelium	UBERON:0005384	96.80	gold quality
endometrium	UBERON:0001295	96.65	gold quality
cervix squamous epithelium	UBERON:0006922	96.39	gold quality
germinal epithelium of ovary	UBERON:0001304	96.37	gold quality
oral cavity	UBERON:0000167	96.35	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.33	gold quality
parietal pleura	UBERON:0002400	96.26	gold quality
squamous epithelium	UBERON:0006914	96.25	gold quality
esophagus squamous epithelium	UBERON:0006920	96.25	gold quality
fallopian tube	UBERON:0003889	96.10	gold quality
oviduct epithelium	UBERON:0004804	96.06	gold quality
epithelial cell of pancreas	CL:0000083	95.98	gold quality
gingival epithelium	UBERON:0001949	95.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	124.05
E-ANND-3	yes	7.99
E-GEOD-124858	no	352.15
E-MTAB-9388	no	9.69

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• These data suggest that Hsp16.2 can prevent the destabilization of mitochondrial membrane systems and could represent a suitable target for modulating cell death pathways. (PMID:17275951)
• Hsp16.2 expression is directly correlated with the histological grade of brain tumors. (PMID:18154656)
• HSPB11 was identified as a novel prognostic marker in patients with high-grade glioma. (PMID:26544773)
• HSPB11 are induced during multiple sclerosis lesion development in white but not grey matter. (PMID:26694816)
• Impaired cooperation between IFT74/BBS22-IFT81 and IFT25-IFT27/BBS19 causes Bardet-Biedl syndrome. (PMID:34888642)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ift25	ENSMUSG00000063172
rattus_norvegicus	Ift25	ENSRNOG00000010241

Protein

Protein identifiers

Intraflagellar transport protein 25 homolog — Q9Y547 (reviewed: Q9Y547)

Alternative names: Heat shock protein beta-11, Heat shock protein family B member 11, Placental protein 25

All UniProt accessions (4): Q9Y547, A6NG08, A6NIR2, X6R7Y7

UniProt curated annotations — full annotation on UniProt →

Function. Component of the IFT complex B required for sonic hedgehog/SHH signaling. May mediate transport of SHH components: required for the export of SMO and PTCH1 receptors out of the cilium and the accumulation of GLI2 at the ciliary tip in response to activation of the SHH pathway, suggesting it is involved in the dynamic transport of SHH signaling molecules within the cilium. Not required for ciliary assembly. Its role in intraflagellar transport is mainly seen in tissues rich in ciliated cells such as kidney and testis. Essential for male fertility, spermiogenesis and sperm flagella formation. Plays a role in the early development of the kidney. May be involved in the regulation of ureteric bud initiation.

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 IFT27. Interacts with IFT88.

Subcellular location. Cell projection. Cilium.

Tissue specificity. Detected in placenta.

Similarity. Belongs to the IFT25 family.

RefSeq proteins (9): NP_001303864, NP_001369178, NP_001369179, NP_001369180, NP_001369181, NP_001369182, NP_001369183, NP_001369190, NP_057210* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000421	FA58C	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR033558	IFT25	Family

Pfam: PF00754

UniProt features (14 total): strand 8, binding site 3, helix 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1TVG	X-RAY DIFFRACTION	1.6
1XPW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y547-F1	94.06	0.90

Functional residue map

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

Ligand- & substrate-binding residues (3): 29; 32; 37

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620924	Intraflagellar transport

MSigDB gene sets: 204 (showing top): GOBP_AXIS_SPECIFICATION, MORF_SMC1L1, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, MORF_UBE2I, MORF_HDAC1, MORF_RAD21, GOBP_MALE_GAMETE_GENERATION, MODULE_16, GNF2_MCM5, GOCC_MICROTUBULE_ORGANIZING_CENTER, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_LEFT_RIGHT_AXIS_SPECIFICATION, GOBP_CILIUM_ORGANIZATION, DELYS_THYROID_CANCER_DN

GO Biological Process (12): skeletal system development (GO:0001501), kidney development (GO:0001822), smoothened signaling pathway (GO:0007224), spermatogenesis (GO:0007283), heart development (GO:0007507), protein transport (GO:0015031), cell differentiation (GO:0030154), lung development (GO:0030324), intraciliary anterograde transport (GO:0035720), cilium assembly (GO:0060271), left/right axis specification (GO:0070986), intraciliary transport (GO:0042073)

GO Molecular Function (2): metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (6): centrosome (GO:0005813), cilium (GO:0005929), intraciliary transport particle A (GO:0030991), intraciliary transport particle B (GO:0030992), ciliary tip (GO:0097542), 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
animal organ development	3
intraciliary transport particle	3
cilium organization	2
cilium	2
protein-containing complex	2
cellular anatomical structure	2
system development	1
renal system development	1
cell surface receptor signaling pathway	1
developmental process involved in reproduction	1
male gamete generation	1
circulatory system development	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cellular developmental process	1
respiratory tube development	1
respiratory system development	1
intraciliary transport	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
axis specification	1
left/right pattern formation	1
transport along microtubule	1
cation binding	1
binding	1
centriole	1
microtubule organizing center	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1324 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IFT25	IFT27	Q9BW83	997
IFT25	IFT22	Q9H7X7	993
IFT25	IFT46	Q9NQC8	992
IFT25	IFT70B	Q8N4P2	991
IFT25	IFT52	Q9Y366	990
IFT25	IFT74	Q96LB3	986
IFT25	IFT81	Q8WYA0	980
IFT25	IFT57	Q9NWB7	979
IFT25	IFT88	Q13099	975
IFT25	IFT54	Q8TDR0	974
IFT25	IFT20	Q8IY31	949
IFT25	IFT56	A0AVF1	918
IFT25	IFT172	Q9UG01	873
IFT25	IFT38	Q96AJ1	859
IFT25	IFT80	Q9P2H3	854

IntAct

69 interactions, top by confidence:

A	B	Type	Score
IFT27	IFT25	psi-mi:“MI:0915”(physical association)	0.940
IFT25	IFT27	psi-mi:“MI:0915”(physical association)	0.940
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
LCA5	SSNA1	psi-mi:“MI:0914”(association)	0.700
IFT25	IFT56	psi-mi:“MI:0914”(association)	0.690
IFT27	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
IFT172	IFT56	psi-mi:“MI:0914”(association)	0.590

BioGRID (54): HSPB11 (Two-hybrid), HSPB11 (Two-hybrid), HSPB11 (Two-hybrid), HSPB11 (Two-hybrid), HSPB11 (Affinity Capture-MS), IFT27 (Affinity Capture-MS), IFT52 (Affinity Capture-MS), IFT74 (Affinity Capture-MS), HSPB11 (Affinity Capture-MS), HSPB11 (Affinity Capture-MS), HSPB11 (Affinity Capture-MS), HSPB11 (Affinity Capture-MS), HSPB11 (Affinity Capture-MS), IFT20 (Affinity Capture-MS), IFT172 (Affinity Capture-MS)

ESM2 similar proteins: A1L1F0, A4IFG2, A5A6P1, A5GFY8, C3K0A7, D9IVE5, O43175, P10688, P10895, P18407, P25335, Q01415, Q02JZ8, Q09913, Q0V9A9, Q1ED21, Q2KIG4, Q32NH8, Q3B8C3, Q3KFK9, Q3TV70, Q48KS4, Q4K8H3, Q4R964, Q4ZVG8, Q58DU8, Q5EAD2, Q5PQR3, Q5R6J8, Q5R7M2, Q61753, Q640T1, Q68FH4, Q6AYP0, Q6DGA6, Q6LPX9, Q86WQ0, Q87YX4, Q8BIP0, Q8C726

Diamond homologs: B8LIX8, Q9D6H2, Q9Y547

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Intraflagellar transport	13	118.4×	1e-23

GO biological processes:

GO term	Partners	Fold	FDR
intraciliary anterograde transport	12	443.5×	3e-29
intraciliary transport	11	257.5×	2e-23
non-motile cilium assembly	5	60.5×	7e-07
smoothened signaling pathway	8	60.4×	2e-11
cilium assembly	12	36.8×	5e-15
spermatogenesis	5	7.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

1060 predictions. Top by Δscore:

Variant	Effect	Δscore
1:53923901:T:TG	donor_loss	1.0000
1:53923902:A:AC	donor_gain	1.0000
1:53923903:C:CC	donor_gain	1.0000
1:53923903:CCA:C	donor_gain	1.0000
1:53928445:CAT:C	acceptor_gain	1.0000
1:53928447:T:C	acceptor_gain	1.0000
1:53928447:T:TC	acceptor_gain	1.0000
1:53939978:CTCTT:C	donor_loss	1.0000
1:53939979:TCTTA:T	donor_loss	1.0000
1:53939980:CTTA:C	donor_loss	1.0000
1:53939981:TTA:T	donor_loss	1.0000
1:53939982:TA:T	donor_loss	1.0000
1:53939983:A:AC	donor_gain	1.0000
1:53939983:AC:A	donor_gain	1.0000
1:53939983:ACCC:A	donor_loss	1.0000
1:53939984:C:CC	donor_gain	1.0000
1:53939984:C:T	donor_loss	1.0000
1:53939984:CC:C	donor_gain	1.0000
1:53939984:CCCAT:C	donor_gain	1.0000
1:53940095:AACC:A	acceptor_loss	1.0000
1:53940096:ACC:A	acceptor_loss	1.0000
1:53940097:CCT:C	acceptor_loss	1.0000
1:53940098:CT:C	acceptor_loss	1.0000
1:53940099:T:A	acceptor_loss	1.0000
1:53946548:AGG:A	donor_loss	1.0000
1:53946551:T:G	donor_loss	1.0000
1:53923948:C:CC	acceptor_gain	0.9900
1:53928436:CTGTA:C	acceptor_gain	0.9900
1:53928441:C:CC	acceptor_gain	0.9900
1:53940093:TTAAC:T	acceptor_gain	0.9900

AlphaMissense

960 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:53930129:A:G	W39R	0.996
1:53930129:A:T	W39R	0.996
1:53930046:A:C	S66R	0.989
1:53930046:A:T	S66R	0.989
1:53930048:T:G	S66R	0.989
1:53930109:A:C	F45L	0.989
1:53930109:A:T	F45L	0.989
1:53930111:A:G	F45L	0.989
1:53921700:A:T	V129E	0.988
1:53928440:A:T	V69E	0.984
1:53940030:G:T	A18D	0.984
1:53921704:A:G	S128P	0.983
1:53921691:A:T	V132D	0.981
1:53930116:C:T	G43E	0.981
1:53921708:A:C	F126L	0.979
1:53921708:A:T	F126L	0.979
1:53921710:A:G	F126L	0.979
1:53930098:A:G	F49S	0.979
1:53921738:T:A	R116S	0.978
1:53921738:T:G	R116S	0.978
1:53930130:A:C	F38L	0.978
1:53930130:A:T	F38L	0.978
1:53930132:A:G	F38L	0.978
1:53921721:G:T	A122D	0.977
1:53930127:C:A	W39C	0.977
1:53930127:C:G	W39C	0.977
1:53930128:C:G	W39S	0.977
1:53930110:A:G	F45S	0.975
1:53921739:C:G	R116T	0.971
1:53921742:A:G	L115S	0.971

dbSNP variants (sampled 300 via entrez): RS1000288372 (1:53928705 T>G), RS1000308348 (1:53922256 T>C), RS1000345246 (1:53919949 C>T), RS1000397661 (1:53919517 C>G), RS1000672830 (1:53941078 T>C,G), RS1000674210 (1:53911220 T>C), RS1000676825 (1:53918203 T>G), RS1000730073 (1:53917822 C>T), RS1000745302 (1:53912903 A>C), RS1000856803 (1:53945920 G>A,C,T), RS1000860244 (1:53937015 A>G), RS1000899832 (1:53935375 A>C), RS1000912007 (1:53943042 G>C), RS1000948359 (1:53924606 G>A), RS1001084417 (1:53931270 G>A)

Disease associations

OMIM: gene MIM:620841 | disease phenotypes: MIM:191830

GenCC curated gene-disease

Mondo (1): renal agenesis (MONDO:0018470)

Orphanet (1): Renal agenesis (Orphanet:411709)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000104	Renal agenesis
HP:0008678	Renal hypoplasia/aplasia

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012353_10	Serum metabolite concentrations in chronic kidney disease	1.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Panobinostat	affects cotreatment, decreases expression	2
Cisplatin	increases expression, affects expression	2
Tretinoin	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases expression, increases abundance	1
triacsin C	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Antineoplastic Agents, Immunological	decreases expression, decreases response to substance	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Vorinostat	increases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	increases expression	1
Demecolcine	decreases expression	1
Estradiol	decreases expression	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Silver Nitrate	decreases expression	1

Clinical trials (associated diseases)

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